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Sample records for adelaide disease severity

  1. Sever's Disease

    MedlinePlus

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

  2. Mosquito communities with trap height and urban-rural gradient in Adelaide, South Australia: implications for disease vector surveillance.

    PubMed

    Johnston, Emily; Weinstein, Phillip; Slaney, David; Flies, Andrew S; Fricker, Stephen; Williams, Craig

    2014-06-01

    Understanding the factors influencing mosquito distribution is important for effective surveillance and control of nuisance and disease vector mosquitoes. The goal of this study was to determine how trap height and distance to the city center influenced the abundance and species of mosquitoes collected in Adelaide, South Australia. Mosquito communities were sampled at two heights (<2 m and ~10 m) along an urban-rural gradient. A total of 5,133 mosquitoes was identified over 176 trap nights. Aedes notoscriptus, Ae. vigilax, and Culex molestus were all more abundant in lower traps while Cx. quinquefasciatus (an ornithophilic species) was found to be more abundant in high traps. Distance to city center correlated strongly with the abundance of Ae. vigilax, Ae. camptorhynchus, Cx. globocoxitus, and Cx. molestus, all of which were most common at the sites farthest from the city and closest to the saltmarsh. Overall, the important disease vectors in South Australia (Ae. vigilax, Ae. camptorhynchus, Ae. notoscriptus, and Cx. annulirostris) were more abundant in low traps farthest from the city and closest to the saltmarsh. The current mosquito surveillance practice of setting traps within two meters of the ground is effective for sampling populations of the important disease vector species in South Australia.

  3. Chronic disease prevalence and associations in a cohort of Australian men: The Florey Adelaide Male Ageing Study (FAMAS)

    PubMed Central

    Martin, Sean A; Haren, Matthew T; Taylor, Anne W; Middleton, Sue M; Wittert, Gary A

    2008-01-01

    Background An increasing proportion of Australia's chronic disease burden is carried by the ageing male. The aim of this study was to determine the prevalence of asthma, cancer, diabetes, angina and musculoskeletal conditions and their relationship to behavioural and socio-demographic factors in a cohort of Australian men. Methods Self-reports of disease status were obtained from baseline clinic visits (August 2002 – July 2003 & July 2004 – May 2005) from 1195 randomly selected men, aged 35–80 years and living in the north-west regions of Adelaide. Initially, relative risks were assessed by regression against selected variables for each outcome. Where age-independent associations were observed with the relevant chronic disease, independent variables were fitted to customized multiadjusted models. Results The prevalence of all conditions was moderately higher in comparison to national data for age-matched men. In particular, there was an unusually high rate of men with cancer. Multiadjusted analyses revealed age as a predictor of chronic conditions (type 2 diabetes mellitus, angina, cancer & osteoarthritis). A number of socio-demographic factors, independent of age, were associated with chronic disease, including: low income status (diabetes), separation/divorce (asthma), unemployment (cancer), high waist circumference (diabetes), elevated cholesterol (angina) and a family history of obesity (angina). Conclusion Socio-demographic factors interact to determine disease status in this broadly representative group of Australian men. In addition to obesity and a positive personal and family history of disease, men who are socially disadvantaged (low income, unemployed, separated) should be specifically targeted by public health initiatives. PMID:18664294

  4. The North West Adelaide Health Study: detailed methods and baseline segmentation of a cohort for selected chronic diseases.

    PubMed

    Grant, Janet F; Chittleborough, Catherine R; Taylor, Anne W; Dal Grande, Eleonora; Wilson, David H; Phillips, Patrick J; Adams, Robert J; Cheek, Julianne; Price, Kay; Gill, Tiffany; Ruffin, Richard E

    2006-04-12

    The North West Adelaide Health Study is a population-based biomedical cohort study investigating the prevalence of a number of chronic conditions and health-related risk factors along a continuum. This methodology may assist with evidence-based decisions for health policy makers and planners, and inform health professionals who are involved in chronic disease prevention and management, by providing a better description of people at risk of developing or already diagnosed with selected chronic conditions for more accurate targeting groups for health gain and improved health outcomes. Longitudinal data will provide information on progression of chronic conditions and allow description of those who move forward and back along the continuum over time. Detailed methods are provided regarding the random recruitment and examination of a representative sample of participants (n = 4060), including the rationale for various processes and valuable lessons learnt. Self-reported and biomedical data were obtained on risk factors (smoking, alcohol consumption, physical activity, family history, body mass index, blood pressure, cholesterol) and chronic conditions (asthma, chronic obstructive pulmonary disease, diabetes) to classify participants according to their status along a continuum. Segmenting this population sample along a continuum showed that 71.5% had at least one risk factor for developing asthma, chronic obstructive pulmonary disease or diabetes. Almost one-fifth (18.8%) had been previously diagnosed with at least one of these chronic conditions, and an additional 3.9% had at least one of these conditions but had not been diagnosed. This paper provides a novel opportunity to examine how a cohort study was born. It presents detailed methodology behind the selection, recruitment and examination of a cohort and how participants with selected chronic conditions can be segmented along a continuum that may assist with health promotion and health services planning.

  5. Fisher in Adelaide.

    PubMed

    Mayo, Oliver

    2014-06-01

    R. A. Fisher spent much of his final 3 years of life in Adelaide. It was a congenial place to live and work, and he was much in demand as a speaker, in Australia and overseas. It was, however, a difficult time for him because of the sustained criticism of fiducial inference from the early 1950s onwards. The article discusses some of Fisher's work on inference from an Adelaide perspective. It also considers some of the successes arising from this time, in the statistics of field experimentation and in evolutionary genetics. A few personal recollections of Fisher as houseguest are provided. This article is the text of a article presented on August 31, 2012 at the 26th International Biometric Conference, Kobe, Japan.

  6. Case-control studies of sporadic cryptosporidiosis in Melbourne and Adelaide, Australia.

    PubMed Central

    Robertson, B.; Sinclair, M. I.; Forbes, A. B.; Veitch, M.; Kirk, M.; Cunliffe, D.; Willis, J.; Fairley, C. K.

    2002-01-01

    Few studies have assessed risk factors for sporadic cryptosporidiosis in industrialized countries, even though it may be numerically more common than outbreaks of disease. We carried out case-control studies assessing risk factors for sporadic disease in Melbourne and Adelaide, which have water supplies from different ends of the raw water spectrum. In addition to examining drinking water, we assessed several other exposures. 201 cases and 795 controls were recruited for Melbourne and 134 cases and 536 controls were recruited for Adelaide. Risk factors were similar for the two cities, with swimming in public pools and contact with a person with diarrhoea being most important. The consumption of plain tap water was not found to be associated with disease. This study emphasizes the need for regular public health messages to the public and swimming pool managers in an attempt to prevent sporadic cryptosporidiosis, as well as outbreaks of disease. PMID:12113486

  7. A Multi-Methodology for improving Adelaide's Groundwater Management

    NASA Astrophysics Data System (ADS)

    Batelaan, Okke; Banks, Eddie; Batlle-Aguilar, Jordi; Breciani, Etienne; Cook, Peter; Cranswick, Roger; Smith, Stan; Turnadge, Chris; Partington, Daniel; Post, Vincent; Pool Ramirez, Maria; Werner, Adrian; Xie, Yueqing; Yang, Yuting

    2015-04-01

    through aquitard. Risk assessment of water resources status by 2050 is achieved via uncertainty quantification of potential future scenarios. This includes several development scenarios (current or increased extraction rate) as well as different outputs from climate change predictions. It is shown that groundwater in the fractured aquifer bedrock in the hills is significantly younger than groundwater in the Adelaide plains area, indicating that the Adelaide groundwater system is, at least, partially recharged by lateral flow from water infiltrated in the hills. However, increasing ages with depth, are indicative of vertical infiltration from rainfall and possible inter-aquifer leakage. A better understanding of processes controlling these two sources of fresh groundwater, as well as evaluating their relative importance to Adelaide's groundwater budget is being thoroughly investigated using the regional numerical groundwater model. The salinity distribution along the coastline is shown not to be simply an equilibrium situation with an intruded seawater wedge extending inland. Tertiary aquifers can still contain old freshwater near the coast, and in deeper layers a hypersaline brine has been identified, which could constitute a previously-overlooked source of salinity. This study is the first comprehensive investigation of the groundwater resources within the Adelaide environment and supports strongly integrated water management of the resource.

  8. Adelaide Bartlett and the Pimlico mystery.

    PubMed Central

    Farrell, M.

    1994-01-01

    In 1886 Adelaide Bartlett stood trial at the Old Bailey for the murder of her husband, Thomas Edwin Bartlett. The court witnessed sensational evidence and the case left questions which remain unanswered. Images p1720-a p1721-a p1723-a p1723-b PMID:7820001

  9. Severe scurvy: an underestimated disease.

    PubMed

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

    2015-09-01

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

  10. The new Adelaide medium frequency Doppler radar

    NASA Astrophysics Data System (ADS)

    Reid, I. M.; Vandepeer, B. G. W.; Dillon, S.; Fuller, B.

    1993-08-01

    The Buckland Park Aerial Array (35 deg S, 138 deg E) is situated about 40 km north of Adelaide on a flat coastal plain. It was designed by Basil Briggs and Graham Elford, and constructed between 1965 and 1968. The first results were published in the late 1960's. Some aspects of the history of the array are described in Briggs (1993). A new MF Doppler Radar utilizing the array has been developed. This paper describes some of the technical details of this new facility.

  11. Smoking and periodontal disease severity.

    PubMed

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

    1995-10-01

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

  12. Radiosensitive Severe Combined Immunodeficiency Disease

    PubMed Central

    Dvorak, Christopher C.; Cowan, Morton J.

    2009-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  14. [Measurement of disease severity in dermatology].

    PubMed

    Deckert, S; Apfelbacher, C; Schmitt, J

    2015-09-01

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

  15. Mesospheric gravity-wave climatology at Adelaide

    NASA Technical Reports Server (NTRS)

    Vincent, R. A.

    1986-01-01

    The MF Adelaide partial-reflection radar has been operating continuously since November 1983. This has enabled a climatology of gravity-wave activity to be constructed for the mesosphere. The data have been analyzed for a medium-period range of 1 to 8 hr. and a longer period range between 8 and 24 hr. covering the inertio-period waves. The tidal motions have been filtered out prior to analysis. For the data analyses so far (Nov. 1983 to Dec. 1984), a number of interesting features emerged. Firstly, the wave activity at heights above 80 km shows a small seimannual variation with season with the activity being strongest in summer and winter. At heights below 80 km however, there is a similar but more marked variation with the weakest amplitudes occurring at the time of the changeovers in the prevailing circulation. If breaking gravity waves are responsible for much of the turbulence in the mesosphere, then the periods March to April and September to October might also be expected to be periods of weak turbulence. The wave field appears to be partially polarized. The meridional amplitudes are larger than the zonal amplitudes, especially in water. It is found that the degree of polarization is about 15% in summer and 30% in winter. The polarized component is found to propagate in the opposite direction to the background flow in the stratosphere, which suggests that the polarization arises through directional filtering of the waves as they propagate up from below.

  16. [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.

  17. Elucidating novel disease mechanisms in severe asthma

    PubMed Central

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

    2016-01-01

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

  18. Resveratrol: A Focus on Several Neurodegenerative Diseases

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Schwartz, Jessica L; Clinton, Tony S

    2011-12-01

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

  20. Severe Spinal Injury in Hirayama Disease

    PubMed Central

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

    2015-01-01

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

  1. Integrated water resource assessment for the Adelaide region, South Australia

    NASA Astrophysics Data System (ADS)

    Cox, James W.; Akeroyd, Michele; Oliver, Danielle P.

    2016-10-01

    South Australia is the driest state in the driest inhabited country in the world, Australia. Consequently, water is one of South Australia's highest priorities. Focus on water research and sources of water in the state became more critical during the Millenium drought that occurred between 1997 and 2011. In response to increased concern about water sources the South Australian government established The Goyder Institute for Water Research - a partnership between the South Australian State Government, the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Flinders University, University of Adelaide and University of South Australia. The Goyder Institute undertakes cutting-edge science to inform the development of innovative integrated water management strategies to ensure South Australia's ongoing water security and enhance the South Australian Government's capacity to develop and deliver science-based policy solutions in water management. This paper focuses on the integrated water resource assessment of the northern Adelaide region, including the key research investments in water and climate, and how this information is being utilised by decision makers in the region.

  2. Severe Primary Raynaud's Disease Treated with Rituximab

    PubMed Central

    Almoallim, Hani

    2016-01-01

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

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

    PubMed

    Shabrawishi, Mohammed; Albeity, Abdurahman; Almoallim, Hani

    2016-01-01

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

  4. Celiac disease presenting as severe osteopenia.

    PubMed

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

    2011-11-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2012-01-01

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

  7. Understanding the Evolution of Multimorbidity: Evidences from the North West Adelaide Health Longitudinal Study (NWAHS)

    PubMed Central

    Ruel, Guillaume; Lévesque, Jean-Frédéric; Stocks, Nigel; Sirois, Caroline; Kroger, Edeltraut; Adams, Robert J.; Doucet, Mariève; Taylor, Anne W.

    2014-01-01

    Objective The aim of this study is to describe the evolution of multimorbidity. Study Design and Setting Data from 1854 South Australians who participated in the North West Adelaide longitudinal Health Study(NWAHS) was collected between baseline (2000–2002) and follow-up (2008–2010). Status for eight chronic diseases (CDs) was determined by biomedical measurement or self-report. Chronic disease (CD) mean age of occurrence and order of appearance was investigated. Results The prevalence of multimorbidity increased from 32% to 64% during the 7.8±1.1 years of follow-up. The estimated mean age of onset of a new CD was significantly older for hypertension, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) and younger for hypercholesterolemia, asthma and other mental problem. Hypercholesterolemia was more likely to develop as a first than as a subsequent CD (39%vs.16%, p<0.0001) while CVD (1%vs.5%, p<0.0001), diabetes (5%vs.11%, p<0.001) and COPD (6%vs.16%, p<0.0001) were less likely. The presence of mood disorders at baseline was associated with an increased risk of developing other mental disorders (36%vs.12%, p<0.0001), diabetes (18%vs.9%, p<0.01) and asthma (30%vs.21%, p<0.05). Conclusion Longitudinal data could be used to study the evolution of multimorbidity and could provide information on CDs mean age of occurrence, order of appearance and impact on the development of future CDs. PMID:24798485

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-02-01

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

  11. Impact ejecta horizon within late precambrian shales, adelaide geosyncline, South australia.

    PubMed

    Gostin, V A; Haines, P W; Jenkins, R J; Compston, W; Williams, I S

    1986-07-11

    A solitary layer of shattered crustal rock fragments has been traced over a distance of 260 kilometers within folded 600-million-year-old Precambrian marine shales of the Adelaide Geosyncline, South Australia. The fragments consist entirely of acid to intermediate volcanics (approximately 1575 million years old) displaying shattered mineral grains, shock lamellae in quartz, and small shatter cones. Fragments reach 30 centimeters in diameter and show evidence of vertical fall emplacement. Available evidence points to derivation of the rock fragments from a distant hypervelocity impact into the Gawler Range Volcanics at Lake Acraman, approximately 300 kilometers west of the Adelaide Geosyncline.

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

    PubMed

    Oshrine, Benjamin; Talano, Julie-An

    2015-04-01

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

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

    PubMed

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

    1996-02-01

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

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

    PubMed

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

    1994-07-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

    Ahrens, P; Weimer, B; Hofmann, D

    1999-07-01

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

  17. 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.

  18. Metabolomic signatures associated with disease severity in multiple sclerosis

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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…

  1. 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

  2. Risk factors for deaths during the 2009 heat wave in Adelaide, Australia: a matched case-control study

    NASA Astrophysics Data System (ADS)

    Zhang, Ying; Nitschke, Monika; Krackowizer, Antoinette; Dear, Keith; Pisaniello, Dino; Weinstein, Philip; Tucker, Graeme; Shakib, Sepehr; Bi, Peng

    2017-01-01

    The extreme heat wave in Australia in 2009 resulted in significantly increased number of daily deaths. The circumstances that lead to deaths during extreme heat have not been explored before in Australia. This study aims to identify the individual and community risk factors for deaths during this extreme heat wave in Adelaide. A matched case-control study was conducted. Cases were those who died in the Adelaide metropolitan area during the heat wave period. For each case, two community controls were randomly selected, matched by age and gender. Face-to-face or telephone interviews were conducted to collect data of demographic information, living environment, social support, health status and behavioural changes during the heat wave. Descriptive analysis, as well as simple and multiple conditional logistic regressions were performed. In total, 82 deaths and 164 matched community controls were included in the analysis, with a median age of 77.5 (range 26.6-100.7). The multiple logistic regression model indicated that, compared with controls, the risk of death during the heat wave was significantly increased for people living alone (AOR = 42.31, 95 % CI 2.3, 792.8) or having existing chronic heart disease (AOR = 22.4, 95 % CI 1.7, 303.0). In addition, having air conditioning in bedrooms (AOR = 0.004, 95 % CI 0.00006, 0.28) and participating in social activities more than once a week (AOR = 0.011, 95 % CI 0.0004, 0.29) indicated significant protective effects. We have identified factors that could significantly impact on the likelihood of deaths during heat waves. Our findings could assist in the development of future intervention programs and policies to reduce mortality associated with a warmer climate.

  3. Growth Differentiation Factor 15 Predicts Chronic Liver Disease Severity

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  6. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

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

  11. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. 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.

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

    PubMed

    McKee, Kathleen E; Hackney, Madeleine E

    2013-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

    Toyofuku, Takahiro; Inoue, Yoshinori

    2016-01-01

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

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

    PubMed

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

    1989-08-01

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

  18. Bats as reservoirs of severe emerging infectious diseases.

    PubMed

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

    2015-07-02

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

  19. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Bertholini, D M; Butler, C S

    2000-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. 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

  5. Environmental determinants of severity in sickle cell disease.

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Turner, Judi A

    2009-01-01

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

  10. 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…

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

    PubMed Central

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

    2015-01-01

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

  12. 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

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

    PubMed

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

    2013-01-01

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

  14. Climate variations and salmonellosis transmission in Adelaide, South Australia: a comparison between regression models

    NASA Astrophysics Data System (ADS)

    Zhang, Ying; Bi, Peng; Hiller, Janet

    2008-01-01

    This is the first study to identify appropriate regression models for the association between climate variation and salmonellosis transmission. A comparison between different regression models was conducted using surveillance data in Adelaide, South Australia. By using notified salmonellosis cases and climatic variables from the Adelaide metropolitan area over the period 1990-2003, four regression methods were examined: standard Poisson regression, autoregressive adjusted Poisson regression, multiple linear regression, and a seasonal autoregressive integrated moving average (SARIMA) model. Notified salmonellosis cases in 2004 were used to test the forecasting ability of the four models. Parameter estimation, goodness-of-fit and forecasting ability of the four regression models were compared. Temperatures occurring 2 weeks prior to cases were positively associated with cases of salmonellosis. Rainfall was also inversely related to the number of cases. The comparison of the goodness-of-fit and forecasting ability suggest that the SARIMA model is better than the other three regression models. Temperature and rainfall may be used as climatic predictors of salmonellosis cases in regions with climatic characteristics similar to those of Adelaide. The SARIMA model could, thus, be adopted to quantify the relationship between climate variations and salmonellosis transmission.

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

    PubMed

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

    2012-01-01

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

  16. Local variability in respiratory syncytial virus disease severity

    PubMed Central

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

    1997-01-01

    

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

 PMID:9487963

  17. Genetic Influences on Cystic Fibrosis Lung Disease Severity

    PubMed Central

    Weiler, Colleen A.; Drumm, Mitchell L.

    2013-01-01

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

  18. Orthodontic approach for patients with severe periodontal disease.

    PubMed

    Arun, Tülin; Sayinsu, Korkmaz; Nalbantgil, Didem

    2005-01-01

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

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

    PubMed

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

    1984-09-01

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

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

    SciTech Connect

    Ciddio, Manuela; Gatto, Marino Casagrandi, Renato

    2015-03-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  2. Simultaneous observations of the phase-locked 2 day wave at Adelaide, Cerro Pachon, and Darwin

    NASA Astrophysics Data System (ADS)

    Walterscheid, R. L.; Hecht, J. H.; Gelinas, L. J.; MacKinnon, A.; Vincent, R. A.; Reid, I. M.; Franke, S. J.; Zhao, Y.; Taylor, M. J.; Pautet, P. D.

    2015-03-01

    The Southern Hemisphere summer 2 day wave (TDW) is the most dramatic large-scale event of the upper mesosphere. The winds accelerate over ~1 week, may attain > 70 m/s, and are often accompanied by a near disappearance of the diurnal tide and stabilization of the period close to 48 h. We denote this as the phase-locked 2 day wave (PL/TDW). We have examined airglow and meteor radar (MR) wind data from the Andes Lidar Observatory (Cerro Pachon, Chile:30°S, 289.3°E), MR data from Darwin (12.5°S, 131°E) and airglow and medium frequency radar data from the University of Adelaide (34.7°S, 138.6°E) for the behavior of the TDW during the austral summers of 2010, 2012, and 2013. The Cerro Pachon and Adelaide sites are located at similar latitudes separated in longitude by about 120°. We find a remarkable coincidence between the TDW oscillations at Chile and Adelaide for the period January-February 2010. The oscillations are nearly in phase in terms of local time and the minima and maxima repeat at nearly the same local time from cycle to cycle consistent with a phase-locked wave number 3 TDW. Data for this and other years (including Darwin) show that the amplitude of the diurnal tide decreases when the TDW is largest and that this occurs when the period is close to 48 h. These observations support the proposal that the PL/TDW is a subharmonic parametric instability wherein the diurnal tide transfers energy to a TDW that is resonant at nearly 48 h.

  3. Gravity wave motions and momentum fluxes in the middle atmosphere at Adelaide, Australia

    NASA Technical Reports Server (NTRS)

    Vincent, R. A.; Fritts, D. C.

    1985-01-01

    A study was made of gravity wave momentum fluxes in the middle atmosphere using data collected during June 1984 at Adelaide, Australia (35 deg S). The primary objectives were to identify that portion of the gravity wave spectrum that contributes most of the momentum transport and flux divergence and to examine the temporal variability of wave energies and momentum fluxes. The data were obtained with an HF (2 MHz) radar operated in a Doppler configuration with two coplanar off-vertical beams. This technique provides a direct measure of the vertical flux of horizontal momentum due to an arbitrary spectrum of gravity wave and other motions in the plane of the radar beams.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2006-09-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

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

  8. The effect of temperature on different Salmonella serotypes during warm seasons in a Mediterranean climate city, Adelaide, Australia.

    PubMed

    Milazzo, A; Giles, L C; Zhang, Y; Koehler, A P; Hiller, J E; Bi, P

    2016-04-01

    Changing trends in foodborne disease are influenced by many factors, including temperature. Globally and in Australia, warmer ambient temperatures are projected to rise if climate change continues. Salmonella spp. are a temperature-sensitive pathogen and rising temperature can have a substantial effect on disease burden affecting human health. We examined the relationship between temperature and Salmonella spp. and serotype notifications in Adelaide, Australia. Time-series Poisson regression models were fit to estimate the effect of temperature during warmer months on Salmonella spp. and serotype cases notified from 1990 to 2012. Long-term trends, seasonality, autocorrelation and lagged effects were included in the statistical models. Daily Salmonella spp. counts increased by 1·3% [incidence rate ratio (IRR) 1·013, 95% confidence interval (CI) 1·008-1·019] per 1 °C rise in temperature in the warm season with greater increases observed in specific serotype and phage-type cases ranging from 3·4% (IRR 1·034, 95% CI 1·008-1·061) to 4·4% (IRR 1·044, 95% CI 1·024-1·064). We observed increased cases of S. Typhimurium PT9 and S. Typhimurium PT108 notifications above a threshold of 39 °C. This study has identified the impact of warm season temperature on different Salmonella spp. strains and confirms higher temperature has a greater effect on phage-type notifications. The findings will contribute targeted information for public health policy interventions, including food safety programmes during warmer weather.

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2011-08-01

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

  11. Literacy--A Focus on the Future; Proceedings of the Australian Reading Conference (1st, Adelaide, August 1975)

    ERIC Educational Resources Information Center

    Elliott, Claire, Ed.; Anderson, Jonathon, Ed.

    The papers published in this volume were delivered at the First Australian Reading Conference, which was held in Adelaide in August 1975. Topics of discussion included, among others, preservice and inservice teacher education, facilities in reading, the development and use of reading materials, student motivation, children's literature, reading…

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2010-11-01

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

  16. Basement-cover interaction in the Adelaide Foldbelt, South Australia: the development of an arcuate foldbelt

    NASA Astrophysics Data System (ADS)

    Clarke, Geoffrey L.; Powell, Roger

    1989-02-01

    The upper Proterozoic- to Cambrian-aged sedimentary and volcanic rocks comprising the Adelaide Foldbelt were deformed and, in places, metamorphosed during the Cambro-Ordovician Delamerian Orogeny. Tectonic fabrics developed in the central portion of the foldbelt (Mt. Lofty Ranges) demonstrate westward transport during the orogeny. The sigmoidal shape outlined by the Kangaroo Is., Mt. Lofty Ranges, Olary portion of the foldbelt is interpreted to have been the result of dextral wrench faulting in the lower- to mid-Proterozoic basement. Thus, cover rocks overlying such basement wrench fault zones would have suffered a transpressional stress regime, giving rise to the observed fold axis oriented at an oblique angle to the thrust boundary. In the northern portion of the foldbelt (Northern Flinders Ranges), wrench faulting is interpreted to have accommodated considerable basement shortening which initiated a basement-cover décollement and resulted in thrust-bound pop-up structures in the cover.

  17. Lessons From a 17-Year Radiosurgery Experience at the Royal Adelaide Hospital

    SciTech Connect

    Roos, Daniel E.; Brophy, Brian P.; Taylor, James

    2012-01-01

    Purpose: To illustrate some of the potential pitfalls of cranial stereotactic radiosurgery (SRS) and its planning based on prospectively gathered data from a 17-year experience at the Royal Adelaide Hospital. Methods and Materials: More than 250 treatments have been planned since 1993 using previously described standard SRS techniques for intracranial benign and malignant lesions. Results: Five case studies are presented (1 meningioma, 1 acoustic neuroma, 2 solitary brain metastasis, 1 arteriovenous malformation), each of which demonstrates at least one salutary lesson. Conclusions: Because SRS delivers a highly conformal dose distribution, it is unforgiving of any geographic miss due to inaccurate outlining and thus dependent on neuroradiological expertise and collaboration. There are also potentially significant implications of misdiagnosis in SRS cases without histological proof-in particular, presumed brain metastases.

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

    PubMed

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

    2009-02-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2013-10-01

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

  1. Association between thyroid autoimmunity and fibromyalgic disease severity.

    PubMed

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

    2007-12-01

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

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

    PubMed Central

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2012-04-01

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

  8. Sever's Disease

    MedlinePlus

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

  9. Sever's Disease

    MedlinePlus

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

  10. Survival of Salmonella adelaide and fecal coliforms in coarse sands of the swan costal plain, Western Australia.

    PubMed Central

    Parker, W F; Mee, B J

    1982-01-01

    The survival of Salmonella adelaide and fecal coliforms in two coarse sands influenced by two sources of septic tank effluent was studied. The experiments were conducted in conditions that reflected the soil environment beneath functioning septic tank systems. Significant differences in survival were found with different effluent sources. In one experiment the survival of S. adelaide was similar to that of fecal coliforms; in the other it was not. The nonuniform, multiphasic nature of survival curves was variability observed in these experiments suggests that the application of such survival data for establishing management criteria for septic tank systems--by, for example, the use of soil moisture characteristic curves to give estimates of movement in the soil--is inappropriate. PMID:7103482

  11. 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.

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    PubMed

    Resch, Bernhard; Manzoni, Paolo; Lanari, Marcello

    2009-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Simultaneous Observations of the Phase-Locked Two Day Wave at Adelaide and Cerro Pachon

    NASA Astrophysics Data System (ADS)

    Walterscheid, R. L.; Hecht, J. H.; Vincent, R. A.; Franke, S. J.; Taylor, M. J.; Pautet, P.; Zhao, Y.

    2013-12-01

    The phase locked two day wave (PL/TDW) during austral summer is the most dramatic large scale event of the upper mesosphere. The PL/TDW wave can achieve amplitudes exceeding 70 m/s and involve the entire southern hemisphere and much of the northern hemisphere. The winds accelerate over a period of about 1 week and are accompanied by a near disappearance of the diurnal tide and stabilization of the two-day wave period at close to 48 hours. We have examined meteor wind data from the Andes Lidar Observatory at Cerro Pachon, Chile (30S, 70.1W) and MF radar data from the University of Adelaide (34.7S, 138.6E) located at similar latitudes. We find a remarkable coincidence between the oscillations. When adjustments for the separation in longitude are made the oscillations are nearly in phase. The amplitude of the oscillation is significantly greater at Chili, where winds approach 100 m/s. The diurnal tide is greatly diminished at both locations. These observations support the explanation that the PL/TDW is a subharmonic parametric instability of the diurnal tide (Walterscheid and Vincent, JGR, 1996). We will also present analysis of airglow data for the two-day wave at both locations.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Neugroschl, Judith; Wang, Sophia

    2012-01-01

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

  19. 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

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

    Habara, Alawi

    2016-01-01

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

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

    PubMed

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

    2012-12-01

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

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

    PubMed

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

    2001-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2003-04-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. 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.…

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2010-06-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. 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.

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2016-02-15

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

  18. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Evaluation of a heat warning system in Adelaide, South Australia, using case-series analysis

    PubMed Central

    Nitschke, Monika; Tucker, Graeme; Hansen, Alana; Williams, Susan; Zhang, Ying; Bi, Peng

    2016-01-01

    Background Heatwave warning systems aim to assist in reducing health effects during extreme heat. Evaluations of such systems have been limited. This study explored the effect of a heatwave warning programme on morbidity and mortality in Adelaide, South Australia, by comparing extreme events in 2009 and 2014, the latter with exposure to the preventive programme. Methods The health outcomes during the two heatwaves were compared using the incidence rate ratios (IRRs) of daily ambulance call-outs, emergency presentations and mortality data during the heatwaves compared with non-heatwave periods during the warm seasons. Excess or reduced numbers of cases were calculated and the differences in cases between the two heatwaves were estimated. Results IRRs for total ambulance call-outs and emergency presentations were lower during the 2014 heatwaves compared with the 2009 event. The estimated differences in health-specific outcomes between 2009 and 2014 were statistically significant with 207 (59%) for cardiac-related call-outs, 134 (30%) for renal and 145 (56%) for heat-related emergency presentations. Mortality was not reduced in 2014. There were an estimated 34.5 excess deaths in 2009 and 38.2 in 2014. Conclusions Morbidity outcomes were reduced significantly during the 2014 event. The fact that cardiac, renal and heat-related diagnoses were significantly reduced is likely to be associated with the intervention in 2014, which comprised a public warning through media and intense preventive measures directed to individual populations at risk. Further analysis of risk factors of mortality during heatwaves should be explored. PMID:27436672

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2012-11-01

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed Central

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

    2017-01-01

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

  6. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Bullock, Roger

    2006-01-01

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

  9. 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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1981-08-01

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

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

    PubMed

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

    2000-06-05

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

  13. 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.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2012-01-01

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

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

    PubMed

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

    2011-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Wakefield, Denis

    2014-08-01

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

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

    PubMed Central

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil

    PubMed Central

    Campanharo, Felipe F.; Cecatti, Jose G.; Haddad, Samira M.; Parpinelli, Mary A.; Born, Daniel; Costa, Maria L.; Mattar, Rosiane

    2015-01-01

    Background To evaluate maternal heart disease as a cause or complicating factor for severe morbidity in the setting of the Brazilian Network for Surveillance of Severe Maternal Morbidity. Methods and Findings Secondary data analysis of this multicenter cross-sectional study was implemented in 27 referral obstetric units in Brazil. From July 2009 to June 2010, a prospective surveillance was conducted among all delivery hospitalizations to identify cases of severe maternal morbidity (SMM), including Potentially Life-Threatening Conditions (PLTC) and Maternal Near Miss (MNM), using the new criteria established by the WHO. The variables studied included: sociodemographic characteristics, clinical and obstetric history of the women; perinatal outcome and the occurrence of maternal outcomes (PLTC, MNM, MD) between groups of cardiac and non-cardiac patients. Only heart conditions with hemodynamic impact characterizing severity of maternal morbidity were considered. 9555 women were included in the Network with severe pregnancy-related complications: 770 maternal near miss cases and 140 maternal death cases. A total of 293 (3.6%) cases were related to heart disease and the condition was known before pregnancy in 82.6% of cases. Maternal near miss occurred in 15% of cardiac disease patients (most due to clinical-surgical causes, p<0.001) and 7.7% of non-cardiac patients (hemorrhagic and hypertensive causes, p<0.001). Maternal death occurred in 4.8% of cardiac patients and in 1.2% of non-cardiac patients, respectively. Conclusions In this study, heart disease was significantly associated with a higher occurrence of severe maternal outcomes, including maternal death and maternal near miss, among women presenting with any severe maternal morbidity. PMID:26650684

  7. Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry.

    PubMed

    Yardimci, Nilgul; Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla

    2016-01-01

    Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD.

  8. Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry

    PubMed Central

    Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla

    2016-01-01

    Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. PMID:27843673

  9. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy

    PubMed Central

    Trollet, Capucine; Stojkovic, Tanya; de Becdelievre, Alix; Perie, Sophie; Pouget, Jean; Eymard, Bruno

    2017-01-01

    Objective: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. The genetic cause is an expanded (GCN)n mutation in the PABPN1 gene encoding for the polyadenylate-binding protein nuclear 1. We hypothesized a potential correlation between the size of the (GCN)n expansion and the severity of the phenotype. To do this, we characterized the distribution of the genotypes as well as their correlation with age at diagnosis and phenotypical features in a large cohort of heterozygous and homozygous patients with OPMD in France with a confirmed molecular diagnosis of PABPN1. Methods: We explored 354 unrelated index cases recruited between 1999 and 2014 in several neuromuscular centers in France. Results: This cohort allowed us to characterize the frequency of mutated alleles in the French population and to demonstrate a statistical correlation between the size of the expansion and the mean age at diagnosis. We also confirmed that homozygous patients present with a more severe disease. Conclusions: It has been difficult to establish phenotype–genotype correlations because of the rare nature of this disease. Our work demonstrates that patients with OPMD with longer PABPN1 expansion are on average diagnosed at an earlier age than patients with a shorter expansion, confirming that polyalanine expansion size plays a role in OPMD, with an effect on disease severity and progression. PMID:28011929

  10. Disease severity estimates - effects of rater accuracy and assessments methods for comparing treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of disease is fundamental to the discipline of plant pathology, and estimates of severity are often made visually. However, it is established that visual estimates can be inaccurate and unreliable. In this study estimates of Septoria leaf blotch on leaves of winter wheat from non-treated ...

  11. The effects of rater bias and assessment method used to estimate disease severity on hypothesis testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of bias (over and underestimates) in estimates of disease severity on hypothesis testing using different assessment methods was explored. Nearest percent estimates (NPE), the Horsfall-Barratt (H-B) scale, and two different linear category scales (10% increments, with and without addition...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Cat-scratch disease with severe pleuritis in a 6-year-old girl.

    PubMed

    Kimura, Sasagu; Hasegawa, Shunji; Yanagihara, Masashi; Inoue, Hirofumi; Matsushige, Takeshi; Tsuneoka, Hidehiro; Ichiyama, Takashi; Ohga, Shouichi

    2015-06-01

    We present the case of a 6-year-old girl with cat-scratch disease (CSD), who developed severe pleuritis without lymphadenitis. Bartonella henselae DNA was detected on real-time polymerase chain reaction (PCR) analysis of whole blood. This is the first report of CSD diagnosed on real-time PCR using whole blood.

  14. 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)

  15. Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.

    PubMed

    Pérez-Fuentes, Ricardo; Guégan, Jean-François; Barnabé, Christian; López-Colombo, Aurelio; Salgado-Rosas, Hilda; Torres-Rasgado, Enrique; Briones, Bernardo; Romero-Díaz, Mónica; Ramos-Jiménez, Judith; Sánchez-Guillén, María del Carmen

    2003-03-01

    Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease.

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

    PubMed Central

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

    2016-01-01

    Background: Anecdotal evidence indicates that some patients with dementia exhibit novel or increased positive behaviors, such as painting or singing, after the disease onset. Due to the lack of objective measures, however, the frequency and nature of these changes has not been formally investigated. Objective: This study aimed to systematically identify changes in these behaviors in the two most common younger-onset dementia syndromes: Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD). Methods: Sixty-three caregivers of patients with dementia (32 caregivers of AD patients and 31 caregivers of bvFTD patients) participated in the study. Caregivers rated the presence and frequency of positive and negative behavior changes after the onset of dementia using the Hypersensory and Social/Emotional Scale (HSS) questionnaire, focusing on three domains: sensory processing, cognitive skills, and social/emotional processing. Six composites scores were obtained reflecting these three domains (two composite scores for each domain). Differences across scores and ratios of increased and decreased behaviors were analyzed between AD and bvFTD, at different disease severity levels. Results: After disease onset, significant changes in the sensory processing domain were observed across disease severity levels, particularly in AD. Composite scores of the other domains did not change significantly. Importantly, however, some novel or increased positive behaviors were present in between 10% (Music activities) and 70% (Hypersensitivity) of AD and bvFTD patients, regardless of disease severity. Conclusions: We provide the first systematic investigation of positive behaviors in AD and bvFTD. The newly developed HSS questionnaire is a valid measure to characterize changes and progression of positive behaviors in patients with dementia. PMID:27472884

  17. 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

  18. Severe neuroinvasive West Nile virus infection in a child with undiagnosed Addison's disease

    PubMed Central

    Messacar, Kevin; Cree-Green, Melanie; Lovell, Mark; Anderson, Marsha S.; Dominguez, Samuel R.

    2014-01-01

    This report describes a case of West Nile virus (WNV) meningoencephalitis in a child who presented with fever, headache, seizures, and altered mental status, as well as hyponatremia and bronzing of the skin. Findings that led to the diagnosis of WNV included plasma-cell pleocytosis of the cerebrospinal fluid (CSF) and linear chorioretinitis on ophthalmologic exam. The diagnosis was confirmed by a positive serum and CSF WNV IgM. The acute WNV infection triggered an adrenal crisis which uncovered a new diagnosis of underlying Addison's disease. This is the first case report of severe neuroinvasive WNV disease in a pediatric patient with primary adrenal insufficiency. Neuroinvasive WNV disease is uncommon in children, but may have a more severe presentation in those with certain underlying medical conditions. PMID:25133095

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

    PubMed

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

    2016-12-01

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

  20. Non-linear increase of respiratory diseases and their costs under severe air pollution.

    PubMed

    Shen, Ying; Wu, Yiyun; Chen, Guangdi; Van Grinsven, Hans J M; Wang, Xiaofeng; Gu, Baojing; Lou, Xiaoming

    2017-05-01

    China is experiencing severe and persistent air pollution, with concentrations of fine particulate matters (PM2.5) reaching unprecedentedly high levels in many cities. Quantifying the detrimental effects on health and their costs derived from high PM2.5 levels is crucial because of the unsolved challenges to mitigate air pollution in the following decades. Using the daily monitoring data on PM2.5 concentrations and clinic visits, we found a non-linear increase of respiratory diseases, but not for other diseases (e.g., digestive diseases) under severe air pollution. We found an increase of respiratory diseases by 1% for each 10 μg m(-3) increase in PM2.5 when the annual average daily PM2.5 concentration was less than 50 μg m(-3); while this ratio was doubled (around 2%) with the daily PM2.5 concentration larger than 50 μg m(-3). Under severe air pollution (PM2.5 concentration >150 μg m(-3)), the respiratory diseases increased by over 50% compared to that in clean days. Children are more sensitive to the severe air pollution. The increase of clinic visits, especially for adults, was observed mainly in bigger (>500 beds) hospitals. Re-allocating medical resources (e.g., doctors) from big hospitals to community hospitals can benefit the respiratory patients due to air pollution. The total medical cost of clinic visits of respiratory diseases derived from PM2.5 pollution was estimated at 17.2-57.0 billion Yuan in 2014 in China, accounting for 0.5-1.6% of national total health expenditure. Because these medical costs only represent a small part of total health cost derived from air pollution, the reduction of associated health costs would be an important co-benefit of implementation of air pollution preventive strategies.

  1. 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.

  2. Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome.

    PubMed

    Forsythe, Elizabeth; Sparks, Kathryn; Best, Sunayna; Borrows, Sarah; Hoskins, Bethan; Sabir, Ataf; Barrett, Timothy; Williams, Denise; Mohammed, Shehla; Goldsmith, David; Milford, David V; Bockenhauer, Detlef; Foggensteiner, Lukas; Beales, Philip L

    2017-03-01

    Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1-19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet-Biedl syndrome-related renal disease attending the United Kingdom national Bardet-Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4-5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10, mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b-5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet-Biedl syndrome and identifies risk factors to be considered in genetic counseling.

  3. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    PubMed Central

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  4. Staphylokinase promotes the establishment of Staphylococcus aureus skin infections while decreasing disease severity.

    PubMed

    Kwiecinski, Jakub; Jacobsson, Gunnar; Karlsson, Maria; Zhu, Xuefeng; Wang, Wanzhong; Bremell, Tomas; Josefsson, Elisabet; Jin, Tao

    2013-09-01

    Skin infections are frequently caused by Staphylococcus aureus and can lead to a fatal sepsis. The microbial mechanisms controlling the initiation and progression from mild skin infection to a severe disseminated infection remain poorly understood. Using a combination of clinical data and in vitro and ex vivo assays, we show that staphylokinase, secreted by S. aureus, promoted the establishment of skin infections in humans and increased bacterial penetration through skin barriers by activating plasminogen. However, when infection was established, the interaction between staphylokinase and plasminogen did not promote systemic dissemination but induced the opening and draining of abscesses and decreased disease severity in neutropenic mice. Also, increased staphylokinase production was associated with noninvasive S. aureus infections in patients. Our results point out the dual roles of staphylokinase in S. aureus skin infections as promoting the establishment of infections while decreasing disease severity.

  5. 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.

  6. Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey

    PubMed Central

    Johnson, Lorraine; Wilcox, Spencer; Mankoff, Jennifer

    2014-01-01

    Overview. The Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQoL) indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD) and compares the severity of CLD to other chronic conditions. Methods. Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods. Results. Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs. Conclusions. CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed by this

  7. Comparisons between two biochemical markers in evaluating periodontal disease severity: a cross-sectional study

    PubMed Central

    2014-01-01

    Background The purpose of this study was to compare two biochemical markers, which have been previously used to determine the degrees of alveolar bone destruction, in evaluating periodontal disease severity. Methods The WF6 epitope of chondroitin sulfate (CS) and the alkaline phosphatase (ALP) levels were determined in gingival crevicular fluid (GCF) samples collected from patients with various degrees of disease severity, including ten patients with gingivitis (50 gingivitis sites) and 33 patients with chronic periodontitis (including gingivitis, slight, moderate, and severe periodontitis sites; n = 50 each), as well as from ten healthy volunteers (50 healthy sites) by Periopaper strips. The levels of CS and ALP were measured by an ELISA and a fluorometric assay, respectively. Results The results demonstrated low levels of CS and ALP in non-destructive and slightly destructive periodontitis sites, whereas significantly high levels of these two biomolecules were shown in moderately and severely destructive sites (p < 0.05). Although a significant difference in CS levels was found between moderate and severe periodontitis sites, no difference in ALP levels was found. Stronger correlations were found between CS levels and periodontal parameters, including probing depth, loss of clinical attachment levels, gingival index and plaque index, than between ALP levels and these parameters. Conclusions It is suggested that the CS level is a better diagnostic marker than the ALP level for evaluating distinct severity of chronic periodontitis. PMID:25174345

  8. Comorbidity Cohort (2C) study: Cardiovascular disease severity and comorbid osteoarthritis in primary care

    PubMed Central

    2012-01-01

    Background Two of the commonest chronic diseases experienced by older people in the general population are cardiovascular diseases and osteoarthritis. These conditions also commonly co-occur, which is only partly explained by age. Yet, there have been few studies investigating specific a priori hypotheses in testing the comorbid interaction between two chronic diseases and related health and healthcare outcomes. It is also unknown whether the stage or severity of the chronic disease influences the comorbidity impact. The overall plan is to investigate the interaction between cardiovascular severity groups (hypertension, ischaemic heart disease and heart failure) and osteoarthritis comorbidity, and their longitudinal impact on health and healthcare outcomes relative to either condition alone. Methods From ten general practices participating in a research network, adults aged 40 years and over were sampled to construct eight exclusive cohort groups (n = 9,676). Baseline groups were defined on the basis of computer clinical diagnostic data in a 3-year time-period (between 2006 and 2009) as: (i) without cardiovascular disease or osteoarthritis (reference group), (ii) index cardiovascular disease groups (hypertension, ischaemic heart disease and heart failure) without osteoarthritis, (iii) index osteoarthritis group without cardiovascular disease, and (vi) index cardiovascular disease groups comorbid with osteoarthritis. There were three main phases to longitudinal follow-up. The first (survey population) was to invite cohorts to complete a baseline postal health questionnaire, with 10 monthly brief interval health questionnaires, and a final 12-month follow-up questionnaire. The second phase (linkage population) was to link the collected survey data to patient clinical records with consent for the 3-year time-period before baseline, during the 12-month survey period and the 12 months after final questionnaire (total 5 years). The third phase (denominator

  9. Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease.

    PubMed

    Garcia-Nuñez, Marian; Millares, Laura; Pomares, Xavier; Ferrari, Rafaela; Pérez-Brocal, Vicente; Gallego, Miguel; Espasa, Mateu; Moya, Andrés; Monsó, Eduard

    2014-12-01

    Bronchial colonization by potentially pathogenic microorganisms (PPMs) is often demonstrated in chronic obstructive pulmonary disease (COPD), but culture-based techniques identify only a portion of the bacteria in mucosal surfaces. The aim of the study was to determine changes in the bronchial microbiome of COPD associated with the severity of the disease. The bronchial microbiome of COPD patients was analyzed by 16S rRNA gene amplification and pyrosequencing in sputum samples obtained during stable disease. Seventeen COPD patients were studied (forced expiratory volume in the first second expressed as a percentage of the forced vital capacity [FEV1%] median, 35.0%; interquartile range [IQR], 31.5 to 52.0), providing a mean of 4,493 (standard deviation [SD], 2,598) sequences corresponding to 47 operational taxonomic units (OTUs) (SD, 17) at a 97% identity level. Patients were dichotomized according to their lung function as moderate to severe when their FEV1% values were over the median and as advanced when FEV1% values were lower. The most prevalent phyla in sputum were Proteobacteria (44%) and Firmicutes (16%), followed by Actinobacteria (13%). A greater microbial diversity was found in patients with moderate-to-severe disease, and alpha diversity showed a statistically significant decrease in patients with advanced disease when assessed by Shannon (ρ = 0.528; P = 0.029, Spearman correlation coefficient) and Chao1 (ρ = 0.53; P = 0.028, Spearman correlation coefficient) alpha-diversity indexes. The higher severity that characterizes advanced COPD is paralleled by a decrease in the diversity of the bronchial microbiome, with a loss of part of the resident flora that is replaced by a more restricted microbiota that includes PPMs.

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

    SciTech Connect

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

    2014-06-10

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

  11. Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity

    PubMed Central

    Lofgren, Shane; Aren, Kathleen; Arroyo, Esperanza; Cheung, Peggie; Kuo, Alex; Valenzuela, Antonia; Haemel, Anna; Wolters, Paul J.; Gordon, Jessica; Spiera, Robert; Assassi, Shervin; Boin, Francesco; Chung, Lorinda; Fiorentino, David; Utz, Paul J.; Whitfield, Michael L.

    2016-01-01

    Systemic sclerosis (SSc) is a rare autoimmune disease with the highest case-fatality rate of all connective tissue diseases. Current efforts to determine patient response to a given treatment using the modified Rodnan skin score (mRSS) are complicated by interclinician variability, confounding, and the time required between sequential mRSS measurements to observe meaningful change. There is an unmet critical need for an objective metric of SSc disease severity. Here, we performed an integrated, multicohort analysis of SSc transcriptome data across 7 datasets from 6 centers composed of 515 samples. Using 158 skin samples from SSc patients and healthy controls recruited at 2 centers as a discovery cohort, we identified a 415-gene expression signature specific for SSc, and validated its ability to distinguish SSc patients from healthy controls in an additional 357 skin samples from 5 independent cohorts. Next, we defined the SSc skin severity score (4S). In every SSc cohort of skin biopsy samples analyzed in our study, 4S correlated significantly with mRSS, allowing objective quantification of SSc disease severity. Using transcriptome data from the largest longitudinal trial of SSc patients to date, we showed that 4S allowed us to objectively monitor individual SSc patients over time, as (a) the change in 4S of a patient is significantly correlated with change in the mRSS, and (b) the change in 4S at 12 months of treatment could predict the change in mRSS at 24 months. Our results suggest that 4S could be used to distinguish treatment responders from nonresponders prior to mRSS change. Our results demonstrate the potential clinical utility of a novel robust molecular signature and a computational approach to SSc disease severity quantification. PMID:28018971

  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 εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  13. Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?

    PubMed Central

    Duraković, Nadira; Krečak, Ivan; Perić, Zinaida; Milošević, Milan; Desnica, Lana; Pulanić, Dražen; Pusic, Iskra; Kušec, Vesna; Vrhovac, Radovan; Pavletic, Steven Z.; Nemet, Damir

    2016-01-01

    Aim To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. Methods This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician’s Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. Results YKL-40 levels were significantly higher in cGVHD patients than in controls (P = 0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P = 0.017). YKL-40 level significantly positively correlated with disease severity (P < 0.001; correlation coefficient 0.455), and activity estimated using Clinician’s Impression of Activity (P = 0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P = 0.085; correlation coefficient 0.296). Conclusion YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD. PMID:27374825

  14. The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease.

    PubMed

    Mioshi, Eneida; Foxe, David; Leslie, Felicity; Savage, Sharon; Hsieh, Sharpley; Miller, Laurie; Hodges, John R; Piguet, Olivier

    2013-01-01

    Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD- behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)-or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD.

  15. Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius

    PubMed Central

    Stenglein, Mark D.; Jacobson, Elliott R.; Wozniak, Edward J.; Wellehan, James F. X.; Kincaid, Anne; Gordon, Marcus; Porter, Brian F.; Baumgartner, Wes; Stahl, Scott; Kelley, Karen; Towner, Jonathan S.

    2014-01-01

    ABSTRACT A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. PMID:25205093

  16. Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity.

    PubMed

    Cameron, Simon J S; Lewis, Keir E; Huws, Sharon A; Lin, Wanchang; Hegarty, Matthew J; Lewis, Paul D; Mur, Luis A J; Pachebat, Justin A

    2016-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease. The bacterial metagenomes within sputum samples from eight COPD patients and ten 'healthy' smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus. The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations. Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism. This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity.

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

    PubMed Central

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

    2012-01-01

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

  18. The Correlation of CD206, CD209, and Disease Severity in Behçet's Disease with Arthritis

    PubMed Central

    Suh, Chang-Hee; Kim, Hyoun-Ah

    2017-01-01

    The purpose of this study was to clarify the role of pattern recognition receptors in Behçet's disease (BD). The frequencies of several pattern recognition receptors (CD11b, CD11c, CD32, CD206, CD209, and dectin-1) were analyzed in patients with BD by flow cytometry, and cytokine levels, interleukin- (IL-) 18, IL-23, and IL-17A, were compared in plasma. The analysis was performed in active (n = 13) and inactive (n = 13) stages of BD patients. Rheumatoid arthritis patients (n = 19), as a disease control, and healthy control (HC) (n = 19) were enrolled. The frequencies of CD11b+ and CD32+ cells were significantly increased in active BD patients compared to HC. Disease severity score was correlated to CD11c+, CD206+, and CD209+ in whole leukocytes and CD11b+, CD11c+, CD206+, CD209+, and Dectin-1+ in granulocytes. The plasma levels of IL-17A were significantly different between HC and active BD. IL-18 showed significant difference between active and inactive BD patients. From this study, we concluded the expressions of several pattern recognition receptors were correlated to the joint symptoms of BD. PMID:28377641

  19. The impact of illness in patients with moderate to severe gastro-esophageal reflux disease

    PubMed Central

    El-Dika, Samer; Guyatt, Gordon H; Armstrong, David; Degl'innocenti, Alessio; Wiklund, Ingela; Fallone, Carlo A; Tanser, Lisa; van Zanten, Sander Veldhuyzen; Heels-Ansdell, Diane; Wahlqvist, Peter; Chiba, Naoki; Barkun, Alan N; Austin, Peggy; Schünemann, Holger J

    2005-01-01

    Background Gastro-esophageal reflux disease (GERD) is a common disease. It impairs health related quality of life (HRQL). However, the impact on utility scores and work productivity in patients with moderate to severe GERD is not well known. Methods We analyzed data from 217 patients with moderate to severe GERD (mean age 50, SD 13.7) across 17 Canadian centers. Patients completed three utility instruments – the standard gamble (SG), the feeling thermometer (FT), and the Health Utilities Index 3 (HUI 3) – and several HRQL instruments, including Quality of Life in Reflux and Dyspepsia (QOLRAD) and the Medical Outcomes Short Form-36 (SF-36). All patients received a proton pump inhibitor, esomeprazole 40 mg daily, for four to six weeks. Results The mean scores on a scale from 0 (dead) to 1 (full health) obtained for the FT, SG, and HUI 3 were 0.67 (95% CI, 0.64 to 0.70), 0.76 (95% CI, 0.75 to 0.80), and 0.80 (95% CI, 0.77 to 0.82) respectively. The mean scores on the SF-36 were lower than the previously reported Canadian and US general population mean scores and work productivity was impaired. Conclusion GERD has significant impact on utility scores, HRQL, and work productivity in patients with moderate to severe disease. Furthermore, the FT and HUI 3 provide more valid measurements of HRQL in GERD than the SG. After treatment with esomeprazole, patients showed improved HRQL. PMID:16004616

  20. Predictors of progression to severe Alzheimer’s disease in an incidence sample

    PubMed Central

    Rabins, Peter V.; Schwartz, Sarah; Black, Betty S.; Corcoran, Christopher; Fauth, Elizabeth; Mielke, Michele; Christensen, Jessica; Lyketsos, Constantine; Tschanz, JoAnn

    2013-01-01

    Background Little is known about factors influencing time to severe Alzheimer’s disease (AD). Methods Incident cases of AD in the Cache County Memory Study were identified. Severe AD was defined as Mini-Mental State Examination score of ≤10 or Clinical Dementia Rating Scale score of 3; cases with either Mini-Mental State Examination score of ≥16 or Clinical Dementia Rating <2 were not categorized as severe AD. Kaplan–Meier, log-rank tests, and Cox analyses were used to identify demographic, clinical, and genetic correlates of time to progression to severe AD. Results Sixty-eight of 335 cases of incident AD developed severe dementia. In bivariate analyses, female gender, less than high school education, at least one clinically significant Neuropsychiatric Inventory domain at baseline, and the youngest and oldest ages exhibited shorter time to severe AD. In competing risk analysis, subjects with mild or at least one clinically significant Neuropsychiatric Inventory domain score, and subjects with worse health were more likely to progress to severe dementia or death. Conclusions Demographic and clinical variables predict progression to severe AD. Further study should examine whether these relationships are causal or correlational. PMID:23123228

  1. 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.

  2. What Counts as Quality in Education? Australian College of Educators (ACE) National Conference Proceedings (Adelaide, Australia, September 11-12, 2014)

    ERIC Educational Resources Information Center

    Ghirelli, Paola S., Ed.

    2014-01-01

    The 2014 Australian College of Educators (ACE) National Conference was held September 11-12 in Adelaide, Australia, with the theme, "What counts as quality in education?" There has been concern with a general downward trend in Australia's performance on international measures of student achievement, but there is equal concern over the…

  3. Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias

    PubMed Central

    Kazui, Hiroaki; Yoshiyama, Kenji; Kanemoto, Hideki; Suzuki, Yukiko; Sato, Shunsuke; Hashimoto, Mamoru; Ikeda, Manabu; Tanaka, Hibiki; Hatada, Yutaka; Matsushita, Masateru; Nishio, Yoshiyuki; Mori, Etsuro; Tanimukai, Satoshi; Komori, Kenjiro; Yoshida, Taku; Shimizu, Hideaki; Matsumoto, Teruhisa; Mori, Takaaki; Kashibayashi, Tetsuo; Yokoyama, Kazumasa; Shimomura, Tatsuo; Kabeshita, Yasunobu; Adachi, Hiroyoshi; Tanaka, Toshihisa

    2016-01-01

    Background/Aims Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD). Methods We gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer’s disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR). Results Significant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD. Conclusions As dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear. PMID:27536962

  4. Human Immunodeficiency Virus Disease Severity, Psychiatric Symptoms, and Functional Outcomes in Perinatally Infected Youth

    PubMed Central

    Nachman, Sharon; Chernoff, Miriam; Williams, Paige; Hodge, Janice; Heston, Jerry; Gadow, Kenneth D.

    2012-01-01

    Objective To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. Design Cross-sectional analysis of entry data from an observational, prospective 2-year study. Logistic and linear regression models adjusted for potential confounders were used. Setting Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. Participants Youth aged 6 to 17 years who had HIV infection (N=319). Main Exposures Antiretroviral treatment and perinatal HIV infection. Main Outcome Measures Youth and primary care-givers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social, and academic functioning; and quality of life. Results Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms, older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms, higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage at study entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms. A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. Conclusion Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic, and social

  5. Severe infectious diseases of childhood as monogenic inborn errors of immunity.

    PubMed

    Casanova, Jean-Laurent

    2015-12-22

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

  6. 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

  7. Autonomic nervous system dysfunction and their relationship with disease severity in children with atopic asthma.

    PubMed

    Emin, Ozkaya; Esra, Gursoy; Aysegül, Demir; Ufuk, Erenberk; Ayhan, Sogut; Rusen, Dundaroz M

    2012-09-30

    The involvement of autonomic imbalance has been reported in the pathogenesis of allergic diseases. The aim of this study was to investigate the association between the clinical severity of childhood asthma with autonomic nervous system (ANS) dysfunction and to define whether the severity of asthma correlates with ANS activity. In this case-control study, we evaluated the ANS activity by testing heart rate variability (HRV) and sympathetic skin response (SRR) in 77 asthmatic children, age 7-12 yrs, who had no co-morbidity and compared them with 40 gender- and age-matched control subjects. According to the severity of their asthma, study subjects were further divided into three groups: I (mild asthmatics), II (moderate asthmatics), and III (severe asthmatics). Inter-group ANS scale scores differed significantly (p<0.01) between Groups I and III and between Groups II and III. Combined use of HRV and SSR provides a higher degree of sensitivity for assessing disease severity in cases of pediatric asthma.

  8. Mechanisms regulating immunity and disease severity following high and low virulence BVDV type 2 infection in neonatal calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute bovine viral diarrhea virus (BVDV) infection can result in a range of disease outcomes from subclinical in the case of low virulence (LV) strains, to anorexia, fever, bloody diarrhea, and death in cases of severe acute disease. Despite the significant range of clinical disease severity, it rem...

  9. Violet diode laser-induced chlorophyll fluorescence: a tool for assessing mosaic disease severity in cassava (Manihot esculenta Crantz) cultivars.

    PubMed

    Anderson, Benjamin; Eghan, Moses J; Asare-Bediako, Elvis; Buah-Bassuah, Paul K

    2012-01-01

    Violet diode laser-induced chlorophyll fluorescence was used in agronomical assessment (disease severity and average yield per plant). Because cassava (Manihot esculenta Crantz) is of economic importance, improved cultivars with various levels of affinity for cassava mosaic disease were investigated. Fluorescence data correlated with cassava mosaic disease severity levels and with the average yield per plant.

  10. Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson's disease.

    PubMed

    Barbieri, Fabio A; Polastri, Paula F; Baptista, André M; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Beretta, Victor S; Gobbi, Lilian T B

    2016-04-01

    The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson's disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n=8) and bilateral group (n=11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups×medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups×medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior-posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior-posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks.

  11. Hispanic Americans and African Americans with multiple sclerosis have more severe disease course than Caucasian Americans.

    PubMed

    Ventura, Rachel E; Antezana, Ariel O; Bacon, Tamar; Kister, Ilya

    2016-11-01

    Whether disease course in Hispanic Americans (HA) with multiple sclerosis (MS) is different from Caucasian Americans (CA) or African Americans (AA) is unknown. We compared MS severity in the three main ethnic populations in our tertiary MS clinics using disease duration-adjusted rank score of disability: Patient-Derived Multiple Sclerosis Severity Score (P-MSSS). The age- and gender-adjusted P-MSSS was significantly higher in HA (3.9 ± 2.6) and AA (4.5 ± 3.0) compared to CA (3.4 ± 2.6; p < 0.0001 for both). Adjusting for insurance did not change these results. These findings suggest that HA, as AA, have more rapid disability accumulation than CA.

  12. Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000.

    PubMed

    Tyndall, A; Passweg, J; Gratwohl, A

    2001-07-01

    An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning. Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported. Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA. Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA. After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and IBMTR data forms was emphasised.

  13. P-wave dispersion and its relationship with the severity of the disease in patients with stable coronary artery disease

    PubMed Central

    Akin, Fatih; Firatli, Inci; Katkat, Fahrettin; Gurmen, Tevfik; Ayca, Burak; Kalyoncuoglu, Muhsin; Abaci, Okay; Sari, Mustafa; Ersanli, Murat; Kucukoglu, Serdar; Yigit, Zerrin

    2014-01-01

    OBJECTIVE: P- wave dispersion (PD) is an indicator of inhomogeneous and discontinuous propagation of sinus impulses. In the present study we aimed to investigate the PD and its association with the severity of the disease. in patients with stable coronary artery disease. METHODS: We prospectively analyzed 60 subjects with coronary artery disease (CAD) and 25 subjects with nor-mal coronary angiograms (control group). The maximum and minimum P-wave duration and PD were measured from the 12-lead surface electrocardiograms. The CAD severity was assessed by the severity score (Gensini score) and the number of vessels involved (vessel score). RESULTS: P max was longer in CAD group compared with the control group (p<0.001). PD was greater in the CAD group, compared with the control group (p<0.001). However, P min did not differ between the two groups. In bi-variate correlation, increased PD was correlated with presence of diabetes mellitus (r=0.316, p=0.014), smoking (r=0.348, p=0.006), left ventricular ejection fraction (r=-0.372, p=0.003), vessel score (r=0.848, p=0.001), and Gensini score (r=0.825, p=0.001). Multiple linear regression analysis showed that PD was independently associ¬ated with vessel score ((3=0.139, p=0.002) and Gensini score ((3=0.132, p=0.007). CONCLUSION: PD was greater in patients with CAD than in controls and it was associated with CAD severity. PMID:28058305

  14. Creation of a nonsurgical papilla in orthodontic treatment with severe periodontal disease: a case report.

    PubMed

    Sato, Shuichi; Nomura, Naoyuki; Kawashima, Hideyuki; Ito, Koichi

    2007-04-01

    This case report describes the nonsurgical creation of an interdental papilla in orthodontic therapy of a patient with severe periodontal disease. A large diastema between the maxillary incisors was closed completely, and the lost interdental papilla was re-created by orthodontic therapy after nonsurgical periodontal therapy. Radiographs showed improvement of the bone defect. Periodontal/orthodontic soft tissue manipulation is a nonsurgical technique that can lead to reformation of the interdental papilla, provided that periodontal health is maintained.

  15. A Systematic Review of Assessment and Treatment of Moderate to Severe Alzheimer's Disease

    PubMed Central

    Schmitt, Frederick A.; Wichems, Christine H.

    2006-01-01

    Objective: The systematic, large-scale study of therapies for moderate to severe Alzheimer's disease (AD) is a relatively recent advancement in the field. This review describes for the general practitioner the characterization of moderate to severe AD, discusses the development of metrics sensitive to the constellation of symptoms in these patients, and critically evaluates the use of those measures in moderate to severe AD clinical trials. Data Sources: Published clinical trials obtained by MEDLINE searches used the following key words: moderate AD, severe AD, donepezil, rivastigmine, galantamine, memantine, and anti-dementia agents. Clinical trials were limited by language (English), study type (clinical trial), and publication dates (1990–2005). Study Selection: Nine clinical trials comprise the studies conducted to date in moderate to severe AD and include 5 prospective randomized clinical trials (3 for memantine, 2 for donepezil) and 4 retrospective subanalyses (2 for galantamine, 2 for rivastigmine) of primary datasets. Data Extraction: Clinical trials are summarized and major findings are reviewed. Data Synthesis: The data reviewed support the decision to initiate and maintain treatment in moderate to severe AD patients. Conclusions: The development and implementation of improved metrics for moderate to severe AD patients has revealed that meaningful benefits are attainable in this patient population by treatment with the N-methyl-D-aspartate receptor antagonist memantine. Evidence also indicates a benefit from cholinesterase inhibitor treatment, although further study of these agents in this patient population is warranted. PMID:16912819

  16. [Several common biases and control measures during sampling survey of eye diseases in China].

    PubMed

    Guan, Huai-jin

    2008-06-01

    Bias is a common artificial error during sampling survey in eye diseases, and is a major impact factor for validity and reliability of the survey. The causes and the control measures of several biases regarding current sampling survey of eye diseases in China were analyzed and discussed, including the sampling bias, non-respondent bias, and diagnostic bias. This review emphasizes that controlling bias is the key to ensure quality of sampling survey. Random sampling, sufficient sample quantity, careful examination and taking history, improving examination rate, accurate diagnosis, strict training and preliminary study, as well as quality control can eliminate or minimize biases and improve the sampling survey quality of eye diseases in China

  17. Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine.

    PubMed Central

    Posthuma, E F; Westendorp, R G; van der Sluys Veer, A; Kluin-Nelemans, J C; Kluin, P M; Lamers, C B

    1995-01-01

    A 19 year old man with a history of Crohn's disease treated with azathioprine and prednisone, died after a primary infection with Epstein-Barr virus. He had the characteristics of the virus associated haemophagocytic syndrome, a rare complication of viral infections, which consists of fever, constitutional symptoms, hepatosplenomegaly, liver function and coagulation abnormalities, and hypertriglyceridaemia. Additionally, there was pain, cytopenia, and histiocytic hyperplasia in the bone marrow, spleen, or lymph nodes. This severe complication has been reported previously in renal transplant patients, but not in those with inflammatory bowel disease taking azathioprine. The immunosuppressive therapy may have contributed to this fatal complication of infectious mononucleosis, and this complication should be considered when treating a patient with inflammatory bowel disease with azathioprine. Images p312-a PMID:7883236

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

    PubMed

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

    1978-10-01

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

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

    PubMed

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

    2010-06-01

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

  20. 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

  1. Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis model.

    PubMed

    Kim, Kyoung Soo; Kim, Myung-Hwan; Yeom, Mijung; Choi, Hyun Mi; Yang, Hyung-In; Yoo, Myung Chul; Hahm, Dae-Hyun

    2012-12-01

    This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.

  2. AGER -429T/C Is Associated with an Increased Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet; Abely, M.; Belleguic, C.; Bellon, G.; Bessaci, K.; Bonnel, A.S.; Brémont, F.; Brouard, J.; Bui, S.; Chiron, R.; Chumbi-Flores, R.; Clement, A.; Corvol, H.; Dalphin, J.C.; Dalphin, M.L.; David, V.; de Miranda, S.; Derelle, J.; Domblides, P.; Dominique, S.; Dubus, J.C.; Durieu, I.; Dury, S.; Ellaffi, M.; Epaud, R.; Fanton, A.; Fayon, M.; Fleurence, E.; Foucaud, P.; Ginies, J.L.; Godbert, B.; Grenet, D.; Guillot, M.; Héraud, M. C.; Housset, B.; Hubert, D.; Huet, F.; Kessler, R.; Labbé, A.; Laurans, M.; le Bourgeois, M.; le Roux, P.; Llerena, C.; Loeuille, G.A.; Marguet, C.; Mely, L.; Moisan-Petit, V.; Munck, A.; Murris-Espin, M.; Nove Josserand, R.; Pautard, J.C.; Pin, I.; Pramil, S.; Prevotat, A.; Rault, G.; Reix, P.; Remus, N.; Renouil, M.; Reynaud-Gaubert, M.; Richaud Thiriez, B.; Roussey, M.; Sermet-Gaudelus, I.; Stremler, N.; Uffredi, M.L.; Urban, T.; Vigneron, P.; Wallaert, B.; Weiss, L.

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease. PMID:22860029

  3. AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.

    PubMed

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

  4. Lipoprotein (a) Levels in Relation to Severity of Coronary Artery Disease in North Indian Patients

    PubMed Central

    Ashfaq, Fauzia; Goel, Pravin Kumar; Sethi, Rishi; Khan, Mohd Idrees; Ali, Wahid; Idris, Mohd Zafar

    2013-01-01

    Background: Lipoprotein (a) [Lp (a)] is an established risk marker of coronary artery disease which is independent from other risk factors. Objective: The aim was to address the association between Lp (a) and CAD risk in North Indians. To evaluate whether high levels of lipoprotein (a) [Lp (a)] is a predictor of risk and is related to the severity of CAD. Materials and Methods: This was a cross-sectional study done on 360 patients presenting with chest pain. Coronary angiography revealed CAD in 270 patients and 90 patients without CAD. Lipoprotein (a) level, lipid profile, fasting blood glucose, anthropometric and clinical parameters were analyzed. Results: Lipoprotein (a) 21.0 mg/dL is associated with the presence of coronary lesions (P = 0.0001). A highly significant difference in Lp (a) levels was observed between normal coronaries vs. single-vessel disease, double-and triple-vessel disease ( P < 0.0001). Body mass index (BMI) was significantly raised in CAD group compared to normal coronary. Conclusion: Multivariate analysis found that Lp (a) was considered an independent predictor for severity of CAD and Lp (a) levels 21.0 mg/dL are associated with severe patterns of coronary atherosclerosis. PMID:23580919

  5. 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.

  6. Awareness of and attitudes towards heat waves within the context of climate change among a cohort of residents in Adelaide, Australia.

    PubMed

    Akompab, Derick A; Bi, Peng; Williams, Susan; Grant, Janet; Walker, Iain A; Augoustinos, Martha

    2012-12-20

    Heat waves are a public health concern in Australia and unprecedented heat waves have been recorded in Adelaide over recent years. The aim of this study was to examine the perception and attitudes towards heat waves in the context of climate change among a group of residents in Adelaide, an Australian city with a temperate climate. A cross-sectional study was conducted in the summer of 2012 among a sample of 267 residents. The results of the survey found that television (89.9%), radio (71.2%), newspapers (45.3%) were the main sources from which respondents received information about heat waves. The majority of the respondents (73.0%) followed news about heat waves very or somewhat closely. About 26.6% of the respondents were extremely or very concerned about the effects of heat waves on them personally. The main issues that were of personal concern for respondents during a heat wave were their personal comfort (60.7%), their garden (48.7%), and sleeping well (47.6%). Overall, respondents were more concerned about the impacts of heat waves to the society than on themselves. There was a significant association between gender (χ² = 21.2, df = 3, p = 0.000), gross annual household income (p = 0.03) and concern for the societal effects of heat waves. Less than half (43.2%) of the respondents believed that heat waves will extremely or very likely increase in Adelaide according to climate projections. Nearly half (49.3%) believed that the effects of heat waves were already being felt in Adelaide. These findings may inform the reframing and communication strategies for heat waves in Adelaide in the context of climate change.

  7. Awareness of and Attitudes towards Heat Waves within the Context of Climate Change among a Cohort of Residents in Adelaide, Australia

    PubMed Central

    Akompab, Derick A.; Bi, Peng; Williams, Susan; Grant, Janet; Walker, Iain A.; Augoustinos, Martha

    2012-01-01

    Heat waves are a public health concern in Australia and unprecedented heat waves have been recorded in Adelaide over recent years. The aim of this study was to examine the perception and attitudes towards heat waves in the context of climate change among a group of residents in Adelaide, an Australian city with a temperate climate. A cross-sectional study was conducted in the summer of 2012 among a sample of 267 residents. The results of the survey found that television (89.9%), radio (71.2%), newspapers (45.3%) were the main sources from which respondents received information about heat waves. The majority of the respondents (73.0%) followed news about heat waves very or somewhat closely. About 26.6% of the respondents were extremely or very concerned about the effects of heat waves on them personally. The main issues that were of personal concern for respondents during a heat wave were their personal comfort (60.7%), their garden (48.7%), and sleeping well (47.6%). Overall, respondents were more concerned about the impacts of heat waves to the society than on themselves. There was a significant association between gender (χ² = 21.2, df = 3, p = 0.000), gross annual household income (p = 0.03) and concern for the societal effects of heat waves. Less than half (43.2%) of the respondents believed that heat waves will extremely or very likely increase in Adelaide according to climate projections. Nearly half (49.3%) believed that the effects of heat waves were already being felt in Adelaide. These findings may inform the reframing and communication strategies for heat waves in Adelaide in the context of climate change. PMID:23343978

  8. Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

    PubMed Central

    Potts, James A.; Gibbons, Robert V.; Rothman, Alan L.; Srikiatkhachorn, Anon; Thomas, Stephen J.; Supradish, Pra-on; Lemon, Stephenie C.; Libraty, Daniel H.; Green, Sharone; Kalayanarooj, Siripen

    2010-01-01

    Background Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. Methods and Findings We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different categories of dengue disease severity to distinguish between patients at elevated risk of developing a severe dengue illness and those at low risk. A diagnostic algorithm using WBC count, percent monocytes, platelet count, and hematocrit achieved 97% sensitivity to identify patients who went on to develop DSS while correctly excluding 48% of non-severe cases. Addition of an indicator of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC count, percent neutrophils, AST, platelet count, and age. Conclusions This study identified two easily applicable diagnostic algorithms using early clinical indicators obtained within the first 72 hours of illness onset. The algorithms have high sensitivity to distinguish patients at elevated risk of developing severe dengue illness from patients at low risk, which included patients with mild dengue and other non-dengue febrile illnesses. Although these algorithms need to be validated in other populations, this study highlights the potential usefulness of specific clinical indicators early in illness. PMID:20689812

  9. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease.

    PubMed

    Montgomery, Gregory S; Sagel, Scott D; Taylor, Amy L; Abman, Steven H

    2006-04-01

    Cystic fibrosis (CF) patients with advanced lung disease are at risk for developing pulmonary vascular disease and pulmonary hypertension, characterized by progressive exercise intolerance beyond the exercise-limiting effects of airways disease in CF. We report on a patient with severe CF lung disease who experienced clinically significant improvements in exercise tolerance and pulmonary hypertension without changing lung function during sildenafil therapy.

  10. 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

  11. Impact of the severity of chronic periodontal disease on quality of life.

    PubMed

    Meusel, Dayse R D Z; Ramacciato, Juliana C; Motta, Rogério H L; Brito Júnior, Rui B; Flório, Flávia M

    2015-06-01

    We examined the impact of the severity of periodontal disease on quality of life in adults with chronic periodontitis. One hundred patients (age, 30-58 years) who were assisted at the Basic Health Care Unit in the city of Passo Fundo, RS, Brazil underwent clinical examination of all standing teeth, including gingival bleeding on probing, probing depth, and clinical attachment level, and were divided into those with mild/moderate (n = 49; group G1) and severe (n = 51; group G2) chronic periodontitis. The participants were then interviewed, using a structured questionnaire. The Brazilian Oral Health Impact Profile (OHIP-14Br) questionnaire was used to assess oral health-related quality of life. Associations were investigated, and those with a P value of less than 0.2 were tested using multiple logistic regression models. Those with a P value of 0.05 or less were considered significant. There was a significant association between G2 and education level (P = 0.00051). OHIP-14Br score was higher for G2 (24.1) than for G1 (18.2) (P = 0.0455). Severe chronic periodontitis was associated with low education level (≤8 years) (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.3) and pronunciation difficulties (OR, 3.1; 95% CI, 1.0-9.3). In conclusion, periodontal disease severity was inversely associated with quality of life among Brazilian adults.

  12. Chronic nitrate enrichment decreases severity and induces protection against an infectious disease.

    PubMed

    Smallbone, Willow; Cable, Jo; Maceda-Veiga, Alberto

    2016-05-01

    Excessive fertilisation is one of the most pernicious forms of global change resulting in eutrophication. It has major implications for disease control and the conservation of biodiversity. Yet, the direct link between nutrient enrichment and disease remains largely unexplored. Here, we present the first experimental evidence that chronic nitrate enrichment decreases severity and induces protection against an infectious disease. Specifically, this study shows that nitrate concentrations ranging between 50 and 250mgNO3(-)/l reduce Gyrodactylus turnbulli infection intensity in two populations of Trinidadian guppies Poecilia reticulata, and that the highest nitrate concentration can even clean the parasites from the fish. This added to the fact that host nitrate pre-exposure altered the fish epidermal structure and reduced parasite intensity, suggests that nitrate protected the host against the disease. Nitrate treatments also caused fish mortality. As we used ecologically-relevant nitrate concentrations, and guppies are top-consumers widely used for mosquito bio-control in tropical and often nutrient-enriched waters, our results can have major ecological and social implications. In conclusion, this study advocates reducing nitrate level including the legislative threshold to protect the aquatic biota, even though this may control an ectoparasitic disease.

  13. Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS. PMID:25116424

  14. Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease

    SciTech Connect

    Dunn, R.F.; Uren, R.F.; Sadick, N.; Bautovich, G.; McLaughlin, A.; Hiroe, M.; Kelly, D.T.

    1982-10-01

    To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 +/- 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 +/- 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p less than 0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p less than 0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.

  15. Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease

    SciTech Connect

    Dunn, R.F.; Uren, R.F.; Sadick, N.; Bautovich, G.; McLaughlin, A.; Hiroe, M.; Kelly, D.T.

    1982-10-01

    To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 +/- 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 +/- 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p<0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p<0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.

  16. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis.

    PubMed

    O'Sullivan, David; Green, Laura; Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS.

  17. Computed tomography phenotypes in severe, early-onset chronic obstructive pulmonary disease.

    PubMed

    Hersh, Craig P; Jacobson, Francine L; Gill, Ritu; Silverman, Edwin K

    2007-12-01

    Subjects with severe chronic obstructive pulmonary disease (COPD) may have marked differences in emphysema severity on chest computed tomography (CT) scans. Although many patients with severe COPD will have chest CTs performed during their clinical care, chest CTs have not been widely included in epidemiologic and genetic studies of COPD. We sought to determine whether chest CT scans performed for clinical indications can provide useful data in an epidemiologic study of COPD and to determine whether chest CT scans can be used to define subtypes of severe, early-onset COPD. Clinical chest CT scans on 91 probands in the Boston Early-Onset COPD Study were retrospectively reviewed by 2 pulmonologists and 1 to 2 chest radiologists, using a semi-quantitative emphysema severity score, ranging from 0-24. 88 of 91 chest CT scans were suitable for emphysema analysis. There was a wide range of emphysema severity, from mild to severe (1.3-23.7). Emphysema-predominant subjects (upper 3 quartiles of emphysema scores) had more severe airflow obstruction than airway-predominant subjects (lowest quartile of emphysema scores): FEV(1) 17.4% vs. 22.4% predicted, p=0.009. A higher percentage of airway-predominant subjects had a positive bronchodilator response (28.6% vs. 6.7%, p=0.009). Airway-predominant subjects also had a higher frequency of physician-diagnosed asthma (p=0.04) and a trend towards higher serum immunoglobulin E levels (p=0.09). Analysis of siblings of early-onset COPD probands suggested a genetic contribution to the subgroups. Using clinical chest CT scans, we were able to identify an airway-predominant subgroup with asthma-like features among subjects with severe, early-onset COPD.

  18. Exploration of the perceptions, barriers and drivers of pharmacogenomics practice among hospital pharmacists in Adelaide, South Australia.

    PubMed

    Dias, M M; Ward, H M; Sorich, M J; McKinnon, R A

    2014-06-01

    There is little literature regarding the barriers to the uptake of pharmacogenomics (PG) in pharmacy practice, especially with respect to Australia. To date, pharmacists have seldom been engaged in discussions of these issues. This study aimed to obtain an in-depth understanding of these barriers by interviewing pharmacists in Adelaide, South Australia. Ethics approved semistructured interviews were carried out with 21 public hospital pharmacists. Analysis of the data identified themes including: confidence to engage in PG, clinician acceptance of a pharmacist PG role, and the importance of timely and relevant PG education. Interviewees thought that pharmacists could have a greater participation in PG in the future, but they questioned whether this would be possible at the moment given, among other factors, existing time and work constraints.

  19. Association of Serum Irisin Concentrations with Presence and Severity of Coronary Artery Disease

    PubMed Central

    Deng, Wen

    2016-01-01

    Background Irisin, an exercise-induced myokine, is closely correlated with obesity and body mass index. Obesity is one risk factor of coronary artery disease (CAD). Therefore, the present study aimed to determine if serum irisin concentrations are correlated with the presence and severity of CAD. Material/Methods Serum irisin concentrations were determined in 350 patients with CAD and in 214 healthy subjects. The severity of CAD was assessed by coronary atherosclerosis index (CAI). Results Serum irisin concentrations were significantly lower in CAD patients compared with healthy controls. Multivariable logistic regression analysis revealed that serum irisin concentrations were an independent determinant of the presence of CAD. In addition, Pearson correlation analysis showed that serum irisin concentrations were negatively correlated with CAI in CAD patients. Conclusions Decreased serum irisin concentrations may be associated with the presence and severity of CAD. PMID:27815563

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

    PubMed

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

    2008-02-01

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

  1. Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease

    PubMed Central

    Lu, Miao; Tu, Su; Wang, Xiangming; Zhou, Chuanwei; Wang, Sen; Pang, Sisi; Qian, Jin; Ge, Yiyue; Guo, Yan

    2017-01-01

    Objectives. To investigate the potential association of a set of serum cytokines with the severity of coronary artery disease (CAD). Methods. A total of 201 patients who underwent coronary angiography for chest discomfort were enrolled. The concentrations of serum IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-9, and IL-17 were determined by xMAP multiplex technology. The CAD severity was assessed by Gensini score (GS). Results. The serum levels of TNF-α, IL-6, IL-9, IL-10, and IL-17 were significantly higher in high GS group (GS ≥ 38.5) than those in low GS group (GS < 38.5). Positive correlations were also found between these cytokines and the severity of CAD. After adjustment for other associated factors, three serum cytokines (IL-6, IL-9, and IL-17) and two clinical risk factors (creatinine and LDL-C) were identified as the independent predictors of increased severity of CAD. ROC curve analysis revealed that the logistic regression risk prediction model had a good performance on predicting CAD severity. Conclusions. Combinatorial analysis of serum cytokines (IL-6, IL-9, and IL-17) with clinical risk factors (creatinine and LDL-C) may contribute to the evaluation of the severity of CAD and may help guide the risk stratification of angina patients, especially in primary health facilities and in the catheter lab resource-limited settings. PMID:28349060

  2. Surgical treatment of patients with kidney and bladder cancer in case of severe concomitant cardiovascular diseases.

    PubMed

    Davydov, M I; Akchurin, R S; Gerasimov, S S; Belov, Yu V; Matveev, V B; Brand, Ya B; Cheban, O I

    2014-01-01

    It was operated 17 patients with kidney and bladder cancer against the background of severe concomitant coronary artery disease (52.9%), aortic aneurysm (35.3%) or combination of coronary artery disease with Leriche syndrome (5.9%) or hemodynamically significant stenosis of internal carotid artery (5.9%). Patients were operated for the period from 1998 to 2012. All patients were male at the age from 39 to 80 years (mean 62.1 years). The first stage of kidney cancer was diagnosed in 8 (53.3%) patients, the second stage - in 1 (6.7%) patient, the third stage - in 2 (13.3%) patients and the fourth stage was observed in 4 (26.7%) patients. Bladder cancer had 1 and 2 stages. Simultaneous operations were performed in 3 (17.6%) patients. 12 (70.6%) patients were operated consequentially. Surgery for kidney cancer was not done in 2 (11.8%) of 17 patients because of patient death after coronary bypass surgery or patient refusal of surgery after carotid arteries stenting. Intraoperative and postoperative complications have been developed in 9 (52.9%) of 17 patients. 2 (11.8%) patients died. The complications frequency and mortality after simultaneous operations were 25% (1 of 4) and 0. These parameters were 57.1% (8 of 14) and 14.3% respectively in case of consequent tactics. It was not observed myocardial infarction and aortic aneurysm rupture after surgeries for kidney and bladder cancer. Overall 1, 3, 5 - year survival of patients with kidney cancer and severe concomitant cardiovascular diseases was 100%, 73.3% and 52.4% respectively. It was concluded that surgical treatment of severe concomitant coronary artery disease and aortic aneurysm in patients with kidney and bladder cancer decreases risk of myocardial infarction and aortic aneurysm rupture in intraoperative and postoperative periods.

  3. Visual Analysis for Detection and Quantification of Pseudomonas cichorii Disease Severity in Tomato Plants

    PubMed Central

    Rajendran, Dhinesh Kumar; Park, Eunsoo; Nagendran, Rajalingam; Hung, Nguyen Bao; Cho, Byoung-Kwan; Kim, Kyung-Hwan; Lee, Yong Hoon

    2016-01-01

    Pathogen infection in plants induces complex responses ranging from gene expression to metabolic processes in infected plants. In spite of many studies on biotic stress-related changes in host plants, little is known about the metabolic and phenotypic responses of the host plants to Pseudomonas cichorii infection based on image-based analysis. To investigate alterations in tomato plants according to disease severity, we inoculated plants with different cell densities of P. cichorii using dipping and syringe infiltration methods. High-dose inocula (≥ 106 cfu/ml) induced evident necrotic lesions within one day that corresponded to bacterial growth in the infected tissues. Among the chlorophyll fluorescence parameters analyzed, changes in quantum yield of PSII (ΦPSII) and non-photochemical quenching (NPQ) preceded the appearance of visible symptoms, but maximum quantum efficiency of PSII (Fv/Fm) was altered well after symptom development. Visible/near infrared and chlorophyll fluorescence hyperspectral images detected changes before symptom appearance at low-density inoculation. The results of this study indicate that the P. cichorii infection severity can be detected by chlorophyll fluorescence assay and hyperspectral images prior to the onset of visible symptoms, indicating the feasibility of early detection of diseases. However, to detect disease development by hyperspectral imaging, more detailed protocols and analyses are necessary. Taken together, change in chlorophyll fluorescence is a good parameter for early detection of P. cichorii infection in tomato plants. In addition, image-based visualization of infection severity before visual damage appearance will contribute to effective management of plant diseases. PMID:27493605

  4. Revisiting Unplanned Endotracheal Extubation and Disease Severity in Intensive Care Units.

    PubMed

    Chuang, Ming-Lung; Lee, Chai-Yuan; Chen, Yi-Fang; Huang, Shih-Feng; Lin, I-Feng

    2015-01-01

    Most reports regarding unplanned extubation (UE) are case-control studies with matching age and disease severity. To avoid diminishing differences in matched factors, this study with only matching duration of mechanical ventilation aimed to re-examine the risk factors and the factors governing outcomes of UE in intensive care units (ICUs). This case-control study was conducted on 1,775 subjects intubated for mechanical ventilation. Thirty-seven (2.1%) subjects with UE were identified, and 156 non-UE subjects were randomly selected as the control group. Demographic data, acute Physiological and Chronic Health Evaluation II (APACHE II) scores, and outcomes of UE were compared between the two groups. Logistic regression analysis was used to identify the risk factors of UE. Milder disease, younger age, and higher Glasgow Coma Scale (GCS) scores with more frequently being physically restrained (all p<0.05) were related to UE. Logistic regression revealed that APACHE II score (odds ratio (OR) 0.91, p<0.01), respiratory infection (OR 0.24, p<0.01), physical restraint (OR 5.36, p<0.001), and certain specific diseases (OR 3.79-5.62, p<0.05) were related to UE. The UE patients had a lower ICU mortality rate (p<0.01) and a trend of lower in-hospital mortality rate (p = 0.08). Cox regression analysis revealed that in-hospital mortality was associated with APACHE II score, age, shock, and oxygen used, all of which were co-linear, but not UE. The results showed that milder disease with higher GCS scores thereby requiring a higher use of physical restraints were related to UE. Disease severity but not UE was associated with in-hospital mortality.

  5. A severe renal bleeding as a complication of coumarin therapy in Behçet's disease.

    PubMed

    Remková, Anna; Milatová, Eva; Fuchsbergerová, Michaela

    2010-07-01

    Behçet's disease is a systemic inflammatory disease, which predisposes patients to venous or arterial thrombosis. We report a case of 41-year-old patient who presented for several years with recurrent fevers, arthralgias, episodes of skin eruptions and recurrent bilateral deep venous ileofemoral thromboses, extending into the inferior vena cava, despite the oral anticoagulant therapy. Additionally, he also reported recurrent aphthous oral and genital lesions, and eye problems. A laboratory picture of chronic inflammation, normocytic anaemia and a finding of lupus anticoagulant/antiphospholipid antibodies were observed. PET raised a high suspicion of vasculitic PTT-lupus anticoagulant process, involving the large vessels. During an anticoagulant therapy by warfarin (dose in upper limit of therapeutic range), the left kidney had to be removed because of acute retroperitoneal haemorrhage. On histologic examination, the picture of nephritis was described. A detailed retrospective reevaluation of complex history as well as other clinical findings strongly raised the suspicion of a systemic vasculitic syndrome, such as Behçet's disease, accompanied by antiphospholipid syndrome. The patient responded well to the combination of colchicine and anticoagulant therapy by low-molecular-weight heparin. The episodes of fever, skin eruptions and other symptoms disappeared. We assume that this is a case of an unusual course of Behçet's disease presenting with a rare kidney involvement. Kidney disorder complicated the oral anticoagulant therapy for recurrent venous thromboses and led to the excessive renal bleeding, requiring nephrectomy. Recognition that nephritis is associated with Behçet's disease may be useful to prevent severe renal bleeding in relation to anticoagulant therapy.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  8. 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

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

    PubMed

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

    2016-04-01

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

  10. Interleukin 15 Levels in Serum May Predict a Severe Disease Course in Patients with Early Arthritis

    PubMed Central

    González-Álvaro, Isidoro; Ortiz, Ana M.; Alvaro-Gracia, José María; Castañeda, Santos; Díaz-Sánchez, Belen; Carvajal, Inmaculada; García-Vadillo, J. Alberto; Humbría, Alicia; López-Bote, J. Pedro; Patiño, Esther; Tomero, Eva G.; Vicente, Esther F.; Sabando, Pedro; García-Vicuña, Rosario

    2011-01-01

    Background Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). Methodology and Results Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06–0.18]; p<0.001) or ACPA (0.34 [0.01–0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18–2.7; p = 0.007). Conclusions Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for

  11. Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia.

    PubMed

    Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

    2005-04-01

    Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age-matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 +/- 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 +/- 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 +/- 3.8). Disease symptomatology was assessed using the Unified Huntington's Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age-matched (mean age, 48.9 +/- 13.0, range, 26-76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects.

  12. Maternal behavioural risk factors for severe childhood diarrhoeal disease in Kinshasa, Zaire.

    PubMed

    Dikassa, L; Mock, N; Magnani, R; Rice, J; Abdoh, A; Mercer, D; Bertrand, W

    1993-04-01

    This study examines the relationship between severe diarrhoeal disease and maternal knowledge and behaviours related to hygiene and sanitation. Some 107 paediatric cases admitted to two hospitals in Kinshasa, Zaire in 1988 were matched on age and nearest-neighbour status to 107 controls. Personal interviews and observational methods were used to assess knowledge and behaviours related to hygiene and sanitation. Cases and controls had equivalent socioeconomic status, demographic profiles and access to water and sanitation facilities. However, cases generally exhibited lower levels of knowledge and less sanguine sanitary practices than did controls. Of particular interest was the finding that very specific behavioural items distinguished cases from controls. The disposal of the child faeces and household garbage and mother's knowledge that poor caretaker cleanliness was a cause of diarrhoea in children showed the strongest associations with risk of diarrhoea. There was an exponential relationship between the number of these items a mother answered incorrectly and the odds of diarrhoeal disease. The risk attributable to these three variables was as high as 70%. These findings provide further support for the view that focused educational interventions may have a substantial impact on the occurrence of severe diarrhoeal disease in low-income countries.

  13. SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy

    PubMed Central

    Pegoraro, E.; Hoffman, E.P.; Piva, L.; Gavassini, B.F.; Cagnin, S.; Ermani, M.; Bello, L.; Soraru, G.; Pacchioni, B.; Bonifati, M.D.; Lanfranchi, G.; Angelini, C.; Kesari, A.; Lee, I.; Gordish-Dressman, H.; Devaney, J.M.; McDonald, C.M.

    2011-01-01

    Objective: Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient–patient variability in disease onset and progression and response to glucocorticoids is seen, suggesting genetic or environmental modifiers. Methods: Two DMD cohorts were used as test and validation groups to define genetic modifiers: a Padova longitudinal cohort (n = 106) and the Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history cohort (n = 156). Single nucleotide polymorphisms to be genotyped were selected from mRNA profiling in patients with severe vs mild DMD, and genome-wide association studies in metabolism and polymorphisms influencing muscle phenotypes in normal volunteers were studied. Results: Effects on both disease progression and response to glucocorticoids were observed with polymorphism rs28357094 in the gene promoter of SPP1 (osteopontin). The G allele (dominant model; 35% of subjects) was associated with more rapid progression (Padova cohort log rank p = 0.003), and 12%–19% less grip strength (CINRG cohort p = 0.0003). Conclusions: Osteopontin genotype is a genetic modifier of disease severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in inclusion criteria in DMD clinical trials would reduce intersubject variance, and increase sensitivity of the trials, particularly in older subjects. PMID:21178099

  14. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis

    PubMed Central

    Koopman, Frieda A.; Chavan, Sangeeta S.; Miljko, Sanda; Grazio, Simeon; Sokolovic, Sekib; Schuurman, P. Richard; Mehta, Ashesh D.; Levine, Yaakov A.; Faltys, Michael; Zitnik, Ralph; Tracey, Kevin J.; Tak, Paul P.

    2016-01-01

    Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the “inflammatory reflex,” is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases. PMID:27382171

  15. HIV-1 Promoter Single Nucleotide Polymorphisms Are Associated with Clinical Disease Severity

    PubMed Central

    Feng, Rui; Moldover, Brian; Passic, Shendra; Aiamkitsumrit, Benjamas; Dampier, Will; Wojno, Adam; Kilareski, Evelyn; Blakey, Brandon; Ku, Tse-Sheun Jade; Shah, Sonia; Sullivan, Neil T.; Jacobson, Jeffrey M.; Wigdahl, Brian

    2016-01-01

    The large majority of human immunodeficiency virus type 1 (HIV-1) markers of disease progression/severity previously identified have been associated with alterations in host genetic and immune responses, with few studies focused on viral genetic markers correlate with changes in disease severity. This study presents a cross-sectional/longitudinal study of HIV-1 single nucleotide polymorphisms (SNPs) contained within the viral promoter or long terminal repeat (LTR) in patients within the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. HIV-1 LTR SNPs were found to associate with the classical clinical disease parameters CD4+ T-cell count and log viral load. They were found in both defined and undefined transcription factor binding sites of the LTR. A novel SNP identified at position 108 in a known COUP (chicken ovalbumin upstream promoter)/AP1 transcription factor binding site was significantly correlated with binding phenotypes that are potentially the underlying cause of the associated clinical outcome (increase in viral load and decrease in CD4+ T-cell count). PMID:27100290

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

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

    PubMed

    Han, Sushan; Mansfield, Kristin G

    2014-04-01

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

  19. Complex two-gene modulation of lung disease severity in children with cystic fibrosis

    PubMed Central

    Dorfman, Ruslan; Sandford, Andrew; Taylor, Chelsea; Huang, Baisong; Frangolias, Daisy; Wang, Yongqian; Sang, Richard; Pereira, Lilian; Sun, Lei; Berthiaume, Yves; Tsui, Lap-Chee; Paré, Peter D.; Durie, Peter; Corey, Mary; Zielenski, Julian

    2008-01-01

    Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function. PMID:18292811

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

    PubMed

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

    2008-05-06

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

  1. Reduced severity of histopathological lesions in mink selected for tolerance to Aleutian mink disease virus infection.

    PubMed

    Farid, A Hossain; Ferns, Linda E

    2017-04-01

    The objective of this study was to measure the effect of selection for tolerance on the severity of the Aleutian disease (AD) lesions in mink. Sensitivity and specificity of antibody detection in the blood by counter-immunoelectrophoresis (CIEP) relative to the presence of Aleutian mink disease virus (AMDV) in the spleen by PCR in naturally infected farmed mink were also estimated. Carcasses of 680 sero-positive (CIEP-P) black mink from 28 farms in Nova Scotia, Canada, and from 132 sero-negative (CIEP-N) mink from 14 of these farms were collected at pelting time. A total of 116 of the CIEP-P mink were from three farms where animals have been selected for tolerating AD for almost 20years. The severity of the AD lesions was assessed by histopathological examination of kidneys, lungs, heart, brain and liver on a scale of 0 to 4. Sensitivity and specificity of CIEP relative to PCR were 0.97 and 0.85, respectively, and 16.5% of CIEP-N mink were PCR positive, which could be one of the reasons for the failure of virus eradication by CIEP in Canada. The CIEP-N and tolerant CIEP-P animals had 9.39 and 6.23 greater odds of showing lower lesion severity, respectively, than the CIEP-P animals (P<0.01). The CIEP-N mink had a slightly higher chance (P=0.07) of showing lower lesion severity (odds ratio 1.51) compared with tolerant CIEP-P mink. The results suggested that tolerant mink had significantly reduced severity of AD lesions despite having anti-viral antibodies and carrying the virus.

  2. Steroid therapy in clinically stable but serologically active systemic lupus erythematosus prevents severe disease flares.

    PubMed

    Cardiel, Mario H; Almagro, Raúl Menor

    2007-05-01

    Evaluation of: Tseng CE, Buyon JP, Kim M et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54, 3623-3632 (2006). Systemic lupus erythematosus is an autoimmune disease of unknown origin. Flares and remissions are commonly seen in clinical settings. These clinical flares can have several degrees of severity, some of which require intensive immunosuppressive treatment and/or hospitalization. Clinicians treating these patients have looked at different strategies for prevention, early detection and prompt treatment of a lupus flare. Clinical information and laboratory findings have been proposed to reach these goals and preventive steroid adjustment has even been used in some cases without convincing results. This paper presents results from a controlled, multicenter, double-blind clinical trial evaluating the effectiveness of short-term corticosteroid treatment for preventing severe flares in which elevations of C3a by 50% were accompanied by a 25% increase in the anti-double-stranded DNA titer in patients with inactive or stable/active systemic lupus erythematosus. Results suggest that this strategy can prevent severe lupus flares.

  3. Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity

    PubMed Central

    Weinberg, J. Brice; Volkheimer, Alicia D.; Rubach, Matthew P.; Florence, Salvatore M.; Mukemba, Jackson P.; Kalingonji, Ayam R.; Langelier, Charles; Chen, Youwei; Bush, Margaret; Yeo, Tsin W.; Granger, Donald L.; Anstey, Nicholas M.; Mwaikambo, Esther D.

    2016-01-01

    We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO insufficiency, and disease severity in Tanzanian children with falciparum malaria. Compared to control children (n = 106), children with moderately severe (n = 77) and severe falciparum malaria (n = 129) had significantly higher mononuclear cell arginase 1 mRNA, protein, and enzyme activity; lower NOS2 mRNA; lower plasma arginine; and higher plasma IL-10, IL-13, and IL-4. In addition, monocyte CD206 and CD163 and plasma soluble CD163 were elevated. Multivariate logistic regression analysis revealed a significant correlation of risk of severe malaria with both plasma IL-10 and soluble CD163 levels. Monocyte M2 skewing likely contributes to NO bioinsufficiency in falciparum malaria in children. Treatments that reverse the M2 polarization may have potential as adjunctive treatment for malaria. PMID:27385484

  4. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed

    Baird, J K; Basri, H; Weina, P; MaGuire, J D; Barcus, M J; Picarema, H; Elyazar, I R F; Ayomi, E; Sekartuti

    2003-08-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection.

  5. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed Central

    Baird, J. K.; Basri, H.; Weina, P.; MaGuire, J. D.; Barcus, M. J.; Picarema, H.; Elyazar, I. R. F.; Ayomi, E.; Sekartuti

    2003-01-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection. PMID:12948380

  6. 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

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

    PubMed Central

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

    2014-01-01

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

  8. Gene regulations in HBV-related liver cirrhosis closely correlate with disease severity.

    PubMed

    Lee, Seram; Kim, Soyoun

    2007-09-30

    Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

  9. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    PubMed

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

  10. Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension

    PubMed Central

    da Penha, Juliano Gomes; Zorzanelli, Leina; Barbosa-Lopes, Antonio Augusto; Atik, Edimar; Miana, Leonardo Augusto; Tanamati, Carla; Caneo, Luiz Fernando; Miura, Nana; Aiello, Vera Demarchi; Jatene, Marcelo Biscegli

    2015-01-01

    Background Transposition of the great arteries (TGA) is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level. Objective Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure. Methods Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included. Results After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced. Conclusion The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis. PMID:26559982

  11. Severe Kawasaki disease in a 3-month-old patient: a case report

    PubMed Central

    2013-01-01

    Background Kawasaki disease is a multi-system vasculitis which usually occurs in children under 5 years of age. In infants under three months of age, it is very rare and usually associated with a high incidence of incomplete or atypical forms, often unresponsive to treatment. This condition increases the risk of cardiovascular complications such as coronary artery aneurysms. Case presentation We describe a 3-month-old infant who developed early and severe aneurysms in three coronary arteries despite a timely administration of intravenous immunoglobulins, followed by three days of intravenous methylprednisolone. Conclusion This case report underlines that the development of coronary artery aneurysm correlates with a delayed diagnosis and treatment, incomplete or atypical forms of the disease, and additionally the severity of clinical presentation, especially in cases of very young infants below 3 months of age. Our case is notable because of the very young age of the patient, the severity of clinical presentation with an early development of coronary artery aneurysms and the unresponsiveness to the therapy. PMID:24294914

  12. 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

  13. Genetic Polymorphisms of TLR4 and MICA are Associated with Severity of Trachoma Disease in Tanzania

    PubMed Central

    Abbas, Muneer; Berka, Noureddine; Khraiwesh, Mozna; Ramadan, Ali; Apprey, Victor; Furbert-Harris, Paulette; Quinn, Thomas; Brim, Hassan; Dunston, Georgia

    2016-01-01

    Aim To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. Methods The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan®, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. Results The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. Conclusion TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic. PMID:27559544

  14. Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity

    PubMed Central

    Liu, Qing-Quan; Zhou, Ya-Qun; Liu, Hui-Quan; Qiu, Wen-Hui; Liu, Hui; Hu, Ting-Yang; Xu, Qing; Lv, Yong-Man; Wu, Kong-Ming

    2016-01-01

    Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients. We found that DACH1 expression was decreased in the nephropathy group relative to healthy controls. DACH1 staining in the glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively with serum creatinine (r = −0.37, p < 0.01). In vitro, DACH1 overexpression in human podocytes or HK2 cells decreased expression of cyclin D1, but increased expression of p21 and p53, which suggested that DACH1 overexpression in human podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together, These findings indicate that DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. These data suggest that DACH1 is a potential a marker of disease progression and severity for glomerular diseases. PMID:27888806

  15. Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

    PubMed

    Burcham, Philip C

    2017-01-17

    Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

  16. Haematological profile in leprosy. Part II--Relationship to severity of disease and treament status.

    PubMed

    Karat, A B; Rao, P S

    1978-01-01

    321 adult male lepromatous leprosy patients were studied for relationship between haematological findings, severity of disease and duration of treatment. Significant changes were noticed in relation in haemoglobin concentration, serum vitamin B12 and serum folate levels, serum albumin and globulin. No significant changes were observed in serum iron levels in relation to disease and treatment status. With rising bacterial load, there was a trend towards lower haemoglobin concentration, higher vitamin B12 level and lowered serum folate levels. Serum albumin showed a significant decline, while serum globulin showed a significant rise. The findings are discussed in relation to replacement of bone marrow by lepromatous tissue as well as possible interference in the metabolism of haematinics by M. leprae. The exact mechanism of neurlogical deficit in leprosy in relation to deficiency of vitamin B12 and folic acid need to be further elucidated.

  17. Frequency of the severe combined immunodeficiency disease gene among horses in Morocco.

    PubMed

    Piro, M; Benjouad, A; Tligui, N S; El Allali, K; El Kohen, M; Nabich, A; Ouragh, L

    2008-09-01

    Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring among Arabian or crossbred Arabian horses. The genetic defect responsible was previously identified as a 5-base pair deletion in the gene encoding the catalytic subunit of the DNA dependant protein kinase (DNA-PKcs). This study was carried out to determine the frequency of SCID and identify horses carrying the gene for SCID among Arabian and Arabian crossbred stallions and mares in Morocco using a DNA-based test. Twenty-one horses were SCID carriers: 14 (7%) Arabians, 6 (4%) Arab-Barbs and one (33%) Anglo-Arab. After analysing their genealogy, 3 imported stallions were identified that disseminated the mutant gene of DNA-PKcs in Morocco.

  18. Blood dendritic cell frequency declines in idiopathic Parkinson's disease and is associated with motor symptom severity.

    PubMed

    Ciaramella, Antonio; Salani, Francesca; Bizzoni, Federica; Pontieri, Francesco E; Stefani, Alessandro; Pierantozzi, Mariangela; Assogna, Francesca; Caltagirone, Carlo; Spalletta, Gianfranco; Bossù, Paola

    2013-01-01

    The role of inflammation in Parkinson's Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson's Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation.

  19. Patient coping strategies in COPD across disease severity and quality of life: a qualitative study

    PubMed Central

    Brien, Sarah B; Lewith, George T; Thomas, Mike

    2016-01-01

    Quality of life (QoL) has a weak relationship with lung function (LF) impairment in COPD; some cope well despite poor LF, whereas others suffer disproportionate QoL impairment despite well-preserved LF. Adjuvant non-pharmacological interventions such as rehabilitation and psychological/behavioural support may help if acceptable and targeted appropriately, but they are under-used and sometimes declined by patients. This study aimed to explore and understand variations in experiences and coping strategies in patients with different severities of disease and disease-specific QoL. Thirty-four participants were purposively sampled across a spectrum of LF and QoL impairment, to cover a grid of sub-groups (‘very severe LF, good QoL’, moderate LF, poor QoL’ and so on). Semi-structured interviews, digitally recorded, were analysed by thematic analysis. Data saturation was achieved. Four themes emerged: symptom impact, coping strategies, coping challenges and support needs. Most of them described using multiple coping strategies, yet over half reported significant challenges coping with COPD, including psychological impact, non-acceptance of diagnosis and/or disease progression, effects of co-morbidities and inadequate self-management skills. Approximately half of the participants wanted further help, ideally non-pharmacological, across all LF impairment groups but mainly with lower QoL. Those with lower QoL additionally reported greater psychological distress and greater use of non-pharmacological support strategies where accessible. Patients who develop effective coping strategies have a better QoL independent of objective LF, whereas others cope poorly, are aware of this and report more use of non-pharmacological approaches. This study suggests that severely impaired QoL, irrelevant of lung function, is a powerful patient-centred indication to explore the positive benefits of psychological and behavioural support for distressed COPD patients. PMID:27629237

  20. Computed Tomography Scans as an Objective Measure of Disease Severity in Chronic Rhinosinusitis

    PubMed Central

    Likness, Micah M.; Pallanch, John F.; Sherris, David A.; Kita, Hirohito; Mashtare, Terry L.; Ponikau, Jens U.

    2014-01-01

    Objectives A truly objective method of measuring disease severity in chronic rhinosinusitis (CRS) has only recently existed. We evaluated computed tomography (CT) scans of CRS patients using this novel objective 3D computerized system and compared results with a novel 2D computerized analysis of a single coronal slice through the osteomeatal complex (OMC) and subjective methods including Lund-Mackay and Zinreich’s modified Lund-Mackay. Study Design Prospective multicenter study. Setting Two academic tertiary referral centers. Subjects and Methods Forty-six adults with a diagnosis of CRS underwent CT examination and received an intramuscular triamcinolone injection, dosage weight dependent, followed by CT scan 4 to 5 weeks later. Recruitment lasted 21 months. Scans were evaluated with all 4 scoring methods over 5 months. Results The Lin’s concordance class correlation (CCC) of the OMC method revealed the best correlation to the 3D volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund-Mackay methods (0.824). Posttreatment results demonstrated that both the OMC (0.824) and Zinreich’s (0.778) methods had strong agreement with the 3D volumetric methods and were very sensitive to change, whereas the Lund-Mackay (0.545) had only moderate agreement. Conclusion Computerized CT analysis provides the most comprehensive, objective, and reproducible method of measuring disease severity and is very sensitive to change induced by treatment intervention. A 2D coronal image through the OMC provides a valid, user-friendly method of assessing CRS and is representative of CRS severity in all sinuses. Zinreich’s subjective method correlated well overall, but the Lund-Mackay method lagged behind in disease representation and sensitivity to change. PMID:24301090

  1. 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

  2. L-Dopa induced dyskinesias in Parkinsonian mice: disease severity or L-Dopa history

    PubMed Central

    Shan, Lufei; Diaz, Oscar; Zhang, Yajun; Ladenheim, Bruce; Cadet, Jean-Lud; Chiang, Yung-Hsiao; Olson, Lars; Hoffer, Barry J.; Bäckman, Cristina M.

    2016-01-01

    In Parkinson's disease, the efficacy of L-Dopa treatment changes over time, as dyskinesias emerge with previously beneficial doses. Using MitoPark mice, that models mitochondrial failure in dopamine (DA) neurons and mimics the progressive loss of dopamine observed in Parkinson’s disease, we found that the severity of DA denervation and associated adaptations in striatal neurotransmission at the time of initiation of L-Dopa treatment determines development of L-Dopa induced dyskinesias. We treated 20-week, and 28-week old MitoPark mice with L-Dopa (10 mg/kg i.p. twice a day) and found locomotor responses to be significantly different. While all MitoPark mice developed sensitization to L-Dopa treatment over time, 28-week old MitoPark mice with extensive striatal DA denervation developed abnormal involuntary movements rapidly and severely after starting L-Dopa treatment, as compared to a more gradual escalation of movements in 20-week old animals that started treatment at earlier stages of degeneration. Our data support that it is the extent of loss of DA innervation that determines how soon motor complications develop with L-Dopa treatment. Gene array studies of striatal neurotransmitter receptors revealed changes in mRNA expression levels for DA, serotonin, glutamate and GABA receptors in striatum of 28-week old MitoPark mice. Our results support that delaying L-Dopa treatment until Parkinson’s disease symptoms become more severe does not delay the development of L-Dopa-induced dyskinesias. MitoPark mice model genetic alterations known to impair mitochondrial function in a subgroup of Parkinson patients and provide a platform in which to study treatments to minimize the development of dyskinesia. PMID:26086365

  3. Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000

    PubMed Central

    Tyndall, A; Passweg, J; Gratwohl, A

    2001-01-01

    An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning.
  Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported.
  Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA.
Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA.
  After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and

  4. [Perioperative Management of a Patient with Severe Parkinson's Disease with Intravenous Levodopa Administration].

    PubMed

    Terashima, Satoko; Yanagido, Yurina; Watabe, Akira; Yamane, Masahiro; Morimoto, Yuji

    2015-08-01

    A 70-year-old man with severe Parkinson's disease was scheduled for thoracic aortic aneurysm resection and aortic valve replacement. We administered levodopa intravenously during the perioperative period to avoid the malignant syndrome which is reported to arise with abrupt cessation of anti-Parkinson's drugs. The dose of intravenous administration was tapered with the resumption of oral intake. No manifestation of malignant syndrome was observed. We measured blood concentrations of levodopa several times during the perioperative period. The concentration of levodopa during the surgery was relatively high; however no adverse events of overdose (e.g. dyskinesis) occurred. In the postoperative period, administration of levodopa was changed to the oral route and serum levels of levodopa showed a notable decrease, the cause of which may be poor absorption through the digestive system during the perioperative period. Therefore, in the peri- and post-operative periods, it is necessary to take great care when reducing the infusion dose.

  5. Safety and efficacy of defibrotide for the treatment of severe hepatic veno-occlusive disease.

    PubMed

    Richardson, Paul G; Ho, Vincent T; Giralt, Sergio; Arai, Sally; Mineishi, Shin; Cutler, Corey; Antin, Joseph H; Stavitzski, Nicole; Niederwieser, Dietger; Holler, Ernst; Carreras, Enric; Soiffer, Robert

    2012-08-01

    Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). VOD may occur in up to 62% of patients undergoing SCT, with onset generally within the first month after SCT. In severe cases, 100-day mortality is in excess of 80%. Current management consists of best supportive care, with no agents to date approved for treatment in the USA or the EU. Defibrotide, a polydisperse oligonucleotide, has been shown in phase II and III trials to improve complete response and survival in patients undergoing SCT with severe VOD. This article reviews our current understanding of VOD, and examines recent clinical findings on defibrotide for the treatment and prophylaxis of VOD.

  6. Single photon emission computed tomography in Alzheimer's disease. Abnormal iofetamine I 123 uptake reflects dementia severity

    SciTech Connect

    Johnson, K.A.; Holman, B.L.; Mueller, S.P.; Rosen, T.J.; English, R.; Nagel, J.S.; Growdon, J.H.

    1988-04-01

    To determine whether abnormalities in regional cerebral functional activity estimated by iofetamine hydrochloride I 123 and single photon emission computed tomography can be detected in mild or moderate as well as severe cases of Alzheimer's disease (AD), we performed iofetamine I 123-single photon emission computed tomography in 37 patients with probable AD (nine patients with mild, 18 patients with moderate, and ten patients with severe dementia) and nine age-matched control subjects. Iofetamine I 123 uptake was measured in right and left frontal, temporal, parietal, and occipital cortices. Mean (right and left) iofetamine I 123 activity was lowest in the parietal region of patients with AD and was significantly reduced in the other three regions compared with control subjects. Only in the parietal region was lower relative iofetamine I 123 activity associated with an impaired level of patient function and with cognitive deficit.

  7. Olfactory functions in patients with psoriasis vulgaris: correlations with the severity of the disease.

    PubMed

    Aydın, Ersin; Tekeli, Hakan; Karabacak, Ercan; Altunay, İlknur Kıvanç; Aydın, Çigdem; Çerman, Aslı Aksu; Altundağ, Aytuğ; Salihoğlu, Murat; Çayönü, Melih

    2016-08-01

    It is well known that psoriasis is not only limited to skin, but a systemic autoimmune disease with various comorbidities. Olfactory dysfunction, one of as a common but lesser known symptom of patients with autoimmune diseases, often presents with smell loss. The aim of this study was to assess the olfactory functions in patients with psoriasis and to compare with healthy controls. A total of 50 patients with psoriasis and 43 control subjects were included to the study. The clinical severity of psoriasis was calculated by psoriasis area and severity index (PASI). Patients were classified into two groups according to PASI score as mild (PASI ≤10) and moderate-severe (PASI >10). Olfactory function was evaluated with "Sniffin'Sticks" test. Total test scores (max. 48 points) of threshold, discrimination, and identification (TDI) were classified as normal olfaction = normosmia (>30.3 points), decreased olfaction = hyposmia (16.5-30.3 points) and loss of olfaction = anosmia (<16.5 points). Psoriasis patients had significantly lower smell scores compared with healthy controls (p < 0.001). Of the 50 psoriasis patients, 40 (80 %) were hyposmic. We found negative correlation between TDI and PASI (r = -0.34, p = 0.014). The TDI scores of the patients with moderate-severe psoriasis (PASI score >10) were found to be significantly lower than the patients with mild psoriasis (PASI ≤10) (p < 0.001). Olfactory dysfunction in patients with psoriasis could be thought as a comorbidity as in other inflammatory disorders. Physicians should be aware of olfactory impairment when evaluating psoriasis patients in their clinical practice.

  8. Severe multivessel coronary artery disease and high-sensitive troponin T

    PubMed Central

    Huziuk, Inga Magdalena

    2015-01-01

    Introduction A key problem in stable coronary artery disease (CAD) is non-invasive identification of patients with severe multivessel CAD. Determination of biomarkers that have pro-inflammatory properties (C-reactive protein – hsCRP) and indicate heart muscle ischemia (high-sensitive troponin T – hsTnT) can contribute to the improvement of stratification in this regard. The aim of the study The aim of the study was to identify factors associated with the presence of multivessel CAD in clinically stable men. Material and methods The study included 92 symptomatic men (mean age 64.05 ± 9.42 years) with preserved left ventricular function, scheduled for elective coronary angiography. Patients were divided and analyzed in two groups: with multivessel coronary artery disease (2-3-vessel disease, n = 46) vs. without multivessel coronary artery disease (n = 46). Results Patients with multivessel CAD had significantly higher levels of hsTnT (0.01 vs. 0.007, p = 0.0021) and fasting glucose (6.0 vs. 5.45, p = 0.0112). Based on the drawn ROC curves, the cut-off points were determined for hsTnT ≥ 0.0085 ng/ml and fasting plasma glucose ≥ 5.85 mmol/l. From multivariate analysis only hsTnT in concentration higher than the cut-off point enhanced the risk of multivessel CAD (OR 4.286, 95% CI: 1.79-10.263, p = 0.001). Conclusions In men with stable CAD, preserved systolic left ventricular function and non-high cardiovascular risk determined from the initial concentration of hsCRP, elevated level of hsTnT was independently associated with the risk of multivessel coronary artery disease. PMID:26336496

  9. A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

    PubMed Central

    Zhang, Dingmei; Li, Ruolin; Zhang, Wangjian; Li, Guowei; Ma, Zhanzhong; Chen, Xiashi; Du, Zhicheng; Li, Zhiyuan; Guo, Pi; Lin, Zhuochen; Lu, Jiahai; Hao, Yuantao

    2017-01-01

    The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD. PMID:28084311

  10. 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

  11. Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

    PubMed Central

    Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z. M.; Murray, Toby B. J.; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J.; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W.; Garden, O. James; Iredale, John P.; Uings, Iain J.; Liddle, John; Wright, Wayne L.; Dukes, George; Webster, Scott P.; Mole, Damian J.

    2016-01-01

    Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID:27669975

  12. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    PubMed Central

    Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R

    2005-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622

  13. Blood count parameters can predict the severity of coronary artery disease

    PubMed Central

    Uysal, Hilal Bektas; Dağlı, Bekir; Akgüllü, Cağdaş; Avcil, Mücahit; Zencir, Cemil; Ayhan, Mediha; Sönmez, Hulki Meltem

    2016-01-01

    Background/Aims Because of the inflammatory nature of coronary artery disease (CAD), both platelets and white blood cells have been investigated for years. The aim of this study was to investigate the relationships between some prominently hematologic blood count parameters (mean platelet volume [MPV], neutrophil to lymphocyte ratio [NLR]) and the severity of CAD by using Gensini scores. Methods A total of 194 patients, who had undergone coronary angiography, enrolled in this study. The control group consisted of 42 patients who had normal coronary arteries. Remaining CAD patients were divided into two groups according to their Gensini scores. Results NLR and MPV were higher in the severe atherosclerosis group compared with the mild atherosclerosis group (p = 0.007, p = 0.005, respectively). The Gensini score showed significant correlations with NLR (r = 0.20, p = 0.011), MPV (r = 0.23, p = 0.004) and high density lipoprotein cholesterol (r = –0.161, p = 0.047). Using a cut-off level of 2.54, NLR predicted severe atherosclerosis with a sensitivity of 74% and specificity of 53% (area under curve [AUC], 0.627; 95% confidence interval [CI], 0.545 to 0.704; p = 0.004). MPV values above 10.4 predicted severe atherosclerosis with a sensitivity of 39% and specificity of 90% (AUC, 0.631; 95% CI, 0.549 to 0.708; p = 0.003). In the multiple logistic regression analysis, high levels of NLR (odds ratio [OR], 1.450; 95% CI, 1.080 to 1.945; p = 0.013) and MPV (OR, 1.622; 95% CI, 1.147 to 2.295; p = 0.006) were found to be independent predictors of severe atherosclerosis. Conclusions Our study suggests that both NLR and MPV are predictors of severe atherosclerosis and may be used for the prediction and identification of cardiac risks in CAD patients. PMID:27052265

  14. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson's disease.

    PubMed

    Niccolini, Flavia; Foltynie, Thomas; Reis Marques, Tiago; Muhlert, Nils; Tziortzi, Andri C; Searle, Graham E; Natesan, Sridhar; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Piccini, Paola; Politis, Marios

    2015-10-01

    pallidal loss of PDE10A expression, which is associated with Parkinson's duration and severity of motor symptoms and complications. PDE10A is an enzyme that could be targeted with novel pharmacotherapy, and this may help improve dopaminergic signalling and striatal output, and therefore alleviate symptoms and complications of Parkinson's disease.

  15. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria.

    PubMed

    Nylund, L; Nermes, M; Isolauri, E; Salminen, S; de Vos, W M; Satokari, R

    2015-02-01

    The reports on atopic diseases and microbiota in early childhood remain contradictory, and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r = -0.54, P = 0.002) and with the abundance of butyrate-producing bacteria (r = -0.52, P = 0.005). During the 3-month follow-up, microbiota diversity increased (P < 0.001) and scoring atopic dermatitis values decreased (P < 0.001) in all infants. This decrease coincided with the increase in bacteria related to butyrate-producing Coprococcus eutactus (r = -0.59, P = 0.02). In conclusion, the high diversity of microbiota and high abundance of butyrate-producing bacteria were associated with milder eczema, thus suggesting they have a role in alleviating symptoms of atopic eczema.

  16. Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

    PubMed Central

    Sachan, Rekha; Patel, ML; Gaurav, Amrita; Gangwar, Radheshyam; Sachan, Pushpalata

    2014-01-01

    Background: Vascular endothelial dysfunction is considered central to the pathogenesis of hypertensive disorders of pregnancy (HDP). Serum level of neutrophil gelatinase-associated lipocalin (NGAL) is closely related to endothelial injury. The aim of this study was to examine the correlation of serum NGAL with disease severity in HDP. Materials and Methods: This prospective case-control study was carried out for one year. After informed consent, ethical clearance, total 1,850 pregnant women were screened. Analysis was performed on 142 cases of HDP and 31 healthy controls. Quantitative measurement of serum NGAL levels was done by the enzyme linked immunosorbent assay (ELISA) technique, by using sandwich ELISA kit. Results: Mean serum NGAL value in patients with oliguria was significantly higher when compared with non-oliguric patients (P < 0.001). Serum NGAL had a positive correlation with systolic blood pressure (r ~ 0.5973), diastolic blood pressure (r ~ 0.6195), blood urea (r ~ 0.4392), serum creatinine (r ~ 0.6112), serum uric acid (r ~ 0.3878). Sensitivity and specificity of serum NGAL using a cut-off value of 545 pg/ml, for the diagnosis of HDP, was 97.89% and 93.55% respectively, using 95% confidence interval. Conclusion: Between the two groups, we found that serum NGAL had a positive correlation with disease severity and better sensitivity and specificity in the evaluation of HDP. PMID:25538909

  17. The extent of ultrastructural spinal cord pathology reflects disease severity in experimental autoimmune encephalomyelitis.

    PubMed

    Gruppe, Traugott L; Recks, Mascha S; Addicks, Klaus; Kuerten, Stefanie

    2012-09-01

    Experimental autoimmune encephalomyelitis (EAE) has been studied for decades as an animal model for human multiple sclerosis (MS). Here we performed ultrastructural analysis of corticospinal tract (CST) and motor neuron pathology in myelin oligodendrocyte glycoprotein (MOG) peptide 35-55- and MP4-induced EAE of C57BL/6 mice. Both models were clinically characterized by ascending paralysis. Our data show that CST and motor neuron pathology differentially contributed to the disease. In both MOG peptide- and MP4-induced EAE pathological changes in the CST were evident. While the MP4 model also encompassed severe motor neuron degeneration in terms of rough endoplasmic reticulum alterations, the presence of intracytoplasmic vacuoles and nuclear dissolution, both models showed motor neuron atrophy. Features of axonal damage covered mitochondrial swelling, a decrease in nearest neighbor neurofilament distance (NNND) and an increase of the oligodendroglial cytoplasm inner tongue. The extent of CST and motor neuron pathology was reflective of the severity of clinical EAE in MOG peptide- and MP4-elicited EAE. Differential targeting of CNS gray and white matter are typical features of MS pathology. The MOG peptide and MP4 model may thus be valuable tools for downstream studies of the mechanisms underlying these morphological disease correlates.

  18. Chemical attenuation of Plasmodium in the liver modulates severe malaria disease progression.

    PubMed

    Lewis, Matthew D; Behrends, Jochen; Sá E Cunha, Cláudia; Mendes, António M; Lasitschka, Felix; Sattler, Julia M; Heiss, Kirsten; Kooij, Taco W A; Prudêncio, Miguel; Bringmann, Gerhard; Frischknecht, Friedrich; Mueller, Ann-Kristin

    2015-05-15

    Cerebral malaria is one of the most severe complications of malaria disease, attributed to a complicated series of immune reactions in the host. The syndrome is marked by inflammatory immune responses, margination of leukocytes, and parasitized erythrocytes in cerebral vessels leading to breakdown of the blood-brain barrier. We show that chemical attenuation of the parasite at the very early, clinically silent liver stage suppresses parasite development, delays the time until parasites establish blood-stage infection, and provokes an altered host immune response, modifying immunopathogenesis and protecting from cerebral disease. The early response is proinflammatory and cell mediated, with increased T cell activation in the liver and spleen, and greater numbers of effector T cells, cytokine-secreting T cells, and proliferating, proinflammatory cytokine-producing T cells. Dendritic cell numbers, T cell activation, and infiltration of CD8(+) T cells to the brain are decreased later in infection, possibly mediated by the anti-inflammatory cytokine IL-10. Strikingly, protection can be transferred to naive animals by adoptive transfer of lymphocytes from the spleen at very early times of infection. Our data suggest that a subpopulation belonging to CD8(+) T cells as early as day 2 postinfection is responsible for protection. These data indicate that liver stage-directed early immune responses can moderate the overall downstream host immune response and modulate severe malaria outcome.

  19. Can a normal peak expiratory flow exclude severe chronic obstructive pulmonary disease?

    PubMed Central

    Perez-Padilla, R.; Vollmer, W. M.; Vázquez-García, J. C.; Enright, P. L.; Menezes, A. M. B.; Buist, A. S.

    2011-01-01

    SUMMARY BACKGROUND Chronic obstructive pulmonary disease (COPD) is underdiagnosed. One barrier to diagnosis is the limited availability of spirometry testing, but in adults at risk for COPD, a normal pre-bronchodilator (pre-BD) peak expiratory flow (PEF) may rule out clinically significant COPD. OBJECTIVE To identify post-BD airway obstruction using data from 13 708 individuals aged ≥40 years from the PLATINO and BOLD studies. METHODS We evaluated different cut-off points of pre-BD. The PEF was obtained from a diagnostic-quality spirometer (not a mechanical PEF meter). At least one of the following COPD risk factors was present in 77% of the subjects: chronic respiratory symptoms; exposure to tobacco smoke, biomass smoke or dust in the workplace; or a previous diagnosis of asthma, COPD, emphysema or chronic bronchitis. RESULTS Although the positive predictive value was low as expected, a pre-BD PEF of ≥70% predicted effectively ruled out Stages III and IV COPD of the Global Initiative for Chronic Obstructive Lung Disease. Among those with at least one risk factor, only 12% would require confirmatory spirometry using this criterion. CONCLUSIONS Adding PEF measurement to a screening questionnaire may rule out severe to very severe COPD without the need for pre- and post-BD spirometry testing. Confirmation is needed from a study using inexpensive PEF meters or pocket spirometers with a staged screening protocol. PMID:19275802

  20. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

    PubMed Central

    van der Crabben, Saskia N.; Hennus, Marije P.; McGregor, Grant A.; Ritter, Deborah I.; Nagamani, Sandesh C.S.; Wells, Owen S.; Harakalova, Magdalena; Chinn, Ivan K.; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M.; Terheggen-Lagro, Suzanne W.; van Lieshout, Stef; van Roosmalen, Markus J.; Renkens, Ivo; Duran, Karen; Nijman, Isaac J.; Kloosterman, Wigard P.; Hennekam, Eric; van Hasselt, Peter M.; Wheeler, David A.; Palecek, Jan J.; Lehmann, Alan R.; Oliver, Antony W.; Pearl, Laurence H.; Plon, Sharon E.; Murray, Johanne M.

    2016-01-01

    The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

  1. Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

    PubMed Central

    Rodriguez-Roisin, Roberto; Tetzlaff, Kay; Watz, Henrik; Wouters, Emiel FM; Disse, Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter MA

    2016-01-01

    The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of −0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis. PMID:27578972

  2. Novel α-galactosidase A mutation in patients with severe cardiac manifestations of Fabry disease.

    PubMed

    Duro, Giovanni; Musumeci, M Beatrice; Colomba, Paolo; Zizzo, Carmela; Albeggiani, Giuseppe; Mastromarino, Vittoria; Volpe, Massimo; Autore, Camillo

    2014-02-10

    Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of α-galactosidase A (α-gal A), a lysosomal hydrolase. This inactivation is responsible for the accumulation of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. Fabry is considered a rare disease, with an incidence of 1:40,000; however, there are good reasons to believe that it is often seen but rarely diagnosed. To date, more than 600 mutations have been identified in human GLA gene that are responsible for FD. We describe the case of a 54-year-old male patient, who presented with left ventricular hypertrophy, chronic renal failure and acroparaesthesias, which are considered to be specific features of FD. Clinical and instrumental investigations showed several cardiovascular manifestations. The molecular analysis of GLA gene revealed a novel mutation in the fifth exon, called N249K, and the enzymatic analysis showed no α-galactosidase A activity. Family screening detected the same mutation in some relatives and also the enzymatic analysis confirmed the diagnosis of FD. In conclusion, these data suggest that the N249K mutation may be associated with cardiac manifestations of FD combined with other classical features of the disease.

  3. CRIg-expressing peritoneal macrophages are associated with disease severity in patients with cirrhosis and ascites

    PubMed Central

    Irvine, Katharine M.; Banh, Xuan; Gadd, Victoria L.; Wojcik, Kyle K.; Ariffin, Juliana K.; Jose, Sara; Lukowski, Samuel; Baillie, Gregory J.; Sweet, Matthew J.; Powell, Elizabeth E.

    2016-01-01

    Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. The proportion of CRIghi macrophages differed between patients and in the same patient over time, and a high proportion of CRIghi macrophages was associated with reduced disease severity (model for end-stage liver disease) score. As compared with CRIglo macrophages, CRIghi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities among CRIghi cells, human macrophages, and mouse F4/80hi resident peritoneal macrophages and among CRIglo macrophages, human monocytes, and mouse F4/80lo monocyte-derived peritoneal macrophages. These data suggest that CRIghi and CRIglo macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable among patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients. PMID:27699269

  4. Mechanisms of corticosteroid resistance in severe asthma and chronic obstructive pulmonary disease (COPD).

    PubMed

    Adcock, Ian M; Marwick, John; Casolari, Paolo; Contoli, Marco; Chung, Kian Fan; Kirkham, Paul; Papi, Alberto; Caramori, Gaetano

    2010-01-01

    Inhaled glucocorticoids, also know as corticosteroids (ICS), revolutionized the treatment of asthma by suppressing airways inflammation and ICS therapy now forms the basis of treatment of asthma of all severities. More recently and usually in combination with a long-acting β-agonist (LABA), ICS use has been established in the treatment of chronic obstructive pulmonary disease (COPD). In asthma, ICS improves asthma control, lung function and prevents exacerbations, including hospital admissions and probably decreases mortality. Similar effects are seen in COPD but to a much lesser degree, however, an improvement in symptoms such as breathlessness and reduction in exacerbations occur particularly in more advanced disease with ICS. Chronic inflammation is a feature of both asthma and COPD, although there are differences in the site and characteristics of the inflammatory response. ICS have proven to be less effective in patients with severe asthma, smoking asthmatics and in patients with COPD. ICS act by binding to and activating specific cytosolic receptors (GR), which then translocate to the nucleus where they regulate gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. GR is able to selective repress specific inflammatory genes by differing actions on specific intracellular signalling pathways and transcription factors such as nuclear factor κB and on kinases pathways. Abnormal activation of these pathways may result in glucocorticoid resistance. Although, ICS/LABA combinations will remain the main focus of treatment of airways diseases in the near future; other combinations that improve the efficacy of ICS by reducing the abnormal activation of pathways that cause glucocorticoid resistance will be developed.

  5. Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

    PubMed Central

    Peacock, Munro; Bilezikian, J. P.; Bolognese, M. A.; Borofsky, Michael; Scumpia, Simona; Sterling, L. R.; Cheng, Sunfa; Shoback, Dolores

    2011-01-01

    Context: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. Objective: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity. Design and Setting: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. Patients : Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15). Intervention: The intervention in this study was treatment with cinacalcet for up to 4.5 yr. Outcomes: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period. Results: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories. Conclusions: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated. PMID:20943783

  6. Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

    PubMed Central

    Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

    2014-01-01

    Background Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. Objective To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Methods Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. Results In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). Conclusion The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction. PMID:24553982

  7. Efficacy Projection of Obiltoxaximab for Treatment of Inhalational Anthrax across a Range of Disease Severity

    PubMed Central

    Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; O'Connor, Edward; Gonzales, Nestor; Mondick, John; French, Jonathan; Stark, Gregory V.; Fisher, Alan C.; Casey, Leslie S.

    2016-01-01

    Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment bacteremia and toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg obiltoxaximab. In two macaque studies, 16 mg/kg obiltoxaximab reduced toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment bacteremia and toxemia levels inversely correlated with survival. Overall, obiltoxaximab monotherapy neutralized PA and increased survival across the range of disease severity, indicating clinical benefit of toxin neutralization with obiltoxaximab in both early and late stages of inhalational anthrax. PMID:27431222

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

    PubMed Central

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

    2016-01-01

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

  9. Complement activity is associated with disease severity in multifocal motor neuropathy

    PubMed Central

    Vlam, Lotte; Cats, Elisabeth A.; Harschnitz, Oliver; Jansen, Marc D.; Piepers, Sanne; Veldink, Jan Herman; Franssen, Hessel; Stork, Abraham C.J.; Heezius, Erik; Rooijakkers, Suzan H.M.; Herpers, Bjorn L.; van Strijp, Jos A.; van den Berg, Leonard H.

    2015-01-01

    Objective: To investigate whether high innate activity of the classical and lectin pathways of complement is associated with multifocal motor neuropathy (MMN) and whether levels of innate complement activity or the potential of anti-GM1 antibodies to activate the complement system correlate with disease severity. Methods: We performed a case-control study including 79 patients with MMN and 79 matched healthy controls. Muscle weakness was documented with Medical Research Council scale sum score and axonal loss with nerve conduction studies. Activity of the classical and lectin pathways of complement was assessed by ELISA. We also determined serum mannose-binding lectin (MBL) concentrations and polymorphisms in the MBL gene (MBL2) and quantified complement-activating properties of anti-GM1 IgM antibodies by ELISA. Results: Activity of the classical and lectin pathways, MBL2 genotypes, and serum MBL concentrations did not differ between patients and controls. Complement activation by anti-GM1 IgM antibodies was exclusively mediated through the classical pathway and correlated with antibody titers (p < 0.001). Logistic regression analysis showed that both high innate activity of the classical pathway of complement and high complement-activating capacity of anti-GM1 IgM antibodies were significantly associated with more severe muscle weakness and axonal loss. Conclusion: High innate activity of the classical pathway of complement and efficient complement-activating properties of anti-GM1 IgM antibodies are determinants of disease severity in patients with MMN. These findings underline the importance of anti-GM1 antibody–mediated complement activation in the pathogenesis and clinical course of MMN. PMID:26161430

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

    PubMed Central

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

    2013-01-01

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

  11. Genetic predisposition in NAFLD and NASH: impact on severity of liver disease and response to treatment.

    PubMed

    Dongiovanni, Paola; Anstee, Quentin M; Valenti, Luca

    2013-01-01

    Liver fat deposition related to systemic insulin resistance defines non-alcoholic fatty liver disease (NAFLD) which, when associated with oxidative hepatocellular damage, inflammation, and activation of fibrogenesis, i.e. non-alcoholic steatohepatitis (NASH), can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease and the leading cause of altered liver enzymes in Western countries. Epidemiological, familial, and twin studies provide evidence for an element of heritability of NAFLD. Genetic modifiers of disease severity and progression have been identified through genome-wide association studies. These include the Patatin-like phosholipase domain-containing 3 (PNPLA3) gene variant I148M as a major determinant of inter-individual and ethnicity-related differences in hepatic fat content independent of insulin resistance and serum lipid concentration. Association studies confirm that the I148M polymorphism is also a strong modifier of NASH and progressive hepatic injury. Furthermore, a few large multicentre case-control studies have demonstrated a role for genetic variants implicated in insulin signalling, oxidative stress, and fibrogenesis in the progression of NAFLD towards fibrosing NASH, and confirm that hepatocellular fat accumulation and insulin resistance are key operative mechanisms closely involved in the progression of liver damage. It is now important to explore the molecular mechanisms underlying these associations between gene variants and progressive liver disease, and to evaluate their impact on the response to available therapies. It is hoped that this knowledge will offer further insights into pathogenesis, suggest novel therapeutic targets, and could help guide physicians towards individualised therapy that improves clinical outcome.

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

    PubMed

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

    2012-01-01

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

  13. Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity.

    PubMed

    Wang, Wei; Shinto, Lynne; Connor, William E; Quinn, Joseph F

    2008-02-01

    Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment. Fasting plasma carotenoids were measured in 36 AD subjects and 10 control subjects by HPLC. Correlations between plasma carotenoid levels, red blood cell (RBC) n-3 fatty acids, and dementia severity were examined in AD patients. Moderately severe AD patients (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and beta-carotene, compared to mild AD patients (MMSE=24-27) or controls. Among AD patients, variables (lutein, beta-carotene, RBC docosahexaenoic acid (DHA) and LDL-cholesterol) were significantly correlated with MMSE. A lower MMSE score was associated with lower lutein, beta-carotene and RBC DHA levels, and a higher LDL-cholesterol level. These variables explained the majority of variation in dementia severity (55% of variance in MMSE). Lutein, beta-carotene and beta-cryptoxanthin were positively correlated with RBC DHA in AD patients. The association between higher carotenoids levels and DHA and higher MMSE scores, supports a protective role of both types of nutrients in AD. These findings suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in strategies to slow the rate of cognitive decline.

  14. Relationship between nutritional risk and exercise capacity in severe chronic obstructive pulmonary disease in male patients

    PubMed Central

    Shan, Xizheng; Liu, Jinming; Luo, Yanrong; Xu, Xiaowen; Han, Zhiqing; Li, Hailing

    2015-01-01

    Objective The nutritional status of chronic obstructive pulmonary disease (COPD) patients is associated with their exercise capacity. In the present study, we have explored the relationship between nutritional risk and exercise capacity in severe male COPD patients. Methods A total of 58 severe COPD male patients were enrolled in this study. The patients were assigned to no nutritional risk group (n=33) and nutritional risk group (n=25) according to the Nutritional Risk Screening (NRS, 2002) criteria. Blood gas analysis, conventional pulmonary function testing, and cardiopulmonary exercise testing were performed on all the patients. Results Results showed that the weight and BMI of the patients in the nutritional risk group were significantly lower than in the no nutritional risk group (P<0.05). The pulmonary diffusing capacity for carbon monoxide of the no nutritional risk group was significantly higher than that of the nutritional risk group (P<0.05). Besides, the peak VO2 (peak oxygen uptake), peak O2 pulse (peak oxygen pulse), and peak load of the nutritional risk group were significantly lower than those of the no nutritional risk group (P<0.05) and there were significantly negative correlations between the NRS score and peak VO2, peak O2 pulse, or peak load (r<0, P<0.05). Conclusion The association between exercise capacity and nutritional risk based on NRS 2002 in severe COPD male patients is supported by these results of this study. PMID:26150712

  15. Severe lactose intolerance in a patient with coronary artery disease and ischemic cardiomyopathy.

    PubMed

    Craveiro Barra, Sérgio Nuno; Gomes, Pedro; Leitão Marques, António

    2012-12-01

    A 72-year-old man with severe lactose intolerance was admitted for non-ST-segment elevation myocardial infarction. The coronary angiogram revealed occlusion of the distal third of the first diagonal artery and several non-significant lesions. The pre-discharge echocardiogram revealed moderate left ventricular systolic dysfunction. Discharged on dual antiplatelet therapy, rosuvastatin, perindopril and carvedilol, he was repeatedly readmitted in the following days for abdominal pain/bloating, diarrhea and nausea despite avoiding food products containing lactose. To date, there has been no comprehensive study on the relationship between lactose intolerance and coronary disease, nor has its impact on therapeutics been appropriately addressed. Intolerance to lactose-containing prescription medicines is an extremely rare phenomenon and few strategies are available to overcome this condition, as it has received little attention from the scientific community. Commercial forms of the lactase enzyme and probiotics can limit symptom severity, but different routes of administration, different brands of the same medicine or completely different medicines may be necessary. Some measures were proposed to our patient and, soon afterwards, he was completely asymptomatic in both gastrointestinal and cardiovascular terms.

  16. Chemerin level in pregnancies complicated by preeclampsia and its relation with disease severity and neonatal outcomes.

    PubMed

    Cetin, Orkun; Kurdoglu, Zehra; Kurdoglu, Mertihan; Sahin, H Guler

    2017-02-01

    The aims of this prospective study were to detect maternal serum chemerin level in patients with preeclampsia and investigate its association with disease severity and neonatal outcomes. Maternal serum chemerin levels were significantly elevated in severe preeclamptic women (394.72 ± 100.01 ng/ml) compared to mild preeclamptic women (322.11 ± 37.60 ng/ml) and healthy pregnant women (199.96 ± 28.05 ng/ml) (p = .001). Maternal serum chemerin levels were positively correlated with systolic and diastolic blood pressure, C-reactive protein levels, homeostasis model assessment of insulin resistance, proteinuria, AST, ALT, and duration of hospitalisation. Gestational week at delivery, birthweight, and APGAR scores at 1 and 5 min were negatively correlated with maternal serum chemerin level. A maternal serum chemerin level of >252.0 ng/ml indicated preeclampsia with 95.5% sensitivity and 95.7% specificity. There was a positive correlation between maternal serum chemerin level and severity of preeclampsia. Additionally, adverse neonatal outcomes were significantly associated with high maternal serum chemerin levels.

  17. A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease

    PubMed Central

    2017-01-01

    Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement. PMID:28250998

  18. Severe to profound deafness may be associated with MYH9-related disease: report of 4 patients.

    PubMed

    Canzi, P; Pecci, A; Manfrin, M; Rebecchi, E; Zaninetti, C; Bozzi, V; Benazzo, M

    2016-10-01

    MYH9-related disease (MYH9-RD) is a rare genetic syndromic disorder characterised by congenital thrombocytopenia and is associated with the risk of developing progressive sensorineural hearing loss, nephropathy and presenile cataracts during childhood or adult life. All consecutive patients enrolled in the Italian Registry for MYH9-RD with severe to profound deafness were included in a retrospective study. The study population involved 147 Italian patients with MYH9-RD: hearing loss was identified in 52% of cases and only 4 patients (6%) presented severe to profound deafness at a mean age of 33 years. Deafness was associated with mild spontaneous bleeding in all patients and with kidney involvement in 3 cases. Cochlear implantation was carried out in 3 cases with benefit, and no major complications were observed. Diagnosis was performed about 28 years after the first clinical manifestation of MYH9-RD, which was never suspected by an otolaryngologist. The clinical and diagnostic aspects of 4 patients with severe to profound deafness are discussed with a focus on therapeutic implications.

  19. Circulating Angiopoietin-1 Is Not a Biomarker of Disease Severity or Prognosis in Pulmonary Hypertension

    PubMed Central

    Sommer, Natascha; Schmidt, Thomas; Seeger, Werner; Ghofrani, Hossein Ardeschir; Schermuly, Ralph; Gall, Henning

    2016-01-01

    Background Circulating angiopoietin-1 (Ang-1) has been linked to pulmonary hypertension (PH) in experimental studies. However, the clinical relevance of Ang-1 as a biomarker in PH remains unknown. We aimed to investigate the prognostic and clinical significance of Ang-1 in PH using data from the prospectively recruiting Giessen PH Registry. Methods Patients with suspected PH (without previous specific pulmonary arterial hypertension [PAH] therapy) who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic PAH, connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC (non-PH controls). The association of Ang-1 levels with disease severity (6-minute walk distance and pulmonary hemodynamics) was assessed using linear regression, and the impact of Ang-1 levels on transplant-free survival (primary endpoint) and clinical worsening was assessed using Kaplan—Meier curves, receiver operating characteristic (ROC) analyses, and Cox regression. Results 151 patients (39, 39, 32, and 41 with idiopathic PAH, CTD-PAH, PH-LHD, and CTEPH, respectively) and 41 non-PH controls were included. Ang-1 levels showed no significant difference between groups (p = 0.8), and no significant associations with disease severity in PH subgroups (p ≥ 0.07). In Kaplan—Meier analyses, Ang-1 levels (stratified by quartile) had no significant impact on transplant-free survival (p ≥ 0.27) or clinical worsening (p ≥ 0.51) in PH subgroups. Regression models found no significant association between Ang-1 levels and outcomes (p ≥ 0.31). ROC analyses found no significant cut-off that would maximize sensitivity and specificity. Conclusions Despite a strong pathophysiological association in experimental studies, this first comprehensive

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

    PubMed

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

    2016-04-01

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

  1. The Role of Cerebrovascular Disease on Cognitive and Functional Status and Psychosis in Severe Alzheimer’s Disease

    PubMed Central

    Kim, Julia; Schweizer, Tom A.; Fischer, Corinne E.; Munoz, David G.

    2016-01-01

    Background: The pathophysiology behind psychosis in patients with Alzheimer’s disease (AD) remains unknown. Recently, vascular risk factors have been recognized as important modifiers of the clinical presentation of AD. Objective: The purpose of our study is to investigate the mechanism through which vascular risk factors mediate psychosis and whether or not it involves cerebrovascular lesions. Methods: Data was provided by the National Alzheimer’s Coordinating Centre. The Uniform Data Set was used to collect information on subject-reported history of vascular risk factors, clinician-reported state of cognitive performance, and presence of psychosis based on the Neuropsychiatric Inventory Questionnaire (NPI-Q). The Neuropathology Data Set was used to evaluate the presence of vascular lesions and the severity of AD pathology. Subjects with high probability of AD based on the NIA/AA Reagan criteria were included in the analysis. Results: We identified 1,459 patients with high probability of AD and corresponding NPI-Q scores. We confirmed the association between hypertension and diabetes on psychosis, specifically in delusions and the co-occurrence of delusions and hallucinations. Furthermore, the presence of white matter rarefaction based on pathological evaluation was associated with hallucinations. A history of vascular risk factors was positively associated with vascular lesions. However, vascular lesions in the presence of vascular risk factors did not increase the likelihood of psychosis. Furthermore, vascular lesions were not associated with greater cognitive or functional impairments in this group with severe AD pathology. Conclusion: Vascular risk factors and vascular lesions are independently associated with psychosis in patients with severe AD. However, vascular lesions are not the mechanism through which vascular risk factors mediate psychosis. PMID:27662301

  2. Micro- and nano-mechanics of osteoarthritic cartilage: The effects of tonicity and disease severity.

    PubMed

    Moshtagh, P R; Pouran, B; van Tiel, J; Rauker, J; Zuiddam, M R; Arbabi, V; Korthagen, N M; Weinans, H; Zadpoor, A A

    2016-06-01

    The present study aims to discover the contribution of glycosaminoglycans (GAGs) and collagen fibers to the mechanical properties of the osteoarthritic (OA) cartilage tissue. We used nanoindentation experiments to understand the mechanical behavior of mild and severe osteoarthritic cartilage at micro- and nano-scale at different swelling conditions. Contrast enhanced micro-computed tomography (EPIC-μCT) was used to confirm that mild OA specimens had significantly higher GAGs content compared to severe OA specimens. In micro-scale, the semi-equilibrium modulus of mild OA specimens significantly dropped after immersion in a hypertonic solution and at nano-scale, the histograms of the measured elastic modulus revealed three to four components. Comparing the peaks with those observed for healthy cartilage in a previous study indicated that the first and third peaks represent the mechanical properties of GAGs and the collagen network. The third peak shows considerably stiffer elastic modulus for mild OA samples as compared to the severe OA samples in isotonic conditions. Furthermore, this peak clearly dropped when the tonicity increased, indicating the loss of collagen (pre-) stress in the shrunk specimen. Our observations support the association of the third peak with the collagen network. However, our results did not provide any direct evidence to support the association of the first peak with GAGs. For severe OA specimens, the peak associated with the collagen network did not drop when the tonicity increased, indicating a change in the response of OA cartilage to hypertonicity, likely collagen damage, as the disease progresses to its latest stages.

  3. Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection

    PubMed Central

    Koskela, Sirpa; Laine, Outi; Mäkelä, Satu; Pessi, Tanja; Tuomisto, Sari; Huhtala, Heini; Karhunen, Pekka J.; Pörsti, Ilkka; Mustonen, Jukka

    2015-01-01

    Introduction Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection. Patients and Methods Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped. Results The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT-homozygotes) had higher maximum level of serum creatinine than the carriers of G-allele (GT-heterozygotes and GG-homozygotes; median 326, range 102–1041 vs. median 175, range 51–1499 μmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3–14 vs. median 6, range 2–15 days; p = 0.032). The rare A-allele carriers (i.e. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74–170 vs.116, range 86–162 mmHg, p = 0.019, and median 68, range 40–90 vs. 72, range 48–100 mmHg; p = 0.003, respectively). Conclusions Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection. PMID:26561052

  4. Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans.

    PubMed

    Bénard, Stève; Wright, Claire; Voisine, Jimmy; Olivier, Catherine W; Gaudelus, Joël

    2016-01-01

    Invasive meningococcal disease (IMD) is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts (clinicians and social workers): a 6-year-old child with purpura fulminans with amputation of both legs below the knee (case A) and a 3-year-old with meningitis and severe neurological sequelae (case B). Additional scenarios included other typical sequelae of IMD such as chronic kidney disease (CKD), profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs (2013) were mainly obtained from the literature and the National Health Insurance (NHI). Time horizon was based on life expectancies of patients (77 and 55 years, respectively). A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances. purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount (€1,480,545). Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost (€2,267,251). The first year is the most expensive in both scenarios (€166,890 and €160,647 respectively). The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost (101,833€ and 258,817€, respectively). This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the

  5. Von Willebrand disease in sub-Saharan Africa: a first severe case reported in Cameroon.

    PubMed

    Tagny, Claude T; Balôgôg, Pauline N; Boehlen, Francoise; Mbanya, Dora

    2016-10-01

    In Cameroon, the Yaoundé Hemophilia Treatment Center (HTC) has so far recorded 121 cases of hemophilia and only 10 cases of von Willebrand disease (VWD). We report the case of a 16-year-old girl, living in the north of Cameroon. She presented with severe meno-metrorrhagia, which had increased drastically within the past 3 months, associated more recently by gum bleeding and epistaxis. The coagulation screen showed a prolonged bleeding time. The clinical profile of this young girl and the findings of less than 5% for von Willebrand factor (VWF):Ag and 10% for VWF Ristocetin cofactor suggests a type 3 VWD. Screening for VWF:Ag and other inherited bleeding disorders in Cameroon is still rudimentary, and although VWD is more common than hemophilia, we report this case to highlight some of the challenges faced in resource-limited contexts.

  6. The effect of chair yoga in older adults with moderate and severe Alzheimer's disease.

    PubMed

    McCaffrey, Ruth; Park, Juyoung; Newman, David; Hagen, Dyana

    2014-01-01

    Using a quasi-experimental single-group design, this study examined the feasibility of older adults with Alzheimer's disease (AD)-type dementia to complete the Sit 'N' Fit Chair Yoga Program. Physical function of participants who completed the program was measured. The nine older adults with AD (mean age = 83) participated in the 8-week Sit 'N' Fit Chair Yoga Program. To measure physical function, the Six-Minute Walk Test, the Gait Speed Test, and the Berg Balance Scale were administered at pre-intervention, 4 weeks, 8 weeks, and 1 month after program completion. All participants completed the program. Positive changes were seen across all physical measures. Further study, using a larger sample and including a control group, is needed to fully determine the effect of the Sit 'N' Fit Chair Yoga Program on older adults with moderate to severe AD.

  7. Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency.

    PubMed

    Booth, C; Algar, V E; Xu-Bayford, J; Fairbanks, L; Owens, C; Gaspar, H B

    2012-06-01

    Adenosine deaminase deficiency is a disorder of purine metabolism manifesting severe combined immunodeficiency (ADA-SCID) and systemic abnormalities. Increased levels of the substrate deoxyadenosine triphosphate (dATP) lead to immunodeficiency and are associated in a murine model with pulmonary insufficiency. We compared a cohort of patients with ADA-SCID and X-linked SCID and found that despite similar radiological and respiratory findings, positive microbiology is significantly less frequent in ADA-SCID patients (p < 0.0005), suggesting a metabolic pathogenesis for the lung disease. Clinicians should be aware of this possibility and correct metabolic abnormalities either through enzyme replacement or haematopoietic stem cell transplant, in addition to treating infectious complications.

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

    PubMed Central

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

    2016-01-01

    Abstract Objective To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. Methods 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. Findings 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). Conclusion 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. PMID:27708472

  9. Metabolite mapping reveals severe widespread perturbation of multiple metabolic processes in Huntington's disease human brain.

    PubMed

    Patassini, Stefano; Begley, Paul; Xu, Jingshu; Church, Stephanie J; Reid, Suzanne J; Kim, Eric H; Curtis, Maurice A; Dragunow, Mike; Waldvogel, Henry J; Snell, Russell G; Unwin, Richard D; Faull, Richard L M; Cooper, Garth J S

    2016-09-01

    Huntington's disease (HD) is a genetically-mediated neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein (Htt) through lengthening of its polyglutamine tract, thus initiating a cascade that ultimately leads to premature death. However, neurodegeneration typically manifests in HD only in middle age, and mechanisms linking the causative mutation to brain disease are poorly understood. Brain metabolism is severely perturbed in HD, and some studies have indicated a potential role for mutant Htt as a driver of these metabolic aberrations. Here, our objective was to determine the effects of HD on brain metabolism by measuring levels of polar metabolites in regions known to undergo varying degrees of damage. We performed gas-chromatography/mass spectrometry-based metabolomic analyses in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine matched controls. In each patient, we measured metabolite content in representative tissue-samples from eleven brain regions that display varying degrees of damage in HD, thus identifying the presence and abundance of 63 different metabolites from several molecular classes, including carbohydrates, amino acids, nucleosides, and neurotransmitters. Robust alterations in regional brain-metabolite abundances were observed in HD patients: these included changes in levels of small molecules that play important roles as intermediates in the tricarboxylic-acid and urea cycles, and amino-acid metabolism. Our findings point to widespread disruption of brain metabolism and indicate a complex phenotype beyond the gradient of neuropathologic damage observed in HD brain.

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

    PubMed

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

    2007-07-01

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

  11. Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease.

    PubMed

    Dancey, D R; Tullis, E D; Heslegrave, R; Thornley, K; Hanly, P J

    2002-03-01

    It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption. Nineteen CF patients (forced expiratory volume in one second 28+/-7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function. CF patients tended to report more awakenings (0.7+/-0.5 versus 0.3+/-0.2 x h(-1), p=0.08), and PSG revealed reduced sleep efficiency (71+/-25 versus 93+/-4%, p=0.004) and a higher frequency of awakenings (4.2+/-2.7 versus 2.4+/-1.4 x h(-1), p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4+/-6.8 versus 94.3+/-1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7+/-3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=10.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict. The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.

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

    PubMed

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

    2015-09-01

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

  13. The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome.

    PubMed

    Ben-Zvi, Ilan; Goldenberg, Ilan; Matetzky, Shlomi; Grossman, Chagai; Elis, Avishay; Gavrielov-Yusim, Natalie; Livneh, Avi

    2016-01-01

    Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case-control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to 120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%, respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%, respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality.

  14. Increased IL17A, IFNG, and FOXP3 Transcripts in Moderate-Severe Psoriasis: A Major Influence Exerted by IL17A in Disease Severity.

    PubMed

    de Oliveira, Priscilla Stela Santana; Pereira, Michelly Cristiny; Silva de Paula, Simão Kalebe; Lima, Emerson Vasconcelos Andrade; Lima, Mariana Modesto de Andrade; de Arruda, Rodrigo Gomes; de Oliveira, Wagner Luís Mendes; Duarte, Ângela Luzia Branco Pinto; Pitta, Ivan da Rocha; Rêgo, Moacyr Jesus Melo Barreto; Galdino da Rocha Pitta, Maira

    2016-01-01

    Psoriasis is a chronic and recurrent dermatitis, mediated by keratinocytes and T cells. Several proinflammatory cytokines contribute to formation and maintenance of psoriatic plaque. The Th1/Th17 pathways and some of IL-1 family members were involved in psoriasis pathogenesis and could contribute to disease activity. Therefore, we sought to analyse skin transcript levels of IL17A, IL22, RORC, IL8, IFNG, IL33, IL36A, FOXP3, and IL10 and correlate with clinic of patients with plaque-type psoriasis. In order to conduct that, we collected punch biopsies from lesional skin and obtained tissue RNA. After reverse transcription, qRT-PCR quantified the relative mRNA expression. The main results revealed increased transcripts levels of IL17A, IFNG, and FOXP3 in moderate-severe patients. Despite this, only IL17A can increase the chance to worsen disease severity. We also observed many significant positive correlations between each transcript. In conclusion, IL17A is elevated in lesional skin from psoriasis patients and plays crucial role in disease severity.

  15. Increased IL17A, IFNG, and FOXP3 Transcripts in Moderate-Severe Psoriasis: A Major Influence Exerted by IL17A in Disease Severity

    PubMed Central

    de Oliveira, Priscilla Stela Santana; Pereira, Michelly Cristiny; Silva de Paula, Simão Kalebe; Lima, Emerson Vasconcelos Andrade; Lima, Mariana Modesto de Andrade; de Arruda, Rodrigo Gomes; Duarte, Ângela Luzia Branco Pinto; Pitta, Ivan da Rocha

    2016-01-01

    Psoriasis is a chronic and recurrent dermatitis, mediated by keratinocytes and T cells. Several proinflammatory cytokines contribute to formation and maintenance of psoriatic plaque. The Th1/Th17 pathways and some of IL-1 family members were involved in psoriasis pathogenesis and could contribute to disease activity. Therefore, we sought to analyse skin transcript levels of IL17A, IL22, RORC, IL8, IFNG, IL33, IL36A, FOXP3, and IL10 and correlate with clinic of patients with plaque-type psoriasis. In order to conduct that, we collected punch biopsies from lesional skin and obtained tissue RNA. After reverse transcription, qRT-PCR quantified the relative mRNA expression. The main results revealed increased transcripts levels of IL17A, IFNG, and FOXP3 in moderate-severe patients. Despite this, only IL17A can increase the chance to worsen disease severity. We also observed many significant positive correlations between each transcript. In conclusion, IL17A is elevated in lesional skin from psoriasis patients and plays crucial role in disease severity. PMID:28042206

  16. Activated Circulating T Follicular Helper Cells Are Associated with Disease Severity in Patients with Psoriasis

    PubMed Central

    Wang, Ying; Yang, Haoyu; Yuan, Weichang; Ren, Jingyi

    2016-01-01

    Circulating T follicular helper (cTfh) cells are known to be involved in numerous immune-mediated diseases, but their pathological role in psoriasis is less fully investigated. Herein, we aimed to identify whether cTfh cells contributed to the pathogenesis of psoriasis. The frequency and function of cTfh cells were compared between patients with psoriasis vulgaris and healthy controls, and the infiltration of Tfh cells was detected between lesional and nonlesional skin tissues of psoriasis patients. Moreover, the dynamic change of cTfh cells before and after acitretin treatment was evaluated. Our results showed both increased frequency and activation (indicated by higher expression of ICOS, PD-1, HLA-DR, and Ki-67 and increased production of IL-21, IL-17, and IFN-γ) of cTfh cells in psoriasis patients. Compared with nonlesional skin tissues of psoriasis patients, the number of infiltrated Tfh cells was significantly increased in psoriasis lesions. In addition, positive correlations between the percentage of cTfh, functional markers on cTfh cells in peripheral blood and disease severity were noted. Furthermore, the frequency of cTfh cells and the levels of cytokines secreted by cTfh cells were all significantly decreased after 1-month treatment. PMID:27774460

  17. High dose anakinra for treatment of severe neonatal Kawasaki disease: a case report

    PubMed Central

    2014-01-01

    We report an 11-week-old female who presented with Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS). The infant presented to the hospital with persistent fever, cough, diarrhea, and emesis, among other symptoms. Her condition quickly began to decompensate, and she developed classic features (conjunctivitis, rash, cracked lips, distal extremity edema) prompting a diagnosis of acute KD. The patient was treated with standard therapy for KD including three doses of intravenous immunoglobulin (IVIG), aspirin, and high dose glucocorticoids with no change in her condition. Due to a high suspicion for MAS, high dose anakinra therapy was initiated resulting in dramatic clinical improvements. She also received one dose of infliximab for concern for coronary artery changes, and over the course of several months, anakinra and high dose glucocorticoids were tapered. Nearly complete reversal of echocardiogram changes were observed after 8 months, and the infant is now off all immunosuppressive therapy. In this case report, we briefly review the importance of early recognition of MAS in pediatric patient populations with rheumatic diseases, and we suggest early initiation of anakinra therapy as a rapid and effective treatment option. PMID:25045337

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

    PubMed

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

    2016-03-01

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

  19. Polymyositis associated with severe interstitial lung disease: remission after three doses of IV immunoglobulin.

    PubMed

    Bakewell, Catherine J; Raghu, Ganesh

    2011-02-01

    Interstitial lung disease associated with polymyositis/dermatomyositis (ILD-PM/DM) often confers a poor prognosis, and optimal treatment of this condition is not well defined. This report describes a 63-year-old man with severe ILD-PM/DM who presented with 5 months of progressive dyspnea and weakness. He had an initial carbon-monoxide-diffusing capacity of 35% predicted and a creatine kinase level of 2,112 U/L. After three monthly doses of immunoglobulin at 2 gm/kg IV, he has sustained clinical remission for > 2 years. IV immunoglobulin has not previously been studied as a first-line agent for rheumatologic diseases, and it is currently used as a salvage therapy. However, if IV immunoglobulin is capable of inducing sustained remission after brief use as a treatment, as demonstrated in this patient, especially in the setting of significant pulmonary involvement, then it merits further consideration for investigation as a first-line therapeutic agent.

  20. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.

  1. A fatal case of severe hemolytic disease of newborn associated with anti-Jk(b).

    PubMed

    Kim, Won Duck; Lee, Young Hwan

    2006-02-01

    The Kidd blood group is clinically significant since the Jk antibodies can cause acute and delayed transfusion reactions as well as hemolytic disease of newborn (HDN). In general, HDN due to anti-Jk(b) incompatibility is rare and it usually displays mild clinical symptoms with a favorable prognosis. Yet, we apparently experienced the second case of HDN due to anti-Jk(b) with severe clinical symptoms and a fatal outcome. A female patient having the AB, Rh(D)-positive blood type was admitted for jaundice on the fourth day after birth. At the time of admission, the patient was lethargic and exhibited high pitched crying. The laboratory data indicated a hemoglobin value of 11.4 mg/dL, a reticulocyte count of 14.9% and a total bilirubin of 46.1 mg/dL, a direct bilirubin of 1.1 mg/dL and a strong positive result (+++) on the direct Coomb's test. As a result of the identification of irregular antibody from the maternal serum, anti-Jk(b) was detected, which was also found in the eluate made from infant's blood. Despite the aggressive treatment with exchange transfusion and intensive phototherapy, the patient died of intractable seizure and acute renal failure on the fourth day of admission. Therefore, pediatricians should be aware of the clinical courses of hemolytic jaundice due to anti-Jk(b), and they should be ready to treat this disease with active therapeutic interventions.

  2. Activity Parameters of Subthalamic Nucleus Neurons Selectively Predict Motor Symptom Severity in Parkinson's Disease

    PubMed Central

    Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A.; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A.; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K.

    2014-01-01

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype. PMID:24790198

  3. Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson's disease.

    PubMed

    Sharott, Andrew; Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K; Moll, Christian K E

    2014-04-30

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.

  4. PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

    PubMed Central

    Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

    2016-01-01

    AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients. PMID:28050240

  5. Reciprocal Transcriptional Regulation of Metabolic and Signaling Pathways Correlates with Disease Severity in Heart Failure

    PubMed Central

    Barth, Andreas S; Kumordzie, Ami; Frangakis, Constantine; Margulies, Kenneth B; Cappola, Thomas P; Tomaselli, Gordon F

    2012-01-01

    Background Systolic heart failure (HF) is a complex systemic syndrome that can result from a wide variety of clinical conditions and gene mutations. Despite phenotypic similarities, characterized by ventricular dilatation and reduced contractility, the extent of common and divergent gene expression between different forms of HF remains a matter of intense debate. Methods and Results Using a meta-analysis of 28 experimental (mouse, rat, dog) and human HF microarray studies, we demonstrate that gene expression changes are characterized by a coordinated and reciprocal regulation of major metabolic and signaling pathways. In response to a wide variety of stressors in animal models of HF, including ischemia, pressure overload, tachypacing, chronic isoproterenol infusion, Chagas disease, and transgenic mouse models, major metabolic pathways are invariably downregulated, while cell signaling pathways are upregulated. In contrast to this uniform transcriptional pattern observed in experimental animal models which recapitulates a fetal gene expression program, human HF microarray studies displayed a greater heterogeneity, with some studies even showing upregulation of metabolic and downregulation of signaling pathways in end-stage human hearts. These discrepant results between animal and human studies are due to a number of factors, prominently cardiac disease and variable exposure to cold cardioplegic solution in non-failing human samples which can downregulate transcripts involved in oxidative phosphorylation (OXPHOS) within the first 6h, thus mimicking gene expression patterns observed in failing samples. Additionally, beta-blockers and ACE-inhibitor use in end-stage human HF was associated with higher levels of myocardial OXPHOS transcripts, thus partially reversing the fetal gene expression pattern. In human failing samples, downregulation of metabolism was associated with hemodynamic markers of disease severity. Conclusions Irrespective of the etiology, gene

  6. Network Modules of the Cross-Species Genotype-Phenotype Map Reflect the Clinical Severity of Human Diseases

    PubMed Central

    Han, Seong Kyu; Kim, Inhae; Hwang, Jihye; Kim, Sanguk

    2015-01-01

    Recent advances in genome sequencing techniques have improved our understanding of the genotype-phenotype relationship between genetic variants and human diseases. However, genetic variations uncovered from patient populations do not provide enough information to understand the mechanisms underlying the progression and clinical severity of human diseases. Moreover, building a high-resolution genotype-phenotype map is difficult due to the diverse genetic backgrounds of the human population. We built a cross-species genotype-phenotype map to explain the clinical severity of human genetic diseases. We developed a data-integrative framework to investigate network modules composed of human diseases mapped with gene essentiality measured from a model organism. Essential and nonessential genes connect diseases of different types which form clusters in the human disease network. In a large patient population study, we found that disease classes enriched with essential genes tended to show a higher mortality rate than disease classes enriched with nonessential genes. Moreover, high disease mortality rates are explained by the multiple comorbid relationships and the high pleiotropy of disease genes found in the essential gene-enriched diseases. Our results reveal that the genotype-phenotype map of a model organism can facilitate the identification of human disease-gene associations and predict human disease progression. PMID:26301634

  7. Decreased serum IL-27 and IL-35 levels are associated with disease severity in neuromyelitis optica spectrum disorders.

    PubMed

    Zhang, Da-Qi; Jia, Kun; Wang, Rong; Li, Ting; Zhao, Ning; Yang, Li-Na; Yang, Li

    2016-04-15

    The interleukin 12 (IL-12) family plays important roles in autoimmune diseases. To explore the roles of the IL-12 family members IL-27 and IL-35 in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD), we determined their serum and cerebral spinal fluid levels and assessed potential correlations with clinical characteristics. Serum IL-27 levels were negatively correlated with disease severity and spinal cord lesion length, while serum IL-35 levels were negatively correlated with disease severity and annual relapse rate. Thus, IL-27 and IL-35 may be important biomarkers of NMOSD severity and these molecules might represent potential therapeutic cytokines for treating NMOSD.

  8. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Spudich, Serena S.; Gritsenko, Marina A.; Fuchs, Dietmar; Liegler, Teri; Zetterberg, Henrik; Camp, David G.; Price, Richard W.; Smith, Richard D.

    2012-03-20

    Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid

  9. Serum Irisin Level Can Predict the Severity of Coronary Artery Disease in Patients with Stable Angina

    PubMed Central

    Efe, Tolga Han; Açar, Burak; Ertem, Ahmet Göktuğ; Yayla, Kadriye Gayretli; Algül, Engin; Ünal, Sefa; Bilgin, Murat; Çimen, Tolga; Kirbaş, Özgür; Yeter, Ekrem

    2017-01-01

    Background and Objectives The recently discovered myokine irisin has a proposed role in adipose tissue metabolism. The aim of this study was to evaluate the relationship between serum irisin level and the coronary artery severity in patients with stable coronary artery disease (CAD). Subjects and Methods Sixty-three patients who underwent coronary angiography (CA) diagnosed with stable CAD and twenty-six patients with normal coronary artery (NCA) were enrolled in the study. Stable CAD patients were divided into two groups as high synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score (≥23) and lower SYNTAX score (<23). Serum irisin level measurement was carried out using human irisin colorimetric enzyme-linked immunosorbent assay (ELISA) commercial kit (AG-45A-0046EK-KI01, Adipogen, San Diego, CA, USA) as recommended by the manufacturer's protocol. Results The patients with stable CAD with a higher SYNTAX score (score ≥23) had significantly lower serum irisin levels (127.91±55.38 ng/mL), as compared the patients with a low SYNTAX score (score <23) (224.69±92.99 ng/mL) and control group (299.54±123.20 ng/mL). Irisin levels showed significant differences between all groups (p<0.001). Conclusion Serum irisin level is an independent predictor of coronary artery severity in patients with stable CAD. PMID:28154590

  10. Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease

    PubMed Central

    Desbois, Anne Claire; Addimanda, Olga; Bertrand, Anne; Deroux, Alban; Pérard, Laurent; Depaz, Raphael; Hachulla, Eric; Lambert, Marc; Launay, David; Subran, Benjamin; Ackerman, Felix; Mariette, Xavier; Cohen, Fleur; Marie, Isabelle; Salvarini, Carlo; Cacoub, Patrice; Saadoun, David

    2016-01-01

    Abstract To report the safety and efficacy of anti-tumor necrosis factor α (TNFα) therapy in severe and refractory neuro-Behçet disease (NBD) patients. Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24–60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months. Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1–6). The median Rankin score was 2 (1–4) at the initiation of anti-TNFα versus 1 (0–4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases. TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population. PMID:27281066

  11. Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients

    PubMed Central

    Morena, Marion; Jaussent, Isabelle; Halkovich, Aurore; Dupuy, Anne-Marie; Bargnoux, Anne-Sophie; Chenine, Leila; Leray-Moragues, Hélène; Klouche, Kada; Vernhet, Hélène; Canaud, Bernard; Cristol, Jean-Paul

    2012-01-01

    Background Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? Methodology/Principal Findings 195 ND-CKD patients (112 males/83 females, 70.8 [27.4–94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100–400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO4) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. Conclusions Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients. PMID:22567137

  12. Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease

    PubMed Central

    Clini, E.; Bianchi, L.; Pagani, M.; Ambrosino, N.

    1998-01-01

    BACKGROUND—Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity.
METHODS—Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV1) and the presence of cor pulmonale (CP) (group 1, FEV1 <35% predicted with CP, n = 15; group 2, FEV1 <35% predicted without CP, n =15; group 3, FEV1 >35% predicted, n = 23). Seventeen normal subjects served as controls.
RESULTS—All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p<0.01 ANOVA). In all subjects % predicted FEV1 correlated slightly with PLNO but not with PNO.
CONCLUSION—Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.

 PMID:10193378

  13. Association between markers of emphysema and more severe chronic obstructive pulmonary disease

    PubMed Central

    Boschetto, P; Quintavalle, S; Zeni, E; Leprotti, S; Potena, A; Ballerin, L; Papi, A; Palladini, G; Luisetti, M; Annovazzi, L; Iadarola, P; De Rosa, E; Fabbri, L M; Mapp, C E

    2006-01-01

    Background The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods Twenty six outpatients with COPD and eight healthy non‐smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)‐9 and tissue inhibitor of metalloproteinase (TIMP)‐1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP‐9, and the MMP‐9/TIMP‐1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema. PMID:16769715

  14. NDVI, scale invariance and the modifiable areal unit problem: An assessment of vegetation in the Adelaide Parklands.

    PubMed

    Nouri, Hamideh; Anderson, Sharolyn; Sutton, Paul; Beecham, Simon; Nagler, Pamela; Jarchow, Christopher J; Roberts, Dar A

    2017-04-15

    This research addresses the question as to whether or not the Normalised Difference Vegetation Index (NDVI) is scale invariant (i.e. constant over spatial aggregation) for pure pixels of urban vegetation. It has been long recognized that there are issues related to the modifiable areal unit problem (MAUP) pertaining to indices such as NDVI and images at varying spatial resolutions. These issues are relevant to using NDVI values in spatial analyses. We compare two different methods of calculation of a mean NDVI: 1) using pixel values of NDVI within feature/object boundaries and 2) first calculating the mean red and mean near-infrared across all feature pixels and then calculating NDVI. We explore the nature and magnitude of these differences for images taken from two sensors, a 1.24m resolution WorldView-3 and a 0.1m resolution digital aerial image. We apply these methods over an urban park located in the Adelaide Parklands of South Australia. We demonstrate that the MAUP is not an issue for calculation of NDVI within a sensor for pure urban vegetation pixels. This may prove useful for future rule-based monitoring of the ecosystem functioning of green infrastructure.

  15. NDVI, scale invariance and the modifiable areal unit problem: An assessment of vegetation in the Adelaide Parklands

    USGS Publications Warehouse

    Nouri, Hamideh; Anderson, Sharolyn; Sutton, Paul; Beecham, Simon; Nagler, Pamela L.; Jarchow, Christopher J; Roberts, Dar A.

    2017-01-01

    This research addresses the question as to whether or not the Normalised Difference Vegetation Index (NDVI) is scale invariant (i.e. constant over spatial aggregation) for pure pixels of urban vegetation. It has been long recognized that there are issues related to the modifiable areal unit problem (MAUP) pertaining to indices such as NDVI and images at varying spatial resolutions. These issues are relevant to using NDVI values in spatial analyses. We compare two different methods of calculation of a mean NDVI: 1) using pixel values of NDVI within feature/object boundaries and 2) first calculating the mean red and mean near-infrared across all feature pixels and then calculating NDVI. We explore the nature and magnitude of these differences for images taken from two sensors, a 1.24 m resolution WorldView-3 and a 0.1 m resolution digital aerial image. We apply these methods over an urban park located in the Adelaide Parklands of South Australia. We demonstrate that the MAUP is not an issue for calculation of NDVI within a sensor for pure urban vegetation pixels. This may prove useful for future rule-based monitoring of the ecosystem functioning of green infrastructure.

  16. Illness perceptions and stress: mediators between disease severity and psychological well-being and quality of life among patients with Crohn’s disease

    PubMed Central

    Zhang, Maochen; Hong, Liwen; Zhang, Tianyu; Lin, Yun; Zheng, Sichang; Zhou, Xiaolin; Fan, Rong; Wang, Zhengting; Zhang, Chenli; Zhong, Jie

    2016-01-01

    Background Disease severity, illness perceptions, coping strategies, stress, psychological well-being, and quality of life were reported to have close relationships. According to the Common Sense Model, illness perceptions and coping strategies could mediate the relationship between illness stimuli and illness outcomes such as psychological health and quality of life. Stress was also associated with the individual’s disease severity, anxiety, depression, and quality of life. Objectives The study aimed to explore the influencing factors of illness outcomes, and to what extent illness perceptions, coping strategies, and stress mediate the relationship between disease severity and anxiety, and depression and quality of life. Methods Our study included 159 patients with Crohn’s disease who were attending a tertiary hospital outpatient clinic or who were hospitalized. Disease severity was measured with the Crohn’s Disease Activity Index. Illness perceptions were measured with the Brief Illness Perceptions Questionnaire. Coping strategies were measured with the Carver Brief Coping Questionnaire. Stress was measured with the Perceived Stress Questionnaire. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale. Quality of life was measured with the Inflammatory Bowel Disease Questionnaire. Results Disease severity, illness perceptions, maladaptive coping, stress, anxiety, depression and quality of life were significantly correlated with each other among patients with Crohn’s disease. Using structural equation modeling to describe the inner relationship of the aforementioned variables, an excellent-fitted model was drawn. (χ2[10]=13.83, P=0.18, χ2/N=1.38, standardized root mean square residual [SRMR] <0.05, root mean square error of approximation [RMSEA] <0.05, goodness of fit index [GFI] >0.97, comparative fit index [CFI] >0.99). Disease severity had a direct influence on illness perceptions. Illness perceptions had a direct

  17. Association between plasma ADAMTS-7 levels and severity of disease in patients with stable obstructive coronary artery disease

    PubMed Central

    Yu, Jie; Zhou, Boda; Yu, Haiyi; Han, Jiangli; Cui, Ming; Zhang, Fuchun; Wang, Guisong; Guo, Lijun; Gao, Wei

    2016-01-01

    Abstract The metalloproteinase family of a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) was reported to be a novel locus associated with human coronary artery disease. This study aimed to investigate plasma ADAMTS-7 levels in stable obstructive CAD patients and elucidate the relationship between plasma ADAMTS-7 levels and the severity of CAD assessed by the Syntax score. This was a single center cross-sectional study performed in 182 CAD patients. ELISA was used to measure plasma ADAMTS-7 levels. All patients were divided into subgroup according to the ADAMTS-7 median in this cohort: high group with ADAMTS-7 ≥0.99 ng/mL and low group with ADAMTS-7 <0.99 ng/mL. Furthermore, all patients were divided into tertiles according to their Syntax scores (low group: Syntax score ≤10.0; moderate group: 10.0 18.0). We followed up the participants continuously until the first major adverse cardiovascular event (MACE) for a mean time of 22.0 months. Plasma ADAMTS-7 levels in the high Syntax score group were significantly higher compared with the low Syntax score group (3.29 [0.08–26.3] ng/mL vs 1.24 [0.15–8.78] ng/mL, P = 0.010). Plasma ADAMTS-7 levels were significantly positively correlated with the Syntax score tertiles (r = 0.157, P = 0.035). Logistic regression analysis indicated that the plasma ADAMTS-7 level was one of the independent predictors for the Syntax score tertiles (B = 1.118, 95% CI: 1.194–7.830, P = 0.020), together with HbA1c (B = 0.946, 95% CI: 1.248–5.312, P = 0.010), uric acid (B = –0.019, 95% CI: 0.974–0.988, P<0.001), and coronary artery calcium score (B = –0.001, 95% CI: 0.998–0.999, P < 0.001). Compared with the low ADAMTS-7 group, the high ADAMTS-7 group had significantly higher Syntax score (17.10±8.42 vs 14.96 ± 8.11, P = 0.047). Kaplan–Meier analysis showed patients in the high plasma ADAMTS-7

  18. Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

    PubMed Central

    2014-01-01

    Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for

  19. Predicting Ebola Severity: A Clinical Prioritization Score for Ebola Virus Disease

    PubMed Central

    Okoni-Williams, Harry Henry; Suma, Mohamed; Mancuso, Brooke; Al-Dikhari, Ahmed; Faouzi, Mohamed

    2017-01-01

    Background Despite the notoriety of Ebola virus disease (EVD) as one of the world’s most deadly infections, EVD has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. With increasingly sensitive EVD diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment. Methods/Principal Findings This retrospective cohort study analyses the clinical characteristics of 158 EVD(+) patients at the GOAL-Mathaska Ebola Treatment Centre, Sierra Leone. The prognostic potential of each characteristic was assessed and incorporated into a statistically weighted disease score. The mortality rate among EVD(+) patients was 60.8% and highest in those aged <5 or >25 years (p<0.05). Death was significantly associated with malaria co-infection (OR = 2.5, p = 0.01). However, this observation was abrogated after adjustment to Ebola viral load (p = 0.1), potentially indicating a pathologic synergy between the infections. Similarly, referral-time interacted with viral load, and adjustment revealed referral-time as a significant determinant of mortality, thus quantifying the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Disorientation was the strongest unadjusted predictor of death (OR = 13.1, p = 0.014) followed by hiccups, diarrhoea, conjunctivitis, dyspnoea and myalgia. Including these characteristics in multivariate prognostic scores, we obtained a 91% and 97% ability to discriminate death at or after triage respectively (area under ROC curve). Conclusions/Significance This study proposes highly predictive and easy-to-use prognostic tools, which stratify the risk of EVD mortality at or after EVD triage. PMID:28151955

  20. Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

    PubMed Central

    Bohnen, Nicolaas I.; Kotagal, Vikas; Müller, Martijn L.T.M; Koeppe, Robert A; Scott, Peter J.H.; Albin, Roger L.; Frey, Kirk A; Petrou, Myria

    2014-01-01

    Background There is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied. Objective To investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations. Methods Cross-sectional study. Patients with PD (n=148; age 65.6±7.4 years, Hoehn and Yahr stage 2.4±0.6, with (n=15) and without (n=133) comorbid type II DM, underwent [11C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [11C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates. Results There were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (−0.98±1.01) compared to the non-diabetics (−0.36±0.91; F=7.78, P=0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F=8.39, P<0.0001). Conclusion Diabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than diseasespecific neurodegenerations. PMID:25454317

  1. Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

    PubMed Central

    Sopic, Miron; Spasojevic-Kalimanovska, Vesna; Kalimanovska-Ostric, Dimitra; Andjelkovic, Kristina; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (ρ = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (ρ = -0.404, P < 0.001 and ρ = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (ρ = 0.353, P = 0.002). Conclusion Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine. PMID:26110037

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

    PubMed

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

    2016-05-01

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

  3. A rare CFTR mutation associated with severe disease progression in a 10-year-old Hispanic patient.

    PubMed

    Soe, Katherine; Gregoire-Bottex, M Myrtha

    2017-02-01

    Cystic fibrosis is a life-shortening multisystem genetic disease. While readily tested, few tests analyze rare gene mutations prevalent among ethnic minorities. This case of a Hispanic child with a rare CF-causing c.233dupT mutation and severe disease emphasizes the need for broad CFTR mutation analyses and genotyping particularly in minority populations.

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

    SciTech Connect

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

    2012-05-01

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

  5. Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective*

    PubMed Central

    Yau, Yunki; Duo, Xizi; Zeng, Ming; Campbell, Beth; Shin, Sean; Luber, Raphael; Redmond, Diane; Leong, Rupert W. L.

    2016-01-01

    Breakdown of the protective gut barrier releases effector molecules and degradation products into the blood stream making serum and plasma ideal as a diagnostic medium. The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring inflammatory bowel disease (IBD) activity, that is less invasive than colonoscopy. Differences in the enriched low mass plasma proteome (<25 kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and “Tier-2” FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by multiple reaction monitoring in plasma and serum including both inflammatory; rheumatoid arthritis controls, and non-inflammatory healthy controls; ulcerative colitis (UC), and Crohn's disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in plasma. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Peptides differentiating controls from IBD originate from secreted phosphoprotein 24 (SPP24, p = 0.000086, 0.009); whereas those in remission and healthy can be differentiated in UC by SPP24 (p = 0.00023, 0.001), α-1-microglobulin (AMBP, p = 0.006) and CD by SPP24 (p = 0.019, 0.05). UC and CD can be differentiated by Guanylin (GUC2A, p = 0.001), and Secretogranin-1 (CHGB p = 0.035). Active and quiescent disease can also be differentiated in UC and CD by CHGB (p ≤ 0.023) SPP24 (p ≤ 0.023) and AMBP (UC p = 0.046). Five peptides discriminating IBD activity and severity had very little-to-no correlation to erythrocyte sedimentation rate, C-reactive protein, white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These proteins have the potential to improve diagnosis and

  6. Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective.

    PubMed

    Wasinger, Valerie C; Yau, Yunki; Duo, Xizi; Zeng, Ming; Campbell, Beth; Shin, Sean; Luber, Raphael; Redmond, Diane; Leong, Rupert W L

    2016-01-01

    Breakdown of the protective gut barrier releases effector molecules and degradation products into the blood stream making serum and plasma ideal as a diagnostic medium. The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring inflammatory bowel disease (IBD) activity, that is less invasive than colonoscopy. Differences in the enriched low mass plasma proteome (<25 kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and "Tier-2" FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by multiple reaction monitoring in plasma and serum including both inflammatory; rheumatoid arthritis controls, and non-inflammatory healthy controls; ulcerative colitis (UC), and Crohn's disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in plasma. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Peptides differentiating controls from IBD originate from secreted phosphoprotein 24 (SPP24, p = 0.000086, 0.009); whereas those in remission and healthy can be differentiated in UC by SPP24 (p = 0.00023, 0.001), α-1-microglobulin (AMBP, p = 0.006) and CD by SPP24 (p = 0.019, 0.05). UC and CD can be differentiated by Guanylin (GUC2A, p = 0.001), and Secretogranin-1 (CHGB p = 0.035). Active and quiescent disease can also be differentiated in UC and CD by CHGB (p ≤ 0.023) SPP24 (p ≤ 0.023) and AMBP (UC p = 0.046). Five peptides discriminating IBD activity and severity had very little-to-no correlation to erythrocyte sedimentation rate, C-reactive protein, white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These proteins have the potential to improve diagnosis and evaluate

  7. Growth Patterns of Clostridium difficile – Correlations with Strains, Binary Toxin and Disease Severity: A Prospective Cohort Study

    PubMed Central

    Tschudin-Sutter, Sarah; Braissant, Olivier; Erb, Stefan; Stranden, Anne; Bonkat, Gernot; Frei, Reno; Widmer, Andreas F.

    2016-01-01

    A broad spectrum of symptoms has been associated with C. difficile infection (CDI). Several studies indicate that toxin-production correlates with growth rates of C. difficile. This study aimed to correlate growth rates of C. difficile with disease severity and strain characteristics. From 01/2003 to 10/2011, strains from a prospective cohort of all inpatients with CDI at the University Hospital Basel, Switzerland were analyzed regarding binary toxin, presence of the tcdC deletion and ribotype. Isothermal microcalorimetry was performed to determine growth rates, quantified by the Gompertz function. Ordered logistic regression models were used to correlate disease severity with strain features and clinical characteristics. Among 199 patients, 31 (16%) were infected with binary toxin-producing strains, of which the tcdC gene-deletion nt117 was detected in 9 (4%). Disease severity was classified as mild in 130 patients (65.3%), as severe in 59 patients (29.7%) and as severe/complicated in 10 patients (5.0%). Growth rates were inversely associated with disease severity in univariable (OR 0.514, 95%CI 0.29–0.91, p = 0.023) and multivariable analyses (OR 0.51, 95%CI 0.26–0.97, p = 0.040). While none of the strain characteristics such as presence of the tcdC gene deletion or binary toxin predicted CDI severity, growth rates were inversely correlated with disease severity. Further investigations are needed to analyze growth-regulators and respective correlations with the level of toxin production in C. difficile, which may be important determinants of disease severity. PMID:27598309

  8. LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B

    PubMed Central

    Poirault-Chassac, Sonia; Adam, Frédéric; Muczynski, Vincent; Aymé, Gabriel; Casari, Caterina; Bordet, Jean-Claude; Soukaseum, Christelle; Rothschild, Chantal; Proulle, Valérie; Pietrzyk-Nivau, Audrey; Berrou, Eliane; Christophe, Olivier D.; Rosa, Jean-Philippe; Lenting, Peter J.; Bryckaert, Marijke; Baruch, Dominique

    2016-01-01

    von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations of von Willebrand factor (vWF) that enhance its binding to platelet glycoprotein Ibα and alter the protein’s multimeric structure. Patients with VWD-type 2B display variable extents of bleeding associated with macrothrombocytopenia and sometimes with thrombopathy. Here, we addressed the molecular mechanism underlying the severe macrothrombocytopenia both in a knockin murine model for VWD-type 2B by introducing the p.V1316M mutation in the murine Vwf gene and in a patient bearing this mutation. We provide evidence of a profound defect in megakaryocyte (MK) function since: (a) the extent of proplatelet formation was drastically decreased in 2B MKs, with thick proplatelet extensions and large swellings; and (b) 2B MKs presented actin disorganization that was controlled by upregulation of the RhoA/LIM kinase (LIMK)/cofilin pathway. In vitro and in vivo inhibition of the LIMK/cofilin signaling pathway rescued actin turnover and restored normal proplatelet formation, platelet count, and platelet size. These data indicate, to our knowledge for the first time, that the severe macrothrombocytopenia in VWD-type 2B p.V1316M is due to an MK dysfunction that originates from a constitutive activation of the RhoA/LIMK/cofilin pathway and actin disorganization. This suggests a potentially new function of vWF during platelet formation that involves regulation of actin dynamics. PMID:27734030

  9. Very severely obese patients have a high prevalence of type 2 diabetes mellitus and cardiovascular disease.

    PubMed

    Vinciguerra, Federica; Baratta, Roberto; Farina, Maria Grazia; Tita, Patrizia; Padova, Giuseppa; Vigneri, Riccardo; Frittitta, Lucia

    2013-06-01

    The prevalence of very severe obesity has increased progressively and faster than other classes of obesity over the last years. It is unclear whether the prevalence of obesity-related complications and health risks increases progressively or reaches a plateau above a certain degree of obesity. The aim of our study was to investigate whether the severity of obesity was correlated with the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose, impaired glucose tolerance (IGT), metabolic syndrome (MS), and cardiovascular diseases (CVDs) in a large cohort of patients with different degrees of obesity. A cross-sectional study was conducted in 938 obese patients without a previous diagnosis of diabetes. Patients were assigned to different categories of obesity: mild-moderate obesity (BMI 30-39.9 kg/m(2)), morbid obesity (BMI 40-49.9 kg/m(2)), and super-obesity (SO, BMI ≥50 kg/m(2)). The prevalence of IGF, IGT, screen-detected T2DM, MS, and CVD was higher in SO patients than in the other groups. Interestingly, the association between SO and either MS or CVD was independent of glucose tolerance status, indicating that factors other than glucose metabolism also favor cardio-metabolic complications in obese patients. In patients without screen-detected T2DM (n = 807), insulin sensitivity and secretion OGTT-derived indexes indicated that SO patients had the worst glucose homeostasis relative to the other categories of obesity, which was indicated by the most reduced disposition index in these patients, a predictor of future T2DM. In conclusion, SO patients have an extremely high prevalence of glucose metabolism deterioration, and cardio-metabolic complications are more prevalent in these patients compared to less obese patients.

  10. Physical Activity, Health Status and Risk of Hospitalization in Patients with Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    Benzo, Roberto P.; Chang, Chung-Chou H.; Farrell, Max H.; Kaplan, Robert; Ries, Andrew; Martinez, Fernando J.; Wise, Robert; Make, Barry; Sciurba, Frank

    2010-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a leading cause of death and 70% of the cost of COPD is due to hospitalizations. Self-reported daily physical activity and health status have been reported as predictors of a hospitalization in COPD but are not routinely assessed. Objectives We tested the hypothesis that self-reported daily physical activity and health status assessed by a simple question were predictors of a hospitalization in a well-characterized cohort of patients with severe emphysema. Methods Investigators gathered daily physical activity and health status data assessed by a simple question in 597 patients with severe emphysema and tested the association of those patient-reported outcomes to the occurrence of a hospitalization in the following year. Multiple logistic regression analyses were used to determine predictors of hospitalization during the first 12 months after randomization. Results The two variables tested in the hypothesis were significant predictors of a hospitalization after adjusting for all univariable significant predictors: >2 h of physical activity per week had a protective effect [odds ratio (OR) 0.60; 95% confidence interval (95% CI) 0.41–0.88] and self-reported health status as fair or poor had a deleterious effect (OR 1.57; 95% CI 1.10–2.23). In addition, two other variables became significant in the multivariate model: total lung capacity (every 10% increase) had a protective effect (OR 0.88; 95% CI 0.78–0.99) and self-reported anxiety had a deleterious effect (OR 1.75; 95% CI 1.13–2.70). Conclusion Self-reported daily physical activity and health status are independently associated with COPD hospitalizations. Our findings, assessed by simple questions, suggest the value of patient-reported outcomes in developing risk assessment tools that are easy to use. PMID:20234126

  11. Daytime Physical Activity and Sleep in Hospitalized Older Adults: Association with Demographic Characteristics and Disease Severity

    PubMed Central

    Beveridge, Claire; Knutson, Kristen; Spampinato, Lisa; Flores, Andrea; Meltzer, David O.; Van Cauter, Eve; Arora, Vineet M.

    2016-01-01

    OBJECTIVES To assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity. DESIGN Prospective cohort study. SETTING University of Chicago Medical Center general medicine wards. PARTICIPANTS Community-dwelling inpatients aged 50 and older (N = 120) MEASUREMENTS Physical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random-effects linear regression analysis was used to examine the association between in-hospital sleep and physical activity. RESULTS From March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51–121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 ± 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 ± 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50–75; youngest quartile 121, 95% CI = 98–145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60–83; lowest tertile 125, 95% CI = 104–147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = −5.65 to −0.43, P = .02) for each additional hour of inpatient sleep. CONCLUSION Older, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community. PMID:26131982

  12. Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia

    PubMed Central

    Albrich, Werner C; Madhi, Shabir A; Adrian, Peter V; van Niekerk, Nadia; Telles, Jean-Noel; Ebrahim, N; Messaoudi, Melina; Paranhos-Baccalà, Glaucia; Giersdorf, Sven; Vernet, Guy; Mueller, Beat; Klugman, Keith P

    2014-01-01

    Objective A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. Methods Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. Results There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). Conclusions In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults. PMID:25113557

  13. Prediction of Coronary Artery Disease Extent and Severity Using Pulse Wave Velocity

    PubMed Central

    Chiha, Joseph; Mitchell, Paul; Gopinath, Bamini; Burlutsky, George; Plant, Adam; Kovoor, Pramesh; Thiagalingam, Aravinda

    2016-01-01

    Background Pulse-wave velocity (PWV) measures aortic stiffness. It is an independent predictor of cardiovascular events and mortality, yet there is paucity in the literature on its association with the severity and extent of coronary artery disease (CAD). Methods To examine the utility of PWV in predicting CAD burden in men and women the PWV was determined in 344 patients (Men = 266, Women = 78) presenting for invasive coronary angiography for the assessment of suspected CAD. Pearson correlations and multivariate analysis were used to evaluate the relationship between these coronary scores, PWV and traditional cardiovascular risk factors. Results Compared to men, women with chest pain had lower mean Extent scores (19.2 vs. 35.6; p = 0.0001) and Gensini scores (23.6 vs. 41.9; p = 0.0001). PWV was similar between men and women (12.35 ± 3.74 vs. 12.43 ± 4.58; p = 0.88) and correlated with Extent score (r = 0.21, p = 0.0001) but not Gensini or vessel score (r = 0.03, p = 0.64 and r = 0.06, p = 0.26, respectively). PWV was associated with Extent score in men (B = 2.25 ± 0.78, p = 0.004 for men and B = 1.50 ± 0.88, p = 0.09 for women). It was not a predictor of Gensini score (B = -0.10, P = 0.90). Conclusion PWV correlates with the extent of CAD, as measured by the ‘Extent’ score in men more than women. However, it does not correlate with the severity of obstructive CAD in either gender. PMID:28005967

  14. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    SciTech Connect

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-07-15

    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{sub 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.

  15. Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community.

    PubMed

    Houben, M L; Coenjaerts, F E J; Rossen, J W A; Belderbos, M E; Hofland, R W; Kimpen, J L L; Bont, L

    2010-07-01

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral load in primary RSV infection. Infants of a healthy birth cohort were included at signs of their first respiratory tract infection. Nasopharyngeal aspirate was obtained within 48-96 hr and disease severity was assessed with a previously published severity scoring model. PCR was applied to test the aspirates in a semi-quantitative way for the presence of 10 respiratory pathogens. In case of multiple infection, the pathogen with the highest load was defined as the primary pathogen. The correlation between disease severity and viral load was analyzed. A total of 82 infants were included over a period of 2 years. Median age at first respiratory tract infection was 3 months. Pathogens were detected in 77 (94%) infants; more than one pathogen was detected in 35 (43%) infants. RSV was present in aspirates of 30 infants; in 16 aspirates RSV was the primary pathogen. A negative correlation between RSV CT-value and disease severity was found in all RSV cases (rho = -0.52, P = 0.003) and in cases with RSV as the primary pathogen (rho = -0.54, P = 0.03). In conclusion, this is the first report on viral loads in previously healthy infants with RSV infection in the community. Disease severity correlated positively with viral load during primary RSV infection.

  16. Mutations in ABCA12 Underlie the Severe Congenital Skin Disease Harlequin Ichthyosis

    PubMed Central

    Kelsell, David P.; Norgett, Elizabeth E.; Unsworth, Harriet; Teh, Muy-Teck; Cullup, Thomas; Mein, Charles A.; Dopping-Hepenstal, Patricia J.; Dale, Beverly A.; Tadini, Gianluca; Fleckman, Philip; Stephens, Karen G.; Sybert, Virginia P.; Mallory, Susan B.; North, Bernard V.; Witt, David R.; Sprecher, Eli; E. M. Taylor, Aileen; Ilchyshyn, Andrew; Kennedy, Cameron T.; Goodyear, Helen; Moss, Celia; Paige, David; Harper, John I.; Young, Bryan D.; Leigh, Irene M.; Eady, Robin A. J.; O’Toole, Edel A.

    2005-01-01

    Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide–polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation. PMID:15756637

  17. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia.

    PubMed

    Nurden, Paquita; Debili, Najet; Vainchenker, William; Bobe, Regis; Bredoux, Raymonde; Corvazier, Elisabeth; Combrie, Robert; Fressinaud, Edith; Meyer, Dominique; Nurden, Alan T; Enouf, Jocelyne

    2006-10-15

    In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ibalpha (GPIbalpha). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIbalpha N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIbalpha, alphaIIb, and beta3 were normally present. Proteins involved in Ca(2+) homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca(2+) ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP(3)-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34(+) cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production.

  18. Severe hemolytic disease of the premature newborn due to RH1 incompatibility: a case report

    PubMed Central

    UWINGABIYE, JEAN; ZAHID, HAFID; LABRINI, FAYÇAL; EL KHAZRAJI, ABDELHAK; YAHYAOUI, ANASS; HADEF, RACHID; MESSAOUDI, NEZHA

    2016-01-01

    We report a case of dramatic outcome of severe hemolytic disease in a newborn due to RH1 incompatibility. A newborn with A RH1 blood group was admitted in the Mohammed V Military Teaching Hospital for the problem of hydrops fetalis associated with RH1 incompatibility. The blood group of his mother, aged 31, was AB RH1-negative and that of his 37 year old father was A RH1. The mother had a history of 4 term deliveries, 3 abortions, and 1 living child. There was no prevention by anti-D immunoglobulin postpartum. The mother’s irregular agglutinin test was positive and the pregnancy was poorly monitored. The laboratory tests of the newborn showed a high total serum bilirubin level (30 mg/L) and macrocytic regenerative anemia (Hemoglobin=4 g/dL, mean corpuscular volume = 183 fL, reticulocytes count =176600/m3). The blood smear showed 1256 erythroblasts per 100 leukocytes, Howell–Jolly bodies and many macrocytes. The direct antiglobulin test was positive. He was transfused with red blood cell concentrates and treated with conventional phototherapy. The evolution was unfavourable; he died three days after the death of his mother. The monitoring of these high-risk pregnancies requires specialized centers and a close collaboration between the gynaecologist and the blood transfusion specialist to strengthen the prevention, as well as clinico-biological monitoring in patients with a history of RH1 fetomaternal alloimunization. PMID:27857529

  19. Heart rate variability in idiopathic dilated cardiomyopathy: relation to disease severity and prognosis.

    PubMed Central

    Yi, G.; Goldman, J. H.; Keeling, P. J.; Reardon, M.; McKenna, W. J.; Malik, M.

    1997-01-01

    OBJECTIVE: To assess the clinical importance of heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (DCM). PATIENTS AND METHODS: Time domain analysis of 24 hour HRV was performed in 64 patients with DCM, 19 of their relatives with left ventricular enlargement (possible early DCM), and 33 healthy control subjects. RESULTS: Measures of HRV were reduced in patients with DCM compared with controls (P < 0.05). HRV parameters were similar in relatives and controls. Measures of HRV were lower in DCM patients in whom progressive heart failure developed (n = 28) than in those who remained clinically stable (n = 36) during a follow up of 24 (20) months (P = 0.0001). Reduced HRV was associated with NYHA functional class, left ventricular end diastolic dimension, reduced left ventricular ejection fraction, and peak exercise oxygen consumption (P < 0.05) in all patients. DCM patients with standard deviation of normal to normal RR intervals calculated over the 24 hour period (SDNN) < 50 ms had a significantly lower survival rate free of progressive heart failure than those with SDNN > 50 ms (P = 0.0002, at 12 months; P = 0.0001, during overall follow up). Stepwise multiple regression analysis showed that SDNN < 50 ms identified, independently of other clinical variables, patients who were at increased risk of developing progressive heart failure (P = 0.0004). CONCLUSIONS: HRV is reduced in patients with DCM and related to disease severity. HRV is clinically useful as an early non-invasive marker of DCM deterioration. PMID:9068391

  20. Validation of the baseline severity stratification of objective functional impairment in lumbar degenerative disc disease.

    PubMed

    Stienen, Martin N; Smoll, Nicolas R; Joswig, Holger; Corniola, Marco V; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P

    2017-03-03

    OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p < 0.001). Patients with mild, moderate, and severe OFI had increased leg pain by 0.90 (p = 0.044), 1.54 (p < 0.001), and 1.94 (p < 0.001); increased ODI by 7.99 (p = 0.004), 12.64 (p < 0.001), and 17.13 (p < 0.001); and decreased SF-12 PCS by -2.57 (p = 0.049), -3.63 (p = 0.003), and -6.23 (p < 0.001), respectively. CONCLUSIONS The OFI BSS is a valid measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.

  1. Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease

    PubMed Central

    Hawkins, P; Johnson, L; Nikoletou, D; Hamnegard, C; Sherwood, R; Polkey, M; Moxham, J

    2002-01-01

    Background: The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined. Methods: Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV1) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (VE), heart rate, and arterialised venous plasma lactate concentration [La+] were measured before and after each test. Results: Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La+] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI –7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (ΔL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=–0.7, p=0.0006). Conclusions: PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation. PMID:12324670

  2. Framingham Risk Score underestimates cardiovascular disease risk in severe psoriatic patients: implications in cardiovascular risk factors management and primary prevention of cardiovascular disease.

    PubMed

    Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Martins da Silva, Berta; Selores, Manuela

    2013-11-01

    Severe psoriasis has been associated with increase cardiovascular mortality, due to a higher prevalence of traditional cardiovascular risk factors and premature atherosclerosis, as a consequence of its systemic inflammation. Recently, it has been estimated that severe psoriasis may confer an increased 6.2% on long-term risk of cardiovascular disease based on Framingham Risk Score, which can have practical implications in the treatment of cardiovascular risk factors and primary prevention of cardiovascular disease, as treatment guidelines account for the risk of cardiovascular disease in treatment goals. The aim of this study was to analyze the influence of the attributable risk of severe psoriasis on long-term risk of cardiovascular disease and its implication on the correct treatment of cardiovascular risk factors and primary prevention of cardiovascular disease on a real-world cohort of patients. One hundred severe psoriasis patients without psoriatic arthritis or previous cardiovascular disease were evaluated and it was found that more than half of the patients were reclassified to a higher cardiovascular risk category with important clinical implications on the correct management of their cardiovascular risk factors and primary prevention of cardiovascular disease, as a considerable proportion of patients with hypertension, hypercholesterolemia and coronary heart disease equivalent risk were not being correctly managed.

  3. Severe and refractory peptic ulcer disease: the diagnostic dilemma: case report and comprehensive review.

    PubMed

    Guzzo, James L; Duncan, Mona; Bass, Barbara L; Bochicchio, Grant V; Napolitano, Lena M

    2005-11-01

    The recognition of Helicobacter pylori infection as a cause of peptic ulcer disease, medical regimens to eradicate the organism, and the widespread use of proton pump inhibition to suppress gastric acid secretion have revolutionized the management of peptic ulcer disease. As a result, successful medical management of peptic ulcer disease has largely supplanted the need for gastric surgery by general surgeons. Surgery is reserved for complications of the disease, refractory disease, or rare causes of ulcer disease such as gastrinoma and Zollinger-Ellison syndrome. In this report, we describe a case of intractable peptic ulcer disease that progressed to gastric outlet obstruction despite maximal medical therapy. We review the diagnostic studies utilized to evaluate the potential etiologies of peptic ulcer disease and the difficulty in diagnosing gastrinoma and Zollinger-Ellison in the setting of potent medical acid suppression therapy.

  4. The ethics of a proposed study of hematopoietic stem cell transplant for children with "less severe" sickle cell disease.

    PubMed

    Nickel, Robert S; Hendrickson, Jeanne E; Haight, Ann E

    2014-08-07

    Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ(0)-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD.

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease

    PubMed Central

    Gill, Joan C.; Castaman, Giancarlo; Windyga, Jerzy; Kouides, Peter; Ragni, Margaret; Leebeek, Frank W. G.; Obermann-Slupetzky, Ortrun; Chapman, Miranda; Fritsch, Sandor; Pavlova, Borislava G.; Presch, Isabella

    2015-01-01

    This phase 3 trial evaluated the safety and hemostatic efficacy of a recombinant von Willebrand factor (rVWF) for treatment of bleeds in severe von Willebrand disease (VWD). rVWF was initially administered together with recombinant factor VIII (rFVIII) and subsequently alone, as long as hemostatic factor VIII activity (FVIII:C) levels were maintained. Pharmacokinetics (PK) were evaluated in a randomized cross-over design (rVWF vs rVWF:rFVIII at 50 IU VWF:ristocetin cofactor activity [RCo]/kg). Bleed control for all treated bleeds (N = 192 bleeds in 22 subjects) was rated good or excellent (96.9% excellent; 119 of 122 minor, 59 of 61 moderate, and 6 of 7 major bleeds) on a 4-point scale (4 = none to 1 = excellent). A single infusion was effective in 81.8% of bleeds. Treatment success, defined as the number of subjects with a mean efficacy rating of <2.5, was 100%. The PK profile of rVWF was not influenced by rFVIII (mean VWF:RCo terminal half-life: 21.9 hours for rVWF and 19.6 hours for rVWF:rFVIII). FVIII:C levels increased rapidly after rVWF alone, with hemostatic levels achieved within 6 hours and sustained through 72 hours after infusion. Eight adverse events (AEs; 6 nonserious AEs in 4 subjects and 2 serious AEs [chest discomfort and increased heart rate, without cardiac symptomatology] concurrently in 1 subject) were associated with rVWF. There were no thrombotic events or severe allergic reactions. No VWF or FVIII inhibitors, anti-VWF binding antibodies, or antibodies against host cell proteins were detected. These results show that rVWF was safe and effective in treating bleeds in VWD patients and stabilizes endogenous FVIII:C, which may eliminate the need for rFVIII after the first infusion. This trial was registered at www.clinicaltrials.gov as #NCT01410227. PMID:26239086

  8. Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Soler, Néstor; Agustí, Carlos; Angrill, Joaquim; De la Bellacasa, Jorge Puig; Torres, Antoni

    2007-01-01

    Background Antibiotics are commonly prescribed in exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of bacteria in these exacerbations is controversial. Objective To identify clinical predictors of bacterial infection as a cause of exacerbation, considering the protected specimen brush (PSB) as the gold standard. Methods Clinical data, sputum and PSB samples were collected from 40 patients with COPD requiring hospitalisation due to severe exacerbations who had not received previous antibiotic treatment. Results Quantitative cultures of PSB samples (n = 40) yielded 23 potential pathogenic microorganisms (PPMs) at concentrations of ⩾102 colony‐forming units/ml in 18 (45%) patients. Sputum samples were obtained from all 40 patients. Culture of good‐quality sputum samples (n = 18) yielded 16 PPMs corresponding to 14 (35%) patients. The concordance between the PSB and sputum rate was high (κ = 0.85, p<0.002). The self‐reporting patient observation of sputum purulence (odds ratio (OR) 27.20 (95% confidence interval (CI) 4.60 to 60.69), p = 0.001), the percentage predicted forced expiratory volume in 1 s (FEV1%) <50 (OR 2.27 (95% CI 1.55 to 3.21), p = 0.014), >4 exacerbations in the past year (OR 6.9 (95% CI 0.08 to 1.08), p = 0.028) and previous hospitalisations due to COPD (OR 4.13 (95% CI 1.02 to 16.07), p = 0.041) were associated with the presence of PPMs in the distal airways. The operative characteristics for predicting distal airway infection when patients presented with purulent exacerbation were as follows: sensitivity 89.5%, specificity 76.2%, positive predicted value 77.3% and negative predicted value 88.9%. Conclusions The self‐reporting presence of purulence in the sputum, as well as common previous exacerbations and hospitalisations due to COPD in patients with severe airflow obstruction (FEV1% <50) predict the presence of bacterial infection in the distal airways. The use of these

  9. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease.

    PubMed

    Gill, Joan C; Castaman, Giancarlo; Windyga, Jerzy; Kouides, Peter; Ragni, Margaret; Leebeek, Frank W G; Obermann-Slupetzky, Ortrun; Chapman, Miranda; Fritsch, Sandor; Pavlova, Borislava G; Presch, Isabella; Ewenstein, Bruce

    2015-10-22

    This phase 3 trial evaluated the safety and hemostatic efficacy of a recombinant von Willebrand factor (rVWF) for treatment of bleeds in severe von Willebrand disease (VWD). rVWF was initially administered together with recombinant factor VIII (rFVIII) and subsequently alone, as long as hemostatic factor VIII activity (FVIII : C) levels were maintained. Pharmacokinetics (PK) were evaluated in a randomized cross-over design (rVWF vs rVWF:rFVIII at 50 IU VWF:ristocetin cofactor activity [RCo]/kg). Bleed control for all treated bleeds (N = 192 bleeds in 22 subjects) was rated good or excellent (96.9% excellent; 119 of 122 minor, 59 of 61 moderate, and 6 of 7 major bleeds) on a 4-point scale (4 = none to 1 = excellent). A single infusion was effective in 81.8% of bleeds. Treatment success, defined as the number of subjects with a mean efficacy rating of <2.5, was 100%. The PK profile of rVWF was not influenced by rFVIII (mean VWF:RCo terminal half-life: 21.9 hours for rVWF and 19.6 hours for rVWF:rFVIII). FVIII : C levels increased rapidly after rVWF alone, with hemostatic levels achieved within 6 hours and sustained through 72 hours after infusion. Eight adverse events (AEs; 6 nonserious AEs in 4 subjects and 2 serious AEs [chest discomfort and increased heart rate, without cardiac symptomatology] concurrently in 1 subject) were associated with rVWF. There were no thrombotic events or severe allergic reactions. No VWF or FVIII inhibitors, anti-VWF binding antibodies, or antibodies against host cell proteins were detected. These results show that rVWF was safe and effective in treating bleeds in VWD patients and stabilizes endogenous FVIII : C, which may eliminate the need for rFVIII after the first infusion. This trial was registered at www.clinicaltrials.gov as #NCT01410227.

  10. Adverse learning strategy: the Adelaide Diagnostic Learning Inventory and its subscale replicability in a medical student population.

    PubMed

    Welch, G; Pearce, K; Lewis, M; Mellsop, G

    1990-03-01

    The Adelaide Diagnostic Learning Inventory (ADLIMS) is a measure of learning styles and learning pathologies that was designed to investigate the impact of traditional approaches to learning versus problem-based learning and to identify students whose approach to learning tasks predicted poor academic performance. In this study, some important psychometric properties of the ADLIMS were examined, including its factor structure. In this study, factor replicability across samples was argued to provide a more robust and psychologically meaningful factor solution than that which can be obtained using traditional mathematical criteria. The results of the factor analysis did not confirm the presence of the four factor solution earlier reported for the ADLIMS, but did identify three clear factors that had very high replicability. An inspection of the items comprising these three factors showed that factor 1 tapped subjective distress related to poor study habits, lack of motivation to study, and distraction from social activities. Factor 2 tapped distress arising from high achievement expectations that were hampered by superficial or disorganized study habits that did not enable the student to grasp the relationships between concepts and ideas. Factor 3 tapped positive feelings and a sense of satisfaction associated with a problem-based approach to the learning of new study material. Although the internal reliability of the ADLIMS subscales met the requirements of a measure to be used in general research such as in the investigation of correlates among groups of medical students, they did not meet the higher requirements of a measure to be used to identify or predict individuals with pathological learning styles.

  11. Seasonal variations of the nighttime O(1S) and OH (8-3) airglow intensity at Adelaide, Australia

    NASA Astrophysics Data System (ADS)

    Reid, Iain M.; Spargo, Andrew J.; Woithe, Jonathan M.

    2014-06-01

    We analyze 15 years of atomic oxygen (OI) 558 nm and hydroxyl (OH) (8-3) 730 nm nightglow emission intensities from heights near 96 and 87 km, respectively, measured using filter photometers at the Buckland Park Field Station (34.6°S, 138.6°E) near Adelaide, Australia. The intensity of both emissions exhibits clear seasonal and interannual periodicities, with annual, semiannual, and quasi-biennial oscillations, as well as a solar cycle influence. In addition, there is a terannual and 4.1 year component in the OI airglow intensity and both a quasi-biennial and quasi-triennial oscillation in the OH intensity. The results are in very good agreement with simultaneous collocated measurements made with an imager, and with global satellite climatologies of OI and OH intensities reported for the Wind Imaging Interferometer instrument. The mean value of the OI annual oscillation intensity is the same as that of the semiannual oscillation at this location to within the experimental uncertainty. The OI annual oscillation maximizes in summer, and the semiannual oscillation maximizes in autumn and spring, with the largest maximum in autumn. The terannual component in the OI nightglow maximizes in early summer, autumn, and spring. The quasi-biennial oscillation in the OI nightglow takes its first maximum value in autumn 1996, and the 4.1 year period in this emission first maximizes in summer 1998. The OH annual and semiannual oscillation intensities also agree to within the experimental uncertainties and are observed to peak in early winter. The quasi-biennial and quasi-triennial oscillations in this emission take their first maximum value in summer 1996.

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

    PubMed

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

    2006-06-01

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

  13. Dynamics of Dengue Disease Severity Determined by the Interplay Between Viral Genetics and Serotype-Specific Immunity

    PubMed Central

    OhAinle, Molly; Balmaseda, Angel; Macalalad, Alexander R.; Tellez, Yolanda; Zody, Michael C.; Saborío, Saira; Nuñez, Andrea; Lennon, Niall J.; Birren, Bruce W.; Gordon, Aubree; Henn, Matthew R.; Harris, Eva

    2015-01-01

    The rapid spread of dengue is a worldwide public health problem. In two clinical studies of dengue in Managua, Nicaragua, we observed an abrupt increase in disease severity across several epidemic seasons of dengue virus serotype 2 (DENV-2) transmission. Waning DENV-1 immunity appeared to increase the risk of severe disease in subsequent DENV-2 infections after a period of cross-protection. The increase in severity coincided with replacement of the Asian/American DENV-2 NI-1 clade with a new virus clade, NI-2B. In vitro analyses of viral isolates from the two clades and analysis of viremia in patient blood samples support the emergence of a fitter virus in later, relative to earlier, epidemic seasons. In addition, the NI-1 clade of viruses was more virulent specifically in children who were immune to DENV-1, while DENV-3 immunity was associated with more severe disease among NI-2B infections. Our data demonstrate that the complex interaction between viral genetics and population dynamics of serotype-specific immunity contribute to the risk of severe dengue disease. Furthermore, this work provides insights into viral evolution and the interaction between viral and immunological determinants of viral fitness and virulence. PMID:22190239

  14. 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.

  15. An audit of pharyngeal gonorrhoea treatment in a public sexual health clinic in Adelaide, South Australia.

    PubMed

    Hustig, A; Bell, C; Waddell, R

    2013-05-01

    In recent times there have been changes to guidelines regarding the management of gonorrhoea, from both the Centers for Disease Control and Prevention in 2010 and the British Association for Sexual Health and HIV (BASHH) in 2011. Coinciding with their release we conducted a clinical audit of our treatment protocol for gonorrhoea. In 2010, local data on the minimum inhibitory concentrations for Neisseria gonorrhoeae indicated an increase in local isolates that were less sensitive to ceftriaxone (11.6% c.f. 5.3% in 2009). We have a long history of using 250 mg of ceftriaxone to treat all standard sites of gonorrhoea infection followed with tests of cure in all cases. In a retrospective clinical audit of an 11-year period from 2000 up to and including 2010 we identified six test-of-cure failures over 11 years after treating a total of 215 patients with pharyngeal gonorrhoea.

  16. Seasonality of infectious diseases and severe acute respiratory syndrome-what we don't know can hurt us.

    PubMed

    Dowell, Scott F; Ho, Mei Shang

    2004-11-01

    The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.

  17. Validity of Type D personality in Iceland: association with disease severity and risk markers in cardiac patients.

    PubMed

    Svansdottir, Erla; Karlsson, Hrobjartur D; Gudnason, Thorarinn; Olason, Daniel T; Thorgilsson, Hordur; Sigtryggsdottir, Unnur; Sijbrands, Eric J; Pedersen, Susanne S; Denollet, Johan

    2012-04-01

    Type D personality has been associated with poor prognosis in cardiac patients. This study investigated the validity of the Type D construct in Iceland and its association with disease severity and health-related risk markers in cardiac patients. A sample of 1,452 cardiac patients completed the Type D scale (DS14), and a subgroup of 161 patients completed measurements for the five-factor model of personality, emotional control, anxiety, depression, stress and lifestyle factors. The Icelandic DS14 had good psychometric properties and its construct validity was confirmed. Prevalence of Type D was 26-29%, and assessment of Type D personality was not confounded by severity of underlying coronary artery disease. Regarding risk markers, Type D patients reported more psychopharmacological medication use and smoking, but frequency of previous mental problems was similar across groups. Type D is a valid personality construct in Iceland, and is associated with health-related risk markers, but not cardiac disease severity.

  18. Marked eosinophilia in a patient with history of severe atypical Kawasaki disease.

    PubMed

    O'Byrne, Michael L; Cohen, Meryl S

    2013-01-01

    An infant with recent atypical, treatment-refractory Kawasaki disease presented with marked eosinophilia. Workup failed to identify an etiology. The eosinophilia spontaneously resolved. Eosinophilia has been observed in the acute phase of Kawasaki disease, but has not been reported following recovery.

  19. Minimizing crop damage through understanding relationships between pyrethrum phenology and ray blight disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The most damaging foliar disease of pyrethrum in Australia is ray blight caused by Stagonosporopsis tanaceti. The probability of growers incurring economic losses caused by this disease has been substantially reduced by the implementation of a prophylactically-applied spring fungicide program. Th...

  20. Potassium influences forage bermudagrass yield and fungal leaf disease severity in Mississippi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leaf spot diseases are associated with K deficiency in forage bermudagrass. In 2010, a natural disease epiphytotic caused by six species of Bipolaris, Curvularia, and Exserohilum (dematiaceous hyphomycetes) was evaluated in 56 plots of ‘Tifton 44' bermudagrass in Mississippi. Pathogen occurrence, di...

  1. Reversible improvement in severe freezing of gait from Parkinson's disease with unilateral interleaved subthalamic brain stimulation.

    PubMed

    Brosius, Stephanie N; Gonzalez, Christopher L; Shuresh, Joshita; Walker, Harrison C

    2015-12-01

    Freezing of gait causes considerable morbidity in patients with Parkinson's disease and is often refractory to conventional treatments. In this double-blind, randomized evaluation, unilateral interleaved deep brain stimulation in the subthalamic nucleus/substantia nigra pars reticulata region significantly improved freezing of gait in a patient with advanced Parkinson's disease.

  2. Evidence for Prion-Like Mechanisms in Several Neurodegenerative Diseases: Potential Implications for Immunotherapy

    PubMed Central

    2013-01-01

    Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases. While the impact of TSEs on human health is relatively minor, these diseases are having a major influence on how we view, and potentially treat, other more common neurodegenerative disorders. Until recently, TSEs encapsulated a distinct category of neurodegenerative disorder, exclusive in their defining characteristic of infectivity. It now appears that similar mechanisms of self-propagation may underlie other proteinopathies such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. This link is of scientific interest and potential therapeutic importance as this route of self-propagation offers conceptual support and guidance for vaccine development efforts. Specifically, the existence of a pathological, self-promoting isoform offers a rational vaccine target. Here, we review the evidence of prion-like mechanisms within a number of common neurodegenerative disorders and speculate on potential implications and opportunities for vaccine development. PMID:24228054

  3. The use of digital artery sympathectomy as a salvage procedure for severe ischemia of Raynaud's disease and phenomenon.

    PubMed

    McCall, T E; Petersen, D P; Wong, L B

    1999-01-01

    We retrospectively reviewed the effectiveness of digital artery sympathectomy as a last resort to prevent amputation in severe cases of Raynaud's disease and phenomenon. Seven patients underwent digital artery sympathectomy as a salvage procedure to prevent amputation. The patients developed cold intolerance secondary to atherosclerosis or collagen vascular disease. The results were analyzed using the criteria of ulcer healing and the prevention of amputation. In 6 of the 7 patients, the digital ulcers healed and amputation was avoided.

  4. 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 Central

    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

    2016-01-01

    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. PMID:27893415

  5. 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.

  6. Influenza Pneumonia Surveillance among Hospitalized Adults May Underestimate the Burden of Severe Influenza Disease

    PubMed Central

    Ortiz, Justin R.; Neuzil, Kathleen M.; Cooke, Colin R.; Neradilek, Moni B.; Goss, Christopher H.; Shay, David K.

    2014-01-01

    Background Studies seeking to estimate the burden of influenza among hospitalized adults often use case definitions that require presence of pneumonia. The goal of this study was to assess the extent to which restricting influenza testing to adults hospitalized with pneumonia could underestimate the total burden of hospitalized influenza disease. Methods We conducted a modelling study using the complete State Inpatient Databases from Arizona, California, and Washington and regional influenza surveillance data acquired from CDC from January 2003 through March 2009. The exposures of interest were positive laboratory tests for influenza A (H1N1), influenza A (H3N2), and influenza B from two contiguous US Federal Regions encompassing the study area. We identified the two outcomes of interest by ICD-9-CM code: respiratory and circulatory hospitalizations, as well as critical illness hospitalizations (acute respiratory failure, severe sepsis, and in-hospital death). We linked the hospitalization datasets with the virus surveillance datasets by geographic region and month of hospitalization. We used negative binomial regression models to estimate the number of influenza-associated events for the outcomes of interest. We sub-categorized these events to include all outcomes with or without pneumonia diagnosis codes. Results We estimated that there were 80,834 (95% CI 29,214–174,033) influenza-associated respiratory and circulatory hospitalizations and 26,760 (95% CI 14,541–47,464) influenza-associated critical illness hospitalizations. When a pneumonia diagnosis was excluded, the estimated number of influenza-associated respiratory and circulatory hospitalizations was 24,816 (95% CI 6,342–92,624). The estimated number of influenza-associated critical illness hospitalizations was 8,213 (95% CI 3,764–20,799). Around 30% of both influenza-associated respiratory and circulatory hospitalizations, as well as influenza-associated critical illness hospitalizations did not

  7. Periodontal disease severity and cancer risk in postmenopausal women: The Buffalo OsteoPerio Study

    PubMed Central

    Mai, Xiaodan; LaMonte, Michael J.; Hovey, Kathleen M.; Freudenheim, Jo L.; Andrews, Christopher A.; Genco, Robert J.; Wactawski-Wende, Jean

    2015-01-01

    Purpose Few prospective studies have reported on relationships between objective periodontal disease (PD) measures and cancer risk. This association was examined in 1,337 postmenopausal women participating in the Buffalo OsteoPerio Study. Methods Oral alveolar crestal bone height (ACH) was measured using oral radiographs. Incident cancers were adjudicated with medical records. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between ACH and incident cancer outcomes were estimated using Cox proportional hazards models. Results There were 203 confirmed total incident cancer cases during follow-up (12.2±4.2 years). After adjusting for age and smoking, there were no statistically significant associations between ACH-defined PD categories and total cancer risk (mild/moderate vs. none: HR=1.33, 95%CI: 0.91–1.94; severe vs. none: HR=1.20, 95%CI: 0.77–1.86). ACH-defined PD categories were not associated with common site-specific cancers. Whole mouth mean and worst site ACH (per 1mm loss) were significantly associated with increased risk of lung (adjusted HR=1.81, 95% CI: 1.30–2.54; adjusted HR=1.34, 95% CI: 1.08–1.66, respectively), but not total or other site-specific cancer. Smoking status modified the associations between continuous ACH variables and total cancer risk; measures of PD were associated with total cancer among smokers but not never-smokers (interaction p=0.02 and p<0.01 for whole mouth mean and worst site ACH, respectively). Conclusions ACH-defined PD was associated with total cancer risk in ever but not never-smoking postmenopausal women. Whole mouth mean and worst site ACH were associated with increased lung cancer risk. However, these results need to be interpreted cautiously given the small number of lung cancer cases (n=18). Further research utilizing a larger sample is warranted to confirm the relationships among oral bone loss, site-specific cancers, and total cancer. PMID:26661782

  8. The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Dichtel, Laura E; Corey, Kathleen E; Misdraji, Joseph; Bredella, Miriam A; Schorr, Melanie; Osganian, Stephanie A; Young, Brian J; Sung, Joshua C; Miller, Karen K

    2017-01-01

    Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. Methods: A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. Results: Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. Conclusions: Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets. PMID

  9. Somatic cell genetics of adenosine deaminase expression and severe combined immunodeficiency disease in humans.

    PubMed

    Koch, G; Shows, T B

    1980-07-01

    The somatic cell hybrid method has been used to study the number and different types of human genes involved in the expression of adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) in normal cells and cells from a patient with ADA-deficient severe combined immunodeficiency disease (SCID). Genetic and biochemical characterization of ADA in SCID and the ADA tissue-specific isozymes in normal human cells indicates that additional genes, besides the ADA structural gene on chromosome 20, are involved in ADA expression. Human chromosome 6 encodes a gene, ADCP-1, whose presence is necessary for the expression of an ADA-complexing protein in human-mouse somatic cell hybrids [Koch, G. & Shows, T. B. (1978) Proc. Natl. Acad. Sci. USA 75, 3876-3880]. We report the identification of a second gene, ADCP-2, on human chromosome 2, that is also involved in the expression of the ADA-complexing protein. The data indicate that these two ADCP genes must be present in the same cell for that cell to express the complexing protein. Human-mouse somatic cell hybrids, in which the human parental cells were fibroblastss from an individual with ADA-deficient SCID, also required human chromosomes 2 and 6 to express the ADA-complexing protein, indicating that neither ADCP-1 nor ADCP-2 is involved in the ADA deficiency in SCID. The SCID-mouse hybrid cells expressed no human ADA even when human chromosome 20 had been retained. The deficiency of human ADA in these hybrids maps to human chromosome 20, and therefore is not due to the repression or inhibiton of ADA or its product by unlinked genes or gene products. We propose that the expression of the polymeric ADA tissue isozymes in human cells requires at least three genes: ADA on chromosome 20, ADCP-1 on chromosome 6, and ADCP-2 on chromosome 2. A genetic scheme is presented and the different genes involved in ADA expression and their possible functions are discussed.

  10. Use of recombinant erythropoietin for the management of severe hemolytic disease of the newborn of a K0 phenotype mother.

    PubMed

    Manoura, Antonia; Korakaki, Eftychia; Hatzidaki, Eleftheria; Saitakis, Emmanuel; Maraka, Sofia; Papamastoraki, Isabella; Matalliotakis, Emmanuel; Foundouli, Kaliopi; Giannakopoulou, Christine

    2007-01-01

    Very few people do not express any Kell antigens on their red blood cells (K0 phenotype). They can be immunized by transfusion or pregnancy and develop antibodies against Kell system antigens. These maternal antibodies can cause severe hemolytic disease of the fetus/newborn, as a result of the suppression of erythropoiesis and hemolysis. Multiple intrauterine transfusions in the management of severe hemolytic disease have been shown to cause erythropoietic suppression as well. Recombinant erythropoietin has been successfully used in the management of late anemia of infants with Rh hemolytic disease and in 1 case of KEL1 (Kell)-associated hemolytic disease. The authors present the case of severe hemolytic disease of a newborn due to KEL5 (Ku) isoimmunization of his K0 phenotype mother. Regular intrauterine transfusions were performed to manage the severe fetal anemia (Hb 3 g/dL). A male infant was born at the 36th week of gestation having normal hemoglobin (15.8 g/dL) and developed only mild hyperbilirubinemia. On the 15th day of life, the infant's hematocrit had fallen to 27.3%, with low reticulocyte count and low erythropoietin level. The infant was managed successfully with recombinant erythropoietin.

  11. A retrospective, cross-sectional study reveals that women with CRSwNP have more severe disease than men

    PubMed Central

    Stevens, Whitney W; Peters, Anju T; Suh, Lydia; Norton, James E; Kern, Robert C; Conley, David B; Chandra, Rakesh K; Tan, Bruce K; Grammer, Leslie C; Harris, Kathleen E; Carter, Roderick G; Kato, Atsushi; Urbanek, Margrit; Schleimer, Robert P; Hulse, Kathryn E

    2015-01-01

    Up to 50% of patients with chronic rhinosinusitis (CRS) have comorbid asthma, and we have reported that a subset of CRS patients who have nasal polyps (CRSwNP) have elevated autoantigen-specific antibodies within their nasal polyps (NP). While increases in the prevalence and/or severity of both asthma and autoimmunity in women are well characterized, it is not known whether CRSwNP is more severe or frequent in women than men. We sought to determine whether CRSwNP demonstrated sex-specific differences in frequency and/or severity. Using a retrospectively collected database of tertiary care patients (n = 1393), we evaluated the distribution of sex in patients with CRSwNP with or without comorbid asthma or aspirin hypersensitivity. We further compared the severity of sinus disease between men and women with CRSwNP. Although women comprised 55% of CRS patients without NP (CRSsNP), a significantly smaller proportion of CRSwNP patients were female (38%, P < 0.001). Interestingly, women with CRSwNP were significantly more likely than men to have comorbid asthma (P < 0.001), and 61% of patients with the most severe form of disease (aspirin-exacerbated respiratory disease (CRSwNP plus asthma plus aspirin sensitivity)) were women (P < 0.05). Women with CRSwNP were significantly more likely to have taken oral steroids, and were more likely to have a history of revision surgeries (P < 0.05) compared to men. These data suggest that women with CRSwNP have more severe disease than men in a tertiary care setting. Future studies are needed to elucidate the mechanisms that drive disease severity in men and women, paving the way for the development of personalized treatment strategies for CRSwNP based on sex. PMID:25866636

  12. Predictors of severe disease in a hospitalized population of children with acute viral lower respiratory tract infections.

    PubMed

    Pedraza-Bernal, Angela M; Rodriguez-Martinez, Carlos E; Acuña-Cordero, Ranniery

    2016-05-01

    Although predictors of severe viral acute lower respiratory infections (ALRIs) in children have been reported, there have been few research studies performed in low- and middle-income countries (LMIC). The aim of the present study was to determine predictors of disease severity in a population of Colombian children <5 years of age with ALRI. In a prospective cohort study, we determined independent predictors of severe ALRI in a hospitalized population of children under 5 years old with ALRI during a 1-year period. We included both underlying disease conditions and the infecting respiratory viruses as predictor variables of severe disease. We defined severe disease as the necessity of pediatric intensive care unit admission. Of a total of 1,180 patients admitted with a diagnosis of ALRI, 416 (35.3%) were included because they were positive for any kind of respiratory virus. After controlling for potential confounders, it was found that a history of pulmonary hypertension (RR 3.62; CI 95% 2.38-5.52; P < 0.001) and a history of recurrent wheezing (RR 1.77; CI 95% 1.12-2.79; P = 0.015) were independent predictors of severe disease. The present study shows that respiratory viruses are significant causes of ALRI in infants and young children in Colombia, a typical tropical LMIC, especially during the rainy season. Additionally, the results of the present study show that clinical variables such as a history of pulmonary hypertension and a history of recurrent wheezing are more relevant for predicting ALRI severity than the infecting respiratory viruses.

  13. Three-dimensional quantitative imaging of telomeres in buccal cells identifies mild, moderate, and severe Alzheimer's disease patients.

    PubMed

    Mathur, Shubha; Glogowska, Aleksandra; McAvoy, Elizabeth; Righolt, Christiaan; Rutherford, Jaclyn; Willing, Cornelia; Banik, Upama; Ruthirakuhan, Myuri; Mai, Sabine; Garcia, Angeles

    2014-01-01

    Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001).

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

    PubMed

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

    2017-02-24

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

  15. Severe, chronic proliferative kidney disease (PKD) induced in rainbow trout Oncorhynchus mykiss held at a constant 18 degrees C.

    PubMed

    Morris, D J; Ferguson, H W; Adams, A

    2005-09-23

    Proliferative kidney disease (PKD), caused by the myxozoan parasite Tetracapsuloides bryosalmonae, is well documented as a seasonal disease of rainbow trout Oncorhynchus mykiss. Water temperatures influence the course of the infection both within the fish and the invertebrate host, the recovery of fish from the disease being accelerated with decreasing water temperatures. During this study, groups of rainbow trout were held at a constant temperature (18 degrees C) for a sustained period of time following initial exposure to T. bryosalmonae. While the majority of these fish had recovered from the clinical disease after 9 mo, 10% remained infected, showing clinical signs of disease. A histological study revealed that the majority exhibited very high parasite loads and unusually severe symptoms of PKD. This demonstrates that while most rainbow trout can recover from PKD independent of water temperature, there exists a sub-population that cannot.

  16. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    PubMed Central

    Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-01-01

    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 log10 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. PMID:25776759

  17. Complement driven innate immune response to malaria: fuelling severe malarial diseases.

    PubMed

    Silver, Karlee L; Higgins, Sarah J; McDonald, Chloe R; Kain, Kevin C

    2010-08-01

    Severe malaria remains a major cause of global mortality. The innate immune response to infection is a key determinant of malaria severity and outcome. The complement system plays a key role in initiating and augmenting innate immune responses, including inflammation, endothelial activation, opsonization and coagulation, processes which have been implicated in malaria pathogenesis. In this review, we discuss the evidence supporting a role for excessive complement activation in the pathogenesis of severe malaria.

  18. Severe extensor tendon attrition and multiple tendon ruptures resulting from Kienböck's disease.

    PubMed

    Ramkumar, S; Josty, I C; Sykes, P J

    2000-12-01

    Kienböck's disease is a rare but recognized cause of chronic wrist pain. Occasionally, complications arise leading to tendon rupture. The authors present the first reported case of attrition to all extensors of the hand, and extensor tendon rupture to the little finger in a patient with a 45-year history of Kienböck's disease. This is also the first reported incidence of this complication in whites. Clinical features, surgical management, and the successful outcome are discussed.

  19. Severe panuveitis in neuro-Behçet’s disease in Malaysia: a case series

    PubMed Central

    Othman, Khairuddin; Liza-Sharmini, Ahmad Tajudin; Ibrahim, Mohtar; Tharakan, John; Yanai, Ryoji; Zunaina, Embong

    2017-01-01

    Behçet’s disease (BD) is a multisystemic disease that is very rare in Malaysia. About 5% of patients develop central nervous system involvement, termed neuro-Behçet’s. Neuro-Behçet’s is one of the most serious causes of long-term morbidity and mortality. We report two cases of neuro-Behçet’s associated with uveitis (ocular BD) highlighting the clinical presentation, diagnostic measurement, and therapeutic management of these cases. PMID:28223848

  20. Failure of dipyridamole-thallium myocardial imaging to detect severe coronary disease

    SciTech Connect

    Chin, W.; Go, R.; Lenehan, S.; Underwood, D.A.

    1989-09-01

    Three patients referred for peripheral vascular surgery who died of coronary artery disease complications despite normal dipyridamole-thallium scans are discussed. Although recent literature has shown enthusiasm for this test in this clinical setting, the dipyridamole-thallium scans are not absolute and patients remain at risk for major coronary artery events. Careful clinical screening and awareness of the signs of left main coronary disease on thallium images are important in the evaluation of these patients.

  1. Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

    PubMed Central

    Moe, Nina; Krokstad, Sidsel; Stenseng, Inger Heimdal; Christensen, Andreas; Skanke, Lars Høsøien; Risnes, Kari Ravndal; Nordbø, Svein Arne; Døllner, Henrik

    2017-01-01

    Background It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). Methods We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. Results A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Conclusions Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children. PMID:28095451

  2. [Evaluation of severity of harm to health caused by trauma aggravating a preceding disease].

    PubMed

    Kapustin, A V

    2003-01-01

    A severity of damage made to the health condition by an injury aggravating a preceding pathology is under discussion. It was demonstrated that such criteria as the time period of temporary disablement as well as the permanent disablement ensure, with respect for clinical data, an objective assessment of a severity done to the health in the discussed cases.

  3. Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity

    PubMed Central

    Grkovic, Lana; Baird, Kristin; Steinberg, Seth M.; Williams, Kirsten M.; Pulanic, Drazen; Cowen, Edward W.; Mitchell, Sandra A.; Hakim, Fran T.; Martires, Kathryn J.; Avila, Daniele N.; Taylor, Tiffani N.; Salit, Rachel B.; Rowley, Scott D.; Zhang, Dan; Fowler, Daniel H.; Bishop, Michael R.; Gress, Ronald E.; Pavletic, Steven Z.

    2011-01-01

    Chronic graft versus host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. 189 adults with cGVHD (33% moderate and 66% severe according to NIH global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of 4 prior systemic therapies (PST) for their cGVHD. Lower albumin (p<0.0001), higher CRP (C-reactive protein; p=0.043), higher platelets (p=0.030) and higher number of PST (p<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (p=0.021) and higher number of PST (p<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity. PMID:22005783

  4. Crop management strategies and disease resistance control the severity of false smut and kernel smut of rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    False smut and kernel smut are common diseases of rice capable of severe epidemics with dramatic yield losses. The importance of rice smuts is often overlooked in the US, and highly susceptible varieties are now being grown on the majority of production acres in the southern rice producing states. O...

  5. Effects of Phytophthora cinnamomi isolate, inoculum delivery method, flood, and drought on vigor, disease severity and mortality of blueberry plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four studies evaluated the effect of Phytophthora cinnamomi isolates, inoculum delivery methods, and flood and drought conditions on vigor, disease severity scores, and survival of blueberry plants grown in pots in the greenhouse. Phytophthora cinnamomi isolates were obtained from blueberry plants ...

  6. Surgical strategies for patients with congenital heart disease and severe pulmonary hypertension in low/middle-income countries

    PubMed Central

    Talwar, Sachin; Keshri, Vikas Kumar; Choudhary, Shiv Kumar; Gupta, Saurabh Kumar; Ramakrishnan, Sivasubramanian; Juneja, Rajnish; Saxena, Anita; Kothari, Shyam Sunder; Airan, Balram

    2015-01-01

    In this review, we discuss specific surgical strategies that are used in patients with congenital heart disease and severe pulmonary arterial hypertension. Our own experience, with the use of unidirectional valved patches in managing these patients, is also discussed in detail. PMID:27326218

  7. Goal Disengagement Capacities and Severity of Disease across Older Adulthood: The Sample Case of the Common Cold

    ERIC Educational Resources Information Center

    Jobin, Joelle; Wrosch, Carsten

    2016-01-01

    This study examined age-related associations between goal disengagement capacities, emotional distress, and disease severity across older adulthood. Given that an age-related increase in the experience of stressors might render important goals unattainable, it is expected that goal disengagement capacities would predict a decrease in the severity…

  8. Effects of glyphosate on Macrophomina phaseolina in vitro and its effects on disease severity of soybean in the field

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laboratory and field studies were conducted to assess the effects of glyphosate on Macrophomina phaseolina culture growth in vitro and the disease severity of charcoal rot in soybean at Stoneville, MS and Jackson, TN. Glyphosate inhibited M. phaseolina growth in a linear dose dependent manner when ...

  9. DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease.

    PubMed Central

    Bortoluzzi, F; Valentini, M; Cernigoi, C; Toffoli, G; Boiocchi, M; Poletti, M; Sozzi, M; Fornasarig, M; Cannizzaro, R; Bertolissi, E

    1995-01-01

    The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis. PMID:7890236

  10. Effects of Phytophthora cinnamomi isolate, inoculum delivery method, flood, and drought on vigor, disease severity and mortality of blueberry plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four studies evaluated the effects of cultivar, inoculum delivery method, flood, and drought on plant vigor, disease severity, and mortality of blueberry plants grown in pots in the greenhouse. Phytophthora cinnamomi isolates were obtained from the root zone of blueberry plants displaying symptoms...

  11. Total revascularization for an epsilon right coronary artery and severe left main disease combined with profound cardiogenic shock

    PubMed Central

    Fang, Hsiu-Yu; Lee, Wei-Chieh; Wu, Chiung-Jen

    2016-01-01

    Abstract Rationale: Severe left main disease combined with right coronary artery occlusion was rarely encountered in our daily practice. Percutaneous coronary intervention in these patients was most challenging due to high probability of hemodynamic changes. Patient Concerns: Here, we report a 67-year-old man with Non–ST-Segment Elevation Myocardial Infarction (NSTEMI) and profound cardiogenic shock and we attempted coronary intervention with total revisualization for severe left main (LM) disease and angulated epsilon right coronary artery total occlusion. He was treated successfully under intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) support. Diagnoses: NSTEMI and profound cardiogenic shock. Interventions: Coronary intervention with total revisualization was performed for severe LM disease and angulated epsilon right coronary artery total occlusion under IABP and ECMO support. Outcomes: IABP and ECMO were removed until cardiac contractile function improved to left ventricular ejection fraction over 40 percentage 1 week later. The patient was discharged after 2 months and had survival for 5 years. Lessons: Coronary intervention could be performed safely in this cardiogenic shock patient with severe LM and triple vessel disease who was supported by IABP and ECMO. Stent deployment for extremely angulated coronary artery was required multiple combination techniques to facilitate the final success. PMID:27977615

  12. Increased coronary artery disease severity in black women undergoing coronary bypass surgery.

    PubMed

    Efird, Jimmy T; O'Neal, Wesley T; Griffin, William F; Anderson, Ethan J; Davies, Stephen W; Landrine, Hope; O'Neal, Jason B; Shiue, Kristin Y; Kindell, Linda C; Bruce Ferguson, T; Randolph Chitwood, W; Kypson, Alan P

    2015-02-01

    Race and sex disparities are believed to play an important role in heart disease. The purpose of this study was to examine the association between race, sex, and number of diseased vessels at the time of coronary artery bypass grafting (CABG), and subsequent postoperative outcomes. The 13,774 patients undergoing first-time, isolated CABG between 1992 and 2011 were included. Trend in the number of diseased vessels between black and white patients, stratified by sex, were analyzed using a Cochran-Armitage trend test. Models were adjusted for age, procedural status (elective vs. nonelective), and payor type (private vs. nonprivate insurance). Black female CABG patients presented with an increasingly greater number of diseased vessels than white female CABG patients (adjusted P(trend) = 0.0021). A similar trend was not observed between black and white male CABG patients (adjusted P(trend) = 0.18). Black female CABG patients were also more likely to have longer intensive care unit and hospital lengths of stay than other race-sex groups.Our findings suggest that black female CABG patients have more advanced coronary artery disease than white female CABG patients. Further research is needed to determine the benefit of targeted preventive care and preoperative workup for this high-risk group.

  13. Spectrum and burden of severe Haemophilus influenzae type b diseases in Asia.

    PubMed Central

    Peltola, H.

    1999-01-01

    The validity of the commonly held view that Haemophilus influenzae type b (Hib) diseases are rare in Asia is challenged in this article by a thorough analysis of the data available, often in languages other than English. The entire spectrum of Hib disease, not only meningitis, was taken into account, and over 100 reports from 25 countries were explored. Hib was the leading agent among nontuberculous childhood meningitis cases in two-thirds of 48 studies from 22 countries. Data from six countries showed that all the classical manifestations of invasive Hib diseases are also found in Asia, except epiglottitis, which was nearly absent. In Hong Kong Special Administrative Region of China Hib disease is rare, but otherwise the incidences seemed not to deviate much from those in Europe until recently, around 25 per 100,000 for meningitis and at least 40 per 100,000 per year for the classical Hib manifestations combined at age 0-4 years. In total, more than 200,000 cases of Hib disease are estimated to occur annually in Asia. Because nonbacteraemic Hib pneumonia remains mostly undetected, the total burden is probably significantly greater. The issue will be fully elucidated only by prospective epidemiological and clinical studies, but awaiting them should not delay large-scale vaccinations against Hib throughout Asia. PMID:10612883

  14. Permafrost and snow monitoring at Rothera Point (Adelaide Island, Maritime Antarctica): Implications for rock weathering in cryotic conditions

    NASA Astrophysics Data System (ADS)

    Guglielmin, Mauro; Worland, M. Roger; Baio, Fabio; Convey, Peter

    2014-11-01

    In February 2009 a new permafrost borehole was installed close to the British Antarctic Survey Station at Rothera Point, Adelaide Island (67.57195°S 68.12068°W). The borehole is situated at 31 m asl on a granodiorite knob with scattered lichen cover. The spatial variability of snow cover and of ground surface temperature (GST) is characterised through the monitoring of snow depth on 5 stakes positioned around the borehole and with thermistors placed at three different rock surfaces (A, B and C). The borehole temperature is measured by 18 thermistors placed at different depths between 0.3 and 30 m. Snow persistence is very variable both spatially and temporally with snow free days per year ranging from 13 and more than 300, and maximum snow depths varying between 0.03 and 1.42 m. This variability is the main cause of high variability in GST, that ranged between - 3.7 and - 1.5 °C. The net effect of the snow cover is a cooling of the surface. Mean annual GST, mean summer GST, and the degree days of thawing and the n-factor of thawing were always much lower at sensor A where snow persistence and depth were greater than in the other sensor locations. At sensor A the potential freeze-thaw events were negligible (0-3) and the thermal stress was at least 40% less than in the other sensor locations. The zero curtain effect at the rock surface occurred only at surface A, favouring chemical weathering over mechanical action. The active layer thickness (ALT) ranged between 0.76 and 1.40 m. ALT was directly proportional to the mean air temperature in summer, and inversely proportional to the maximum snow depth in autumn. ALT temporal variability was greater than reported at other sites at similar latitude in the Northern Hemisphere, or with the similar mean annual air temperature in Maritime Antarctica, because vegetation and a soil organic horizon are absent at the study site. Zero annual amplitude in temperature was observed at about 16 m depth, where the mean annual

  15. Increased Carboxyhemoglobin in Adult Falciparum Malaria is Associated With Disease Severity and Mortality

    PubMed Central

    Yeo, Tsin W.; Lampah, Daniel A.; Kenangalem, Enny; Tjitra, Emiliana; Price, Ric N.; Anstey, Nicholas M.

    2013-01-01

    Heme oxygenase 1 expression is increased in pediatric patients with malaria. The carboxyhemoglobin level (a measure of heme oxygenase 1 activity) has not been assessed in adult patients with malaria. Results of pulse co-oximetry revealed that the mean carboxyhemoglobin level was elevated in 29 Indonesian adults with severe falciparum malaria (10%; 95% confidence interval [CI], 8%–13%) and in 20 with severe sepsis (8%; 95% CI, 5%–12%), compared with the mean levels in 32 patients with moderately severe malaria (7%; 95% CI, 5%–8%) and 36 controls (3.6%; 95% CI, 3%–5%; P < .001). An increased carboxyhemoglobin level was associated with an increased odds of death among patients with severe malaria (odds ratio, 1.2 per percentage point increase; 95% CI, 1.02–1.5). While also associated with severity and fatality, methemoglobin was only modestly increased in patients with severe malaria. Increased carboxyhemoglobin levels during severe malaria and sepsis may exacerbate organ dysfunction by reducing oxygen carriage and cautions against the use of adjunctive CO therapy, which was proposed on the basis of mouse models. PMID:23852587

  16. Correlation between Serum RANTES Levels and the Severity of Parkinson's Disease

    PubMed Central

    Tang, Peng; Chong, Li; Li, Xiaoqing; Liu, Yue; Liu, Peng; Hou, Chen; Li, Rui

    2014-01-01

    Inflammatory mediators may reflect a role of systemic inflammation in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), have been implicated in neurodegenerative diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD patients and age-matched 80 controls were measured. Patients with PD had higher RANTES and IL-6 levels compared with the controls. We found that serum RANTES levels strongly correlated with Hoehn-Yahr score and disease duration in PD patients. This study indicated that patients with PD have an on-going systemic inflammatory profile where the elevated peripheral production of RANTES may play a role in the neurodegenerative process. PMID:25587378

  17. Correlation between serum RANTES levels and the severity of Parkinson's disease.

    PubMed

    Tang, Peng; Chong, Li; Li, Xiaoqing; Liu, Yue; Liu, Peng; Hou, Chen; Li, Rui

    2014-01-01

    Inflammatory mediators may reflect a role of systemic inflammation in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), have been implicated in neurodegenerative diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD patients and age-matched 80 controls were measured. Patients with PD had higher RANTES and IL-6 levels compared with the controls. We found that serum RANTES levels strongly correlated with Hoehn-Yahr score and disease duration in PD patients. This study indicated that patients with PD have an on-going systemic inflammatory profile where the elevated peripheral production of RANTES may play a role in the neurodegenerative process.

  18. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation.

    PubMed

    Shapiro, E G; Lockman, L A; Balthazor, M; Krivit, W

    1995-01-01

    Neuropsychological assessment is essential in providing documentation of the untreated natural history of storage diseases associated with dementia and quantifying the effectiveness of treatment on central nervous system function. Baseline characterization and outcome of bone marrow transplantation (BMT) for three leukodystrophies and three mucopolysaccharidoses are presented. Results suggests that BMT for Hurler syndrome, adrenoleukodystrophy, and globoid cell leukodystrophy can be effective in preventing dementia if done early enough in the disease. Sanfilippo and Hunter syndromes do not benefit and BMT is not recommended. For metachromatic leukodystrophy, BMT is not recommended for symptomatic early-onset forms of the disease. Further longitudinal follow-up is needed to determine whether the benefits outweigh the risks of BMT for late-onset and preclinical metachromatic leukodystrophy.

  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.

  20. Spatial clustering by disease severity among reported Rocky Mountain spotted fever cases in the United States, 2001-2005.

    PubMed

    Adjemian, Jennifer Zipser; Krebs, John; Mandel, Eric; McQuiston, Jennifer

    2009-01-01

    Rocky Mountain spotted fever (RMSF) occurs throughout much of the United States, ranging in clinical severity from moderate to fatal infection. Yet, little is known about possible differences among severity levels across geographic locations. To identify significant spatial clusters of severe and non-severe disease, RMSF cases reported to Centers for Disease Control and Prevention (CDC) were geocoded by county and classified by severity level. The statistical software program SaTScan was used to detect significant spatial clusters. Of 4,533 RMSF cases reported, 1,089 hospitalizations (168 with complications) and 23 deaths occurred. Significant clusters of 6 deaths (P = 0.05, RR = 11.4) and 19 hospitalizations with complications (P = 0.02, RR = 3.45) were detected in southwestern Tennessee. Two geographic areas were identified in north-central North Carolina with unusually low rates of severity (P = 0.001, RR = 0.62 and P = 0.001, RR = 0.45, respectively). Of all hospitalizations, 20% were clustered in central Oklahoma (P = 0.02, RR = 1.43). Significant geographic differences in severity were observed, suggesting that biologic and/or anthropogenic factors may be impacting RMSF epidemiology in the United States.

  1. Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.

    PubMed

    Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thuy, Tran Thi; Tuan, Nguyen Minh; Hoang, Dang Minh; Dung, Nguyen Thi Phuong; Lien, Le Bich; Quy, Nguyen Thien; Hieu, Nguyen Trong; Hieu, Lu Thi Minh; Hien, Tran Tinh; Hung, Nguyen Thanh; Farrar, Jeremy; Simmons, Cameron P

    2008-08-15

    The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3(133-142)-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.

  2. Meaning of living with severe chronic obstructive lung disease: a qualitative study

    PubMed Central

    Marx, Gabriella; Nasse, Maximilian; Stanze, Henrikje; Boakye, Sonja Owusu; Nauck, Friedemann; Schneider, Nils

    2016-01-01

    Objectives To explore what it means for patients to live with chronic obstructive pulmonary disease (COPD) as an incurable and constantly progressing disease. Design Qualitative longitudinal study using narrative and semistructured interviews. This paper presents findings of the initial interviews. Analysis using grounded theory. Setting Lung care clinics and community care in Lower Saxony, Germany. Participants 17 patients with advanced-stage COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) III/IV). Findings Analysis shows that these patients have difficulties accepting their life situation and feel at the mercy of the disease, which could be identified as a core-experienced phenomenon. Over a long period of time, patients have only a vague feeling of being ill, caused by uncertain knowledge, slow progress and doubtful attribution of clinical symptoms of the disease (causal conditions). As an action strategy, patients try to maintain daily routines for as long as possible after diagnosis. Both effective standard and rescue medication, which helps to reduce breathlessness and other symptoms, and the feeling of being faced with one's own responsibility (intervening conditions) support this strategy, whereby patients' own responsibility is too painful to acknowledge. As a consequence, patients try to deny the threat to life for a long period of time. Frequently, they need to experience facing their own limits, often in the form of an acute crisis, to realise their health situation. The experience of the illness is contextualised by a continuous increase in limited mobility and social isolation. Conclusion In order to help patients to improve disease awareness, to accept their life situation and to improve their reduced quality of life, patients may benefit from the early integration of palliative care (PC), considering its multiprofessional patient-centred and team-centred approach. Psychological support and volunteer work, which are relevant

  3. Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

    PubMed Central

    Mohn, Kristin G.-I.; Cox, Rebecca Jane; Tunheim, Gro; Berdal, Jan Erik; Hauge, Anna Germundsson; Jul-Larsen, Åsne; Peters, Bjoern; Oftung, Fredrik

    2015-01-01

    Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza. PMID:26606759

  4. Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity

    PubMed Central

    Hoang, Long Truong; Tolfvenstam, Thomas; Ooi, Eng Eong; Khor, Chiea Chuen; Naim, Ahmand Nazri Mohamed; Ho, Eliza Xin Pei; Ong, Swee Hoe; Wertheim, Heiman F.; Fox, Annette; Van Vinh Nguyen, Chau; Nghiem, Ngoc My; Ha, Tuan Manh; Thi Ngoc Tran, Anh; Tambayah, Paul; Lin, Raymond; Sangsajja, Chariya; Manosuthi, Weerawat; Chuchottaworn, Chareon; Sansayunh, Piamlarp; Chotpitayasunondh, Tawee; Suntarattiwong, Piyarat; Chokephaibulkit, Kulkanya; Puthavathana, Pilaipan; de Jong, Menno D.; Farrar, Jeremy; van Doorn, H. Rogier; Hibberd, Martin Lloyd

    2014-01-01

    Background The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. Methodology/Principal Findings Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. Conclusion/Significances The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients. PMID:25365328

  5. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases

    PubMed Central

    Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-01-01

    Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases. PMID:27436364

  6. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases.

    PubMed

    Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-07-20

    Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases.

  7. ICD-9-CM and ICD-10-CM mapping of the AAST Emergency General Surgery disease severity grading systems: Conceptual approach, limitations, and recommendations for the future.

    PubMed

    Utter, Garth H; Miller, Preston R; Mowery, Nathan T; Tominaga, Gail T; Gunter, Oliver; Osler, Turner M; Ciesla, David J; Agarwal, Suresh K; Inaba, Kenji; Aboutanos, Michel B; Brown, Carlos V R; Ross, Steven E; Crandall, Marie L; Shafi, Shahid

    2015-05-01

    The American Association for the Surgery of Trauma (AAST) recently established a grading system for uniform reporting of anatomic severity of several emergency general surgery (EGS) diseases. There are five grades of severity for each disease, ranging from I (lowest severity) to V (highest severity). However, the grading process requires manual chart review. We sought to evaluate whether International Classification of Diseases, 9th and 10th Revisions, Clinical Modification (ICD-9-CM, ICD-10-CM) codes might allow estimation of AAST grades for EGS diseases. The Patient Assessment and Outcomes Committee of the AAST reviewed all available ICD-9-CM and ICD-10-CM diagnosis codes relevant to 16 EGS diseases with available AAST grades. We then matched grades for each EGS disease with one or more ICD codes. We used the Official Coding Guidelines for ICD-9-CM and ICD-10-CM and the American Hospital Association's "Coding Clinic for ICD-9-CM" for coding guidance. The ICD codes did not allow for matching all five AAST grades of severity for each of the 16 diseases. With ICD-9-CM, six diseases mapped into four categories of severity (instead of five), another six diseases into three categories of severity, and four diseases into only two categories of severity. With ICD-10-CM, five diseases mapped into four categories of severity, seven diseases into three categories, and four diseases into two categories. Two diseases mapped into discontinuous categories of grades (two in ICD-9-CM and one in ICD-10-CM). Although resolution is limited, ICD-9-CM and ICD-10-CM diagnosis codes might have some utility in roughly approximating the severity of the AAST grades in the absence of more precise information. These ICD mappings should be validated and refined before widespread use to characterize EGS disease severity. In the long-term, it may be desirable to develop alternatives to ICD-9-CM and ICD-10-CM codes for routine collection of disease severity characteristics.

  8. Early severe coronary artery disease and aortic coarctation in a child with familial hypercholesterolaemia.

    PubMed

    Labib, Dina; Soliman, Haytham; Said, Kareem; Sorour, Khaled

    2016-11-30

    An 11-year-old boy presented with easy fatigability, multiple xanthomas, and absent pedal pulsations. Laboratory workup showed severe hypercholesterolaemia and non-invasive imaging revealed 'normally functioning' bicuspid aortic valve and tight aortic coarctation. Coronary angiography showed severe right coronary artery (RCA) stenosis. Medical treatment resulted in significant improvement of dyslipidaemia. We successfully performed balloon dilation and stenting of his coarctation, as well as percutaneous coronary intervention for RCA lesion.

  9. Plasma concentration of parasite DNA as a measure of disease severity in falciparum malaria.

    PubMed

    Imwong, Mallika; Woodrow, Charles J; Hendriksen, Ilse C E; Veenemans, Jacobien; Verhoef, Hans; Faiz, M Abul; Mohanty, Sanjib; Mishra, Saroj; Mtove, George; Gesase, Samwel; Seni, Amir; Chhaganlal, Kajal D; Day, Nicholas P J; Dondorp, Arjen M; White, Nicholas J

    2015-04-01

    In malaria-endemic areas, Plasmodium falciparum parasitemia is common in apparently healthy children and severe malaria is commonly misdiagnosed in patients with incidental parasitemia. We assessed whether the plasma Plasmodium falciparum DNA concentration is a useful datum for distinguishing uncomplicated from severe malaria in African children and Asian adults. P. falciparum DNA concentrations were measured by real-time polymerase chain reaction (PCR) in 224 African children (111 with uncomplicated malaria and 113 with severe malaria) and 211 Asian adults (100 with uncomplicated malaria and 111 with severe malaria) presenting with acute falciparum malaria. The diagnostic accuracy of plasma P. falciparum DNA concentrations in identifying severe malaria was 0.834 for children and 0.788 for adults, similar to that of plasma P. falciparum HRP2 levels and substantially superior to that of parasite densities (P < .0001). The diagnostic accuracy of plasma P. falciparum DNA concentrations plus plasma P. falciparum HRP2 concentrations was significantly greater than that of plasma P. falciparum HRP2 concentrations alone (0.904 for children [P = .004] and 0.847 for adults [P = .003]). Quantitative real-time PCR measurement of parasite DNA in plasma is a useful method for diagnosing severe falciparum malaria on fresh or archived plasma samples.

  10. Application of Several Multimedia Approaches to the Teaching of CNS Pharmacology: Parkinson's Disease and Antiparkinsonism Drugs.

    ERIC Educational Resources Information Center

    Faulkner, Thomas P.; Sprague, Jon E.

    1996-01-01

    A multimedia approach to drug therapy for Parkinson's Disease, part of a pharmacy school central nervous system course, integrated use of lecture, textbook, video/graphic technology, the movie "Awakenings," Internet and World Wide Web, and an interactive animated movie. A followup questionnaire found generally positive student attitudes…

  11. Disease severity and yield potential of rice cultivars in organic production systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The market demand for organically produced rice has driven the steady increase in the acreage of organic rice in the U. S., with Texas and California being the largest states. Yield potential and disease management are among the principal challenges associated with organic rice production. We evalua...

  12. Comparison of disease severity and yield potential of rice varieties in two organic cropping systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The market demand for organically produced rice has driven the steady increase in acreage of organic rice in the U. S., with Texas and California having the most acreage. Yield potential and disease management are among the principal challenges associated with organic rice production. Organic rice c...

  13. The use of disease severity variables in predicting efficacy of FOV4 resistance selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2015, 85 Upland (Gossypium hirsutum L.) accessions from the USDA-ARS Cotton Collection and 126 F6 Pima-S6 x Pima-S7 (G. barbadense L.) recombinant inbred lines were evaluated for disease performance under pressure of Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4) in a replicated field trial ...

  14. The alpha-globin genotype does not influence sickle cell disease severity in a retrospective cross-validation study of the pediatric severity score.

    PubMed

    Joly, Philippe; Pondarré, Corinne; Bardel, Claire; Francina, Alain; Martin, Cyril

    2012-01-01

    To validate the recently proposed pediatric severity score (PSS) for sickle cell disease (SCD), we retrospectively assembled clinical data from a cohort of 122 patients with SCD (105 S/S or S/β(0) -thal. and 17 S/C) followed up for at least 2 years. Besides age and α- and β-globin genotypes, four new parameters were also tested against the PSS: duration of data assembly, neonatal screening, use of transcranial Doppler ultrasound to prevent vasculopathies and β-globin gene cluster haplotype. Once again, the PSS clearly differentiated patients by their β-globin genotype (P=0.004) but not by their age during data assembly (P=0.159). But, surprisingly, alpha-gene deletions were not associated with a lower PSS (P=0.604), possibly reflecting the opposite effects of α-thalassemia on global SCD severity. As for the newly tested parameters, the PSS appeared not to be influenced by the duration of data assembly (P=0.071) and neonatal screening (P=0.678) but rather by the introduction of transcranial Doppler ultrasound (P=0.006). Moreover, the Senegal haplotype at the homozygous state may be associated with a lower PSS. Methodologically, our data globally confirm the usefulness of the PSS to identify major etiological factors of SCD gravity. Nevertheless, the score is surely underestimated for patients who have been switched to a chronic therapy before the main SCD complications. Biologically, our study questions about the exact influence of α-thalassemia on global SCD severity.

  15. Annexin-A1 restricts Th17 cells and attenuates the severity of autoimmune disease.

    PubMed

    Yazid, Samia; Gardner, Peter J; Carvalho, Livia; Chu, Colin J; Flower, Roderick J; Solito, Egle; Lee, Richard W J; Ali, Robin R; Dick, Andrew D

    2015-04-01

    Annexin-A1 (Anx-A1) is an endogenous anti-inflammatory molecul