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Sample records for adelaide disease severity

  1. Sever's Disease

    MedlinePlus

    ... Tests How do I know if my child's heel pain is caused by Sever's disease? In Sever's disease, heel pain can be in one or both heels. It ... cut down or stop any activity that causes heel pain. Apply ice to the injured heel for 20 ...

  2. Sever's Disease

    MedlinePlus

    ... Are Reading Upsetting News Reports? What to Say Vaccines: Which Ones & When? Smart School Lunches Emmy-Nominated Video "Cerebral Palsy: Shannon's Story" 5 Things to Know About Zika & Pregnancy Sever's Disease KidsHealth > ...

  3. Adelaide's blackbirding pathologist.

    PubMed

    Allen, P W

    1998-06-01

    Archibald Watson (1849-1940) was the inaugural Elder Professor of Anatomy at the University of Adelaide. He held the position from 1885 to 1919, having previously trained in Gottingen, Paris, and London under some of the most eminent physicians of those times. Before he started his medical studies, he, Dr James Patrick Murray, and several others were involved in the kidnapping ("blackbirding") of Pacific Islanders (Kanakas) to work on South Sea cotton plantations. A number of the victims were killed. Watson and two others were charged with murder and remanded in Levuka to appear in Sydney. Watson absconded, traveled to Europe, and never stood trial; the other two were convicted and sentenced to death. Watson's life as an anatomist, surgeon, pathologist, member of the Adelaide Club, world traveler, Australian Army doctor during the Boer War and World War I, fisherman, and motorcyclist was full of interest and incidents. The events surrounding the autopsy he performed on a case of fibrodysplasia ossificans progressiva and the subsequent preservation of the skeleton in the Anatomy Museum of the University of Adelaide are described. PMID:9845740

  4. Disease Severity Index

    PubMed Central

    Maloney, Clifford J.

    1980-01-01

    Workers studying several diseases have devised severity levels under the term “disease staging” to facilitate both research on the disease and the choice of treatment for individual patients. These categories are usually ad hoc, and hence neither widely accepted nor susceptable to improvement with increasing knowledge. Other workers have developed quantitative assays of the sensitivity of biological organisms under the term bioassay. The present paper applies an adaptation of bioassay to the assessment of the degree of sickness severity of individual patients. In practice using the index requires only a simple table look-up. The feasibility and suitability of the technique were tested on records of 908 metastatic breast cancer patients which happened to be available. Study of other data is highly desirable.

  5. 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.

  6. 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. PMID:26081492

  7. Radiosensitive severe combined immunodeficiency disease.

    PubMed

    Dvorak, Christopher C; Cowan, Morton J

    2010-02-01

    Inherited defects in components of the nonhomologous 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 that are traditionally used for conditioning before allogeneic hematopoietic cell transplantation (HCT). Known causes of radiosensitive SCID include deficiencies of Artemis, DNA ligase IV, DNA-dependent protein kinase catalytic subunit, and Cernunnos-XLF, all of which have been treated with HCT. Because of these patients' sensitivity to certain forms of chemotherapy, the approach to donor selection and the type of conditioning regimen used for a patient with radiosensitive SCID requires careful consideration. Significantly more research needs to be done to determine the long-term outcomes of patients with radiosensitive SCID after HCT and to discover novel nontoxic approaches to HCT that might benefit those patients with intrinsic radiosensitivity and chemosensitivity as well as potentially all patients undergoing an HCT. PMID:20113890

  8. 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

  9. 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.

  10. Severe Darier's disease in a psychiatric patient*

    PubMed Central

    Yang, Jeane Jeong Hoon; Lopes, Roberta Simão; Pereira, Medéia Carolina Fernandes; Tebcherani, Antonio Jose; Pires, Mário Cezar

    2015-01-01

    Darier’s disease is characterized by dense keratotic lesions in the seborrheic areas of the body such as scalp, forehead, nasolabial folds, trunk and inguinal region. It is a rare genodermatosis, an autosomal dominant inherited disease that may be associated with neuropsichiatric disorders. It is caused by ATPA2 gene mutation, presenting cutaneous and dermatologic expressions. Psychiatric symptoms are depression, suicidal attempts, and bipolar affective disorder. We report a case of Darier’s disease in a 48-year-old female patient presenting severe cutaneous and psychiatric manifestations. PMID:26312677

  11. Measurement of disease severity in cutaneous autoimmune diseases

    PubMed Central

    2013-01-01

    The development of disease-specific outcome instruments for several autoimmune skin diseases including cutaneous lupus erythematosus (CLE), dermatomyositis, vitiligo, pemphigus and alopecia areata has facilitated the objective assessment of disease in clinical trials. Validation of these instruments provides reliable tools to measure disease severity and therapeutic effect in clinical studies. However, the existence of multiple outcome measures for each disease and the lack of uniformity between studies has created a challenge in comparing results across trials. Efforts to address this issue include the Core Outcome Measures in Effectiveness Trials (COMET) initiative and international meetings directed at reaching a consensus. Other challenges with the use of outcome measures include difficulties measuring change in mild disease, measuring response in topical studies, and capturing disease activity in skin with extensive post-inflammatory hyperpigmentation. PMID:23755366

  12. Elucidating novel disease mechanisms in severe asthma.

    PubMed

    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

    2016-07-01

    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

  13. 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

  14. Biomarkers of severe dengue disease - a review.

    PubMed

    John, Daisy Vanitha; Lin, Yee-Shin; Perng, Guey Chuen

    2015-01-01

    Dengue virus infection presents a wide spectrum of manifestations including asymptomatic condition, dengue fever (DF), or severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in affected individuals. The early prediction of severe dengue in patients without any warning signs who may later develop severe DHF is very important to choose appropriate intensive supportive therapy since available vaccines for immunization are yet to be approved. Severe dengue responses include T and B cell activation and apoptosis, cytokine storm, hematologic disorders and complement activation. Cytokines, complement and other unidentified factors may transiently act on the endothelium and alter normal fluid barrier function of the endothelial cells and cause plasma leakage. In this review, the host factors such as activated immune and endothelial cells and their products which can be utilized as biomarkers for severe dengue disease are discussed. PMID:26462910

  15. Resveratrol: A Focus on Several Neurodegenerative Diseases.

    PubMed

    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

  16. Resveratrol: A Focus on Several Neurodegenerative Diseases

    PubMed Central

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

    2015-01-01

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

  17. COPD exacerbations by disease severity in England

    PubMed Central

    Merinopoulou, Evie; Raluy-Callado, Mireia; Ramagopalan, Sreeram; MacLachlan, Sharon; Khalid, Javaria Mona

    2016-01-01

    Objectives Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Methods Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). Results From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85) for GOLD A to 2.51 (95% CI: 2.47–2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93) for GOLD A to 7.44 (95% CI: 7.31–7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84). Conclusion Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an

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

    PubMed Central

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

    2014-01-01

    Background and objective Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. Patients and methods In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. Results Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. Conclusion COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity. PMID:25429213

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

    PubMed Central

    2013-01-01

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

  20. Predicting global variation in infectious disease severity

    PubMed Central

    Jensen, Per M.; De Fine Licht, Henrik H.

    2016-01-01

    Background and objectives: Understanding the underlying causes for the variation in case-fatality-ratios (CFR) is important for assessing the mechanism governing global disparity in the burden of infectious diseases. Variation in CFR is likely to be driven by factors such as population genetics, demography, transmission patterns and general health status. We present data here that support the hypothsis that changes in CFRs for specific diseases may be the result of serial passage through different hosts. For example passage through adults may lead to lower CFR, whereas passage through children may have the opposite effect. Accordingly changes in CFR may occur in parallel with demographic transitions. Methodology: We explored the predictability of CFR using data obtained from the World Health Organization (WHO) disease databases for four human diseases: mumps, malaria, tuberculosis and leptospirosis and assessed these for association with a range of population characteristics, such as crude birth and death rates, median age of the population, mean body mass index, proportion living in urban areas and tuberculosis vaccine coverage. We then tested this predictive model on Danish historical demographic and population data. Results: Birth rates were the best predictor for mumps and malaria CFR. For tuberculosis CFR death rates were the best predictor and for leptospirosis population density was a significant predictor. Conclusions and implications: CFR predictors differed among diseases according to their biology. We suggest that the overall result reflects an interaction between the forces driving demographic change and the virulence of human-to-human transmitted diseases. PMID:26884415

  1. Females experience a more severe disease course in Batten disease.

    PubMed

    Cialone, Jennifer; Adams, Heather; Augustine, Erika F; Marshall, Frederick J; Kwon, Jennifer M; Newhouse, Nicole; Vierhile, Amy; Levy, Erika; Dure, Leon S; Rose, Katherine R; Ramirez-Montealegre, Denia; de Blieck, Elisabeth A; Mink, Jonathan W

    2012-05-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood. Symptoms typically present at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. Studies on sex differences in JNCL have yielded mixed results, but parent anecdotes suggest that females experience a more precipitous disease course. Therefore, we sought to determine if sex-based differences exist in JNCL. We used data from the Unified Batten Disease Rating Scale (UBDRS), the Batten Disease Support and Research Association (BDSRA) database, and the PedsQL quality of life (QoL) survey to evaluate sex-based differences in functional independence and time from symptom onset to death. On average, females had JNCL symptom onset one year later and death one year earlier than did males. Despite a later age at onset, females had lower functional capability, earlier loss of independent function, and lower physical QoL. Future research in sex differences in JNCL may help to further understand the biological mechanisms underpinning the disease course and may point to targeted therapies. PMID:22167274

  2. 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...

  3. Severe Clostridium difficile-associated disease in children.

    PubMed

    Pokorn, Marko; Radsel, Anja; Cizman, Milan; Jereb, Matjaz; Karner, Primoz; Kalan, Gorazd; Grosek, Stefan; Andlovic, Alenka; Rupnik, Maja

    2008-10-01

    Three cases of Clostridium difficile-associated disease in children were detected within a short time interval. Intensive therapy was required in 2 cases with colectomy in one of them. One of the severe cases was community-acquired. Two patients had underlying diseases (Hirschprung disease, Down syndrome) and also tested positive for enteric viruses (rotavirus, calicivirus). PMID:18756189

  4. Severe dyspnea as atypical presenting symptom of Madelung's disease

    PubMed Central

    Milisavljevic, D; Zivic, M; Radovanović, Z; Stankovic, P

    2010-01-01

    Madelung's disease (benign symmetrical lipomatosis) is a rare disease of unknown etiology manifesting as symmetric abnormal deposits of adipose tissue in the head, neck and upper trunk. We report a case of a 58-year-old man with a long lasting Madelungs disease in whom progressive fatty tissue accumulation caused a severe inspiratory dyspnea as atypical presenting symptom. The etiopathogenetic, clinico-diagnostic and therapeutic aspects of this rare disease are discussed. Due to its progressive but not so easily predictable enlarging behavior Madelung's disease has not only aesthetic but also functional and sometimes life threatening consequences which need to be treated. PMID:20596272

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

    ERIC Educational Resources Information Center

    Seikel, J. Anthony; And Others

    1990-01-01

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

  6. A biophysical marker of severity in sickle cell disease

    PubMed Central

    Wood, David K.; Soriano, Alicia; Mahadevan, L.; Higgins, John M.; Bhatia, Sangeeta N.

    2013-01-01

    The search for predictive biomarkers of disease has largely focused on molecular indicators; however, mechanical and biophysical markers, which can integrate multiple pathways across length scales, may provide a more global picture of the underlying pathophysiology. Sickle cell disease, the first disease to have its molecular origins decoded, affects millions of people worldwide and has been studied intensively at the molecular, cellular, tissue and organismal level for a century since its initial description. However, there are still few, if any, markers that allow us to characterize the severity of this disease. Because the complications of sickle cell disease are largely due to vaso-occlusive events, we hypothesized that a physical metric characterizing the vaso-occlusive process could serve as a marker of disease severity. Here we use a simple microfluidic device to characterize the dynamics of jamming in physiologically relevant conditions, using the rate of change of the resistance to flow following a sudden deoxygenation event. Our studies show that this single biophysical parameter could be used to distinguish between patients with divergent clinical outcomes, unlike existing laboratory tests. Our assay provides a biophysical marker of disease severity that could be used to guide timing of clinical interventions, to monitor the progression of the disease, and to measure the efficacy of drug response, transfusion, and novel small molecules in an in vitro setting. PMID:22378926

  7. 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

  8. Unmet needs in severe chronic upper airway disease (SCUAD).

    PubMed

    Bousquet, Jean; Bachert, Claus; Canonica, Giorgio W; Casale, Thomas B; Cruz, Alvaro A; Lockey, Richard J; Zuberbier, Torsten

    2009-09-01

    Although the majority of patients with chronic upper airway diseases have controlled symptoms during treatment, many patients have severe chronic upper airway diseases (SCUADs). SCUAD defines those patients whose symptoms are inadequately controlled despite adequate (ie, effective, safe, and acceptable) pharmacologic treatment based on guidelines. These patients have impaired quality of life, social functioning, sleep, and school/work performance. Severe uncontrolled allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, or occupational airway diseases are defined as SCUADs. Pediatric SCUADs are still unclear. In developing countries SCUADs exist, but risk factors can differ from those seen in developed countries. Comorbidities are common in patients with SCUADs and might increase their severity. The present document is the position of a group of experts considering that SCUADs should be considered differently from mild chronic upper airway diseases. It reviews the state of the art, highlighting gaps in our knowledge, and proposes several areas for a better understanding, prevention, and management of SCUADs. This document can also serve to optimize the pharmacoeconomic evaluation of SCUADs by means of comparison with mild chronic upper airway diseases. PMID:19660803

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

    PubMed

    Oshrine, Benjamin; Talano, Julie-An

    2015-04-01

    Sickle cell disease is an inherited hematologic disorder that in its severe form can result in substantial morbidity and early mortality. Patients with this disorder can suffer from severe pain, lung disease, and strokes, resulting in chronic debilitating conditions, end organ dysfunction, and organ failure. The health care costs of caring for these chronically ill patients are substantial. Allogeneic transplantation is a modality that has the potential to cure these patients. To date, matched sibling donor transplantation is widely accepted as a standard of care for pediatric patients. Utilizing alternative donors for transplant is still under investigation, as is transplant for adult patients with sickle cell disease. This review focuses on the most recent data for hematopoietic cell transplantation for patients with sickle cell disease. PMID:26352583

  10. [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. PMID:10444954

  11. Can the Excess Heat Factor Indicate Heatwave-Related Morbidity? A Case Study in Adelaide, South Australia.

    PubMed

    Hatvani-Kovacs, Gertrud; Belusko, Martin; Pockett, John; Boland, John

    2016-03-01

    Although heatwave-related excess mortality and morbidity have been widely studied, results are not comparable spatially and often longitudinally because of different heatwave definitions applied. The excess heat factor (EHF) quantifies heatwave intensity relative to the local climate, enabling cross-regional comparisons. Previous studies have shown a strong relationship between EHFs and daily mortality during severe heatwaves. An extensive study about the relationship between EHFs and daily morbidity compared to the currently applied heatwave thresholds in Adelaide has not yet been undertaken. This paper analyzes the association of EHFs with daily morbidity between 2008 and 2014 in the Adelaide metropolitan region, South Australia, and probes three different approaches to calculate the EHF. The EHF is found to differentiate days with heatwave-related excess morbidity significantly better than other widely used weather parameters, resulting in fewer days per year with heatwave alerts than using previously proposed methods. The volume of excess morbidity can be predicted by the EHF more reliably with a model proposed for the SA Ambulance Service to support their heatwave preparation plan. PMID:26695616

  12. Molecular characterisation and disease severity of leptospirosis in Sri Lanka.

    PubMed

    Bandara, Kanchana Kumari; Weerasekera, Manjula; Gunasekara, Chinthika P; Ranasinghe, Nilantha; Marasinghe, Chamil; Fernando, Neluka

    2015-06-01

    Leptospirosis is a re-emerging zoonotic disease all over the world, important in tropical and subtropical areas. A majority of leptospirosis infected patients present as subclinical or mild disease while 5-10% may develop severe infection requiring hospitalisation and critical care. It is possible that several factors, such as the infecting serovar, level of leptospiraemia, host genetic factors and host immune response, may be important in predisposition towards severe disease. Different Leptospira strains circulate in different geographical regions contributing to variable disease severity. Therefore, it is important to investigate the circulating strains at geographical locations during each outbreak for epidemiological studies and to support the clinical management of the patients. In this study immunochromatography, microscopic agglutination test and polymerase chain reaction were used to diagnose leptospirosis. Further restriction fragment length polymorphism and DNA sequencing methods were used to identify the circulating strains in two selected geographical regions of Sri Lanka. Leptospira interrogans, Leptospira borgpetersenii and Leptospira kirschneri strains were identified to be circulating in western and southern provinces. L. interrogans was the predominant species circulating in western and southern provinces in 2013 and its presence was mainly associated with renal failure. PMID:26061234

  13. Molecular characterisation and disease severity of leptospirosis in Sri Lanka

    PubMed Central

    Bandara, Kanchana Kumari; Weerasekera, Manjula; Gunasekara, Chinthika P; Ranasinghe, Nilantha; Marasinghe, Chamil; Fernando, Neluka

    2015-01-01

    Leptospirosis is a re-emerging zoonotic disease all over the world, important in tropical and subtropical areas. A majority of leptospirosis infected patients present as subclinical or mild disease while 5-10% may develop severe infection requiring hospitalisation and critical care. It is possible that several factors, such as the infecting serovar, level of leptospiraemia, host genetic factors and host immune response, may be important in predisposition towards severe disease. Different Leptospira strains circulate in different geographical regions contributing to variable disease severity. Therefore, it is important to investigate the circulating strains at geographical locations during each outbreak for epidemiological studies and to support the clinical management of the patients. In this study immunochromatography, microscopic agglutination test and polymerase chain reaction were used to diagnose leptospirosis. Further restriction fragment length polymorphism and DNA sequencing methods were used to identify the circulating strains in two selected geographical regions of Sri Lanka. Leptospira interrogans, Leptospira borgpetersenii and Leptospira kirschneri strains were identified to be circulating in western and southern provinces. L. interrogans was the predominant species circulating in western and southern provinces in 2013 and its presence was mainly associated with renal failure. PMID:26061234

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

    PubMed

    Alshukairi, Abeer N; 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

    2016-06-01

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  18. Epidemiology of severe Streptococcus pyogenes disease in Europe.

    PubMed

    Lamagni, Theresa L; Darenberg, Jessica; Luca-Harari, Bogdan; Siljander, Tuula; Efstratiou, Androulla; Henriques-Normark, Birgitta; Vuopio-Varkila, Jaana; Bouvet, Anne; Creti, Roberta; Ekelund, Kim; Koliou, Maria; Reinert, Ralf René; Stathi, Angeliki; Strakova, Lenka; Ungureanu, Vasilica; Schalén, Claes; Jasir, Aftab

    2008-07-01

    The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe. PMID:18463210

  19. Epidemiology of Severe Streptococcus pyogenes Disease in Europe▿

    PubMed Central

    Lamagni, Theresa L.; Darenberg, Jessica; Luca-Harari, Bogdan; Siljander, Tuula; Efstratiou, Androulla; Henriques-Normark, Birgitta; Vuopio-Varkila, Jaana; Bouvet, Anne; Creti, Roberta; Ekelund, Kim; Koliou, Maria; Reinert, Ralf René; Stathi, Angeliki; Strakova, Lenka; Ungureanu, Vasilica; Schalén, Claes; Jasir, Aftab

    2008-01-01

    The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe. PMID:18463210

  20. 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

  1. RISK FACTORS FOR SEVERE HAND, FOOT AND MOUTH DISEASE.

    PubMed

    Owatanapanich, Somchai; Wutthanarungsan, Rochana; Jaksupa, Wipaporn; Thisyakorn, Usa

    2015-05-01

    We studied risk factors associated with severe hand, foot and mouth disease (HFMD) caused by enteroviruses among patients aged less than 15 years admitted to King Narai Hospital, Lopburi, Thailand during 2011-2013. Cases were divided into either mild or severe. Severe cases were those with encephalitis, meningitis, myocarditis, pneumonia, pulmonary edema or respiratory failure. Risk factors for severe infection were evaluated using univariate and multivariate logistic regression analysis. One hundred eighteen patients met the case definition of HFMD. Of these, 95 (80.5%) were classified as mild cases, and 23 (19.5%) as severe cases; there were 5 deaths (4.2%). Of the 23 severe cases, 9 were infected with coxsackievirus A16 (CA16), 8 with enterovirus 71 (EV71) and 4 with both EV71 and CA16. The most common presentations among the severe caseswere: seizures (74%), pneumonia (39%), encephalitis (39%), and meningitis (13%). The clinical manifestations significantly related to severe HFMD on univariate analysis were highest body temperature 39.00C, duration of fever 23 days, absence of skin lesions, diarrhea, dyspnea, seizures and hyperglycemia. The clinical manifestations significantly related to severe HFMD on both univariate and multivariate analyses were age less than 1 year, absence of oral lesions and drowsiness/lethargy. Clinicians should be aware of these factors. Early recognition of severe cases is important to increase the rates of successful outcomes and reduce mortality. PMID:26521518

  2. [Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases].

    PubMed

    Fiessinger, J N; Aiach, M; Lagneau, P; Cormier, J M; Housset, E

    1975-04-20

    38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment. PMID:176733

  3. 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

  4. 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

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

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria 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

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

    PubMed

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

    2014-11-01

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

  7. Management of chronic hepatitis B in severe liver disease

    PubMed Central

    Fung, James; Lai, Ching-Lung; Yuen, Man-Fung

    2014-01-01

    In the past few decades, chronic hepatitis B (CHB) has evolved from a disease that was untreatable and progressive, to one that can be easily controlled with antiviral therapy. However, patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide analogs. These include those with underlying cirrhosis, severe flares of CHB, hepatocellular carcinoma (HCC), and for those undergoing liver transplantation. For those with established cirrhosis, antiviral therapy should be considered for all, as unpredictable flares can still occur, which can be fatal for those with advanced chronic liver disease. However, even with effective viral suppression, the development of HCC can still occur. For patients with severe flares of CHB, although the use of antiviral can improve long term outcomes, a significant proportion may still die without liver transplantation. The short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver disease. In patients with decompensated cirrhosis, liver failure secondary to severe flares, or those with HCC, liver transplantation may be curative. After liver transplantation, long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B infection. The use of hepatitis B immune globulin (HBIG) in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over a decade. With newer and more potent antiviral agents such as tenofovir and entecavir, use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term. PMID:25473157

  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. Oral health of patients with severe rheumatic heart disease.

    PubMed

    Maharaj, Breminand; Vayej, Ahmed C

    2012-07-01

    In order to determine whether adequate attention is paid to the maintenance of good oral health in patients at risk of developing infective endocarditis, we studied 44 black patients with severe rheumatic heart disease before they had cardiac surgery. Plaque and gingival index scores were calculated and panoramic radiographs were done in all patients. There were 17 males and 27 females (mean age: 30.6 years). The plaque and gingival index scores were classified as poor in 31.8 and 54.6% of patients, respectively. Panoramic radiographic findings included caries in 56.8% of patients, peri-apical pathology in 18.1% and retained roots in 22.7% of patients. This study demonstrates that inadequate attention is paid to the maintenance of good oral health in patients with severe rheumatic heart disease. The oral and dental care of patients at risk of developing infective endocarditis needs to be improved. PMID:22836156

  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.

  11. 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

  12. Cardiac parasympathetic activity in severe uncomplicated coronary artery disease.

    PubMed Central

    Nolan, J.; Flapan, A. D.; Reid, J.; Neilson, J. M.; Bloomfield, P.; Ewing, D. J.

    1994-01-01

    BACKGROUND--Previous studies have suggested that coronary artery disease is independently associated with reduced cardiac parasympathetic activity, and that this is important in its pathophysiology. These studies included many patients with complications that might be responsible for the reported autonomic abnormalities. OBJECTIVE--To measure cardiac parasympathetic activity in patients with uncomplicated coronary artery disease. PATIENTS AND METHODS--44 patients of mean (SD) age 56 (8) with severe uncomplicated coronary artery disease (symptoms uncontrolled on maximal medical treatment; > 70% coronary stenosis at angiography; normal ejection fraction; no evidence of previous infarction, diabetes, or hypertension). Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times successive RR intervals exceeded the preceding RR interval by > 50 ms, a previously validated sensitive and specific index of cardiac parasympathetic activity. RESULTS--Mean (range) of counts were: waking 112 (range 6-501)/h, sleeping 198 (0-812)/h, and total 3912 (151-14 454)/24 h. These mean results were unremarkable, and < 10% of patients fell below the lower 95% confidence interval for waking, sleeping, or total 24 hour counts in normal people. There was no relation between the severity of coronary artery disease or the use of concurrent antianginal drug treatment and cardiac parasympathetic activity. CONCLUSION--In contrast with previous reports no evidence of a specific independent association between coronary artery disease and reduced cardiac parasympathetic activity was found. The results of previous studies may reflect the inclusion of patients with complications and not the direct effect of coronary artery disease itself. PMID:7913823

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

    PubMed Central

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

    2016-01-01

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

  14. Chronic obstructive pulmonary disease--diagnosis and classification of severity.

    PubMed

    Viviers, P J; van Zyl-Smit, R N

    2015-09-01

    Chronic obstructive pulmonary disease (COPD) is a common, progressive and preventable non-communicable respiratory disorder. It is often confused with asthma and poorly understood by many lay people. The primary cause of COPD is tobacco smoking, but in the South African (SA) context, biomass fuel exposure/household pollution, tuberculosis, HIV and mining exposure are additional important causes.There is a very high prevalence of COPD in SA and it is the third leading cause of mortality globally.The diagnosis of COPD is based predominantly on symptoms, i.e. progressive shortness of breath and cough in a patient with risk factors–usually smoking. Lung function testing is required to formally make the diagnosis, which places a significant hurdle in correctly identifying COPD in SA, given the limited access to spirometry in many areas. Spirometry is also required to grade the severity of lung function obstruction.Severity assessment, which is used to plan a management strategy (predominantly bronchodilators with inhaled steroids in severe cases), combines symptoms, lung function and exacerbations. Based on these 3 factors, a patient can be categorised into 1 of 4 groups and appropriate management instituted. Additional comorbidities, particularly cardiovascular and mental illness, should also be evaluated.Early identification of COPD, with further avoidance of an aetiological cause such as smoking, is key in preventing disease progression.Appropriate therapy, comprising non-pharmacological and pharmacological interventions and based on a comprehensive severity assessment, should result in symptom improvement and reduced risk for exacerbations. PMID:26636168

  15. 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

  16. The Effects of Adapted Tango on Spatial Cognition and Disease Severity in Parkinson’s Disease

    PubMed Central

    McKee, Kathleen E.; Hackney, Madeleine E.

    2013-01-01

    This study determined effects of community-based adapted tango upon spatial cognition and disease severity in Parkinson’s disease (PD) while controlling for the effects of social interaction. Thirty-three individuals with mild-moderate PD (stage I–III) were assigned to twenty, 90-minute 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 post-intervention. T-tests and ANOVAs evaluated differences. Twenty-three Tango and 8 Education participants finished. Tango participants improved on disease severity (p=0.008), and spatial cognition (p=0.021) compared to Education participants. Tango participants also improved in balance (p=0.038), and executive function (p=0.012). Gains were maintained 10–12 weeks post-intervention. Multimodal exercise with structured syllabi may improve disease severity and spatial cognition. PMID:24116748

  17. 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. PMID:26054697

  18. 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...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Igari, Kimihiro; Kudo, Toshifumi; 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

  1. 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

  2. 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

    2015-07-01

    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. PMID:25997928

  3. CSF neurofilament concentration reflects disease severity in frontotemporal degeneration

    PubMed Central

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

    2014-01-01

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

  4. Disease Severity Indexes and Treatment Evaluation Criteria in Vitiligo

    PubMed Central

    Kawakami, Tamihiro; Hashimoto, Takashi

    2011-01-01

    There is a current lack of consensus regarding methods of assessment of vitiligo. Recently, the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF) were proposed to offer more accurate measures of disease severity indexes and treatment evaluation criteria. It would make sense to combine the VASI with the VETF system. We proposed an original scale for treatment evaluation criteria in vitiligo based on VASI. We plan to add the digital image analysis system, health-related quality of life questionnaire, affected skin location, and skin color in the original scale. PMID:21747840

  5. Disease severity indexes and treatment evaluation criteria in vitiligo.

    PubMed

    Kawakami, Tamihiro; Hashimoto, Takashi

    2011-01-01

    There is a current lack of consensus regarding methods of assessment of vitiligo. Recently, the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF) were proposed to offer more accurate measures of disease severity indexes and treatment evaluation criteria. It would make sense to combine the VASI with the VETF system. We proposed an original scale for treatment evaluation criteria in vitiligo based on VASI. We plan to add the digital image analysis system, health-related quality of life questionnaire, affected skin location, and skin color in the original scale. PMID:21747840

  6. 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

  7. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    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

  8. Severe hypercholesterolemia and liver disease in a 3-year old.

    PubMed

    Patel, Amol M; Brautbar, Ariel; Desai, Nirav K; Wilson, Don P

    2016-01-01

    Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. He was diagnosed with primary sclerosing cholangitis which was confirmed by liver biopsy. Our patient was treated with steroids and immunomodulator therapy which was associated with significant reduction in cholestasis and LDL-C levels. Lipoprotein-X has several properties that make it anti-atherogenic, which raises the question if treatment for hypercholesterolemia should be initiated. PMID:27206954

  9. Severe hypoxia and multiple infarctions resembling Creutzfeldt-Jakob disease.

    PubMed

    Mittelbronn, Michel; Capper, David; Bader, Benedikt; Schittenhelm, Jens; Haybaeck, Johannes; Weber, Petra; Meyermann, Richard; Kretzschmar, Hans A; Wietholter, Horst

    2008-01-01

    Although neuropathological examination is still required for the definite diagnosis of Creutzfeldt-Jakob disease (CJD), specialised clinical assessment predicts probable CJD. Here we present a 73-year-old female patient presenting with rapid cognitive decline, visual, acoustic and cerebellar disturbances, ataxia and EEG changes compatible with early CJD stages. MRI revealed hyperintensities within the thalami, hypothalami, corpora mammillaria, the tectum and the cortex. Initial neuropathological examination showed severe cortical and subcortical spongiosis. However, both immunohistochemistry and Western blotting showed no pathological prion protein. Finally, small infarctions affecting the tectum, tegmentum, corpora mammillaria and global hypoxic-ischaemic changes could be identified as the probable reason for the changes interpreted as CJD-related pathology. Hypoxic-ischaemic CNS alterations mainly affecting the supply area of the basilar artery should be ruled out in case of probable CJD. In addition, severe spongiosis can be misleading in the histological examination, suggesting the diagnosis of a prion-induced spongiform encephalopathy. PMID:18587709

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

    PubMed Central

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

    2009-01-01

    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 participants were analyzed with the Linguistic Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity – the proportion of verbs, proportion of function words, and sentence length – were found to be affected by symptom asymmetry. Greater left-side motor severity (and hence greater right hemisphere dysfunction) was associated with the production of significantly fewer verbs, function words, and shorter sentences. Hence, the production of linguistic complexity in a natural language context was associated with relatively greater right hemisphere involvement. The potential neurobiological mechanisms underlying this effect are discussed. PMID:19751960

  11. 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. PMID:26341524

  12. 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

  13. 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

  14. 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

  15. 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

  16. Ocular Signs Correlate Well with Disease Severity and Genotype in Fabry Disease

    PubMed Central

    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

  17. 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…

  18. Severe Refractory Coeliac Disease with Response Only to Parenteral Nutrition

    PubMed Central

    Ng, Ka Ying Bonnie; Mehta, Ravi; Mohamed, Salma; Mohamed, Zameer; Arnold, Jayantha

    2014-01-01

    Refractory coeliac disease (RCD) is characterised by recurrent or persistent malabsorptive symptoms and villous atrophy, despite strict adherence to a gluten-free diet for at least 6 months and where other causes of malabsorption including malignancy have been excluded. There is limited evidence and guidance on the effective management of these patients. We describe a case of severe RCD in our hospital, with symptoms controlled effectively only by total parenteral nutrition (TPN). This 68-year-old woman initially presented to the clinic with persistent non-bloody diarrhoea and vomiting. A diagnosis of coeliac disease was confirmed with a positive tissue transglutaminase assay and histology. A strict gluten-free diet was ineffective and she represented 6 months later with 13 kg weight loss (16.7%), ongoing abdominal pain and diarrhoea, with bowels opening 16 times a day. She was oedematous, had an albumin of 12 g/l and required hospital admission. She was treated for pancreatic insufficiency and presumptively for small bowel bacterial overgrowth with no resolution of symptoms. We ruled out infectious causes and investigated for small bowel malignancy; all results were negative. Small bowel enteroscopy showed ulcerative jejunitis. She was given 5 days of TPN, following which her symptoms improved and albumin normalised. This was sustained with symptom resolution and weight gain seen at follow-up. TPN successfully and rapidly induced remission in this case. Thus, a short period of TPN should be considered as a potential component of management in patients with severe RCD. PMID:25473387

  19. 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

  20. 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

    2016-05-01

    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.

  1. 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

  2. Presolar Grain Inventories of the Ungrouped C3 Adelaide and the CV3 RBT 04133

    NASA Astrophysics Data System (ADS)

    Davidson, J.; Busemann, H.; Franchi, I. A.; Grady, M. M.

    2010-03-01

    Here we report the presolar grain inventories (silicates, oxides, SiC, and other C-anomalous phases) determined for Adelaide (an ungrouped C3 chondrite) and RBT 04133 (a mildly thermally altered CV3) by NanoSIMS raster ion imaging.

  3. Epithelial transplantation for the management of severe ocular surface disease.

    PubMed Central

    Holland, E J

    1996-01-01

    with unilateral cicatrizing conjunctival disease, the first option should be CAU. For patients with unilateral limbal deficiency, CLAU is the procedure of choice. For patients with bilateral disease Ir-CLAL should be considered first. If this procedure is not available, then consideration of KLAL is warranted. CONCLUSIONS: Classification of the various epithelial transplantation procedures based on anatomy is useful for an accurate comparison and discussion of the procedures. KLAL is a useful technique in the management of severe ocular surface disease due to limbal deficiency. However, patients with preoperative conjunctival keratinization have a poor prognosis. Consideration of a CLAU or a Ir-CLAL should be made for ocular surface disease on the basis of whether the disease is unilateral or bilateral. The importance of HLA and ABO typing, as well as the protocol for immunosuppression in the allograft procedures for limbal deficiency, needs further study. Images FIGURE 2 FIGURE 3A FIGURE 3B FIGURE 3C FIGURE 3D FIGURE 4 FIGURE 5A FIGURE 5B FIGURE 5C FIGURE 5D FIGURE 6A FIGURE 6B FIGURE 6C FIGURE 6D FIGURE 6E FIGURE 6F FIGURE 6G FIGURE 6H FIGURE 7A FIGURE 7B FIGURE 7C FIGURE 8 FIGURE 9A FIGURE 9B FIGURE 9C FIGURE 9D FIGURE 9E FIGURE 9F FIGURE 10A FIGURE 10B FIGURE 10C FIGURE 11 FIGURE 12A FIGURE 12B FIGURE 12C FIGURE 12D FIGURE 12E FIGURE 12F FIGURE 12G FIGURE 12H FIGURE 12I FIGURE 13A FIGURE 13B FIGURE 13C FIGURE 14 FIGURE 15 PMID:8981714

  4. Relation between Voice Handicap Index (VHI) and disease severity in Iranian patients with Parkinson's disease

    PubMed Central

    Karkheiran, Siamak; Moradi, Negin; Shahidi, Gholam Ali; Salehi, Masoud

    2012-01-01

    Background One third of patients with Parkinson's disease (PD) have mentioned “dysphonia” as their most debilitating communication deficit. Patient-based measurements, such as Voice Handicap Index (VHI) add necessary supplementary information to clinical and physiological assessment. There are a few studies about relation between VHI and disease severity in PD, although none of them showed any significant correlation. The goal of this study was to find correlation between these variables in Iranian PD patients. Method This cross-sectional, analytical and non-interventional study was done on 23 PD patients who reported a voice disorder related to their disease. They were selected from attendants of movement disorders clinic of Hazrat Rasool Akram Hospital. The relationship between disease severity (according to Hoehn and Yahr/H&Y and Unified Parkinson's Disease Rating Scale-part3 /UPDRS-III) and VHI questionnaire (and its 3 domains) was investigated based on patients’ sex, UPDRS-III score H&Y and VHI. Results Total VHI and its 3 domains had no relationship with disease severity (H&Y) in all patients and by sex separation. However, there was a positive correlation between VHI and disease severity (UPDRS-III) (r = 0.485). There was also a relation between physical and functional domains of VHI and UPDRS (rP=0.530, rF=0.479) while no relationship observed regarding sex differences. 9 out of 18 UPDRS-III items had strong relationship with VHI (total and 3subscales). Conclusion Iranian PD patients feel handicap according to voice disorder caused by PD. Patient satisfaction of voice decreases with the disease severity and progression. A larger sample size is necessary to find relationship in genders. VHI is an important issue could be offered to be used in PD beside other assessments PMID:23482344

  5. Soluble cell adhesion molecules in human Chagas' disease: association with disease severity and stage of infection.

    PubMed

    Laucella, S; De Titto, E H; Segura, E L; Orn, A; Rottenberg, M E

    1996-12-01

    Formation of inflammatory lesions, one of the pathologic consequences of infection with Trypanosoma cruzi, involves intricate cell-cell interactions in which cell adhesion molecules (CAMs) are involved. Sera from 56 Chagas' disease patients grouped according to disease severity were studied for the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble endothelial selectin (s-E-selectin), soluble vascular cell adhesion molecule-1 (s-VCAM-1), soluble platelet selectin (s-P-selectin), and s-CD44 were studied to determine if they could be used alone or in different combinations as markers for specific diagnostic procedures. Comparisons were made between congenitally, acutely, and chronically infected patients and aged-matched, noninfected individuals, as well as between patients with chronic Chagas' disease grouped according to the severity of their heart-related pathology. No differences in levels of s-CAMs were detected between sera from children with congenital T. cruzi infection and sera from noninfected infants born from chagasic mothers. In contrast, titers of s-ICAM-1, s-VCAM-1, s-selectin, and s-CD44 but not s-P-selectin were significantly increased in sera from patients during the acute phase of infection with T. cruzi. Titers of s-VCAM-1 and s-P-selectin were increased in chronically infected patients. A positive association with disease severity in sera from patients with chronic disease was observed for the levels of s-P-selectin. In contrast, we found no association between clinical symptoms and levels of s-VCAM-1. Patients with chronic disease with severe cardiopathy also showed diminished levels of s-CD44 in comparison with healthy controls or patients with mild disease. The results are discussed in the context of pathology of Chagas' disease. PMID:9025689

  6. The Cutaneous Lupus Erythematosus Disease Area and Severity Index

    PubMed Central

    Bonilla-Martinez, Zuleika L.; Albrecht, Joerg; Troxel, Andrea B.; Taylor, Lynne; Okawa, Joyce; Dulay, Sam; Werth, Victoria P.

    2008-01-01

    Objective To assess the clinical responsiveness of the CLASI (Cutaneous Lupus Erythematosus [CLE] Disease Area and Severity Index). Design Validation cohort. Setting Tertiary referral center. Patients Eight patients with CLE. Intervention Assessment of patients with CLE from baseline until day 56 after starting a new standard of care therapy. Main Outcome Measures Correlation of the baseline to day-56 change in 2 CLASI scales (disease activity and damage), with baseline to day-56 change in the physicians’ and patients’ assessments of patient’s global skin health scores, and the patients’ assessments of pain and itch. Results The change in CLASI activity score highly correlated with the changes in 3 clinical validation measures: physicians’ assessment of skin health (r=0.97; P=.003; n=7), patients’ global skin health score (r=0.85; P=.007; n=8), and pain (r=0.98; P=.004; n=5). Using the Wilcoxon signed-rank test, paired baseline to day-56 changes in CLASI activity and damage scores were analyzed for the 2 subgroups (meaningful change vs nonmeaningful change) composing each validation variable. Change in CLASI activity was significantly different for patients who had a meaningful change in their global skin self-ratings (Z=1.07; P=.03) and approached statistical significance for patients who had a meaningful change in their level of itching (Z=1.83; P=.06) and their physicians’ global skin rating (Z=1.84; P=.06). The CLASI activity score decreases after successful therapeutic intervention, whereas the damage score may increase in scarring forms of CLE. Conclusion The activity score of the CLASI correlates with the improvement of global skin health, pain, and itch and is thus a useful tool to measure clinical response. PMID:18283174

  7. Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity

    PubMed Central

    Barrowman, Jemima; Wiley, Patricia A.; Hudon-Miller, Sarah E.; Hrycyna, Christine A.; Michaelis, Susan

    2012-01-01

    The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE24 cleavage site, underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Likewise, mutations in the ZMPSTE24 gene that result in decreased enzyme function cause a spectrum of diseases that share certain features of premature aging. Twenty human ZMPSTE24 alleles have been identified that are associated with three disease categories of increasing severity: mandibuloacral dysplasia type B (MAD-B), severe progeria (atypical ‘HGPS’) and restrictive dermopathy (RD). To determine whether a correlation exists between decreasing ZMPSTE24 protease activity and increasing disease severity, we expressed mutant alleles of ZMPSTE24 in yeast and optimized in vivo yeast mating assays to directly compare the activity of alleles associated with each disease category. We also measured the activity of yeast crude membranes containing the ZMPSTE24 mutant proteins in vitro. We determined that, in general, the residual activity of ZMPSTE24 patient alleles correlates with disease severity. Complete loss-of-function alleles are associated with RD, whereas retention of partial, measureable activity results in MAD-B or severe progeria. Importantly, our assays can discriminate small differences in activity among the mutants, confirming that the methods presented here will be useful for characterizing any new ZMPSTE24 mutations that are discovered. PMID:22718200

  8. 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.

  9. 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.

  10. 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.

  11. Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity

    PubMed Central

    Mischley, Laurie K.; Standish, Leanna J.; Weiss, Noel S.; Padowski, Jeannie M.; Kavanagh, Terrance J.; White, Collin C.; Rosenfeld, Michael E.

    2016-01-01

    Objectives. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman's rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.

  12. [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. PMID:17119811

  13. Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide

    PubMed Central

    Evers, Melvin M.; Pepers, Barry A.; van Deutekom, Judith C. T.; Mulders, Susan A. M.; den Dunnen, Johan T.; Aartsma-Rus, Annemieke; van Ommen, Gert-Jan B.; van Roon-Mom, Willeke M. C.

    2011-01-01

    To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2′-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)7, also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well. PMID:21909428

  14. Targeting several CAG expansion diseases by a single antisense oligonucleotide.

    PubMed

    Evers, Melvin M; Pepers, Barry A; van Deutekom, Judith C T; Mulders, Susan A M; den Dunnen, Johan T; Aartsma-Rus, Annemieke; van Ommen, Gert-Jan B; van Roon-Mom, Willeke M C

    2011-01-01

    To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2'-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)(7), also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well. PMID:21909428

  15. New Invasive Assessment Measures of Coronary Artery Disease Severity.

    PubMed

    Khanna, Neel; Subramanian, Kathir S; Khera, Sahil; Aronow, Wilbert S; Frishman, William H

    2016-01-01

    Ischemic heart disease is the leading cause of mortality worldwide. The assessment and treatment of patients with ischemic heart disease have advanced greatly over the past decade. Particular attention has been given recently to the recognition of lesions that cause ischemia or that are prone to plaque rupture. New invasive measures of coronary artery disease have been developed, including fractional flow reserve, intravascular ultrasound, optical coherence tomography, and most recently, near-infrared spectroscopy. These technologies have helped to guide the assessment of hemodynamically significant lesions and have shown particular promise in guiding percutaneous coronary interventions. However, mortality and the rate of revascularization have shown mixed results to date. This review seeks to investigate the use and potential benefit of these technologies, with particular attention to clinical end points. PMID:26751263

  16. Atypical Pestivirus and Severe Respiratory Disease in Calves, Europe

    PubMed Central

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

    2011-01-01

    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. PMID:21801648

  17. Parameters of a severe disease course in ulcerative colitis

    PubMed Central

    Stallmach, Andreas; Nickel, Luisa; Lehmann, Thomas; Bokemeyer, Bernd; Bürger, Martin; Hüppe, Dietrich; Kruis, Wolfgang; Nikolaus, Susanna; Preiss, Jan C; Sturm, Andreas; Teich, Niels; Schmidt, Carsten

    2014-01-01

    AIM: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT). METHODS: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy. RESULTS: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can

  18. [Hypothesis of evolutionary origin of several human and animal diseases].

    PubMed

    Pertseva, M N; Shpakov, A O

    2010-01-01

    Studies of our Laboratory in the field of molecular and evolutionary endocrinology have allowed us to put forward a hypothesis about evolutionary origin of endocrine and other diseases of human and animals. This hypothesis is considered using a model of hormonal signal systems. It is based on the concept formulated by the authors about molecular defects in hormonal signal systems as the key causes of endocrine diseases; on evolutionary conservatism of hormonal signal systems, which stems logically from the authors' concept of the prokaryotic origin and endosymbiotic appearance in the course of evolution of chemosignal systems in the higher eukaryotes; from the fact that the process of formation of hormonal signal systems with participation of endosymbiosis including the horizontal transfer of genes is accompanied by transfer not only of normal, but also of the defected genetic material. There are considered examples of the principal possibility of transfer of defected genes between bacteria and eukaryotic organisms. Analysis of the current literature allows suggesting inheritance of pathogenic factors from evolutionary ancestors in the lineage prokaryotes--lower eukaryotes--higher eukaryotes. PMID:20583590

  19. Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease.

    PubMed

    Reed, Berenice Y; Masoumi, Amirali; Elhassan, Elwaleed; McFann, Kim; Cadnapaphornchai, Melissa A; Maahs, David M; Snell-Bergeon, Janet K; Schrier, Robert W

    2011-01-01

    Renal cysts, pain, and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD, we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD, with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log(10). Serum log(10) vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD. PMID:20881939

  20. Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease

    PubMed Central

    Reed, Berenice; Masoumi, Amirali; Elhassan, Elwaleed; McFann, Kim; Cadnapaphornchai, Melissa; Maahs, David; Snell-Bergeon, Janet; Schrier, Robert W.

    2013-01-01

    Renal cysts, pain and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance, and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log10. Serum Log10 vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively correlated with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD. PMID:20881939

  1. 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

  2. Coronary Artery Disease Severity and Cardiovascular Biomarkers in Patients with Peripheral Artery Disease.

    PubMed

    Hikita, Hiroyuki; Shigeta, Takatoshi; Kimura, Shigeki; Takahashi, Atsushi; Isobe, Mitsuaki

    2015-12-01

    Cardiovascular mortality in peripheral artery disease (PAD) patients is higher in critical limb ischemia (CLI) than in intermittent claudication (IC). We sought to evaluate differential characteristics of coronary artery disease (CAD) severity and prognostic biomarkers for cardiovascular events between CLI and IC patients. Coronary angiography was performed on 242 PAD patients (age 73 ± 8 years) with either CLI or IC. High-sensitivity troponin T (hs-TnT), eicosapentaenoic acid-arachidonic acid ratio (EPA/AA), and lipoprotein(a), as biomarkers for prognostic factors, were measured from blood samples. The study patients were divided into a CLI-group (n = 42) and IC-group (n = 200). The Gensini score as an indicator of coronary angiographic severity was higher in the CLI-group than in the IC-group (39.1 ± 31.2 vs. 8.5 ± 8.3, p < 0.0001). Hs-TnT and lipoprotein(a) values were higher in the CLI-group than in the IC-group (0.152 ± 0.186 ng/mL vs. 0.046 ± 0.091, p < 0.0001, 45.9 ± 23.3 mg/dL vs. 26.2 ± 27.7, p = 0.0002, respectively) and EPA/AA was lower in the CLI-group than in the IC-group (0.22 ± 0.11 vs. 0.38 ± 0.29, p = 0.0049, respectively). Greater CAD severity, higher hs-TnT, and lipoprotein(a), and lower EPA/AA were observed in the CLI-group, which may explain higher cardiovascular events in patients with CLI. PMID:26648670

  3. 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

  4. 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...

  5. Volumetric MRI data correlate to disease severity in metachromatic leukodystrophy

    PubMed Central

    Tillema, Jan-Mendelt; Derks, Marloes GM; Pouwels, Petra J W; de Graaf, Pim; van Rappard, Diane F; Barkhof, Frederik; Steenweg, Marjan E; van der Knaap, Marjo S; Wolf, Nicole I

    2015-01-01

    Objective Metachromatic leukodystrophy (MLD) is an inherited lysosomal disorder due to a deficiency in arylsulfatase A with progressive demyelination and neurological decline. This retrospective MRI study investigated the extent of cortical involvement at time of diagnosis, and clinical correlates to both conventional and regional volumetric measures of brain involvement. Methods 3D-T1-weighted MRI scans were used to determine cortical thickness and surface-based cerebral cortical gray matter (GM) and cerebral white matter (WM) volume (GMV and WMV), WM lesions, thalamus, and cerebellum. MRI-MLD severity scores were obtained from FLAIR images. Associations between clinical and imaging data were examined using correlation coefficients. Results Twenty patients with MLD (mean age 13.7 years, range 2–35) and 20 controls (mean age 13.9 years, range 2–40) were included. Compared with control subjects, late-infantile, and juvenile patients (n = 14) had significantly diminished cerebral cortical GMV and thalamus volume (P < 0.05), but did not differ in WMV and cortical thickness. Adult patients (n = 6) showed significantly reduced GMV, WMV and cortical thickness (all P < 0.05). Regional analysis showed statistically significant cortical thinning in the cingulate gyrus and most pronounced thinning with age in the frontal lobe of MLD patients. Intelligence quotient (IQ) correlated with MRI-MLD scores (r = −0.87, P < 0.001). Interpretation Significant cerebral cortical GMV loss is already present in early stages of MLD. IQ correlates with WM severity scores and lesion volume, but not with volumetric measures. In adult presentations, there is more pronounced global atrophy with GMV and WMV loss and accelerated cortical thinning, most prominently in the cingulate gyrus and frontal lobes. PMID:26401514

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

    PubMed

    Quinn, Charles T

    2016-04-01

    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

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

    PubMed Central

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

    2014-01-01

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

  8. Association of the Serum Angiotensin II Level with Disease Severity in Severe Fever with Thrombocytopenia Syndrome Patients.

    PubMed

    Cheng, Jiamei; Li, Huiyu; Jie, Shenghua

    2016-01-01

    Objective Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus. Recent data suggest that the physiological balance of multiple proinflammatory cytokines is substantially changed in cases of severe fever with thrombocytopenia syndrome virus (SFTSV) infection, and the inflammatory response probably plays an important role in disease progression. Angiotensin II is an important active substance of the renin-angiotensin system, and studies have demonstrated that angiotensin II is involved in key events in the inflammatory process and can regulate inflammatory cell responses. Methods In order to elucidate the role of angiotensin II in the pathogenesis of SFTS, we collected serum samples from SFTS patients in the acute or convalescent phase and tested the angiotensin II levels using an enzyme-linked immunosorbent assay as well as SFTSV viral RNA with real-time reverse-transcriptase polymerase chain reaction. Furthermore, we explored possible correlations between the angiotensin II levels and clinical parameters in SFTS patients. Results Our data showed that the serum level of angiotensin II was significantly increased in the acute phase compared with that seen in the convalescent phase and the healthy controls, while there were no significant differences between the convalescent cases and healthy controls (p>0.05). A correlation analysis demonstrated that the level of angiotensin II positively correlated with the SFTS viral RNA load. The angiotensin II levels were also found to be correlated with clinical parameters indicating impairments in organ functions. Moreover, we also found that the angiotensin II levels were significantly increased in the severe cases versus the non-severe cases (p<0.001). Conclusion The serum angiotensin II levels in SFTS patients may be used to stratify the disease severity and are possibly predictive of disease outcomes. PMID:27086801

  9. Common foliar fungi of Populus trichocarpa modify Melampsora rust disease severity.

    PubMed

    Busby, Posy E; Peay, Kabir G; Newcombe, George

    2016-03-01

    Nonpathogenic foliar fungi (i.e. endophytes and epiphytes) can modify plant disease severity in controlled experiments. However, experiments have not been combined with ecological studies in wild plant pathosystems to determine whether disease-modifying fungi are common enough to be ecologically important. We used culture-based methods and DNA sequencing to characterize the abundance and distribution of foliar fungi of Populus trichocarpa in wild populations across its native range (Pacific Northwest, USA). We conducted complementary, manipulative experiments to test how foliar fungi commonly isolated from those populations influence the severity of Melampsora leaf rust disease. Finally, we examined correlative relationships between the abundance of disease-modifying foliar fungi and disease severity in wild trees. A taxonomically and geographically diverse group of common foliar fungi significantly modified disease severity in experiments, either increasing or decreasing disease severity. Spatial patterns in the abundance of some of these foliar fungi were significantly correlated (in predicted directions) with disease severity in wild trees. Our study reveals that disease modification is an ecological function shared by common foliar fungal symbionts of P. trichocarpa. This finding raises new questions about plant disease ecology and plant biodiversity, and has applied potential for disease management. PMID:26565565

  10. Systematic Classification of Disease Severity for Evaluation of Expanded Carrier Screening Panels

    PubMed Central

    Lazarin, Gabriel A.; Hawthorne, Felicia; Collins, Nicholas S.; Platt, Elizabeth A.; Evans, Eric A.; Haque, Imran S.

    2014-01-01

    Professional guidelines dictate that disease severity is a key criterion for carrier screening. Expanded carrier screening, which tests for hundreds to thousands of mutations simultaneously, requires an objective, systematic means of describing a given disease's severity to build screening panels. We hypothesized that diseases with characteristics deemed to be of highest impact would likewise be rated as most severe, and diseases with characteristics of lower impact would be rated as less severe. We describe a pilot test of this hypothesis in which we surveyed 192 health care professionals to determine the impact of specific disease phenotypic characteristics on perceived severity, and asked the same group to rate the severity of selected inherited diseases. The results support the hypothesis: we identified four “Tiers” of disease characteristics (1–4). Based on these responses, we developed an algorithm that, based on the combination of characteristics normally seen in an affected individual, classifies the disease as Profound, Severe, Moderate, or Mild. This algorithm allows simple classification of disease severity that is replicable and not labor intensive. PMID:25494330

  11. 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. PMID:26522685

  12. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model

    PubMed Central

    Bebee, Thomas W.; Dominguez, Catherine E.; Samadzadeh-Tarighat, Somayeh; Akehurst, Kristi L.; Chandler, Dawn S.

    2012-01-01

    Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease associated with low levels of the essential survival motor neuron (SMN) protein. Reduced levels of SMN is due to the loss of the SMN1 gene and inefficient splicing of the SMN2 gene caused by a C>T mutation in exon 7. Global analysis of the severe SMNΔ7 SMA mouse model revealed altered splicing and increased levels of the hypoxia-inducible transcript, Hif3alpha, at late stages of disease progression. Severe SMA patients also develop respiratory deficiency during disease progression. We sought to evaluate whether hypoxia was capable of altering SMN2 exon 7 splicing and whether increased oxygenation could modulate disease in a severe SMA mouse model. Hypoxia treatment in cell culture increased SMN2 exon 7 skipping and reduced SMN protein levels. Concordantly, the treatment of SMNΔ7 mice with hyperoxia treatment increased the inclusion of SMN2 exon 7 in skeletal muscles and resulted in improved motor function. Transfection splicing assays of SMN minigenes under hypoxia revealed that hypoxia-induced skipping is dependent on poor exon definition due to the SMN2 C>T mutation and suboptimal 5′ splice site. Hypoxia treatment in cell culture led to increased hnRNP A1 and Sam68 levels. Mutation of hnRNP A1-binding sites prevented hypoxia-induced skipping of SMN exon 7 and was found to bind both hnRNP A1 and Sam68. These results implicate hypoxic stress as a modulator of SMN2 exon 7 splicing in disease progression and a coordinated regulation by hnRNP A1 and Sam68 as modifiers of hypoxia-induced skipping of SMN exon 7. PMID:22763238

  13. 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…

  14. 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 ...

  15. Chloroquine resistance of Plasmodium falciparum is associated with severity of disease in Nigerian children.

    PubMed

    Olumese, P E; Amodu, O K; Björkman, A; Adeyemo, A A; Gbadegesin, R A; Walker, O

    2002-01-01

    Chloroquine resistance of Plasmodium falciparum in vitro was significantly higher in isolates from patients with severe malaria than those with uncomplicated disease. This association may be due to either progression of uncomplicated to severe disease following chloroquine failure or increased virulence of chloroquine-resistant parasites. The implication of this for antimalarial treatment policy is discussed. PMID:12497979

  16. 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…

  17. 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…

  18. 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

  19. 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.

  20. 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.

  1. 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

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

    PubMed

    Habara, Alawi; Steinberg, Martin H

    2016-04-01

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

  3. Severe Puumala virus infection in a patient with a lymphoproliferative disease treated with icatibant.

    PubMed

    Laine, Outi; Leppänen, Ilona; Koskela, Sirpa; Antonen, Jaakko; Mäkelä, Satu; Sinisalo, Marjatta; Vaheri, Antti; Mustonen, Jukka

    2015-02-01

    Early identification of patients at risk of a severe course of hantaviral disease and lack of effective medication represent a global challenge in the treatment of this emerging infection. We describe a 67-year-old female patient with a history of chronic lymphoproliferative disease involving the spleen and an extremely severe acute Puumala hantavirus infection. She was treated with the bradykinin receptor antagonist icatibant and recovered. She is the second patient with a spleen abnormality and severe Puumala infection treated with icatibant in our hospital. We suggest that patients with spleen abnormalities may be more susceptible to severe hantavirus disease. The activation of the kinin-kallikrein system and the formation of bradykinin in hantavirus-infected endothelial cells indicate that the role of bradykinin receptor antagonist icatibant in the treatment of hantavirus disease is worth studying. PMID:25496418

  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. Group A Streptococcal Bacteremia without a Source is Associated with Less Severe Disease in Children

    PubMed Central

    Gauguet, Stefanie; Ahmed, Asim A.; Zhou, Jing; Pfoh, Elizabeth R.; Ahnger-Pier, Kathryn K.; Harper, Marvin B.; Ozonoff, Al; Wessels, Michael R.; Lee, Grace M.

    2014-01-01

    We analyzed characteristics of 86 Group A streptococcal (GAS) bacteremia cases at Boston Children’s Hospital from 1992-2012. Twenty-three percent of children had severe disease, using ICU admission (18), disability (7), or death (2) as indicators. Children with bacteremia without a source (30% of cases) were less likely to have severe disease than children with focal infections in adjusted models. PMID:25319760

  6. Lesson of the month: selective use of cyclophosphamide in pregnancy for severe autoimmune respiratory disease.

    PubMed

    Nelson-Piercy, Catherine; Agarwal, Sangita; Lams, Boris

    2016-07-01

    We present the cases of two pregnant women who developed severe respiratory compromise in mid pregnancy, one due to rapidly progressive interstitial lung disease associated with mixed connective tissue disease and one secondary to diffuse alveolar haemorrhage due to antiglomerular basement membrane disease. Both were treated with high-dose steroids followed by pulsed intravenous cyclophosphamide. Both women went onto have live births although one baby was growth restricted and preterm. Neither baby had any evidence of congenital abnormalities. PMID:27033023

  7. A severe nervous disease in fancy pigeons caused by paramyxovirus-1 in Saudi Arabia.

    PubMed

    al Afaleq, A I; Abu Elzein, E M; Gameel, A A; Awaad, M; Hassanein, M M

    1993-01-01

    A severe nervous disease struck fancy pigeons for the first time in Saudi Arabia during February-March, 1992. The morbidity rate was 60% while the case fatality rate was 40%. An avian paramyxovirus-1 was isolated from affected pigeons. The disease was reproduced experimentally in pigeons and the virus was reisolated and identified. PMID:8073168

  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. Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy.

    PubMed

    Yamakawa, Kazuo; Takanashi, Masashi; Watanabe, Masao; Nakamura, Noriyuki; Kobayashi, Tomonori; Hasegawa, Masato; Mizuno, Yoshikuni; Tanaka, Shigeki; Mori, Hideo

    2006-12-01

    We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease. PMID:17203597

  11. Frontal functions in depressed and nondepressed Parkinson's disease patients: impact of severity stages.

    PubMed

    Silberman, Cláudia Débora; Laks, Jerson; Capitão, Cláudia Figueiredo; Rodrigues, Cláudia Soares; Moreira, Irene; Vasconcellos, Luiz Felipe Rocha; Engelhardt, Eliasz

    2007-01-15

    Severity of Parkinson's disease (PD) and frontal impairment are positively correlated. Testing frontal functions in depressed/nondepressed PD patients with different severity stages may reveal whether depression leads to this impairment. We aimed to relate severity of PD to frontal functional impairment and to test if negative stimuli/depressive symptoms interfered with frontal tasks. The Stroop test and the Emotional Stroop test were performed by 46 PD patients, 18 of whom were depressed. The Hoehn and Yahr scale assessed severity of the disease. We calculated the difference in seconds for each Stroop card and the interference index (C/D) between depressed and nondepressed patients sharing the same severity of disease. The differences among the groups (depressed and nondepressed) according to the severity of the disease (mild and moderate) were compared using the Mann-Whitney test. The depressed patients had a poorer performance on the test than the nondepressed PD patients, although the difference was not statistically significant. In conclusion, there is a clinically relevant but not statistically significant difference on the performance of frontal tasks between depressed and nondepressed PD patients. Neither depression nor the severity of the disease were determinant to the poorer performance on the Stroop and the Emotional Stroop tests. PMID:17113157

  12. Severity of Anxiety Disorders in Patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Safa, Mitra; Fallah Tafti, Saeed; Talischi, Firrouzeh; Ghassem Boroujerdi, Fatemeh

    2015-01-01

    Objective: Patients with chronic physical diseases sometimes show increased loss of function; such patients need more care. Anxiety is a well-known symptom that is prevalent among chronic obstructive pulmonary disease patients that can prolong and increase the risk of hospitalization. The purpose of this study was to evaluate the severity of anxiety in the mentioned patients and to examine the presence of symptoms and appropriate treatment strategies to understand the role of psychological functions in physical patients. Methods : This was a cross sectional study conducted in Masih Daneshvari Hospital. One hundred forty- three patients entered into the project by accessible method and signed the informed consent; they filled demographic information and Hamilton anxiety and depression questionnaires. Data were analyzed by SPSS-16. Results : Of the participants, 68% were above 60 years of age; 78% were male; 89% were married; and 38% were self-employed. Also, among the participants, 51% were illiterate; 72% had history of smoking; 46% had history of substance abuse; and 49% had moderate to severe anxiety disorder. Moreover, of the patients with severe anxiety, 41.3% had severe muscle spasms; and severe sleeplessness was found in 38.5% of those with severe anxiety disorder. Severe anxiety related symptoms were found in 20.3% of the patients with severe anxiety disorder. Depressed mood was found in 27.3% of the patients with severe anxiety disorder. Severe physical and muscular signs were found in 35.7% of those with severe anxiety disorder. Conclusion : According to our findings, many chronic diseases such as chronic obstructive pulmonary disease may contain anxiety and depression which result in vulnerability. Therefore, evaluation of anxiety in such patients is of importance for alleviating the disease. PMID:26884790

  13. Differential expression of vitamin E and selenium-responsive genes by disease severity in chronic obstructive pulmonary disease.

    PubMed

    Agler, Anne H; Crystal, Ronald G; Mezey, Jason G; Fuller, Jennifer; Gao, Chuan; Hansen, Joyanna G; Cassano, Patricia A

    2013-08-01

    Antioxidant nutritional status is hypothesized to influence chronic obstructive pulmonary disease (COPD) susceptibility and progression. Although past studies relate antioxidants to gene expression, there are no data in patients with COPD. This study investigated the hypothesis that antioxidant status is compromised in patients with COPD, and antioxidant-responsive genes differentially express in a similar pattern. Lung tissue samples from patients with COPD were assayed for vitamin E and gene expression. Selenium and vitamin E were assayed in corresponding plasma samples. Discovery based genome-wide expression analysis compared moderate, severe, and very severe COPD (GOLD II-IV) patients to mild and at-risk/normal (GOLD 0-I). Hypotheses-driven analyses assessed differential gene expression by disease severity for vitamin E-responsive and selenium-responsive genes. GOLD II-IV COPD patients had 30% lower lung tissue vitamin E levels compared to GOLD 0-I participants (p = 0.0082). No statistically significant genome-wide differences in expression by disease severity were identified. Hypothesis-driven analyses of 109 genes found 16 genes differentially expressed (padjusted < 0.05) by disease severity including 6 selenium-responsive genes (range in fold-change -1.39 to 2.25), 6 vitamin E-responsive genes (fold-change -2.30 to 1.51), and 4 COPD-associated genes. Lung tissue vitamin E in patients with COPD was associated with disease severity and vitamin E-responsive genes were differentially expressed by disease severity. Although nutritional status is hypothesized to contribute to COPD risk, and is of therapeutic interest, evidence to date is mainly observational. The findings reported herein are novel, and support a role of vitamin E in COPD progression. PMID:23875740

  14. 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...

  15. A strain of Clover yellow vein virus that causes severe pod necrosis disease in snap bean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2000, the soybean aphid (Aphis glycines) has been associated with severe virus epidemics in snap bean (Phaseolus vulgaris) in the upper Midwestern states, New York, and Ontario, Canada. The causal agent of a disease causing severe mosaic, apical necrosis stunting and extensive pod necrosis wa...

  16. Associations between peripheral blood eosinophil counts in patients with systemic sclerosis and disease severity.

    PubMed

    Ando, Katsutoshi; Nakashita, Tamao; Kaneko, Norihiro; Takahashi, Kazuhisa; Motojima, Shinji

    2016-01-01

    Increased levels of serum pro-fibrotic cytokines have been reported in patients with systemic sclerosis (SSc). Some of these cytokines also play an important role in the differentiation and migration of eosinophils. The aim of this study was to determine whether eosinophilic inflammation is caused in SSc. We retrospectively reviewed the peripheral blood eosinophil counts in 70 untreated patients with SSc and compared them with those in patients with other major collagen diseases. We additionally evaluated a possible association with disease severity. Eosinophil counts were significantly higher levels in patients with SSc than in those with other collagen diseases, whereas total leukocyte counts were not. Eosinophil counts correlated positively with both severe interstitial lung disease (ILD; r = 0.255, p = 0.033) and modified Rodnan total skin thickness score (m-Rodnan TSS) in SSc (r = 0.347, p = 0.003), but did not correlate with ILD severity in other collagen diseases. In conclusion, peripheral eosinophil counts were higher in patients with SSc than in those with other collagen diseases and were correlated with increased disease severity. Our data suggest that eosinophilic inflammation is involved in the pathogenesis and progression of SSc. PMID:27610320

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

    PubMed Central

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

    2009-01-01

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

  18. Correlation of serum homocysteine levels with the severity of coronary artery disease.

    PubMed

    Shenoy, Vijetha; Mehendale, Veena; Prabhu, Krishnananda; Shetty, Ranjan; Rao, Pragna

    2014-07-01

    Coronary artery disease (CAD) has become the most common cause of mortality in the entire world. Homocysteine is implicated as an early atherosclerotic promoter. We studied the relationship between levels of serum homocysteine with severity of coronary artery disease. Total of 70 subjects who scheduled for coronary angiogram consented to participate in this study. In all the patients Gensini scoring system was used to assess the severity of CAD. Venous samples were taken from the patients in fasting state before angiography. Homocysteine levels in patients were measured by enzyme linked immunosorbant method and were compared with respective Genseni scores of participants. Fasting serum homocysteine levels in CAD patients were significantly higher than patients without coronary artery disease (p < 0.001). Also Homocyseine levels correlated significantly with increasing severity of CAD (p < 0.001). Serum homocysteine levels correlated well with the severity of CAD. PMID:24966483

  19. Wheat - Its growth and disease severity as deduced from ERTS-1

    NASA Technical Reports Server (NTRS)

    Kanemasu, E. T.; Niblett, C. L.; Manges, H.; Lenhert, D.; Newman, M. A.

    1974-01-01

    The spectral reflectance of a cropped surface changes as the plant develops. An indicator of crop growth is leaf area index (ratio of green leaf area to soil area). The leaf area index, disease severity, and yield were determined for several winter wheat fields in Kansas during the 1973 growing season. Multispectral scanner (MSS) data from Earth Resources Technology Satellite-1 (ERTS-1) showed a high correlation (r greater than or equal to 0.90) between crop growth and MSS4/MSS5, and crop growth and MSS5/MSS6. Wheat disease severity and yields were significantly correlated at the 5% level with MSS4/MSS6 and with MSS4/MSS7. Further investigation is required before ERTS imagery can be routinely used detecting and estimating disease severity and yield reduction.

  20. 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. PMID:23064367

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

    PubMed Central

    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.

    2012-01-01

    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. PMID:23064367

  2. 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.

  3. 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

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

    PubMed Central

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

    2015-01-01

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

  5. Impact of hospital variables on case mix index as a marker of disease severity.

    PubMed

    Mendez, Carmen M; Harrington, Darrell W; Christenson, Peter; Spellberg, Brad

    2014-02-01

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

  6. Association of Thyroid Function with Severity of Coronary Artery Disease in Euthyroid Patients

    PubMed Central

    Jayaprakash, B.; Shetty, Ranjan; Rau, N.R.

    2015-01-01

    Introduction Thyroid hormone exerts multiple effects on the heart and vascular system. Variations of free T3 have been linked to coronary artery disease. We conducted a study to observe whether there is a relationship between the variation of the serum thyroid hormone levels (TSH, FT3 and FT4) and the presence and severity of CAD in the euthyroid patients. Aim To study association of serum TSH, FT4 and FT3 levels within the normal range with presence and severity of coronary artery disease. Materials and Methods A total of 100 euthyroid patients with stable angina, who underwent coronary angiography were enrolled in the study. Coronary artery disease was defined as >50% stenosis in the luminal diameter in at least one major epicardial coronary artery. The Gensini scoring system was used to define the severity of the CAD and serum TSH, FT3 and FT4 levels were measured by the chemiluminescence method. Results Single vessel disease was found in 23%, double vessel disease in 15% and triple vessel disease in 17% of patients. TSH and FT4 levels were also comparable between the groups. Normal coronary group had significantly higher mean FT3 values than triple vessel disease (p=0.004) and FT3 levels showed an inverse relation with Gensini score (Pearson’s correlation =- 0.30) (p =0.002). A level of FT3 ≤ 2.7 predicted the severity of CAD with a 70% sensitivity and 60% specificity (area under curve (AUC): 0.755, p=0.001). Conclusion In the absence of primary thyroid disease and acute coronary syndrome, the occurrence of CAD is associated with lower serum levels of FT3. FT3 and not the FT4 and TSH levels may be used as an indicator of increased risk for severe CAD. The present study clearly shows the existence of a strong association between the reduction of biologically active T3 and severity of coronary artery disease. However, low T3 state could be at first interpreted as just a biological risk factor of severe coronary artery disease; only the demonstration of

  7. 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.

  8. Endophytic Fusarium verticillioides reduces disease severity caused by Ustilago maydis on maize.

    PubMed

    Lee, Keunsub; Pan, Jean J; May, Georgiana

    2009-10-01

    Endophytic fungi represent diverse taxa that inhabit plant hosts without causing disease symptoms. We used endophytic isolates of Fusarium verticillioides (Sacc.) Nirenberg to understand how endophytic fungi interact with pathogens, in this case, the corn smut pathogen, Ustilago maydis DC (Corda). Endophytic F. verticillioides strains were inoculated onto maize seedlings before, simultaneously, or after inoculation with U. maydis, and the effects on smut disease severity and on plant growth were assessed. When F. verticillioides is simultaneously coinoculated with U. maydis, smut disease severity is significantly decreased and plant growth is increased, compared with other treatments. Controls show that F. verticillioides by itself does not have measurable effects on plant growth. Together, our results suggest that a commonly occurring fungal endophyte on maize, F. verticillioides, ameliorates the effects of a host-specific pathogen, U. maydis, by interfering with the early infection process and limiting disease development, resulting in increased plant growth. PMID:19694816

  9. Immune responses to Leptospira infection: roles as biomarkers for disease severity.

    PubMed

    Chirathaworn, Chintana; Kongpan, Sutthikarn

    2014-01-01

    Various leptospiral components have been identified and shown to be involved in tissue destruction. In addition, immune responses to leptospires have been implicated in target organ damages in severe leptospirosis cases. Several inflammatory mediators were shown to be higher in susceptible animals than in resistant hosts. Moreover, cytokines/chemokines and serum proteins induced following Leptospira infection were suggested to be biomarkers for disease severity in human leptospirosis. This review focuses on the role of immune responses in the severity of leptospirosis. Studies in both animal models and humans are discussed. PMID:24275371

  10. 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

  11. Polyparasitism is associated with increased disease severity in Toxoplasma gondii-infected marine sentinel species.

    PubMed

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

    2011-05-01

    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

  12. Disease severity and functional factors associated with walking performance in polyostotic fibrous dysplasia.

    PubMed

    Paul, Scott M; Gabor, Lisa R; Rudzinski, Scott; Giovanni, David; Boyce, Alison M; Kelly, Marilyn R N; Collins, Michael T

    2014-03-01

    The purpose of this study was to determine the association between measures of disease severity, impairment, and ambulation ability in persons with polyostotic fibrous dysplasia (PFD). A cross-sectional sample of 81 patients (ages 5-57) with polyostotic fibrous dysplasia was evaluated as part of an ongoing study. Subjects were scored on the Skeletal Disease Burden Score (SDBS), completed a 9-minute walk test (9MW), manual muscle testing (MMT), and measurements of range of motion (ROM). Correlations between continuous variables were calculated using the Pearson correlation coefficient and ordinal variables by Spearman correlation coefficient. It was found that subjects with more severe disease walked slower than those with less skeletal disease, with the exception of the youngest subjects. Walking velocity was faster in subjects with better hip strength and range of motion and slower in those with bilateral coxa vara. Those subjects with more severe disease had less range of motion, were weaker at the hips, and more likely to have leg length discrepancy. Skeletal disease severity was associated with hip weakness, leg length discrepancy, and loss of range of motion. In most cases, findings did not differ in the presence or absence of associated endocrinopathies. Skeletal disease severity, MMT and ROM each has an impact on walking efficiency in persons with PFD. These findings suggest that treatment focused on strategies to improve or, at least, maintain hip strength and range of motion, correct leg length discrepancies and hip malalignment may help preserve ambulation ability in persons with PFD and that treatment should begin at a young age. PMID:24316419

  13. 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

  14. Analysis of breastfeeding policies and practices in childcare centres in Adelaide, South Australia.

    PubMed

    Javanparast, Sara; Newman, Lareen; Sweet, Linda; McIntyre, Ellen

    2012-08-01

    Breastfeeding policies and practices were analysed in childcare settings in the metropolitan area of Adelaide, South Australia. Childcare centres were purposively selected based on their geographical location, type and socioeconomic score of the area. Qualitative inquiry approach was employed by undertaking interviews with childcare centres' director or baby house coordinator to explore their perception towards breastfeeding practice and support within their centre. Breastfeeding related policy documents, where available, were also collected during the interviews to triangulate data. A total of 15 face-to-face interviews were conducted. Six childcare centres had a written policy specifically on breastfeeding support, although the technical issues of handling breastmilk were included in most centres' food and nutrition guidelines. Most participants believed that decision to breastfeed is the personal choice of parents, and hence saw the childcare centre's role as supporting parental choice whether it is breastfeeding or not. The provision of physical space to breastfeed and facilities to store the expressed breast milk were the most common practices in support of parents who had chosen to continue breastfeeding. Participants perceived mothers' work-related issues such as distance from the centre, time, and unsupportive workplace the most important barriers that led to early introduction of bottle feeding or breastfeeding cessation. Most childcare centres support breastfeeding in a more passive than active way. Breastfeeding promotion needs to be an integral part of childcare centres training, policy and practice if an increased rate of breastfeeding is to be achieved particularly amongst working mothers. PMID:21948219

  15. Adelaide River virus nucleoprotein gene: analysis of phylogenetic relationships of ephemeroviruses and other rhabdoviruses.

    PubMed

    Wang, Y; Cowley, J A; Walker, P J

    1995-04-01

    The nucleotide sequence of the Adelaide River virus (ARV) genome was determined from the 3' terminus to the end of the nucleoprotein (N) gene. The 3' leader sequence comprises 50 nucleotides and shares a common terminal trinucleotide (3' UGC-), a conserved U-rich domain and a variable AU-rich domain with other animal rhabdoviruses. The N gene comprises 1355 nucleotides from the transcription start sequence (AACAGG) to the poly(A) sequence [CATG(A)7] and encodes a polypeptide of 429 amino acids. The N protein has a calculated molecular mass of 49429 Da and a pI of 5.4 and, like the bovine ephemeral fever virus (BEFV) N protein, features a highly acidic C-terminal domain. Analysis of amino acid sequence relationships between all available rhabdovirus N proteins indicated that ARV and BEFV are closely related viruses (48.3% similarity) which share higher sequence similarity to vesiculoviruses than to lyssaviruses. Phylogenetic trees based on a multiple sequence alignment of all available rhabdovirus N protein sequences demonstrated clustering of viruses according to genome organization, host range and established taxonomic relationships. PMID:9049348

  16. Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases.

    PubMed

    Chen, Rong; Shi, Lisong; Hakenberg, Jörg; Naughton, Brian; Sklar, Pamela; Zhang, Jianguo; Zhou, Hanlin; Tian, Lifeng; Prakash, Om; Lemire, Mathieu; Sleiman, Patrick; Cheng, Wei-Yi; Chen, Wanting; Shah, Hardik; Shen, Yulan; Fromer, Menachem; Omberg, Larsson; Deardorff, Matthew A; Zackai, Elaine; Bobe, Jason R; Levin, Elissa; Hudson, Thomas J; Groop, Leif; Wang, Jun; Hakonarson, Hakon; Wojcicki, Anne; Diaz, George A; Edelmann, Lisa; Schadt, Eric E; Friend, Stephen H

    2016-05-01

    Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Our findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. They also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies. PMID:27065010

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    BACKGROUND Adjustment for differing risks among patients is usually incorporated into newer payment approaches, and current risk models rely on age, gender, and diagnosis codes. It is unknown the extent to which controlling additionally for disease severity improves cost prediction. Failure to adjust for within-disease variation may create incentives to avoid sicker patients. We address this issue among patients with chronic obstructive pulmonary disease (COPD). METHODS Cost and clinical data were collected prospectively from 1,202 COPD patients at Kaiser Permanente. Baseline analysis included age, gender, and diagnosis codes (using the Diagnostic Cost Group Relative Risk Score [RRS]) in a general linear model predicting total medical costs in the following year. We determined whether adding COPD severity measures—FEV1, 6 minute walk test, dyspnea score, body-mass index, and BODE Index (composite of the other four measures)—improved predictions. Separately, we examined household income as a cost predictor. RESULTS Mean costs were $12,334/year. Controlling for RRS, each ½ standard deviation worsening in COPD severity factor was associated with $629 to $1,135 in increased annual costs (all p<0.01). The lowest stratum of FEV1 (<30% normal) predicted $4,098 (95%CI $576–$8,773) additional costs. Household income predicted excess costs when added to the baseline model (p=0.038), but this became non-significant when also incorporating BODE Index. CONCLUSIONS Disease severity measures explain significant cost variations beyond current risk models, and adding them to such models appears important to fairly compensate organizations that accept responsibility for sicker COPD patients. Appropriately controlling for disease severity also accounts for costs otherwise associated with lower socioeconomic status. PMID:23703646

  19. Perception of severity of disease and health locus of control in compliant and noncompliant diabetic patients.

    PubMed

    Alogna, M

    1980-01-01

    Compliant and noncompliant obese, non-insulin-dependent diabetic subjects were assessed using a variety of demographic variables, the health locus of control scale (HLC), and the perception of severity of disease index based on the health belief model. The complaint subjects were significantly older and viewed their illness as significantly more severe than the noncompliant patients. Additionally, they tended to exhibit more of an internal locus of control that the noncompliant patients. PMID:7460724

  20. An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli

    PubMed Central

    Porter, Chad K.; Riddle, Mark S.; Alcala, Ashley N.; Sack, David A.; Chakraborty, Subhra; Gutierrez, Ramiro L.; Savarino, Stephen J.; Darsley, Michael; McKenzie, Robin; DeNearing, Barbara; Steinsland, Hans; Tribble, David R.; Bourgeois, A. Louis

    2016-01-01

    Background Experimental human challenge models have played a major role in enhancing our understanding of infectious diseases. Primary outcomes have typically utilized overly simplistic outcomes that fail to entirely account for complex illness syndromes. We sought to characterize clinical outcomes associated with experimental infection with enterotoxigenic Escherichia coli (ETEC) and to develop a disease score. Methods Data were obtained from prior controlled human ETEC infection studies. Correlation and univariate regression across sign and symptom severity was performed. A multiple correspondence analysis was conducted. A 3-parameter disease score with construct validity was developed in an iterative fashion, compared to standard outcome definitions and applied to prior vaccine challenge trials. Results Data on 264 subjects receiving seven ETEC strains at doses from 1x105 to 1x1010 cfu were used to construct a standardized dataset. The strongest observed correlation was between vomiting and nausea (r = 0.65); however, stool output was poorly correlated with subjective activity-impacting outcomes. Multiple correspondence analyses showed covariability in multiple signs and symptoms, with severity being the strongest factor corresponding across outcomes. The developed disease score performed well compared to standard outcome definitions and differentiated disease in vaccinated and unvaccinated subjects. Conclusion Frequency and volumetric definitions of diarrhea severity poorly characterize ETEC disease. These data support a disease severity score accounting for stool output and other clinical signs and symptoms. Such a score could serve as the basis for better field trial outcomes and gives an additional outcome measure to help select future vaccines that warrant expanded testing in pivotal pre-licensure trials. PMID:26938983

  1. Prospective cohort studies of dengue viral transmission and severity of disease.

    PubMed

    Endy, Timothy P; Yoon, In-Kyu; Mammen, Mammen P

    2010-01-01

    As the four serotypes of dengue virus (DENV) systematically spread throughout the tropical and subtropical regions globally, dengue is increasingly contributing to the overall morbidity and mortality sustained by populations and thereby challenging the health infrastructures of most endemic countries. DENV-human host-mosquito vector interactions are complex and cause in humans either asymptomatic or subclinical DENV infection, mild to severe dengue fever (DF), severe dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Over the past decade, we have seen an increase in research funding and public health efforts to offset the effects of this pandemic. Though multiple vaccine development efforts are underway, the need remains to further characterize the determinants of varying severities of clinical outcomes. Several long-term prospective studies on DENV transmission and dengue severity have sought to define the epidemiology and pathogenesis of this disease. Yet, more studies are required to quantify the disease burden on different populations, explore the impact of DENV serotype-specific transmission on host-responses and dengue severity and measure the economic impact of dengue on a population. In this section, we will review the critical past and recent findings of dengue prospective studies on our understanding of the disease and the potential role of future prospective cohort studies in advancing issues required for vaccine field evaluations. PMID:19802574

  2. 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

  3. Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing

    PubMed Central

    Bell, Callum J.; Dinwiddie, Darrell L.; Miller, Neil A.; Hateley, Shannon L.; Ganusova, Elena E.; Mudge, Joann; Langley, Ray J.; Zhang, Lu; Lee, Clarence C.; Schilkey, Faye D.; Sheth, Vrunda; Woodward, Jimmy E.; Peckham, Heather E.; Schroth, Gary P.; Kim, Ryan W.; Kingsmore, Stephen F.

    2011-01-01

    Of 7028 disorders with suspected Mendelian inheritance, 1139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~10% of pediatric hospitalizations. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening to most severe disease genes has hitherto been impractical. Here, we report a preconception carrier screen for 448 severe recessive childhood diseases. Rather than costly, complete sequencing of the human genome, 7717 regions from 437 target genes were enriched by hybrid capture or microdroplet polymerase chain reaction, sequenced by next-generation sequencing (NGS) to a depth of up to 2.7 gigabases, and assessed with stringent bioinformatic filters. At a resultant 160× average target coverage, 93% of nucleotides had at least 20× coverage, and mutation detection/genotyping had ~95% sensitivity and ~100% specificity for substitution, insertion/deletion, splicing, and gross deletion mutations and single-nucleotide polymorphisms. In 104 unrelated DNA samples, the average genomic carrier burden for severe pediatric recessive mutations was 2.8 and ranged from 0 to 7. The distribution of mutations among sequenced samples appeared random. Twenty-seven percent of mutations cited in the literature were found to be common polymorphisms or misannotated, underscoring the need for better mutation databases as part of a comprehensive carrier testing strategy. Given the magnitude of carrier burden and the lower cost of testing compared to treating these conditions, carrier screening by NGS made available to the general population may be an economical way to reduce the incidence of and ameliorate suffering associated with severe recessive childhood disorders. PMID:21228398

  4. Endothelial dysfunction is associated with the severity of cerebral small vessel disease.

    PubMed

    Nezu, Tomohisa; Hosomi, Naohisa; Aoki, Shiro; Kubo, Satoshi; Araki, Mutsuko; Mukai, Tomoya; Takahashi, Tetsuya; Maruyama, Hirofumi; Higashi, Yukihito; Matsumoto, Masayasu

    2015-04-01

    The pathogenesis of cerebral small vessel disease, a disease that involves white matter lesions (WMLs) and cerebral microbleeds (CMBs), is thought to be associated with endothelial dysfunction. Flow-mediated dilation (FMD) has been used to measure endothelium-dependent vasodilation. The aim of this study was to investigate the association between endothelial function (as measured by FMD) and cerebral small vessel disease. Patients with a history of cerebrovascular disease and comorbidities were enrolled in this study (n=102; 69 males, 70.1±9.2 years). The patients were divided into two groups according to the severity of WMLs, which were assessed by Fazekas classification; grades 0 to 1 as mild WMLs group and grades 2 to 3 as severe WMLs group. A gradient-echo MRI was performed in 96 patients (94.1%) to evaluate whether CMBs were present. The patients in the severe WMLs group (n=40) were older (P=0.001), more frequently exhibited hypertension (P=0.045) and diabetes mellitus (P=0.026) and possessed lower FMD values (P<0.001) than the patients in the mild WMLs group (n=62). CMBs were observed in 30 patients (31.3%). Using receiver operating characteristic curves, the optimal FMD cutoff values for predicting the presence of severe WMLs and CMBs were 3.9% and 3.7%, respectively. On multivariate logistic analysis, FMD <4.0% (odds ratio 9.50; 95% confidence interval 3.55-28.83) was independently associated with severe WMLs. Additionally, FMD <3.8% (5.82; 2.23-16.50) was also associated with the presence of CMBs. Endothelial dysfunction as evaluated by FMD may be predictive of the severity of cerebral small vessel disease. PMID:25672660

  5. Carrier testing for severe childhood recessive diseases by next-generation sequencing.

    PubMed

    Bell, Callum J; Dinwiddie, Darrell L; Miller, Neil A; Hateley, Shannon L; Ganusova, Elena E; Mudge, Joann; Langley, Ray J; Zhang, Lu; Lee, Clarence C; Schilkey, Faye D; Sheth, Vrunda; Woodward, Jimmy E; Peckham, Heather E; Schroth, Gary P; Kim, Ryan W; Kingsmore, Stephen F

    2011-01-12

    Of 7028 disorders with suspected Mendelian inheritance, 1139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~10% of pediatric hospitalizations. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening to most severe disease genes has hitherto been impractical. Here, we report a preconception carrier screen for 448 severe recessive childhood diseases. Rather than costly, complete sequencing of the human genome, 7717 regions from 437 target genes were enriched by hybrid capture or microdroplet polymerase chain reaction, sequenced by next-generation sequencing (NGS) to a depth of up to 2.7 gigabases, and assessed with stringent bioinformatic filters. At a resultant 160x average target coverage, 93% of nucleotides had at least 20x coverage, and mutation detection/genotyping had ~95% sensitivity and ~100% specificity for substitution, insertion/deletion, splicing, and gross deletion mutations and single-nucleotide polymorphisms. In 104 unrelated DNA samples, the average genomic carrier burden for severe pediatric recessive mutations was 2.8 and ranged from 0 to 7. The distribution of mutations among sequenced samples appeared random. Twenty-seven percent of mutations cited in the literature were found to be common polymorphisms or misannotated, underscoring the need for better mutation databases as part of a comprehensive carrier testing strategy. Given the magnitude of carrier burden and the lower cost of testing compared to treating these conditions, carrier screening by NGS made available to the general population may be an economical way to reduce the incidence of and ameliorate suffering associated with severe recessive childhood disorders. PMID:21228398

  6. Copeptin, a Surrogate Marker of Vasopressin, Is Associated with Disease Severity in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Meijer, Esther; Bakker, Stephan J.L.; van der Jagt, Eric J.; Navis, Gerjan; de Jong, Paul E.; Struck, Joachim

    2011-01-01

    Summary Background and objectives Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD. Design, setting, participants, & measurements Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay. Plasma and urinary osmolarity were also measured. To assess disease severity, GFR and effective renal blood flow were measured by continuous infusion of 125I-iothalamate and 131I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry. Results In these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R = 0.47] and albuminuria [R = 0.39] and negatively with GFR [R = −0.58] and effective renal blood flow [R = −0.52], all P < 0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P < 0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P = 0.7, 0.9, and 0.3, respectively). Conclusions On cross-sectional analysis, copeptin is associated with disease severity in ADPKD patients, supporting the results of experimental studies that suggest that vasopressin antagonists have a renoprotective effect in ADPKD and offering a good prospect for clinical studies with these agents. PMID:20930090

  7. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity.

    PubMed

    Keogh, M J; Aribisala, B S; He, J; Tulip, E; Butteriss, D; Morris, C; Gorman, G; Horvath, R; Chinnery, P F; Blamire, Andrew M

    2015-10-01

    Neuroferritinopathy is an autosomal dominant adult-onset movement disorder which occurs due to mutations in the ferritin light chain gene (FTL). Extensive iron deposition and cavitation are observed post-mortem in the basal ganglia, but whether more widespread pathological changes occur, and whether they correlate with disease severity is unknown. 3D-T1w and quantitative T2 whole brain MRI scans were performed in 10 clinically symptomatic patients with the 460InsA FTL mutation and 10 age-matched controls. Voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) were subsequently performed. Clinical assessment using the Unified Dystonia Rating Scale (UDRS) and Unified Huntington's Disease Rating Scale (UHDRS) was undertaken in all patients. VBM detected significant tissue changes within the substantia nigra, midbrain and dentate together with significant cerebellar atrophy in patients (FWE, p < 0.05). Iron deposition in the caudate head and cavitation in the lateral globus pallidus correlated with UDRS score (p < 0.001). There were no differences between groups with VBR. Our data show that progressive iron accumulation in the caudate nucleus, and cavitation of the globus pallidus correlate with disease severity in neuroferritinopathy. We also confirm sub-clinical cerebellar atrophy as a feature of the disease. We suggest that VBM is an effective technique to detect regions of iron deposition and cavitation, with potential wider utility to determine radiological markers of disease severity for all NBIA disorders. PMID:26142024

  8. 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. PMID:12670514

  9. 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

  10. 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)

  11. 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...

  12. Variants in 9p21 Predicts Severity of Coronary Artery Disease in a Chinese Han Population.

    PubMed

    Jing, Jinjin; Su, Li; Zeng, Ying; Tang, Xiaojun; Wei, Jie; Wang, Long; Zhou, Li

    2016-09-01

    Recent genome-wide association studies identified the common genetic variants in 9p21 were associated with the coronary artery disease (CAD). However, whether this locus could predict the severity of CAD in Chinese Han population is unclear. 499 CAD patients who underwent coronary angiography (CAG) have been enrolled for this study. The single-nucleotide polymorphisms rs2383207 and rs2383206 in 9p21 were genotyped in 499 CAG cases and 1519 controls in Chinese Han population. The gene dosage of 9p21 was stratified by the degree of vascular lesions and tested for association with the severity of CAD. Rs2383207 and rs2383206 demonstrated significant associations with 2-vessel and 3-vessel disease (P = 2.0×10(-3) and 1.9×10(-4) , respectively). GG genotypes of rs2383206 occurred higher proportion of left main trunk (LM) disease (P = 6.0×10(-3) ). GG genotypes of rs2383207 occurred higher proportion of left anterior descending artery disease (LAD) and right CAD (RCA) (P = 2.7×10(-6) and 1.6×10(-4) , respectively). The risk allele G of rs2383207 was associated with severity of CAD estimated by the Gensini score (P = 3.6×10(-5) ). Rs2383207 may strongly influence the development of CAD in Chinese Han population. The gene dosage in 9p21 could predict the severity of CAD. PMID:27461153

  13. Host demography influences the prevalence and severity of eelgrass wasting disease.

    PubMed

    Groner, Maya L; Burge, Colleen A; Couch, Courtney S; Kim, Catherine J S; Siegmund, Gregor-Fausto; Singhal, Sonia; Smoot, Samantha C; Jarrell, Ann; Gaydos, Joseph K; Harvell, C Drew; Wyllie-Echeverria, Sandy

    2014-02-19

    Many marine pathogens are opportunists, present in the environment, but causing disease only under certain conditions such as immunosuppression due to environmental stress or host factors such as age. In the temperate eelgrass Zostera marina, the opportunistic labyrinthulomycete pathogen Labyrinthula zosterae is present in many populations and occasionally causes severe epidemics of wasting disease; however, risk factors associated with these epidemics are unknown. We conducted both field surveys and experimental manipulations to examine the effect of leaf age (inferred from leaf size) on wasting disease prevalence and severity in Z. marina across sites in the San Juan Archipelago, Washington, USA. We confirmed that lesions observed in the field were caused by active Labyrinthula infections both by identifying the etiologic agent through histology and by performing inoculations with cultures of Labyrinthula spp. isolated from observed lesions. We found that disease prevalence increased at shallower depths and with greater leaf size at all sites, and this effect was more pronounced at declining sites. Experimental inoculations with 2 strains of L. zosterae confirmed an increased susceptibility of older leaves to infection. Overall, this pattern suggests that mature beds and shallow beds of eelgrass may be especially susceptible to outbreaks of wasting disease. The study highlights the importance of considering host and environmental factors when evaluating risk of disease from opportunistic pathogens. PMID:24553421

  14. Severe viral oesophagitis, pharyngitis, and stomatitis as antecedents of ileocecal Crohn's disease

    PubMed Central

    Waluga, Marek; Budzyńska, Agnieszka; Kajor, Maciej; Hartleb, Marek

    2015-01-01

    We present a 22-year-old male who developed a severe erosive oesophagitis extending to the pharynx and oral cavity without obvious risk factors. Endoscopic image suggested viral aetiology that could not be confirmed by routine serological diagnostics of infections with cytomegalovirus, Epstein-Barr virus, and Herpes simplex virus. The histopathological evaluation also gave no definite clues to the aetiology of the inflammation. Treatment with acyclovir was ineffective, but gancyclovir therapy caused spectacular clinical improvement and healing of erosions. Two months later the patient presented febrile diarrhoea that was a symptom of ileocecal Crohn's disease proven by endoscopy, enterography, and histopathology. It is the first report of severe viral oesophagitis preceding clinical manifestation of Crohn's disease. This observation warrants further study towards the viral aetiology of oral, pharyngeal, and oesophageal erosions, frequently associated with Crohn's disease. PMID:25960815

  15. First report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) causing severe disease in Allomyrina dichotoma in Korea.

    PubMed

    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

  16. Surgical treatment of nonalcoholic fatty liver disease in severely obese patients

    PubMed Central

    Vander Naalt, Steven J; Gurria, Juan P; Holterman, AiXuan L

    2014-01-01

    Obesity is a multi-organ system disease with underlying metabolic abnormalities and chronic systemic inflammation. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of obesity metabolic dysfunction and its associated cardiovascular- and liver-related morbidities and mortality. Our current understanding of NAFLD pathogenesis, disease characteristics, the role of insulin resistance, chronic inflammation, gut–liver and gut–brain crosstalk and the effectiveness of pharmacotherapy is still evolving. Bariatric surgery significantly improves metabolic and NAFLD histology in severely obese patients, although its positive effects on fibrosis are not universal. Bariatric surgery benefits NAFLD through its metabolic effect on insulin resistance, inflammation, and insulinotropic and anorexinogenic gastrointestinal hormones. Further studies are needed to understand the natural course of NAFLD in severely obese patients and the role of weight loss surgery as a primary treatment for NAFLD. PMID:25378958

  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. Perceived Risk of Severe Respiratory Syncytial Virus Disease and Immunoprophylaxis Use Among US Pediatric Specialists.

    PubMed

    Friedman, Deborah M; Domachowske, Joseph B; Wong, Pierre C; Parimi, Prabhu S; Garcia, Daniel F; Marcus, Michael G; La Via, William V; Syed, Iqra A; Szabo, Shelagh M; McLaurin, Kimmie K; Kumar, Veena R

    2016-07-01

    This study was conducted to assess the perception of US pediatric specialists of respiratory syncytial virus (RSV) disease risk and determine their clinical practices regarding immunoprophylaxis for high-risk children. Separate surveys were sent to neonatologists, pediatricians, pediatric pulmonologists, and pediatric cardiologists. Data were collected using structured questions requiring quantitative responses. Most neonatologists and pediatricians (>82.7%) reported a high clinical need for RSV immunoprophylaxis in preterm infants <32 weeks' gestational age. Pediatric pulmonologists and pediatric cardiologists suggested that health conditions indicative of chronic lung disease of prematurity and hemodynamically significant congenital heart disease, respectively, confer eligibility for RSV immunoprophylaxis. Agreement with the changes in the 2014 American Academy of Pediatrics guidance for RSV immunoprophylaxis was mixed among respondents from the 4 specialties. Survey findings may provide a basis to improve education about risk for severe RSV disease and evaluate changes in physician use of RSV immunoprophylaxis based on the 2014 guidance. PMID:26400767

  19. 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. PMID:24106188

  20. Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms

    PubMed Central

    Hinks, Timothy S.C.; Zhou, Xiaoying; Staples, Karl J.; Dimitrov, Borislav D.; Manta, Alexander; Petrossian, Tanya; Lum, Pek Y.; Smith, Caroline G.; Ward, Jon A.; Howarth, Peter H.; Walls, Andrew F.; Gadola, Stephan D.; Djukanović, Ratko

    2015-01-01

    Background Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear. Objective We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients. Methods Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed. Results Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms. Conclusion The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies. PMID:25746968

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

    PubMed

    Johnson, Lorraine; Wilcox, Spencer; Mankoff, Jennifer; Stricker, Raphael B

    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

  2. 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

  3. Hemoptysis in patients of celiac disease with disproportionately severe anemia: tip of the iceberg?

    PubMed Central

    2013-01-01

    Idiopathic Pulmonary Hemosiderosis (IPH) is characterized by the triad of iron deficiency anemia, pulmonary infiltrates and haemoptysis with no recognizable cause. Since the first description of its association with Celiac Disease (CD) by Lane and Hamilton in 1971, only a few isolated cases have been reported in literature. Although it has been considered an uncommon association of two disease entities, recent reports indicate that prevalence of celiac disease is as high as one percent. Further, individually both celiac disease and IPH are known to present as refractory anemia only. We are reporting a young adult with Lane Hamilton Syndrome, who realized that he was having significant gastrointestinal complaints only when they disappeared on gluten free diet (GFD). This case report reiterates the fact that celiac disease should be considered in all patients of IPH because of the therapeutic implications. Further on review of literature, we believe that covert hemoptysis may be responsible for disproportionately severe anemia in patients of celiac disease. Thus, prevalence of this association may be more than currently believed. Further research in this regard may improve our understanding of pathogenesis of celiac disease. PMID:23514358

  4. 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. PMID:26872143

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

    PubMed Central

    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. PMID:26872143

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

    PubMed

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

    2016-03-01

    White-nose syndrome is caused by the fungus Pseudogymnoascus destructans and has killed millions of hibernating bats in North America but the pathophysiology of the disease remains poorly understood. Our objectives were to (1) assess non-destructive diagnostic methods for P. destructans infection compared to histopathology, the current gold-standard, and (2) to evaluate potential metrics of disease severity. We used data from three captive inoculation experiments involving 181 little brown bats (Myotis lucifugus) to compare histopathology, quantitative PCR (qPCR), and ultraviolet fluorescence as diagnostic methods of P. destructans infection. To assess disease severity, we considered two histology metrics (wing area with fungal hyphae, area of dermal necrosis), P. destructans fungal load (qPCR), ultraviolet fluorescence, and blood chemistry (hematocrit, sodium, glucose, pCO2, and bicarbonate). Quantitative PCR was most effective for early detection of P. destructans, while all three methods were comparable in severe infections. Correlations among hyphae and necrosis scores, qPCR, ultraviolet fluorescence, blood chemistry, and hibernation duration indicate a multi-stage pattern of disease. Disruptions of homeostasis occurred rapidly in late hibernation. Our results provide valuable information about the use of non-destructive techniques for monitoring, and provide novel insight into the pathophysiology of white-nose syndrome, with implications for developing and implementing potential mitigation strategies. PMID:26957435

  7. COPD disease severity and the risk of venous thromboembolic events: a matched case–control study

    PubMed Central

    Morgan, Ann D; Herrett, Emily; De Stavola, Bianca L; Smeeth, Liam; Quint, Jennifer K

    2016-01-01

    Background It is generally accepted that people with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE). While it is plausible that the risk of arterial and venous thrombotic events is greater still in certain subgroups of patients with COPD, such as those with more severe airflow limitation or more frequent exacerbations, these associations, in particular those between venous events and COPD severity or exacerbation frequency, remain largely untested in large population cohorts. Methods A total of 3,594 patients with COPD with a first VTE event recorded during January 1, 2004 to December 31, 2013, were identified from the Clinical Practice Research Datalink dataset and matched on age, sex, and general practitioner practice (1:3) to patients with COPD with no history of VTE (n=10,782). COPD severity was staged by degree of airflow limitation (ie, GOLD stage) and by COPD medication history. Frequent exacerbators were defined as patients with COPD with ≥ 2 exacerbations in the 12-month period prior to their VTE event (for cases) or their selection as a control (for controls). Conditional logistic regression was used to estimate the association between disease severity or exacerbation frequency and VTE. Results After additional adjustment for nonmatching confounders, including body mass index, smoking, and heart-related comorbidities, there was evidence for an association between increased disease severity and VTE when severity was measured either in terms of lung function impairment (odds ratio [OR]moderate:mild =1.16; 95% confidence intervals [CIs] =1.03, 1.32) or medication usage (ORsevere:mild/moderate =1.17; 95% CIs =1.06, 1.26). However, there was no evidence to suggest that frequent exacerbators were at greater risk of VTE compared with infrequent exacerbators (OR =1.06; 95% CIs =0.97, 1.15). Conclusion COPD severity defined by airflow limitation or medication usage, but not

  8. 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

  9. Differences in gas exchange between severities of chronic obstructive pulmonary disease.

    PubMed

    Thirapatarapong, Wilawan; Armstrong, Hilary F; Thomashow, Byron M; Bartels, Matthew N

    2013-03-01

    Impaired ventilation on cardiopulmonary exercise test (CPET) is seen in patients with chronic obstructive pulmonary disease (COPD). However, evaluation of the differences of abnormal gas exchange in COPD according to GOLD severity criteria is limited. A retrospective review was performed on all COPD patients referred for CPET at our center between 1998 and 2010. There were 548 patients compared according to GOLD severity. GOLD groups were significantly different from each other in regards to pressure of end-tidal carbon dioxide ( [Formula: see text] ) with progressively higher [Formula: see text] with increasing GOLD severity. Ratio of minute ventilation to carbon dioxide production ( [Formula: see text] ) and exercise capacity as measured by and [Formula: see text] % and work rate in watts% was inversely proportional to GOLD severity. Breathing reserve, minute ventilation, and tidal volume at peak exercise were significantly decreased with increasing disease severity between GOLD groups. We concluded that gas exchange is distinctive among different GOLD severity groups; specifically, GOLD 3 and 4 have a significantly higher [Formula: see text] and a significantly lower [Formula: see text] than GOLD 2. PMID:23318702

  10. Changes in intestinal bacterial communities are closely associated with shrimp disease severity.

    PubMed

    Xiong, Jinbo; Wang, Kai; Wu, Jinfeng; Qiuqian, Linglin; Yang, Kunjie; Qian, Yunxia; Zhang, Demin

    2015-08-01

    Increasing evidence has revealed a close association between intestinal bacterial communities and human health. However, given that host phylogeny shapes the composition of intestinal microbiota, it is unclear whether changes in intestinal microbiota structure in relation to shrimp health status. In this study, we collected shrimp and seawater samples from ponds with healthy and diseased shrimps to understand variations in bacterial communities among habitats (water and intestine) and/or health status. The bacterial communities were clustered according to the original habitat and health status. Habitat and health status constrained 14.6 and 7.7 % of the variation in bacterial communities, respectively. Changes in shrimp intestinal bacterial communities occurred in parallel with changes in disease severity, reflecting the transition from a healthy to a diseased state. This pattern was further evidenced by 38 bacterial families that were significantly different in abundance between healthy and diseased shrimps; moderate changes were observed in shrimps with sub-optimal health. In addition, within a given bacterial family, the patterns of enrichment or decrease were consistent with the known functions of those bacteria. Furthermore, the identified 119 indicator taxa exhibited a discriminative pattern similar to the variation in the community as a whole. Overall, this study suggests that changes in intestinal bacterial communities are closely associated with the severity of shrimp disease and that indicator taxa can be used to evaluate shrimp health status. PMID:25947250

  11. 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

  12. 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

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

    DOE PAGESBeta

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; et al

    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

  15. 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.

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

    PubMed

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

    2011-02-01

    Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

  17. 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. PMID:24277207

  18. 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

  19. 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. PMID:26621750

  20. 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

  1. 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. PMID:26741255

  2. 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

  3. Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

    PubMed Central

    Hong, Yun Soo; Sinn, Dong Hyun; Gwak, Geum-Youn; Cho, Juhee; Kang, Danbee; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-01-01

    AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure (ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis (type A), cirrhosis (type B) and cirrhosis with previous decompensation (type C). RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in types B and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate (85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate (55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different (85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02). CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF. PMID:27076763

  4. 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...

  5. Conventional ultrasound and contrast-enhanced ultrasound in evaluating the severity of Crohn’s disease

    PubMed Central

    Liu, Chang; Xu, Xiao-Rong; Xu, Hui-Xiong; Liu, Zhan-Ju; Zhang, Yi-Feng; Sun, Li-Ping; Xu, Jun-Mei; Liu, Lin-Na; Guo, Le-Hang; Bo, Xiao-Wan

    2015-01-01

    Objective: To evaluate the value of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in determining the severity of active Crohn’s disease. Methods: Thirty-seven patients who were considered to be in active period of Crohn’s disease were included. Conventional ultrasound was employed to measure the thicknesses of interior, exterior and the whole bowel walls. Qualitative and quantitative CEUS analysis of the interior, exterior and the whole intestinal walls were also performed. Correlations between these methods and the severity of Crohn’s disease were assessed. Results: Endoscopy grading system identified 19 patients with mild disease and 18 with severe disease. In discriminating severe Crohn’s disease from mild disease, the cut-off value for the thickness of the entire bowel wall was 6.8 mm by receiver operating characteristic (ROC) analysis, with area under ROC (AUROC) of 0.84, sensitivity of 94.4%, specificity of 68.4%, positive predictive value (PPV) of 61.1%, negative predictive value (NPV) of 69.2%, and Youden’s index of 0.628. The cut-off value for thickness of the interior intestinal wall was 4.8 mm (AUROC, 0.81; sensitivity, 88.9%; specificity, 63.2%; PPV, 85.7%; NPV, 69.6%; Youden’s index, 0.521). The sensitivity, specificity, PPV, NPV, accuracy, and Youden’s index of CEUS qualitative analysis were 100% (18/18), 57.9% (11/19), 64.3% (18/26), 100% (11/11), 78.4% (29/37), and 0.579, respectively. Quantitative comparison revealed that patients with mild disease and those with severe disease differed only in Imax of inner bowel wall enhancement (2746.9 ± 911 vs. 12814.5 ± 9802.4; P = 0.02) and Imax of entire wall enhancement (2106 ± 660 vs. 9864 ± 6994; P = 0.03). The cut-off value for the Imax of the entire bowel wall was 3067, with the AUROC of 0.96, sensitivity of 100%, specificity of 67.7%, PPV of 100%, NPV of 88.9%, and Youden’s index of 0.677; and the cut-off value for the Imax of the interior intestinal layer was 3356

  6. Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma.

    PubMed

    Valet, Robert S; Carroll, Kecia N; Gebretsadik, Tebeb; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Hartert, Tina V

    2014-03-01

    It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings. PMID:24669353

  7. Severe heart disease in an unusual case of familial amyloid polyneuropathy type I.

    PubMed

    Oliveira Santos, Miguel; Brito, Dulce

    2013-09-01

    Familial amyloid polyneuropathy type I (FAP type I) is a rare hereditary systemic amyloidosis caused by the Val30Met mutation in the transthyretin (TTR) gene. The clinical onset and spectrum are variable and depend on phenotypic heterogeneity. Cardiac complications (dysrhythmias and conduction disturbances, cardiomyopathy and dysautonomia) indicate a poor prognosis, even after liver transplantation. We report an atypical case of FAP type I, highlighting the severe cardiac involvement and its complications. Early diagnosis of amyloid heart disease is increasingly important in the context of several clinical trials of promising new and experimental drugs. PMID:23993291

  8. Severe exfoliative erythema of malnutrition in a child with coexisting coeliac and Hartnup's disease.

    PubMed

    Sander, C S; Hertecant, J; Abdulrazzaq, Y M; Berger, T G

    2009-03-01

    Exfoliative erythema of malnutrition is a collective term for skin lesions caused by a combination of multiple deficiencies in vitamins, microelements, essential fatty acids and amino acids. We report a 3-year-old Iraqi girl with malnutrition due to coexisting coeliac and Hartnup's disease. On admission to hospital, she presented with kwashiorkor, anaemia, hepatitis and hypoalbuminia. She had severe skin changes with erythema, desquamation, erosions and diffuse hyperpigmentation involving the whole integument, particularly the perioral area, trunk and legs. She also had angular cheilitis, glossitis, conjunctivitis and diffuse alopecia. After treatment with a high-protein gluten-free diet and supplementation with vitamins and microelements there was a rapid improvement in the skin lesions. The severity of the skin lesions in this case can be explained by the coexistence of two metabolic diseases causing complex malnutrition. PMID:19018792

  9. 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. PMID:361897

  10. Disease Burden Among Individuals with Severe Mental Illness in a Community Setting.

    PubMed

    Baughman, Kristin R; Bonfine, Natalie; Dugan, Sara E; Adams, Richard; Gallagher, Mary; Olds, R Scott; Piatt, Elizabeth; Ritter, Christian

    2016-05-01

    This study examines the prevalence of comorbid physical health conditions within a community sample of individuals with severe mental illness (SMI), compares them to a matched national sample without SMI, and identifies which comorbidities create the greatest disease burden for those with SMI. Self-reported health status, co-morbid medical conditions and perceived disease burden were collected from 203 adults with SMI. Prevalence of chronic health conditions was compared to a propensity-matched sample without SMI from the National Comorbidity Survey-Replication (NCS-R). Compared to NCS-R sample without SMI, our sample with SMI had a higher prevalence of seven out of nine categories of chronic health conditions. Chronic pain and headaches, as well as the number of chronic conditions, were associated with increased disease burden for individuals with SMI. Further investigation of possible interventions, including effective pain management, is needed to improve the health status of this population. PMID:26611625

  11. Relationship of hepatic steatosis severity and coronary artery disease characteristics assessed by coronary CT angiography.

    PubMed

    Tomizawa, Nobuo; Inoh, Shinichi; Nojo, Takeshi; Nakamura, Sunao

    2016-06-01

    The objective of this study was to investigate the relationship between the severity of hepatic steatosis and coronary artery disease characteristics assessed by coronary computed tomography (CT) angiography. This retrospective analysis consisted of 2028 patients. Hepatic steatosis was evaluated by liver attenuation on unenhanced CT and the patients were divided into four groups (≥60 HU, 54-59 HU, 43-53 HU, ≤42 HU). Coronary calcification was calculated using the Agatston method. Obstructive disease was defined as ≥50 % stenosis assessed by CT. A high-risk plaque was defined by a remodeling index >1.1 and low attenuation (<30 HU). Patients with a segment involvement score >4 were determined to have extensive disease. Logistic regression analysis was performed to study multivariate associations. Severity of hepatic steatosis was associated with coronary calcification (p = 0.02), obstructive disease (p < 0.0001), presence of a high-risk plaque (p = 0.0001) and extensive disease (p = 0.001) in the univariate analysis. However, the relationships were attenuated in the multivariate analysis with the exception of obstructive disease (p = 0.04). Liver attenuation of <54 HU was significantly associated with obstructive coronary artery disease independent of conventional risk factors such as age, sex, diabetes mellitus, hypertension, dyslipidemia and smoking (hepatic attenuation 43-53 HU, odds ratio 1.52, 95 % confidence interval 1.11-2.10, p = 0.01; ≤42 HU, odds ratio 1.65, 95 % confidence interval 1.10-2.45, p = 0.02). Although conventional risk factors were stronger predictors of coronary calcification and plaque formation, the severity of hepatic steatosis remained an independent risk factor for obstructive coronary artery disease. Coronary CT angiography may play a potential role in risk stratification for patients with hepatic steatosis. PMID:26831056

  12. Lifestyle changes and beliefs regarding disease severity in patients with chronic hepatitis C.

    PubMed

    Castera, L; Constant, A; Bernard, P-H; de Ledinghen, V; Couzigou, P

    2006-07-01

    The aim of this prospective study was to investigate beliefs regarding disease severity and lifestyle changes following hepatitis C diagnosis in patients with chronic hepatitis C (CHC). One hundred and eighty-five consecutive CHC patients were interviewed by means of self-questionnaires exploring several aspects of their disease. Most patients (93%) identified cirrhosis and liver cancer as the two main complications of CHC. More than half of patients (59%) thought that CHC was always associated with a fatal outcome whereas 3% thought that they would stay healthy. HCV viral load was the most commonly reported factor associated with disease severity. Sex life changes were reported by 107 patients (58%) whereas dietary intake changes were reported by 88 patients (48%). In multivariate analysis, changes in sex life were associated with male gender [odds ratio (OR): 2.57, 95% CI: 1.30-5.08, P < 0.007], perceived disease severity (OR: 1.02, 95% CI: 1.00-1.03, P < 0.03) and anxiety (OR: 1.05, 95% CI: 1.01-1.08, P < 0.003), whereas changes in dietary intake were associated with age (OR: 1.04, 95% CI: 1.02-1.08, P < 0.003) and anxiety (OR: 1.04, 95% CI: 1.01-1.08, P < 0.006). Our results show the considerable impact of CHC diagnosis on patients' lifestyle. They emphasize the need for improving CHC patient counselling in order to avoid unnecessary sex life and dietary intake changes. PMID:16792542

  13. Association of Soluble Fibrinogen-like Protein 2 with the Severity of Coronary Artery Disease.

    PubMed

    Cheng, Jing; Chen, Yingying; Xu, Banglong; Wu, Jixiong; He, Fei

    2016-01-01

    Objective The purpose of this study was to investigate the relationship between circulating soluble fibrinogen-like protein 2 (sFGL2) concentrations and the severity of coronary artery disease (CAD) in patients who underwent first-time angiography for suspected CAD. Methods Serum sFGL2 concentrations were measured in 102 consecutive patients by an enzyme-linked immunosorbent assay (ELISA). The number of circulating CD4(+)CD25(+)CD127(low) T regulatory cells (Tregs) was determined by flow cytometry and effecter cytokines, including transforming growth factor-β1 and interleukin-10 (IL-10), were also evaluated by an ELISA. Associations between sFGL2 and Tregs with angiographic indexes of the severity of CAD (i.e., number of diseased vessels and the modified Gensini score) were estimated. Results The sFGL2 levels in patients with angiographically confirmed CAD were significantly lower than those in patients with normal coronary arteries (26.95±8.53 vs. 9.88±5.46 ng/mL, p<0.001). Significant correlations were observed between the serum sFGL2 level and number of diseased vessels (r=-0.860, p<0.001) and modified Gensini score (r=-0.833, p<0.001). Using a multivariate analysis, the serum sFGL2 level was independently associated with the presence and severity of CAD. Conclusion The serum sFGL2 levels are significantly lower in the presence of CAD and correlate with the severity of the disease. Further clinical studies are needed to confirm the use of sFGL2 as a biomarker for the detection and extent of CAD. PMID:27580532

  14. Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

    PubMed Central

    Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

    2014-01-01

    Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

  15. DJ-1 Knockout Augments Disease Severity and Shortens Survival in a Mouse Model of ALS

    PubMed Central

    Lev, Nirit; Barhum, Yael; Lotan, Itay; Steiner, Israel; Offen, Daniel

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, neurodegenerative disorder, characterized by the degeneration of motor neurons. Oxidative stress plays a central role in the disease progression, in concert with an enhanced glutamate excitotoxicity and neuroinflammation. DJ-1 mutations, leading to the loss of functional protein, cause familial Parkinson’s disease and motor neuron disease in several patients. DJ-1 responds to oxidative stress and plays an important role in the cellular defense mechanisms. We aimed to investigate whether loss of functional DJ-1 alters the disease course and severity in an ALS mouse model. To this end we used mice that express the human SOD1G93A mutation, the commonly used model of ALS and knockout of DJ-1 mice to generate SOD1 DJ-1 KO mice. We found that knocking out DJ-1in the ALS model led to an accelerated disease course and shortened survival time. DJ-1 deficiency was found to increase neuronal loss in the spinal cord associated with increased gliosis in the spinal cord and reduced antioxidant response that was regulated by the Nrf2 mechanism.The importance of DJ-1 in ALS was also illustrated in a motor neuron cell line that was exposed to glutamate toxicity and oxidative stress. Addition of the DJ-1 derived peptide, ND-13, enhanced the resistance to glutamate and SIN-1 induced toxicity. Thus, our results maintain that DJ-1 plays a role in the disease process and promotes the necessity of further investigation of DJ-1 as a therapeutic target for ALS. PMID:25822630

  16. Peripheral artery disease in korean patients undergoing percutaneous coronary intervention: prevalence and association with coronary artery disease severity.

    PubMed

    Kim, Eun Kyoung; Song, Pil Sang; Yang, Jeong Hoon; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Gwon, Hyeon-Cheol; Lee, Sang Hoon; Hong, Kyung Pyo; Park, Jeong Euy; Kim, Duk-kyung; Choi, Seung-Hyuk

    2013-01-01

    Peripheral artery disease (PAD) is an important marker for the risk stratification of patients with coronary artery disease (CAD). We investigated the prevalence of PAD in patients undergoing percutaneous coronary intervention (PCI) with CAD and the relationship between ankle-brachial pressure index (ABPI) and CAD severity. A total of 711 patients undergoing PCI for CAD from August 2009 to August 2011 were enrolled. PAD diagnosis was made using the ABPI. The prevalence of PAD was 12.8%. In PAD patients, mean values of right and left ABPI were 0.71 ± 0.15 and 0.73 ± 0.15. Patients with PAD had a higher prevalence of left main coronary disease (14.3% vs 5.8%, P = 0.003), more frequently had multivessel lesions (74.9% vs 52.1%, P < 0.001) and had higher SYNTAX score (18.2 ± 12.3 vs 13.1 ± 8.26, P = 0.002). Using multivariate analysis, we determined that left main CAD (OR, 2.954; 95% CI, 1.418-6.152, P = 0.004) and multivessel CAD (OR, 2.321; 95% CI, 1.363-3.953, P = 0.002) were both independently associated with PAD. We recommend that ABPI-based PAD screening should be implemented in all patients undergoing PCI with CAD, especially in severe cases. PMID:23341717

  17. Lymphoblast Oxidative Stress Genes as Potential Biomarkers of Disease Severity and Drug Effect in Friedreich's Ataxia

    PubMed Central

    Hayashi, Genki; Cortopassi, Gino

    2016-01-01

    There is no current approved therapy for the ultimately lethal neuro- and cardio-degenerative disease Friedreich's ataxia (FA). Finding minimally-invasive molecular biomarkers of disease progression and drug effect could support smaller, shorter clinical trials. Since we and others have noted a deficient oxidative stress response in FA, we investigated the expression of 84 genes involved in oxidative stress, signaling, and protection in control and FA lymphoblasts ranging from 460 to 1122 GAA repeats. Several antioxidant genes responded in a dose-dependent manner to frataxin expression at the mRNA and protein levels, which is inversely correlated with disease progression and severity. We tested the effect of experimental Friedreich’s ataxia therapies dimethyl fumarate (DMF) and type 1 histone deacetylase inhibitor (HDACi) on biomarker mRNA expression. We observed that exposure of lymphoblasts to DMF and HDACi dose-dependently unsilenced frataxin expression and restored the potential biomarkers NCF2 and PDLIM1 expression to control levels. We suggest that in addition to frataxin expression, blood lymphoblast levels of NCF2 and PDLIM1 could be useful biomarkers for disease progression and drug effect in future clinical trials of Friedreich’s ataxia. PMID:27078885

  18. Lymphoblast Oxidative Stress Genes as Potential Biomarkers of Disease Severity and Drug Effect in Friedreich's Ataxia.

    PubMed

    Hayashi, Genki; Cortopassi, Gino

    2016-01-01

    There is no current approved therapy for the ultimately lethal neuro- and cardio-degenerative disease Friedreich's ataxia (FA). Finding minimally-invasive molecular biomarkers of disease progression and drug effect could support smaller, shorter clinical trials. Since we and others have noted a deficient oxidative stress response in FA, we investigated the expression of 84 genes involved in oxidative stress, signaling, and protection in control and FA lymphoblasts ranging from 460 to 1122 GAA repeats. Several antioxidant genes responded in a dose-dependent manner to frataxin expression at the mRNA and protein levels, which is inversely correlated with disease progression and severity. We tested the effect of experimental Friedreich's ataxia therapies dimethyl fumarate (DMF) and type 1 histone deacetylase inhibitor (HDACi) on biomarker mRNA expression. We observed that exposure of lymphoblasts to DMF and HDACi dose-dependently unsilenced frataxin expression and restored the potential biomarkers NCF2 and PDLIM1 expression to control levels. We suggest that in addition to frataxin expression, blood lymphoblast levels of NCF2 and PDLIM1 could be useful biomarkers for disease progression and drug effect in future clinical trials of Friedreich's ataxia. PMID:27078885

  19. Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

    PubMed

    McIntosh, Roger C; Ironson, Gail; Antoni, Michael; Fletcher, Mary Ann; Schneiderman, Neil

    2016-02-01

    Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network. PMID:26143246

  20. 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. PMID:23637479

  1. Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease.

    PubMed

    Bale, P M; Kan, A E; Dorney, S F

    1994-01-01

    We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation of hepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes. PMID:8066004

  2. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. PMID:26209500

  3. Preventing severe respiratory syncytial virus disease: passive, active immunisation and new antivirals.

    PubMed

    Murray, Joanna; Saxena, Sonia; Sharland, Mike

    2014-05-01

    In most high-income countries palivizumab prophylaxis is considered safe, efficacious and cost-effective for preventing respiratory syncytial virus (RSV) hospital admissions among specific subgroups of infants born preterm, with chronic lung disease or with congenital heart disease. Virtually all babies acquire RSV during infancy and previously healthy babies are not eligible to receive palivizumab. Emerging evidence suggests some benefit of palivizumab use in reducing recurrent wheeze among infants born preterm. Better longitudinal studies are needed to examine its clinical and cost-effectiveness on recurrent and chronic respiratory illness and associated healthcare burden on resources in the community and hospitals. Since 99% of child deaths attributed to RSV occur in resource poor countries where expensive prophylaxis is not available or affordable, palivizumab has limited potential to impact on the current global burden of RSV lower respiratory tract infection (LRTI). A range of candidate vaccines for active immunisation against RSV are now in clinical trials. Two promising new antivirals are also currently in phase I/II trials to test their effectiveness in preventing severe RSV LRTI. These agents may be effective in preventing severe disease and phase III studies are in development. In the absence of effective active immunisation against RSV infection, population level approaches to prevent severe RSV LRTI should continue to focus on reducing prenatal and environmental risk factors including prematurity, smoking and improving hygiene practices. PMID:24464977

  4. Therapeutic plasma exchange in antisynthetase syndrome with severe interstitial lung disease.

    PubMed

    Omotoso, Bolanle A; Ogden, Melissa I; Balogun, Rasheed A

    2015-12-01

    Antisynthetase syndrome (ASS) is a rare condition characterized by interstitial lung disease (ILD), inflammatory myositis, fever, Raynaud phenomenon, mechanic's hand, and inflammatory polyarthritis in the setting of antibodies to amino acyl-transfer RNA synthetases, with anti-Jo-1 antibody being the most common. Prognosis is very poor especially when there is associated ILD. To date, there is no standardized treatment for ILD associated ASS. Therapy is based on the use of steroids alone or in combination with other immunosuppressive agents, especially in severe or refractory cases. The role of therapeutic plasma exchange (TPE) in the management of this rare condition has not been established. Here, we report a case of severe ILD associated ASS in a 41-year-old woman who did not show clinical or laboratory response after six doses of high dose steroids and a dose of IV cyclophosphamide. Because of the aggressive nature of her disease and poor prognostic indices present, a decision was made to add TPE to her treatment. She underwent five sessions of TPE. At the end of the 5th session, the anti-Jo-1 antibody levels dropped to 3.6 AI (antibody index) and her creatinine kinase (CK) level from 875 to 399 U L(-1) (Units per liter) with overall improvement in her respiratory status. This case suggests TPE may be a promising treatment option in patients with ILD associated ASS refractory to steroids and other immunosuppressive therapy, particularly those with severe disease. PMID:25727180

  5. Effects of dance on balance and gait in severe Parkinson disease: A case study

    PubMed Central

    Hackney, Madeleine E.; Earhart, Gammon M.

    2009-01-01

    Purpose: Dance may improve functional mobility in individuals with mild - moderate Parkinson disease (PD), yet dance effects in severe PD remain unexamined. This study's purpose was to evaluate the feasibility and effects of partnered tango classes on balance, endurance and quality of life in an individual with severe PD. Design: Over 10 weeks, the participant attended 20, 1-hour tango classes for individuals with PD. Balance, walking, and quality of life were evaluated before and after the intervention and at a one-month follow-up in this single case design. Caregiver burden was also assessed at all time points. Results: The participant improved on the Berg balance scale, 6 minute walk test, and functional reach. He reported increased balance confidence and improved quality of life as measured by the Parkinson Disease Questionnaire-39 summary index. Gains were maintained at the one-month follow-up. Caregiver burden increased from baseline immediately post-intervention and at follow-up. Conclusion: Twenty partnered tango lessons improved balance, endurance, balance confidence, and quality of life in a participant with severe PD. This is the first report of the use of dance as rehabilitation for an individual with advanced disease who primarily used a wheelchair for transportation. PMID:20205582

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

    PubMed Central

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

    2015-01-01

    Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

  7. Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

    PubMed Central

    Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

    2014-01-01

    AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT. PMID:25320538

  8. 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. PMID:26995268

  9. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

    PubMed Central

    BRAVO-TOBAR, Iván Darío; NELLO-PÉREZ, Carlota; FERNÁNDEZ, Alí; MOGOLLÓN, Nora; PÉREZ, Mary Carmen; VERDE, Juan; CONCEPCIÓN, Juan Luis; RODRIGUEZ-BONFANTE, Claudina; BONFANTE-CABARCAS, Rafael

    2015-01-01

    SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease. PMID:26603224

  10. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY.

    PubMed

    Bravo-Tobar, Iván Darío; Nello-Pérez, Carlota; Fernández, Alí; Mogollón, Nora; Pérez, Mary Carmen; Verde, Juan; Concepción, Juan Luis; Rodriguez-Bonfante, Claudina; Bonfante-Cabarcas, Rafael

    2015-01-01

    Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease. PMID:26603224

  11. Increased type I collagen degradation correlates with disease severity in rheumatoid arthritis.

    PubMed Central

    Hakala, M; Risteli, L; Manelius, J; Nieminen, P; Risteli, J

    1993-01-01

    OBJECTIVES--To assess the extent and clinical significance of type I collagen degradation in rheumatoid arthritis (RA). METHODS--Serum samples from 90 consecutive patients with RA from a cross-sectional population based study and 90 age- and sex-matched controls were analysed with the new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS--Patients with RA had significantly higher concentrations of ICTP than the controls. ICTP correlated strongly with measures of impairment in RA, such as the erosive state of joint disease (ES) (r = 0.57, p < 0.001) and Keitel function test (KFT) (r = 0.49, p < 0.001), and more weakly with various disease activity markers. When erythrocyte sedimentation rate (ESR), ES or KFT were used as indicators of disease severity among the patients with disease duration over five years, ICTP distinguished the more serious RA from milder cases. CONCLUSIONS--Elevated serum concentrations of ICTP are common in RA and are associated with signs of aggressive disease. PMID:8311537

  12. 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

  13. The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease.

    PubMed

    Conejero, Laura; Potempa, Krzysztof; Graham, Christine M; Spink, Natasha; Blankley, Simon; Salguero, Francisco J; Pankla-Sranujit, Rungnapa; Khaenam, Prasong; Banchereau, Jacques F; Pascual, Virginia; Chaussabel, Damien; Lertmemongkolchai, Ganjana; O'Garra, Anne; Bancroft, Gregory J

    2015-10-01

    Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. In this study, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic, or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL-10, TREM1, and IFN signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodeling, including matrix metalloproteases and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-γ, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL-10, TREM1, and IFN signaling, revealing the common immune response occurring in both mice and humans. PMID:26311902

  14. The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease

    PubMed Central

    Spink, Natasha; Blankley, Simon; Salguero, Francisco J.; Pankla-Sranujit, Rungnapa; Khaenam, Prasong; Banchereau, Jacques F.; Pascual, Virginia; Chaussabel, Damien; Lertmemongkolchai, Ganjana

    2015-01-01

    Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicaemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. Here, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL10, TREM1 and IFN-signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodelling, including MMPs and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-γ, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL10, TREM1 and IFN-signaling, revealing the common immune response occurring in both mice and humans. PMID:26311902

  15. Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease.

    PubMed

    Stobbelaar, Kim; Van Hoorenbeeck, Kim; Lequesne, Monique; De Dooy, Jozef; Ho, Erwin; Vlieghe, Erika; Ieven, Margaretha; Verhulst, Stijn

    2016-01-01

    BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism. PMID:27498677

  16. A correlation study between ankle brachial pressure index and the severity of coronary artery disease.

    PubMed

    Benyakorn, Thoetphum; Kuanprasert, Sarun; Rerkasem, Kittipan

    2012-06-01

    Previous studies have shown that there was a correlation between low ankle brachial pressure index (ABPI) and the presence of the coronary artery disease (CAD). However, few studies have investigated the correlation between ABPI and the severity of CAD by using a scoring system. The authors aimed to investigate this correlation by using ABPI and CAD diagnosed by coronary angiography (CAG). A total of 213 consecutive patients awaiting CAG in Maharaj Nakorn Chiang Mai Hospital from July 2009 to November 2009 were enrolled in this study. The ABPI was measured before CAG. The severity of CAD was graded on CAG by using SYNTAX scores. The authors found a significantly negative correlation between ABPI and SYNTAX scores (correlation coefficient = -.172, P = .01). The authors concluded that ABPI appeared to correlate negatively with the severity of CAD in the Thai population. PMID:22561522

  17. Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease

    PubMed Central

    Stobbelaar, Kim; Van Hoorenbeeck, Kim; Lequesne, Monique; De Dooy, Jozef; Ho, Erwin; Vlieghe, Erika; Ieven, Margaretha; Verhulst, Stijn

    2016-01-01

    Patient: Female, 10 Final Diagnosis: Sepsis Symptoms: Fever • hypotension • not tollerating enteral feeds • respiratory deterioration Medication: — Clinical Procedure: IV antibiotics • lungtransplantion Specialty: Pediatrics and Neonatology Objective: Unusual clinical course Background: Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. Case Report: We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. Conclusions: As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism. PMID:27498677

  18. 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

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

    PubMed

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

    2016-08-01

    Pathogen infection in plants induces complex responses ranging from gene expression to metabolic processes in infected plants. In spite of many studies on biotic stress-related changes in host plants, little is known about the metabolic and phenotypic responses of the host plants to Pseudomonas cichorii infection based on image-based analysis. To investigate alterations in tomato plants according to disease severity, we inoculated plants with different cell densities of P. cichorii using dipping and syringe infiltration methods. High-dose inocula (≥ 10(6) cfu/ml) induced evident necrotic lesions within one day that corresponded to bacterial growth in the infected tissues. Among the chlorophyll fluorescence parameters analyzed, changes in quantum yield of PSII (ΦPSII) and non-photochemical quenching (NPQ) preceded the appearance of visible symptoms, but maximum quantum efficiency of PSII (Fv/Fm) was altered well after symptom development. Visible/near infrared and chlorophyll fluorescence hyperspectral images detected changes before symptom appearance at low-density inoculation. The results of this study indicate that the P. cichorii infection severity can be detected by chlorophyll fluorescence assay and hyperspectral images prior to the onset of visible symptoms, indicating the feasibility of early detection of diseases. However, to detect disease development by hyperspectral imaging, more detailed protocols and analyses are necessary. Taken together, change in chlorophyll fluorescence is a good parameter for early detection of P. cichorii infection in tomato plants. In addition, image-based visualization of infection severity before visual damage appearance will contribute to effective management of plant diseases. PMID:27493605

  20. Development and Validation of a Disease Severity Scoring Model for Pediatric Sepsis

    PubMed Central

    HU, Li; ZHU, Yimin; CHEN, Mengshi; LI, Xun; LU, Xiulan; LIANG, Ying; TAN, Hongzhuan

    2016-01-01

    Background: Multiple severity scoring systems have been devised and evaluated in adult sepsis, but a simplified scoring model for pediatric sepsis has not yet been developed. This study aimed to develop and validate a new scoring model to stratify the severity of pediatric sepsis, thus assisting the treatment of sepsis in children. Methods: Data from 634 consecutive patients who presented with sepsis at Children’s hospital of Hunan province in China in 2011–2013 were analyzed, with 476 patients placed in training group and 158 patients in validation group. Stepwise discriminant analysis was used to develop the accurate discriminate model. A simplified scoring model was generated using weightings defined by the discriminate coefficients. The discriminant ability of the model was tested by receiver operating characteristic curves (ROC). Results: The discriminant analysis showed that prothrombin time, D-dimer, total bilirubin, serum total protein, uric acid, PaO2/FiO2 ratio, myoglobin were associated with severity of sepsis. These seven variables were assigned with values of 4, 3, 3, 4, 3, 3, 3 respectively based on the standardized discriminant coefficients. Patients with higher scores had higher risk of severe sepsis. The areas under ROC (AROC) were 0.836 for accurate discriminate model, and 0.825 for simplified scoring model in validation group. Conclusions: The proposed disease severity scoring model for pediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which has important clinical significance in evaluating the severity of pediatric sepsis and predicting its progress. PMID:27516993

  1. Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

    PubMed

    Tummala, Sudhakar; Roy, Bhaswati; Park, Bumhee; Kang, Daniel W; Woo, Mary A; Harper, Ronald M; Kumar, Rajesh

    2016-10-01

    Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc. PMID:27315771

  2. Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

    PubMed

    Rasmuson, J; Pourazar, J; Mohamed, N; Lejon, K; Evander, M; Blomberg, A; Ahlm, C

    2016-04-01

    Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments. PMID:26873376

  3. Hedgehog Pathway Activation Parallels Histologic Severity of Injury and Fibrosis in Human Nonalcoholic Fatty Liver Disease

    PubMed Central

    Guy, Cynthia D.; Suzuki, Ayako; Zdanowicz, Marzena; Abdelmalek, Manal F.; Burchette, James; Unalp, Aynur; Diehl, Anna Mae

    2012-01-01

    The Hedgehog (Hh) signaling pathway mediates several processes that are deregulated in patients with the metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis). The severity of nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome generally correlate. Therefore, we hypothesized that the level of Hh pathway activation would increase in parallel with the severity of liver damage in NAFLD. To assess potential correlations between known histologic and clinical predictors of advanced liver disease and Hh pathway activation, immunohistochemistry was performed on liver biopsies from a large well-characterized cohort of NAFLD patients (n=90) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Database 1 study. Increased Hh activity (evidenced by accumulation of Hh-ligand producing cells and Hh-responsive target cells) strongly correlated with portal inflammation, ballooning, and fibrosis stage (each p<0.0001), supporting a relationship between Hh pathway activation and liver damage. Pathway activity also correlated significantly with markers of liver repair, including numbers of hepatic progenitors and myofibroblastic cells (both p<0.03). In addition, various clinical parameters that have been linked to histologically-advanced NAFLD, including increased patient age (p<0.005), BMI (p<0.002), waist circumference (p<0.0007), homeostatic model assessment of insulin resistance (HOMA-IR) (p<0.0001) and hypertension (p<0.02), correlated with hepatic Hh activity. Conclusion: In NAFLD patients, the level of hepatic Hh pathway activity is highly correlated with the severity of liver damage and with metabolic syndrome parameters that are known to be predictive of advanced liver disease. Hence, deregulation of the Hh signaling network may contribute to the pathogenesis and sequelae of liver damage that develops with the metabolic syndrome. PMID:22213086

  4. 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.

  5. Development of a prediction formula of Parkinson disease severity by optical coherence tomography.

    PubMed

    Jiménez, Beatriz; Ascaso, Francisco J; Cristóbal, José A; López del Val, Javier

    2014-01-01

    The aims of this study were to assess the peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Parkinson's disease (PD), to determine its correlation with disease severity, and to define a simple biomarker for predicting clinical severity. One hundred two eyes from 52 patients affected by PD were compared with 97 eyes from 50 age-comparable controls. In all patients, peripapillary RNFL thickness was measured by optical coherence tomography (OCT). We used the Unified Parkinson's Disease Rating Scale (UPDRS) total score and measured responses in the on medication state. Eyes from patients with PD had a statistically significant decrease in average peripapillary RNFL thickness compared with control eyes (P < 0.001). This reduction was observed in every quadrant (inferior, superior, nasal [P < 0.001], and temporal [P = 0.017]) in patients with PD. Furthermore, a strong inverse correlation was found between the PD severity measured according to the UPDRS score and the average peripapillary RNFL thickness (r = -0.615; P < 0.001) and PD duration (r = -0.303; P = 0.002). From these results, we defined a regression equation that predicts the UPDRS score from the above-mentioned variables: UPDRS = 81.6 + 29.6 * log PD duration (years) - 0.6 * RFNL thickness (μm). We observed that, as the evolution and severity of PD progress, the peripapillary RNFL layer thickness, as evaluated by OCT, gradually diminishes. These results suggest that the average peripapillary RNFL thickness measured by OCT might be useful as a biomarker to detect the early onset and progression of PD. PMID:24458320

  6. 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

  7. 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

  8. 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

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

    PubMed

    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

    2016-07-19

    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

  10. Disseminated disease severity as a measure of virulence of Mycobacterium tuberculosis in the guinea pig model.

    PubMed

    Palanisamy, Gopinath S; Smith, Erin E; Shanley, Crystal A; Ordway, Diane J; Orme, Ian M; Basaraba, Randall J

    2008-07-01

    Virulence is the measure of pathogenicity of a microorganism as determined by its ability to invade host tissues and to produce severe disease. In the low-dose aerosol guinea pig model the virulence of multiple strains of Mycobacterium tuberculosis was determined by measuring time of survival, bacterial loads in target organs, and the severity of pulmonary and extra-pulmonary lesions. Erdman K01, CSU93/CDC1551 and HN878 had shorter survival times compared to the common laboratory strain H37Rv. After 30 days of the infection bacilli had disseminated from the lungs resulting in microscopically visible lesions in peribronchial lymph nodes, peripancreatic lymph nodes, spleen, liver, pancreas, adrenal and heart. The extent of the lesion necrosis paralleled virulence when survival times were used as a measure as Erdman K01 and the two clinical isolates caused more necrosis and resulted in sooner death in infected animals than the H37Rv. The extent of extra-pulmonary lesion necrosis was a better predictor of virulence than the number of viable bacilli in the tissue. Overall, this study emphasizes the point that extra-pulmonary disease is a prominent feature of the guinea pig model and dissemination to organs not normally assayed such as the heart and adrenal glands should be taken into account in the assessment of the disease process. PMID:18321783

  11. Proposed diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, 2015 version.

    PubMed

    Masaki, Yasufumi; Kawabata, Hiroshi; Takai, Kazue; Kojima, Masaru; Tsukamoto, Norifumi; Ishigaki, Yasuhito; Kurose, Nozomu; Ide, Makoto; Murakami, Jun; Nara, Kenji; Yamamoto, Hiroshi; Ozawa, Yoko; Takahashi, Hidekazu; Miura, Katsuhiro; Miyauchi, Tsutomu; Yoshida, Shinichirou; Momoi, Akihito; Awano, Nobuyasu; Ikushima, Soichiro; Ohta, Yasunori; Furuta, Natsue; Fujimoto, Shino; Kawanami, Haruka; Sakai, Tomoyuki; Kawanami, Takafumi; Fujita, Yoshimasa; Fukushima, Toshihiro; Nakamura, Shigeo; Kinoshita, Tomohiro; Aoki, Sadao

    2016-06-01

    TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia). PMID:27084250

  12. Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome.

    PubMed

    de Paiva, Cintia S; Jones, Dan B; Stern, Michael E; Bian, Fang; Moore, Quianta L; Corbiere, Shani; Streckfus, Charles F; Hutchinson, Diane S; Ajami, Nadim J; Petrosino, Joseph F; Pflugfelder, Stephen C

    2016-01-01

    There is mounting evidence that the microbiome has potent immunoregulatory functions. We assessed the effects of intestinal dysbiosis in a model of Sjögren syndrome (SS) by subjecting mice to desiccating stress (DS) and antibiotics (ABX). We characterized the conjunctival, tongue and fecal microbiome profiles of patients with SS. Severity of ocular surface and systemic disease was graded. 16S ribosomal RNA gene sequencing characterized the microbiota. ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days. Goblet cell density was significantly lower in ABX treated groups compared to controls. Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls. The severity of SS ocular and systemic disease was inversely correlated with microbial diversity. These findings suggest that SS is marked by a dysbiotic intestinal microbiome driven by low relative abundance of commensal bacteria and high relative abundance of potentially pathogenic genera that is associated with worse ocular mucosal disease in a mouse model of SS and in SS patients. PMID:27087247

  13. Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome

    PubMed Central

    de Paiva, Cintia S.; Jones, Dan B.; Stern, Michael E.; Bian, Fang; Moore, Quianta L.; Corbiere, Shani; Streckfus, Charles F.; Hutchinson, Diane S.; Ajami, Nadim J.; Petrosino, Joseph F.; Pflugfelder, Stephen C.

    2016-01-01

    There is mounting evidence that the microbiome has potent immunoregulatory functions. We assessed the effects of intestinal dysbiosis in a model of Sjögren syndrome (SS) by subjecting mice to desiccating stress (DS) and antibiotics (ABX). We characterized the conjunctival, tongue and fecal microbiome profiles of patients with SS. Severity of ocular surface and systemic disease was graded. 16S ribosomal RNA gene sequencing characterized the microbiota. ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days. Goblet cell density was significantly lower in ABX treated groups compared to controls. Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls. The severity of SS ocular and systemic disease was inversely correlated with microbial diversity. These findings suggest that SS is marked by a dysbiotic intestinal microbiome driven by low relative abundance of commensal bacteria and high relative abundance of potentially pathogenic genera that is associated with worse ocular mucosal disease in a mouse model of SS and in SS patients. PMID:27087247

  14. The Search for Genetic Modifiers of Disease Severity in the β-Hemoglobinopathies

    PubMed Central

    Lettre, Guillaume

    2012-01-01

    Sickle cell disease (SCD) and β-thalassemia, two monogenic diseases caused by mutations in the β-globin gene, affect millions of individuals worldwide. These hemoglobin disorders are characterized by extreme clinical heterogeneity, complicating patient management and treatment. A better understanding of this patient-to-patient clinical variability would dramatically improve care and might also guide the development of novel therapies. Studies of the natural history of these β-hemoglobinopathies have identified fetal hemoglobin levels and concomitant α-thalassemia as important modifiers of disease severity. Several small-scale studies have attempted to identify additional genetic modifiers of SCD and β-thalassemia, without much success. Fortunately, improved knowledge of the human genome and the development of new genomic tools, such as genome-wide genotyping arrays and next-generation DNA sequencers, offer new opportunities to use genetics to better understand the causes of the many complications observed in β-hemoglobinopathy patients. Here I discuss the most important factors to consider when planning an experiment to find associations between β-hemoglobinopathy-related complications and DNA sequence variants, with a focus on how to successfully perform a genome-wide association study. I also review the literature and explain why most published findings in the field of SCD modifier genetics are likely to be false-positive reports, with the goal to draw lessons allowing investigators to design better genetic experiments. PMID:23028136

  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. 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

  17. Looking for Measures of Disease Severity in the Frontotemporal Dementia Continuum.

    PubMed

    Premi, Enrico; Gualeni, Vera; Costa, Paolo; Cosseddu, Maura; Gasparotti, Roberto; Padovani, Alessandro; Borroni, Barbara

    2016-04-16

    Frontotemporal dementia (FTD) is characterized by executive dysfunctions, behavioral disturbances, language deficits and extrapyramidal symptoms. Frontotemporal lobar degeneration-modified Clinical Dementia Rating Scale (FTLD modified-CDR) has been proposed to measure disease severity in behavioral variant FTD (bvFTD). No tools of global disease severity are available in the other FTLD phenotypes [primary progressive aphasias (PPAs), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS)]. This would be strategic as outcome measures in clinical trials. To this aim, we evaluated the association between brain volume (voxel based morphometry) and available clinical scales in FTD. In 176 FTD patients (64 bvFTD, 40 PPAs, 32 PSP, 40 CBS), instrumental activities of daily living (ADLs), FTLD-modified CDR, Mini-Mental State Examination (MMSE), Frontal Behavioral Inventory (FBI), and Neuropsychiatry Inventory (NPI) were administered and MRI performed. Whole-brain linear correlation between each clinical rating scale and brain volume was performed. In bvFTD and PPAs, FTLD-modified CDR was associated with regional brain volume, thereby providing evidence for validity of the FTLD-modified CDR. In PSP, none of the clinical indicators were associated with regional brain volume. In CBS, ADLs and MMSE correlated with frontotemporal lower volume. Considering monogenic disease, FTLD-modified CDR was the best measure. In FTD continuum, different measures able to correlate with brain damage should be considered for the different clinical phenotypes or genetic traits. PMID:27104906

  18. Quantification of sickle cells in the peripheral smear as a marker of disease severity.

    PubMed

    Alvarez, Ofelia; Montague, Naomi S; Marin, Marta; O'Brien, Robert; Rodriguez, Maria Matilde

    2015-06-01

    Blinded readers examined peripheral smears of 108 children with steady sickle cell (SC) disease and controls by counting ten 100 × microscope fields and calculating percent of irreversible and reversible SC from total red cell population SC index (SCI). SCI was correlated to disease severity, and transfusion, hydroxyurea, or neither. Controls had a mean of 0.28% SC (range 0-0.64). Children with hemoglobin SS had a mean SCI of 5.12% ± 5.37 (range 0-30). SCI increased 0.33% with each increasing year (p < 0.0001). Patients with SCI >0.64 were 3.32 times as likely to experience clinical complications (p = 0.0124). Although blood transfusions and hydroxyurea decreased percent of SC, 72% treated patients had SCI >0.64, correlating with persistent sickling. This standardized method quantifies SC in peripheral smears. Percent of SC increased with age and correlated with disease severity, especially hemolytic complications, providing readily available information with minimal or no extra cost. PMID:25517885

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

    PubMed

    Nonnemacher, Michael R; Pirrone, Vanessa; 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

  20. 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

  1. 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. PMID:26364678

  2. Mycobacterium avium Complex Infection in a Patient with Sickle Cell Disease and Severe Iron Overload

    PubMed Central

    Jafferjee, Nasima; Thomas, David; Jacobs, Gretta; Meyerson, Howard J.

    2014-01-01

    A 34-year-old female with sickle cell anemia (hemoglobin SS disease) and severe iron overload presented to our institution with the subacute presentation of recurrent pain crisis, fever of unknown origin, pancytopenia, and weight loss. A CT scan demonstrated both lung and liver nodules concerning for granulomatous disease. Subsequent biopsies of the liver and bone marrow confirmed the presence of noncaseating granulomas and blood cultures isolated Mycobacterium avium complex MAC. Disseminated MAC is considered an opportunistic infection typically diagnosed in the immunocompromised and rarely in immunocompetent patients. An appreciable number of mycobacterial infection cases have been reported in sickle cell disease patients without immune dysfunction. It has been reported that iron overload is known to increase the risk for mycobacterial infection in vitro and in vivo studies. While iron overload is primarily known to cause end organ dysfunction, the clinical relationship with sickle cell disease and disseminated MAC infection has not been reported. Clinical iron overload is a common condition diagnosed in the sub-Saharan African population. High dietary iron, genetic defects in iron trafficking, as well as hemoglobinopathy are believed to be the etiologies for iron overload in this region. Patients with iron overload in this region were 17-fold more likely to die from Mycobacterium tuberculosis. Both experimental and clinical evidence suggest a possible link to iron overload and mycobacterial infections; however larger observational studies are necessary to determine true causality. PMID:25544913

  3. Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene

    PubMed Central

    Rabinovich, E; Livneh, A; Langevitz, P; Brezniak, N; Shinar, E; Pras, M; Shinar, Y

    2005-01-01

    Background: Pyrin is a newly recognised intracellular regulator of inflammation, and mutations in MEFV, the gene encoding pyrin, are the cause of familial Mediterranean fever. Objective: To determine if known mutations of MEFV are associated with rheumatoid arthritis (RA) morbidity or can modify RA severity. Methods: The frequency of the three most common MEFV mutations: M694V, V726A, and E148Q, was determined in 98 Israeli patients with RA (74 women, 24 men) and compared with that in 100 healthy subjects matched for origin. RA severity was determined using a new clinical score of 126 grades. The median severity score of mutation carrier and non-carrier groups was compared after confounding measures were eliminated by logistic regression. Results: 17/98 (17%) patients with RA (all women) were heterozygous for common MEFV mutations, predominantly E148Q (12 patients), and one patient was homozygous for the V726A mutation. The overall mutation rate was comparable between patients with RA and healthy subjects. Patients carrying a mutation had a higher median severity score than the non-carrier group (42 v 29, p = 0.0005). The logistic regression model assigned a 15-fold odds ratio for severe RA in carriers, after adjusting for sex, presence of rheumatoid factor, age at onset, and disease duration (n = 97, p = 0.01, 95% CI 1.74 to 128). Conclusion: MEFV, and particularly the E148Q mutation, is an independent modifier of the clinical manifestations of RA. This is the second Th1-type autoimmune disease in which MEFV mutations have been shown to aggravate the clinical status. PMID:15958759

  4. Severe inflammatory bowel disease associated with congenital alteration of transforming growth factor beta signaling.

    PubMed

    Naviglio, Samuele; Arrigo, Serena; Martelossi, Stefano; Villanacci, Vincenzo; Tommasini, Alberto; Loganes, Claudia; Fabretto, Antonella; Vignola, Silvia; Lonardi, Silvia; Ventura, Alessandro

    2014-08-01

    Transforming growth factor beta is a pleiotropic cytokine which plays a central role in the homeostasis of the immune system. A complex dysregulation of its signaling occurs in Loeys-Dietz syndrome, a monogenic disorder caused by mutations of transforming growth factor beta receptors type 1 or type 2, characterized by skeletal involvement, craniofacial abnormalities, and arterial tortuosity with a strong predisposition for aneurysm and dissection. In addition, several immunologic abnormalities have been described in these patients, including an increased risk of allergic disorders as well as eosinophilic gastrointestinal disorders. The occurrence of inflammatory bowel disorders has been also reported, but it is poorly documented. We describe two unrelated children with Loeys-Dietz syndrome affected by severe chronic inflammatory colitis appearing at an early age. The intestinal disease presented similar features in both patients, including a histopathological picture of non-eosinophilic chronic ulcerative colitis, striking elevation of inflammatory markers, and a distinctly severe clinical course leading to failure to thrive, with resistance to multiple immunosuppressive treatments. One of the patients also presented autoimmune thyroiditis. Our report confirms that chronic ulcerative colitis may be associated with Loeys-Dietz syndrome. This finding suggests that an alteration of transforming growth factor beta signaling may by itself predispose to inflammatory colitis in humans, and represent an invaluable model to understand inflammatory bowel diseases. PMID:24486179

  5. 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.

  6. Misfolding of vWF to pathologically disordered conformations impacts the severity of von Willebrand disease.

    PubMed

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

    2014-09-01

    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

  7. Anti-actin IgA antibodies in severe coeliac disease

    PubMed Central

    Granito, A; Muratori, P; Cassani, F; Pappas, G; Muratori, L; Agostinelli, D; Veronesi, L; Bortolotti, R; Petrolini, N; Bianchi, F B; Volta, U

    2004-01-01

    Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P < 0·0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease. PMID:15270857

  8. Dengue Specific Immunoglobulin A Antibody is Present in Urine and Associated with Disease Severity

    PubMed Central

    Zhao, Hui; Qiu, Shuang; Hong, Wen-Xin; Song, Ke-Yu; Wang, Jian; Yang, Hui-Qin; Deng, Yong-Qiang; Zhu, Shun-Ya; Zhang, Fu-Chun; Qin, Cheng-Feng

    2016-01-01

    The kinetics of dengue virus (DENV)-specific IgA antibody in urine and the potential correlation with disease severity remain elusive. In this study, 262 serial urine samples from 78 laboratory-confirmed patients were assayed by a commercial immunoglobulin A (IgA) kit against DENV. All cases were classified into dengue fever (DF) and severe dengue (SD) according to the 2009 WHO/TDR guideline. The total positive rate of IgA in urine was 59%. DENV-specific IgA was detected in urine from day 2 to day 13 after the onset of illness in DF patients; While for SD patients, anti-DENV IgA could be detected till day 14. The positive rate of IgA in patients with secondary infection was higher than that in patients with primary infection. Importantly, during 4–7 days after the onset of illness, the IgA positive rate of SD patients was significantly higher than that of DF patients. Especially, the intensity of IgA signal in SD patients was obviously stronger than that in DF patient at the recovery stage. Overall, our results suggested that the existence of DENV-specific IgA antibodies in urine might be a warning sign for the severity of disease and its measurement might provide valuable guidance for proper patient management. PMID:27250703

  9. Interleukin-31 expression and relation to disease severity in human asthma

    PubMed Central

    Lai, Tianwen; Wu, Dong; Li, Wen; Chen, Min; Yi, Zhennan; Huang, Dan; Jing, Zhiliang; Lü, Yingying; Lv, Quanchao; Li, Dongming; Wu, Bin

    2016-01-01

    Interleukin 31 (IL-31) is a novel T helper type 2 effector cytokine that plays an important role in the pathogenesis of allergic diseases. However, its role in human asthma remains unclear. The aim of this study was to measure IL-31 levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of asthmatics and healthy subjects, and identify its possible correlation to disease severity. We quantified IL-31 levels in the serum of patients with asthma (n = 44), as well as in controls (n = 22). Of these subjects, 9 asthmatics and five controls underwent bronchoscopy with endobronchial biopsy and BALF collection. Our data showed that serum and BALF IL-31 levels were significantly elevated in patients with asthma compared with controls. Expressions of IL-31 and IL-31 receptor (IL-31RA and OSMR) were more prominent in the bronchial tissue in severe compared to mild asthma and controls. Serum IL-31 levels correlated positively with Th2 related cytokines (IL-5, IL-13, and TSLP), asthma severity or total serum immunoglobulin E (IgE), and inversely with asthma control and the forced expiratory volume in 1 second (FEV1). The current data may provide insight into the underlying pathogenesis of asthma, in which IL-31 has an important pathogenic role. PMID:26956917

  10. Dengue Specific Immunoglobulin A Antibody is Present in Urine and Associated with Disease Severity.

    PubMed

    Zhao, Hui; Qiu, Shuang; Hong, Wen-Xin; Song, Ke-Yu; Wang, Jian; Yang, Hui-Qin; Deng, Yong-Qiang; Zhu, Shun-Ya; Zhang, Fu-Chun; Qin, Cheng-Feng

    2016-01-01

    The kinetics of dengue virus (DENV)-specific IgA antibody in urine and the potential correlation with disease severity remain elusive. In this study, 262 serial urine samples from 78 laboratory-confirmed patients were assayed by a commercial immunoglobulin A (IgA) kit against DENV. All cases were classified into dengue fever (DF) and severe dengue (SD) according to the 2009 WHO/TDR guideline. The total positive rate of IgA in urine was 59%. DENV-specific IgA was detected in urine from day 2 to day 13 after the onset of illness in DF patients; While for SD patients, anti-DENV IgA could be detected till day 14. The positive rate of IgA in patients with secondary infection was higher than that in patients with primary infection. Importantly, during 4-7 days after the onset of illness, the IgA positive rate of SD patients was significantly higher than that of DF patients. Especially, the intensity of IgA signal in SD patients was obviously stronger than that in DF patient at the recovery stage. Overall, our results suggested that the existence of DENV-specific IgA antibodies in urine might be a warning sign for the severity of disease and its measurement might provide valuable guidance for proper patient management. PMID:27250703

  11. 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. PMID:26618044

  12. 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

  13. 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

  14. COPD disease severity and innate immune response to pathogen-associated molecular patterns

    PubMed Central

    Fan, Vincent S; Gharib, Sina A; Martin, Thomas R; Wurfel, Mark M

    2016-01-01

    The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student’s t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%–80%) and 16 severe COPD (FEV1 <50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1β. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response. PMID:27019597

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

    PubMed

    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

  16. COPD disease severity and innate immune response to pathogen-associated molecular patterns.

    PubMed

    Fan, Vincent S; Gharib, Sina A; Martin, Thomas R; Wurfel, Mark M

    2016-01-01

    The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student's t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%-80%) and 16 severe COPD (FEV1 <50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1β. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response. PMID:27019597

  17. Severe hand, foot and mouth disease in Shenzhen, South China: what matters most?

    PubMed

    Mou, J; Dawes, M; Li, Y; He, Y; Ma, H; Xie, X; Griffiths, S; Cheng, J

    2014-04-01

    Case report data and a matched case-control study were used to investigate the epidemiological characteristics of hand, foot and mouth disease (HFMD) in children in Shenzhen, China between 2008 and 2011. Multivariate analyses were used to evaluate factors associated with severity of infection. Laboratory tests were performed to determine aetiological identification for samples from 163 severe and fatal cases as well as an outpatient-based HFMD sentinel surveillance system (n = 446). All identified EV71 belonged to sub-genotype C4a. No major changes in the CA16 and EV71 viruses were found until the end of 2011. Annual attack rates and the case-severity ratios (CSRs) rose from 0.82/1000 and 0.56/1000, respectively, in 2008 to 2.12/1000 and 6.13/1000 in 2011. The CSR was higher in migrants than in local residents. The adjusted odds ratio (OR) of having a severe attack for being a migrant was 2.45, having a fever >39°C (OR 5.77), visiting a private clinic (OR 2.65), longer time from symptom onset to diagnosis (OR 1.49), visiting a doctor (OR 1.51), early use of intramuscular pyrazolone (OR 3.36), early use of intravenous glucocorticoids (OR 2.28), or the combination of both (OR 3.75). The mortality and increasing case severity appears to be associated with socioeconomic factors including migration and is of worldwide concern. PMID:23809877

  18. 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

  19. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    PubMed Central

    Lee, Ying-Hsiang; Wu, Yih-Jer; Liu, Chuan-Chuan; Hou, Charles Jia-Yin; Yeh, Hung-I.; Tsai, Cheng-Ho; Shih, Shou-Chuan; Hung, Chung-Lieh

    2011-01-01

    Background. Nonalcoholic fatty liver disease (NAFLD) is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT) and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS) and metabolic risk score (MRS) were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7 ± 7.0 years) met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X2 = 6.12, trend P < 0.001) and FRS (X2 = 5.88, trend P < 0.001). After multivariable adjustment for clinical variables and life styles, the existence of moderate to severe NAFLD was independently associated with abnormal calcium score (P < 0.05). Conclusion. The severity of NAFLD correlated well with metabolic abnormality and was independently predict coronary calcification beyond clinical factors. Our data suggests that NAFLD based on ultrasonogram could positively reflect the burden of coronary calcification. PMID:22254139

  20. Severity grading of chronic obstructive pulmonary disease: the confounding effect of phenotype and thoracic gas compression.

    PubMed

    Pellegrino, Riccardo; Crimi, Emanuele; Gobbi, Alessandro; Torchio, Roberto; Antonelli, Andrea; Gulotta, Carlo; Baroffio, Michele; Papa, Giuseppe Francesco Sferrazza; Dellacà, Raffaele; Brusasco, Vito

    2015-04-01

    Current guidelines recommend severity of chronic obstructive pulmonary disease be graded by using forced expiratory volume in 1 s (FEV1). But this measurement is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis because of larger lung volumes, and this influences severity classification and prognosis. FEV1 was simultaneously measured by spirometry and body plethysmography (FEV1-pl) in 47 subjects with dominant emphysema and 51 with dominant chronic bronchitis. Subjects with dominant emphysema had larger lung volumes, lower diffusion capacity, and lower FEV1 than those with dominant chronic bronchitis. However, FEV1-pl, patient-centered variables (dyspnea, quality of life, exercise tolerance, exacerbation frequency), arterial blood gases, and respiratory impedance were not significantly different between groups. Using FEV1-pl instead of FEV1 shifted severity distribution toward less severe classes in dominant emphysema more than chronic bronchitis. The body mass, obstruction, dyspnea, and exercise (BODE) index was significantly higher in dominant emphysema than chronic bronchitis, but this difference significantly decreased when FEV1-pl was substituted for FEV1. In conclusion, the FEV1 is biased by thoracic gas compression more in subjects with dominant emphysema than in those with chronic bronchitis. This variably and significantly affects the severity grading systems currently recommended. PMID:25414244

  1. Severe gastrointestinal cytomegalovirus disease in two patients with renal vasculitis after immunosuppression.

    PubMed

    Lee, Kian-Guan; Teo, Su-Hooi; Lim, Cynthia; Loh, Alwin; Chidambaram, Viswanath; Choo, Jason

    2016-09-01

    Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies.
. PMID:27443566

  2. rs10865331 associated with susceptibility and disease severity of ankylosing spondylitis in a Taiwanese population.

    PubMed

    Wen, Ya-Feng; Wei, James Cheng-Chung; Hsu, Yu-Wen; Chiou, Hung-Yi; Wong, Henry Sung-Ching; Wong, Ruey-Hong; Ikegawa, Shiro; Chang, Wei-Chiao

    2014-01-01

    Ankylosing spondylitis (AS) is a highly familial rheumatic disorder and is considered as a chronic inflammatory disease. Genetic factors are involved in the pathogenesis of AS. To identify genes which render people susceptible to AS in a Taiwanese population, we selected six single-nucleotide polymorphisms (SNPs) from previous genome-wide association studies (GWASs) which were associated with AS in European descendants and Han Chinese. To assess whether the six SNPs contributed to AS susceptibility and severity in Taiwanese population, 475 AS patients fulfilling the modified New York Criteria and 527 healthy subjects were recruited. We found that rs10865331 was significantly associated with AS susceptibility and with Bath AS Function Index (BASFI). The AA and AG genotypes of rs10865331 were also significantly associated with a higher erythrocyte sedimentation rate. Our findings provided evidence that rs10865331 is associated AS susceptibility and with disease activity (BASFI) in a Taiwanese population. PMID:25184745

  3. 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. PMID:651316

  4. rs10865331 Associated with Susceptibility and Disease Severity of Ankylosing Spondylitis in a Taiwanese Population

    PubMed Central

    Chiou, Hung-Yi; Wong, Henry Sung-Ching; Wong, Ruey-Hong; Ikegawa, Shiro; Chang, Wei-Chiao

    2014-01-01

    Ankylosing spondylitis (AS) is a highly familial rheumatic disorder and is considered as a chronic inflammatory disease. Genetic factors are involved in the pathogenesis of AS. To identify genes which render people susceptible to AS in a Taiwanese population, we selected six single-nucleotide polymorphisms (SNPs) from previous genome-wide association studies (GWASs) which were associated with AS in European descendants and Han Chinese. To assess whether the six SNPs contributed to AS susceptibility and severity in Taiwanese population, 475 AS patients fulfilling the modified New York Criteria and 527 healthy subjects were recruited. We found that rs10865331 was significantly associated with AS susceptibility and with Bath AS Function Index (BASFI). The AA and AG genotypes of rs10865331 were also significantly associated with a higher erythrocyte sedimentation rate. Our findings provided evidence that rs10865331 is associated AS susceptibility and with disease activity (BASFI) in a Taiwanese population. PMID:25184745

  5. Thoracic sympathectomy for peripheral vascular disease can lead to severe bronchospasm and excessive bronchial secretions

    PubMed Central

    Goyal, Vikas Deep; Gupta, Bharti; Kumar, Sanjeev; Pal, Sanjay

    2015-01-01

    A 57-year-old male patient suffering from Buerger's disease presented with pre-gangrenous changes in right foot and ischemic symptoms in right hand. Computed tomographic angiography revealed diffuse distal disease not suitable for vascular bypass and angioplasty. Right lumbar sympathectomy was done using a retroperitoneal approach followed 1 year later by right thoracic sympathectomy using a transaxillary approach. Postoperatively, the patient had severe bronchospasm and excessive secretions in the respiratory tract resistant to theophylline and sympathomimetic group of drugs and without any clinical, laboratory and radiological evidence of infection. The patient was started on anticholinergics in anticipation that sympathectomy might have lead to unopposed cholinergic activity and the symptoms improved rapidly. The patient recovered well and was discharged on 10th post-operative day. PMID:25624604

  6. Severe perianal shingles during azathioprine and budesonide treatment for Crohn's disease-preventable with zoster vaccine?

    PubMed

    Elliott, Timothy Ross; Miller, Charles; Macrae, Finlay A

    2016-01-01

    Patients with inflammatory bowel disease (IBD), particularly those on immunosuppressive medications, suffer a high incidence of, and worse clinical outcomes relating to, herpes zoster (HZ) reactivation. We report on the presentation and management of a patient with Crohn's disease who developed severe perianal HZ after starting azathioprine and oral budesonide treatment. The zoster vaccine may prevent such zoster reactivation in patients with IBD. The zoster vaccine is effective in decreasing the risk of HZ in older adults but its role in younger adults and those with IBD has not been tested prospectively. A review of the potential risks and benefits of this live vaccine in patients with IBD and an approach to further determining its role in this patient population is discussed. PMID:27440857

  7. Socioeconomic status affects pulmonary hypertension disease severity at time of first evaluation

    PubMed Central

    Sahni, Sonu; Talwar, Ankoor; Kohn, Nina; Klinger, James R.

    2016-01-01

    Abstract A low socioeconomic status (SES) has been linked to disproportionate access to health care in many diseases, leading to worse disease severity at initial presentation. There is a paucity of these data in the pulmonary hypertension (PHTN) population. We studied the association of SES, as measured by zip code–based median annual household income, with World Health Organization functional class (WHO-FC) at time of first evaluation in PHTN patients. All patients evaluated at our center with a right heart catheterization revealing a mean pulmonary artery pressure of ≥25 mmHg within 12 months of initial evaluation were considered for the study. Demographics, WHO-FC, and zip codes were obtained from retrospective chart analysis. The 2010 US census was used to obtain zip code–based annual median income. The income groups were divided into quartiles. Patients were categorized by their WHO-FC and zip code–derived median income. Similar analyses were conducted for pulmonary arterial hypertension (PAH) patients. Survival was estimated with the Kaplan-Meier method. Data were analyzed in SAS, and P < 0.05 was considered significant. There were 228 PHTN patients (70 [30.7%] male, 158 [69.3%] female). As median income decreased, the FC at presentation increased, signifying higher disease severity (Spearman correlation: r = −0.161, P < 0.0515). This association between median income groups and WHO-FC at initial evaluation was significant (χ2 test: P < 0.0168). There were 116 PAH patients (32 [27.6%] male, 84 [72.4%] female). There was again a negative relationship between income and initial FC (Spearman correlation: r = −0.0307, P < 0.0007). A lower SES was associated with worse disease, as measured by WHO-FC. PMID:27252845

  8. Socioeconomic status affects pulmonary hypertension disease severity at time of first evaluation.

    PubMed

    Talwar, Arunabh; Sahni, Sonu; Talwar, Ankoor; Kohn, Nina; Klinger, James R

    2016-06-01

    A low socioeconomic status (SES) has been linked to disproportionate access to health care in many diseases, leading to worse disease severity at initial presentation. There is a paucity of these data in the pulmonary hypertension (PHTN) population. We studied the association of SES, as measured by zip code-based median annual household income, with World Health Organization functional class (WHO-FC) at time of first evaluation in PHTN patients. All patients evaluated at our center with a right heart catheterization revealing a mean pulmonary artery pressure of ≥25 mmHg within 12 months of initial evaluation were considered for the study. Demographics, WHO-FC, and zip codes were obtained from retrospective chart analysis. The 2010 US census was used to obtain zip code-based annual median income. The income groups were divided into quartiles. Patients were categorized by their WHO-FC and zip code-derived median income. Similar analyses were conducted for pulmonary arterial hypertension (PAH) patients. Survival was estimated with the Kaplan-Meier method. Data were analyzed in SAS, and P < 0.05 was considered significant. There were 228 PHTN patients (70 [30.7%] male, 158 [69.3%] female). As median income decreased, the FC at presentation increased, signifying higher disease severity (Spearman correlation: r = -0.161, P < 0.0515). This association between median income groups and WHO-FC at initial evaluation was significant (χ(2) test: P < 0.0168). There were 116 PAH patients (32 [27.6%] male, 84 [72.4%] female). There was again a negative relationship between income and initial FC (Spearman correlation: r = -0.0307, P < 0.0007). A lower SES was associated with worse disease, as measured by WHO-FC. PMID:27252845

  9. Symptom cluster, healthcare use and mortality in patients with severe chronic obstructive pulmonary disease

    PubMed Central

    Park, Soo Kyung; Larson, Janet L

    2014-01-01

    Aims and objectives To examine how subgroups of patients with chronic obstructive pulmonary disease, identified by ratings of symptoms (dyspnoea, anxiety, depression and fatigue), affect healthcare use and mortality. Background People with chronic obstructive pulmonary disease often experience multiple symptoms. The importance of multiple symptoms and symptom clusters has received increased attention. However, little is known about symptom clusters and their effect on healthcare use and mortality in this population. Design Descriptive cross-sectional study. Methods This secondary data analysis used data from the National Emphysema Treatment Trial. Participants (n = 597) had severe chronic obstructive pulmonary disease. Descriptive and inferential statistics were used to analyse the data that were drawn from structured interviews, questionnaires and clinical measures. Results Three subgroup clusters emerged based on four symptom ratings. Mean age, proportion with higher education, proportion using oxygen, disease severity, exercise capacity and quality of life differed significantly between subgroups. Participants with high levels of symptoms used healthcare services more and were more likely to have died at the five-year follow-up than those with low levels of symptoms. Symptom cluster subgroups had more significant relationship with mortality than single symptoms. Conclusion Patients with high levels of symptoms require greater clinical attention. Relevance to clinical practice Understanding subgroups of patients, based on symptom ratings and their adverse effect on outcomes, may enable healthcare providers to assess multiple symptoms and identify subgroups of patients at risk of increased healthcare use and mortality. Targeting modifiable symptoms within the cluster may be more beneficial than focusing on a single symptom for certain health-related outcome. PMID:24460846

  10. 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. PMID:23776473

  11. L-Dopa induced dyskinesias in Parkinsonian mice: Disease severity or L-Dopa history.

    PubMed

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

    2015-08-27

    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 (10mg/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

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

    PubMed

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

    2016-07-01

    Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH. PMID:26926086

  13. Obstructive sleep apnea, diagnosed by the Berlin questionnaire and association with coronary artery disease severity

    PubMed Central

    Ghazal, Abdullatef; Roghani, Farshad; Sadeghi, Masoumeh; Amra, Babak; Kermani-Alghoraishi, Mohammad

    2015-01-01

    BACKGROUND Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep-related disorder that is associated with increased risk of hypertension (HTN) and coronary heart disease. This study aimed to evaluate the correlation between the OSAS and coronary artery disease (CAD) severity. METHODS The cross-sectional study was conducted from September 2012 to December 2013. We enrolled 127 patients with chronic stable angina who were referred for coronary angiographic studies in Shahid Chamran and Nour Hospitals in Isfahan, Iran. The Berlin questionnaire (BQ) was used for estimate the probability of OSAS in patients as a low or high probability. Demographic characteristics and metabolic risk factors including diabetes mellitus, HTN, obesity, and smoking also were recorded. The severity of CAD was assessed and compared based on the Gensini score with Mann-Whitney U statistical test. Independent t-test for continuous variables and chi-square test for categorical variables were used. RESULTS Totally, 65.4% of subjects were considered as high and 34.6% as low probability for OSAS, which 81.1% of them had CAD. There was a significant difference between body mass index, systolic blood pressure, diastolic blood pressure, and ischemic heart disease drug consumption with OSAS probability (P < 0.0500). CAD was accompanied by OSAS significantly (P = 0.0260). The Gensini score was significantly higher in patients with high OSAS probability (100.4 ± 69.1 vs. 65.3 ± 68.9; P = 0.0030). OSAS also increase odds of CAD based on regression analysis (odds ratio, 95% confidence interval = 2.7). CONCLUSION This study indicates that more severe CAD is associated with high OSAS probability identified by BQ. PMID:26715932

  14. Keratin variants are over-represented in primary biliary cirrhosis and associate with disease severity

    PubMed Central

    Zhong, Bihui; Strnad, Pavel; Selmi, Carlo; Invernizzi, Pietro; Tao, Guo-Zhong; Caleffi, Angela; Chen, Minhu; Bianchi, Ilaria; Podda, Mauro; Pietrangelo, Antonello; Gershwin, M. Eric; Omary, M. Bishr

    2009-01-01

    Keratins 8 and 18 (K8/K18) variants predispose carriers to the development of end-stage liver disease and patients with chronic hepatitis C to disease progression. Hepatocytes express K8/K18 while biliary epithelia express K8/K18/K19. K8-null mice, which are predisposed to liver injury, spontaneously develop anti-mitochondrial antibodies (AMA) and have altered hepatocyte mitochondrial size and function. There is no known association of K19 with human disease and no known association of K8/K18/K19 with human autoimmune liver disease. We tested the hypothesis that K8/K18/K19 variants associate with primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterized by the presence of serum AMA. In doing so, we analyzed the entire exonic regions of K8/K18/K19 in 201 Italian patients and 200 control blood bank donors. Six disease-associated keratin heterozygous variants were identified in patients versus controls (K8 G62C/R341H/V380I, K18 R411H, and K19 G17S). Four variants were novel and included K19 G17S/V229M/N184N and K18 R411H. Overall, heterozygous keratin variants were found in 17 of 201 (8.5%) PBC patients and 4 of 200 (2%) blood bank donors (p<0.004, OR=4.53, 95% CI=1.5-13.7). Of the K19 variants, K19 G17S was found in 3 patients but not in controls; and all K8 R341H (8 patients and 3 controls) associated with concurrent presence of the previously-described intronic K8 IVS7+10delC deletion. Notably, keratin variants associated with disease severity (12.4% variants in Ludwig stage III/IV versus 4.2% in stages I/II; p<0.04, OR=3.25, 95% CI=1.02-10.40), but not with the presence of AMA. Conclusion: K8/K18/K19 variants are overrepresented in Italian PBC patients, and associate with liver disease progression. Therefore, we hypothesize that K8/K18/K19 variants may serve as genetic modifiers in PBC. PMID:19585610

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

    PubMed Central

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

    2013-01-01

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

  16. Novel variation at chr11p13 associated with cystic fibrosis lung disease severity.

    PubMed

    Dang, Hong; Gallins, Paul J; Pace, Rhonda G; Guo, Xue-Liang; Stonebraker, Jaclyn R; Corvol, Harriet; Cutting, Garry R; Drumm, Mitchell L; Strug, Lisa J; Knowles, Michael R; O'Neal, Wanda K

    2016-01-01

    Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism. PMID:27408752

  17. Novel variation at chr11p13 associated with cystic fibrosis lung disease severity

    PubMed Central

    Dang, Hong; Gallins, Paul J; Pace, Rhonda G; Guo, Xue-liang; Stonebraker, Jaclyn R; Corvol, Harriet; Cutting, Garry R; Drumm, Mitchell L; Strug, Lisa J; Knowles, Michael R; O’Neal, Wanda K

    2016-01-01

    Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism. PMID:27408752

  18. Autologous stem cell transplantation for severe autoimmune diseases: a 10-year experience.

    PubMed

    Gualandi, F; Bruno, B; Van Lint, M T; Luchetti, S; Uccelli, A; Capello, E; Mancardi, G L; Bacigalupo, A; Marmont, A

    2007-09-01

    The first autologous hematopoietic stem cell transplantation in Europe for a patient with severe refractory systemic lupus erythematosus (SLE) was performed in Genoa in 1996. Since then, 32 patients with a wide spectrum of autoimmune diseases (ADs) received autologous transplants, 22 of them with multiple sclerosis (MS). There were no fatal adverse events. All patients had complete or very good partial remissions, but relapses were frequent, especially in SLE, though never as aggressive as pretransplant. The mechanism of action of this intervention remains not completely understood, as briefly discussed here. PMID:17911461

  19. 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.

  20. A risk factor analysis on disease severity in 47 premature infants with bronchopulmonary dysplasia

    PubMed Central

    Li, Yan; Cui, Yazhou; Wang, Chao; Liu, Xiao; Han, Jinxiang

    2015-01-01

    Summary Bronchopulmonary Dysplasia (BPD) is a rare chronic lung disease and one of the most difficult complications to treat in premature infants. With the progress at the medical treatment level, an increasing number of BPD premature infants are born, meanwhile, they would be at an increasing risk for numerous complications and rehospitalization because BPD affects many vital organ systems. The pathogenesis of BPD is clearly multifactorial. As the prognosis is closely connected with the severity of BPD, early diagnosis and treatment are of great help to control the development of BPD. This article focuses on risk factors that could influence the severity of BPD in order to provide a reliable basis for early diagnosis, treatment, and better patient assessment. PMID:25984426

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

    PubMed Central

    Herrmann, Nathan; Gauthier, Serge

    2008-01-01

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

  2. 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. PMID:27299882

  3. Recurrent, severe wheezing is associated with morbidity and mortality in adults with sickle cell disease

    PubMed Central

    Cohen, Robyn T.; Madadi, Anusha; Blinder, Morey A.; DeBaun, Michael R.; Strunk, Robert C.; Field, Joshua J.

    2014-01-01

    Prior studies of asthma in children with sickle cell disease (SCD) were based on reports of a doctor-diagnosis of asthma with limited description of asthma features. Doctor-diagnoses of asthma may represent asthma or wheezing unrelated to asthma. Objectives of this study were to determine if asthma characteristics are present in adults with a doctor-diagnosis of asthma and/or wheezing, and to examine the relationship between doctor-diagnosis of asthma, wheezing and SCD morbidity. This was an observational cohort study of 114 adults with SCD who completed respiratory symptom questionnaires and had serum IgE measurements. A subset of 79 participants completed pulmonary function testing. Survival analysis was based on a mean prospective follow-up of 28 months and data were censored at the time of death or loss to follow-up. Adults reporting a doctor-diagnosis of asthma (N = 34) were more likely to have features of asthma including wheeze, eczema, family history of asthma, and an elevated IgE level (all P < 0.05). However, there was no difference in pain or ACS rate, lung function, or risk of death between adults with and without a doctor-diagnosis of asthma. In contrast, adults who reported recurrent, severe episodes of wheezing (N = 34), regardless of asthma, had twice the rates of pain and ACS, decreased lung function and increased risk of death compared with adults without recurrent, severe wheezing. Asthma features were not associated with recurrent, severe wheezing. Our data suggest that wheezing in SCD may occur independently of asthma and is a marker of disease severity. PMID:21809369

  4. Increased serum osteopontin levels in autistic children: relation to the disease severity.

    PubMed

    Al-ayadhi, Laila Y; Mostafa, Gehan A

    2011-10-01

    Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P<0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P=0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P=0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied. PMID:21521652

  5. Pulmonary function tests and impulse oscillometry in severe chronic obstructive pulmonary disease patients’ offspring

    PubMed Central

    Amra, Babak; Borougeni, Victoria Beigi; Golshan, Mohammad; Soltaninejad, Forogh

    2015-01-01

    Background: Several studies have showed an increased prevalence of airflow obstruction in first degree relatives of individuals with chronic obstructive pulmonary disease (COPD). Considering no specific research had evaluated airway resistance in offspring of patients with severe COPD, we utilized a spirometry and a impulse oscillometry (IO) to evaluate this population. Materials and Methods: In this case control study, from November 2011 to July 2012, we consecutively evaluated 54 offsprings of severe COPD patients (case group) admitted in the pulmonary ward, affiliated to the Isfahan University of Medical Sciences and control group. Pulmonary function tests and the IO were obtained for both groups. Student's t-test was used for inter-group comparisons, and P values below 0.05 were taken as significant. Results: Abnormal increased airway resistance was seen in cases in comparison with controls (R5 Hz [46.29%, P = 0.01], R25 Hz [42.59%, P < 0.001]). Also, considering the spirometry, case group had pulmonary function parameters less than control group (forced vital capacity [FVC]; P = 0.02, forced expiratory volume in 1st s; P < 0.001, forced expiratory flow (FEF) 25-75; P < 0.001, FEF 25-75/FVC; P < 0.001) but they were in normal range. Conclusion: This study demonstrated increased airway resistance among the severe COPD offsprings. The IO may be a sensitive tool for detection of high risk subjects in families with COPD. PMID:26622261

  6. 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

  7. Population programs for the detection of couples at risk for severe monogenic genetic diseases.

    PubMed

    Zlotogora, Joël

    2009-08-01

    Population genetic screening programs for carrier detection of severe genetic disorders exist worldwide, mainly for beta-thalassemia. These screening programs are either mandatory or voluntary. In several Arab countries and Iran, the state has made thalassemia carrier detection mandatory, while tests for detecting carriers are required by the religious authorities in Cyprus. In all the existing mandatory genetic screening programs, the couples have to get the information about the tests before marriage, but the decision whether or not to marry is left to them. Voluntary programs exist for instance in several Mediterranean countries for the prevention of thalassemia and for several genetic diseases among Jews. While voluntary programs leave the decision to be screened or not to the individual, a major problem is that in many cases awareness about the existence of screening tests is very sparse. Some programs, for instance in Canada or Australia, therefore provide education about genetic tests and screening at school in order to allow the individuals to be able to make an informed decision about their reproductive choices. PMID:19390864

  8. Characterization of severe hand, foot, and mouth disease in Shenzhen, China, 2009-2013.

    PubMed

    Huang, Yun; Zhou, Yuanping; Lu, Hong; Yang, Hong; Feng, Qianjin; Dai, Yingchun; Chen, Long; Yu, Shouyi; Yao, Xiangjie; Zhang, Hailong; Jiang, Ming; Wang, Yujie; Han, Ning; Hu, Guifang; He, Yaqing

    2015-09-01

    Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, especially by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Patients infected with different enteroviruses show varied clinical symptoms. The aim of this study was to determine whether the etiological spectrum of mild and severe HFMD changed, and the association between pathogens and clinical features. From 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. A dynamic view of the etiological spectrum of mild and severe HFMD in Shenzhen city of China was provided. EV71 accounted for the majority proportion of severe HFMD cases and fatalities during 2009-2013. CA16 and EV71 were gradually replaced by coxsackievirus A6 (CA6) as the most common serotype for mild HFMD since 2010. Myoclonic jerk and vomiting were the most frequent severe symptoms. Nervous system complications, including aseptic encephalitis and aseptic meningitis were observed mainly in patients infected by EV71. Among EV71, CA16, CA6, and CA10 infection, fever and pharyngalgia were more likely to develop, vesicles on the hand, foot, elbow, knee and buttock were less likely to develop in patients infected with CA10. Vesicles on the mouth more frequently occurred in the patients with CA6, but less in the patient with EV71. Associations between diverse enterovirus serotypes and various clinical features were discovered in the present study, which may offer further insight into early detection, diagnosis and treatment of HFMD. PMID:25951788

  9. 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. PMID:26210536

  10. Evaluation of the traditional and revised WHO classifications of Dengue disease severity.

    PubMed

    Narvaez, Federico; Gutierrez, Gamaliel; Pérez, Maria Angeles; Elizondo, Douglas; Nuñez, Andrea; Balmaseda, Angel; Harris, Eva

    2011-11-01

    Dengue is a major public health problem worldwide and continues to increase in incidence. Dengue virus (DENV) infection leads to a range of outcomes, including subclinical infection, undifferentiated febrile illness, Dengue Fever (DF), life-threatening syndromes with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. The long-standing World Health Organization (WHO) dengue classification and management scheme was recently revised, replacing DF, Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) with Dengue without Warning Signs, Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure). We evaluated the traditional and revised classification schemes against clinical intervention levels to determine how each captures disease severity using data from five years (2005-2010) of a hospital-based study of pediatric dengue in Managua, Nicaragua. Laboratory-confirmed dengue cases (n = 544) were categorized using both classification schemes and by level of care (I-III). Category I was out-patient care, Category II was in-patient care that did not meet criteria for Category III, which included ICU admission, ventilation, administration of inotropic drugs, or organ failure. Sensitivity and specificity to capture Category III care for DHF/DSS were 39.0% and 75.5%, respectively; sensitivity and specificity for SD were 92.1% and 78.5%, respectively. In this data set, DENV-2 was found to be significantly associated with DHF/DSS; however, this association was not observed with the revised classification. Among dengue-confirmed cases, the revised WHO classification for severe dengue appears to have higher sensitivity and specificity to identify cases in need of heightened care, although it is no longer as

  11. Changing prevalence of severe congenital heart disease: a population-based study.

    PubMed

    Egbe, Alexander; Uppu, Santosh; Lee, Simon; Ho, Deborah; Srivastava, Shubhika

    2014-10-01

    Although the epidemiology of congenital heart disease (CHD) has been described, the authors believe changes in prenatal factors such as termination of pregnancy for fetal anomaly and prenatal vitamin supplementation have altered the birth prevalence of severe CHD. This population-based study reviewed the Nationwide Inpatient Sample (NIS) database and identified all cases with a severe CHD diagnosis among all live birth entries from 1999 to 2008. A time trend analysis then was performed for specific severe CHD diagnoses stratified by race, socioeconomic status, and geographic location. Overall, severe CHD prevalence was 147.4 per 100,000 live births, with a temporal decrease in prevalence from 168.9 per 100,000 in 1999 to 129.3 per 100,000 in 2008 (p = 0.03). Among the 12 severe CHD diagnoses included in our cohort, the prevalence of truncus arteriosus (p = 0.02), tetralogy of Fallot (p = 0.001), hypoplastic left heart syndrome (p = 0.001), and pulmonary atresia (p = 0.01) decreased significantly during the study period. The observed prevalence trends varied significantly by race (Caucasians), socioeconomic class (upper income quartiles), and geographic location (Northeast and West regions). The study findings showed a temporal decrease in severe CHD prevalence, which varied by race, socioeconomic status, and geographic location. The authors speculated that the observed trend might be due to increased termination of fetuses with prenatally diagnosed CHD. The impact of sociodemographic variables on the observed prevalence trend might be due to differences in access to specialized perinatal care and fetal heart programs or because of variability in termination of pregnancy. PMID:24823884

  12. Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity.

    PubMed

    Wang, S-M; Ho, T-S; Lin, H-C; Lei, H-Y; Wang, J-R; Liu, C-C

    2012-06-01

    Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 ± 14.7 months) were younger than patients with herpangina/HFMD (35.8 ± 26.4 months) or ANS dysregulation (33.9 ± 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71. PMID:21983920

  13. 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. PMID:22806903

  14. Awareness and knowledge of prophylaxis for infective endocarditis in patients with severe rheumatic heart disease.

    PubMed

    Maharaj, B; Vayej, A C

    2013-03-01

    Prevention of infective endocardit s (IE) is mportant because it has a high mortalty rate.This study sets out to to gather information from patients who were at risk of developing IE of their knowledge of the need for prophylaxis for the disease. Forty-one black patients suffering from severe rheumatic heart disease (RHD) were interviewed. Only one patient (2.4%) was regularly visiting a dentist to maintain good oral health and only five (12.2%) had received advice about the need for antibiotic cover prior to dental extraction. The vast majority of patients (97.5%) visited a dentist only when driven by dental pain, 36.6 % had to travel for more than an hour to reach their nearest dentist, and 87.8% indicated that they brushed their teeth. It may be concluded that in this group of black patients with severe RHD there was a lack of knowledge of the need for and of measures recommended for prophylaxs against IE. In addition, attempts by the health care team to ensure good oral health and access to dental care for these patients were inadequate, if not non-existent. PMID:23951767

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

    PubMed

    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; Orange, Jordan S; 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; van Haaften, Gijs

    2016-08-01

    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

  16. 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. PMID:25413686

  17. The Relationship between P & QT Dispersions and Presence & Severity of Stable Coronary Artery Disease

    PubMed Central

    Yıldırım, Erkan; Ipek, Emrah; Cengiz, Mahir; Aslan, Kursat; Poyraz, Esra; Demirelli, Selami; Bayantemur, Murat; Ermis, Emrah; Ciftci, Cavlan

    2016-01-01

    Background and Objectives The study aimed to evaluate the correlation between electrocardiographic (ECG) parameters and presence and extent of coronary artery disease (CAD) to indicate the usefulness of these parameters as predictors of severity in patients with stable CAD. Subjects and Methods Two hundred fifty patients, without a history of any cardiovascular event were included in the study. The ECG parameters were measured manually by a cardiologist before coronary angiography. The patients were allocated into five groups: those with normal coronary arteries (Group 1), non-critical coronary lesions (Group 2), one, two and three vessel disease (Group 3, Group 4 and Group 5, respectively. Results Group 1 had the lowest P wave dispersion (PWD) and P wave (Pmax), QT interval (QTmax), QT dispersion (QTd), corrected QT dispersion (QTcd) and QT dispersion ratio (QTdR), while the patients in group 5 had the highest values of these parameters. Gensini score and QTmax, QTd, QTcmax, QTcd, QTdR, Pmax, and PWD were positively correlated. QTdR was the best ECG parameter to differentiate group 1 and 2 from groups with significant stenosis (groups 3, 4, and 5) (area under curve [AUC] 0.846). QTdR was the best ECG parameter to detect coronary arterial narrowing lesser than 50% and greater than 50%, respectively (AUC 0.858). Conclusion Presence and severity of CAD can be determined by using ECG in patients with stable CAD and normal left ventricular function. PMID:27482261

  18. Ophthalmologic correlates of disease severity in children and adolescents with Wolfram syndrome

    PubMed Central

    Hoekel, James; Chisholm, Smith Ann; Al-Lozi, Amal; Hershey, Tamara; Tychsen, Lawrence

    2015-01-01

    Purpose To describe an ophthalmic phenotype in children at relatively early stages of Wolfram syndrome. Methods Quantitative ophthalmic testing of visual acuity, color vision, automated visual field sensitivity, optic nerve pallor and cupping, and retinal nerve fiber layer (RNFL) thickness assessed by optical coherence tomography (OCT) was performed in 18 subjects 5–25 years of age. Subjects were also examined for presence or absence of afferent pupillary defects, cataracts, nystagmus, and strabismus. Results Subnormal visual acuity was detected in 89% of subjects, color vision deficits in 94%, visual field defects in 100%, optic disk pallor in 94%, abnormally large optic nerve cup:disk ratio in 33%, thinned RNFL in 100%, afferent pupillary defects in 61%, cataracts in 22%, nystagmus in 39%, and strabismus in 39% of subjects. RNFL thinning (P < 0.001), afferent pupillary defects (P = 0.01), strabismus (P = 0.04), and nystagmus (P = 0.04) were associated with more severe disease using the Wolfram United Rating Scale. Conclusions Children and adolescents with Wolfram syndrome have multiple ophthalmic markers that correlate with overall disease severity. RNFL thickness measured by OCT may be the most reliable early marker. PMID:25439303

  19. Role of Maternal Antibodies in Infants with Severe Diseases Related to Human Parechovirus Type 31

    PubMed Central

    Aizawa, Yuta; Watanabe, Kanako; Oishi, Tomohiro; Hirano, Harunobu; Hasegawa, Isao

    2015-01-01

    Human parechovirus type 3 (HPeV3) is an emerging pathogen that causes sepsis and meningoencephalitis in young infants. To test the hypothesis that maternal antibodies can protect this population, we measured neutralizing antibody titers (NATs) to HPeV3 and other genotypes (HPeV1 and HPeV6) in 175 cord blood samples in Japan. The seropositivity rate (>1:32) for HPeV3 was 61%, similar to that for the other genotypes, but decreased significantly as maternal age increased (p<0.001). Furthermore, during the 2014 HPeV3 epidemic, prospective measurement of NATs to HPeV3 in 45 patients with severe diseases caused by HPeV3 infection showed low NATs (<1:16) at onset and persistently high NATs (>1:512) until age 6 months. All intravenous immunoglobulin samples tested elicited high NATs to HPeV3. Our findings indicate that maternal antibodies to HPeV3 may help protect young infants from severe diseases related to HPeV3 and that antibody supplementation may benefit these patients. PMID:26485714

  20. Acute Atherothrombotic Disease and Severe Bleeding: A Difficult Clinical Presentation in Medical Practice.

    PubMed

    Căldăraru, Cristina; Popa, C; Fruntelată, Ana; Bălănescu, Ş

    2015-01-01

    Management of antithrombotic therapy in elderly patients with unstable atherothrombotic disease and increased risk of bleeding is a major clinical challenge. We report the case of a 79 year- old diabetic man with rheumatoid arthritis on both oral corticosteroids and NSAID therapy with mild renal dysfunction, who presented to our hospital because of disabling claudication. Prior to admission he had several episodes of TIA. He also had recurrent small rectal bleeding and mild anemia attributed to his long-standing hemorrhoid disease. Angiography showed a sub-occlusive left internal carotid artery stenosis associated with a significant LAD stenosis and complex peripheral artery disease. Cataclysmic bleeding and hemorrhagic shock occurred in the third day post admission. Withdrawal of all antithrombotic treatment, blood transfusion and emergency sigmoidectomy were performed for bleeding colonic diverticulosis. Subsequently antiplatelet therapy was reinitiated and the patient successfully underwent left carotid artery endarterectomy and LAD stenting. He was discharged from hospital on the 21(st) day post admission and is doing well at 24 months follow-up. PMID:26939212

  1. N17 Modifies Mutant Huntingtin Nuclear Pathogenesis and Severity of Disease in HD BAC Transgenic Mice

    PubMed Central

    Gu, Xiaofeng; Cantle, Jeffrey P.; Greiner, Erin R.; Lee, C.Y. Daniel; Barth, Albert M.; Gao, Fuying; Park, Chang Sin; Zhang, Zhiqiang; Sandoval-Miller, Susana; Zhang, Richard L.; Diamond, Marc; Mody, Istvan; Coppola, Giovanni

    2015-01-01

    SUMMARY The nucleus is a critical subcellular compartment for the pathogenesis of polyglutamine disorders, including Huntington’s disease (HD). Recent studies suggest the first 17-amino-acid domain (N17) of mutant Huntingtin (mHTT) mediates its nuclear exclusion in cultured cells. Here, we test whether N17 could be a molecular determinant of nuclear mHTT pathogenesis in vivo. BAC transgenic mice expressing mHTT lacking the N17 domain (BACHD-ΔN17) show dramatically accelerated mHTT pathology exclusively in the nucleus, which is associated with HD-like transcriptionopathy. Interestingly, BACHD-ΔN17 mice manifest more overt disease-like phenotypes than the original BACHD mice, including body weight loss, movement deficits, robust striatal neuronal loss, and neuroinflammation. Mechanistically, N17 is necessary for nuclear exclusion of small mHTT fragments that are part of nuclear pathology in HD. Together, our study suggests that N17 modifies nuclear pathogenesis and disease severity in HD mice by regulating subcellular localization of known nuclear pathogenic mHTT species. PMID:25661181

  2. Race/ethnicity and disease severity in IgA nephropathy

    PubMed Central

    Hall, Yoshio N; Fuentes, Eloisa F; Chertow, Glenn M; Olson, Jean L

    2004-01-01

    Background Relatively few U.S.-based studies in chronic kidney disease have focused on Asian/Pacific Islanders. Clinical reports suggest that Asian/Pacific Islanders are more likely to be affected by IgA nephropathy (IgAN), and that the severity of disease is increased in these populations. Methods To explore whether these observations are borne out in a multi-ethnic, tertiary care renal pathology practice, we examined clinical and pathologic data on 298 patients with primary glomerular lesions (IgAN, focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease) at the University of California San Francisco Medical Center from November 1994 through May 2001. Pathologic assessment of native kidney biopsies with IgAN was conducted using Haas' classification system. Results Among individuals with IgAN (N = 149), 89 (60%) were male, 57 (38%) white, 53 (36%) Asian/Pacific Islander, 29 (19%) Hispanic, 4 (3%) African American and 6 (4%) were of other or unknown ethnicity. The mean age was 37 ± 14 years and median serum creatinine 1.7 mg/dL. Sixty-six patients (44%) exhibited nephrotic range proteinuria at the time of kidney biopsy. The distributions of age, gender, mean serum creatinine, and presence or absence of nephrotic proteinuria and/or hypertension at the time of kidney biopsy were not significantly different among white, Hispanic, and Asian/Pacific Islander groups. Of the 124 native kidney biopsies with IgAN, 10 (8%) cases were classified into Haas subclass I, 12 (10%) subclass II, 23 (18%) subclass III, 30 (25%) subclass IV, and 49 (40%) subclass V. The distribution of Haas subclass did not differ significantly by race/ethnicity. In comparison, among the random sample of patients with non-IgAN glomerular lesions (N = 149), 77 (52%) patients were male, 51 (34%) white, 42 (28%) Asian/Pacific Islander, 25 (17%) Hispanic, and 30 (20%) were African American. Conclusions With the caveats of referral and biopsy biases, the race

  3. Fully Automated Assessment of the Severity of Parkinson’s Disease from Speech

    PubMed Central

    Bayestehtashk, Alireza; Asgari, Meysam; Shafran, Izhak; McNames, James

    2014-01-01

    For several decades now, there has been sporadic interest in automatically characterizing the speech impairment due to Parkinson’s disease (PD). Most early studies were confined to quantifying a few speech features that were easy to compute. More recent studies have adopted a machine learning approach where a large number of potential features are extracted and the models are learned automatically from the data. In the same vein, here we characterize the disease using a relatively large cohort of 168 subjects, collected from multiple (three) clinics. We elicited speech using three tasks – the sustained phonation task, the diadochokinetic task and a reading task, all within a time budget of 4 minutes, prompted by a portable device. From these recordings, we extracted 1582 features for each subject using openSMILE, a standard feature extraction tool. We compared the effectiveness of three strategies for learning a regularized regression and find that ridge regression performs better than lasso and support vector regression for our task. We refine the feature extraction to capture pitch-related cues, including jitter and shimmer, more accurately using a time-varying harmonic model of speech. Our results show that the severity of the disease can be inferred from speech with a mean absolute error of about 5.5, explaining 61% of the variance and consistently well-above chance across all clinics. Of the three speech elicitation tasks, we find that the reading task is significantly better at capturing cues than diadochokinetic or sustained phonation task. In all, we have demonstrated that the data collection and inference can be fully automated, and the results show that speech-based assessment has promising practical application in PD. The techniques reported here are more widely applicable to other paralinguistic tasks in clinical domain. PMID:25382935

  4. Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide.

    PubMed

    Tiev, K P; Cabane, J; Aubourg, F; Kettaneh, A; Ziani, M; Mouthon, L; Duong-Quy, S; Fajac, I; Guillevin, L; Dinh-Xuan, A T

    2007-07-01

    The alveolar concentration of exhaled nitric oxide (CA,(NO)) is increased in patients with systemic sclerosis (SSc), but whether this increase is related to the severity of interstitial lung disease (ILD) in SSc has not yet been investigated. In total, 58 SSc patients prospectively underwent pulmonary function tests (PFTs), echocardiogram and fibrosis scoring on pulmonary computed tomography (CT). Patients were divided into two groups according to the presence (or not) of ILD. Measurements of CA,(NO) were assessed in all SSc patients and compared with those obtained in 19 healthy volunteers. Relationships were sought between CA,(NO) PFTs and CT scan fibrosis scores. Overall, CA,(NO) was significantly increased in SSc patients (median (range) 6.2 (3.8-9.9) ppb) as compared with controls (2.0 (1.2-3.0) ppb). Among SSc patients, CA,(NO) was significantly higher in patients with ILD compared with patients without ILD (n = 33, 7.5 (5.2-11.9) ppb versus n = 25, 4.9 (3.1-7.0) ppb, respectively). CA,(NO) was inversely related to total lung capacity (r = -0.34) and the diffusing capacity of the lung for carbon monoxide (r = -0.37) and was directly related to CT scan fibrosis scores (r = 0.36). An increased alveolar concentration of exhaled nitric oxide could, at least in part, either reflect or contribute to the severity of lung disease and could be used to noninvasively assess the extent of interstitial lung disease in systemic sclerosis. PMID:17428812

  5. Intense immunosuppressive therapy followed by autologous peripheral blood selected progenitor cell reinfusion for severe autoimmune disease.

    PubMed

    Musso, M; Porretto, F; Crescimanno, A; Bondi, F; Polizzi, V; Scalone, R

    2001-02-01

    Autologous stem cell transplantation (HSCT) has been shown to be effective in curing a large spectrum of autoimmune disorders. Case reports are being collected in the EBMT/EULAR Autoimmune Disease Stem Cell Project registry, which reports transplant-related mortality (TRM) of 6%. In order to reduce TRM and preserve the anti-autoimmune effect we evaluated a more immunoablative as opposed to myeloablative conditioning regimen for the autotransplant of severe immunomediated diseases. We enrolled patients affected by systemic lupus erythematosus (SLE: 3 patients), by autoimmune thrombocytopenic purpura (AITP: one patient), by thrombotic thrombocytopenic purpura (TTP: one patient), by pure red cell aplasia (PRCA: one patient), and by a severe cryoglobulinemia (one patient). All patients were mobilized with cyclophosphamide (Cy) 4 g/m2 + G-csf. Conditioning regimen consisted of Cy 50 mg/kg/day (days -6 and -5); anti-T-globulin (ATG) 10 mg/kg/day and 6-methylprednisolone (PDN) 1 g/day (days -4, -3, and -2). Immunomagnetically selected CD34+ cells were re-infused on day 0. In three patients neutrophil count fell below 0.5 x 10(9)/l, while a PLT count below 20 x 10(9)/l was registered in two patients. Extrahematological toxicity was very low. Four patients (2 SLE, 1 TTP, 1 cryoglobulinemia) are in complete corticosteroid-free remission with a median follow up of 335 days. The third SLE patient improved considerably; however, he still needs low-dose corticosteroid maintenance. The AITP and PRCA patients achieved a CR but soon relapsed; nevertheless, the procedure restored a steroid-sensitive status. The use of this immunoablative conditioning regimen in auto-HSCT transplant was shown to be effective in controlling disease progression and could be a valuable strategy in reducing TRM. PMID:11421302

  6. Fully Automated Assessment of the Severity of Parkinson's Disease from Speech.

    PubMed

    Bayestehtashk, Alireza; Asgari, Meysam; Shafran, Izhak; McNames, James

    2015-01-01

    For several decades now, there has been sporadic interest in automatically characterizing the speech impairment due to Parkinson's disease (PD). Most early studies were confined to quantifying a few speech features that were easy to compute. More recent studies have adopted a machine learning approach where a large number of potential features are extracted and the models are learned automatically from the data. In the same vein, here we characterize the disease using a relatively large cohort of 168 subjects, collected from multiple (three) clinics. We elicited speech using three tasks - the sustained phonation task, the diadochokinetic task and a reading task, all within a time budget of 4 minutes, prompted by a portable device. From these recordings, we extracted 1582 features for each subject using openSMILE, a standard feature extraction tool. We compared the effectiveness of three strategies for learning a regularized regression and find that ridge regression performs better than lasso and support vector regression for our task. We refine the feature extraction to capture pitch-related cues, including jitter and shimmer, more accurately using a time-varying harmonic model of speech. Our results show that the severity of the disease can be inferred from speech with a mean absolute error of about 5.5, explaining 61% of the variance and consistently well-above chance across all clinics. Of the three speech elicitation tasks, we find that the reading task is significantly better at capturing cues than diadochokinetic or sustained phonation task. In all, we have demonstrated that the data collection and inference can be fully automated, and the results show that speech-based assessment has promising practical application in PD. The techniques reported here are more widely applicable to other paralinguistic tasks in clinical domain. PMID:25382935

  7. 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

  8. Polymorphisms associated with expression of BPIFA1/BPIFB1 and lung disease severity in cystic fibrosis.

    PubMed

    Saferali, Aabida; Obeidat, Ma'en; Bérubé, Jean-Christophe; Lamontagne, Maxime; Bossé, Yohan; Laviolette, Michel; Hao, Ke; Nickle, David C; Timens, Wim; Sin, Don D; Postma, Dirkje S; Strug, Lisa J; Gallins, Paul J; Paré, Peter D; Bingle, Colin D; Sandford, Andrew J

    2015-11-01

    BPI fold containing family A, member 1 (BPIFA1) and BPIFB1 are putative innate immune molecules expressed in the upper airways. Because of their hypothesized roles in airway defense, these molecules may contribute to lung disease severity in cystic fibrosis (CF). We interrogated BPIFA1/BPIFB1 single-nucleotide polymorphisms in data from an association study of CF modifier genes and found an association of the G allele of rs1078761 with increased lung disease severity (P = 2.71 × 10(-4)). We hypothesized that the G allele of rs1078761 is associated with decreased expression of BPIFA1 and/or BPIFB1. Genome-wide lung gene expression and genotyping data from 1,111 individuals with lung disease, including 51 patients with CF, were tested for associations between genotype and BPIFA1 and BPIFB1 gene expression levels. Findings were validated by quantitative PCR in a subset of 77 individuals. Western blotting was used to measure BPIFA1 and BPIFB1 protein levels in 93 lung and 101 saliva samples. The G allele of rs1078761 was significantly associated with decreased mRNA levels of BPIFA1 (P = 4.08 × 10(-15)) and BPIFB1 (P = 0.0314). These findings were confirmed with quantitative PCR and Western blotting. We conclude that the G allele of rs1078761 may be detrimental to lung function in CF owing to decreased levels of BPIFA1 and BPIFB1. PMID:25574903

  9. Living and dying with severe chronic obstructive pulmonary disease: multi-perspective longitudinal qualitative study

    PubMed Central

    Kendall, Marilyn; Murray, Scott A; Worth, Allison; Levack, Pamela; Porter, Mike; MacNee, William; Sheikh, Aziz

    2011-01-01

    Objectives To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD. Design Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months. Interviews were transcribed and analysed both thematically and as narratives. Participants 21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients. Setting Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9. Results Eleven patients died during the study period. Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together). Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.” Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition. Professional carers’ familiarity with the patients’ condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease. Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population. Conclusions Our findings challenge current assumptions underpinning provision of end of life care for people with COPD. The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care. Careful

  10. 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

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

    PubMed

    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

  12. Disease Severity and Mortality Can Be Independently Regulated in a Mouse Model of Experimental Graft versus Host Disease

    PubMed Central

    Galvani, Rômulo G.; Lemos, Ramon; Areal, Rômulo B.; Salvador, Pollyanna A.; Zamboni, Dario S.; Wanderley, João Luiz M.; Bonomo, Adriana

    2015-01-01

    Graft versus host disease (GVHD) is the major limitation of allogeneic hematopoietic stem cell transplantation (HSCT) presenting high mortality and morbidity rates. However, the exact cause of death is not completely understood and does not correlate with specific clinical and histological parameters of disease. Here we show, by using a semi-allogeneic mouse model of GVHD, that mortality and morbidity can be experimentally separated. We injected bone marrow-derived dendritic cells (BMDC) from NOD2/CARD15-deficient donors into semi-allogeneic irradiated chimaeras and observed that recipients were protected from death. However, no protection was observed regarding clinical or pathological scores up to 20 days after transplantation. Protection from death was associated with decreased bacterial translocation, faster hematologic recovery and epithelial integrity maintenance despite mononuclear infiltration at day 20 post-GVHD induction with no skew towards different T helper phenotypes. The protected mice recovered from aGVHD and progressively reached scores compatible with healthy animals. Altogether, our data indicate that severity and mortality can be separate events providing a model to study transplant-related mortality. PMID:25643148

  13. Endoscopic evaluation of celiac disease severity and its correlation with histopathological aspects of the duodenal mucosa

    PubMed Central

    Bonatto, Mauro W.; Kotze, Luiz; Orlandoski, Marcia; Tsuchyia, Ricardo; de Carvalho, Carlos A.; Lima, Doryane; Kurachi, Gustavo; Orso, Ivan R.B.; Kotze, Lorete

    2016-01-01

    Background and study aims: Celiac disease (CD) is a chronic systemic autoimmune disorder affecting genetically predisposed individuals, triggered and maintained by the ingestion of gluten. Triggered and maintained by the ingestion of gluten, celiac disease is a chronic systemic autoimmune disorder affecting genetically predisposed individuals. Persistent related inflammation of the duodenal mucosa causes atrophy architecture detectable on esophagogastroduodenoscopy (EGD) and histopathology. We investigated the association between endoscopic features and histopathological findings (Marsh) for duodenal mucosa in celiac disease patients and propose an endoscopic classification of severity. Patients and methods: Between January 2000 and March 2010, an electronic database containing 34,540 EDGs of patients aged > 14 years was searched for cases of CD. Out of 109 cases, 85 met the inclusion criteria: conventional EGD combined with chromoendoscopy, zoom and biopsy. EGD types 0, I and II corresponds to Marsh grades 0, 1 and 2, respectively, while EGD type III corresponds to Marsh grade 3 and 4. Results: Five patients (5.8 %) were EGD I but not Marsh grade 1; 25 patients (29.4 %) were EGD II, 4 of whom (16 %) were classified as Marsh grade 2; and 55 patients (64.7 %) were EGD III, 51 (92.7 %) of whom were classified as Marsh grades 3 and 4. The Spearman correlation coefficient (r = 0.33) revealed a significant association between the methods (P = 0.002). Conclusions: Changes in the duodenal mucosa detected on EGD were significantly and positively associated with histopathologic findings. The use of chromoendoscopy in addition to conventional EGD enhances changes in the duodenal mucosa and permits diagnosis of CD, even in routine examinations. The proposed endoscopic classification is practical and easily reproducible and provides valuable information regarding disease extension. PMID:27556094

  14. Altered cortical thickness related to clinical severity but not the untreated disease duration in schizophrenia.

    PubMed

    Xiao, Yuan; Lui, Su; Deng, Wei; Yao, Li; Zhang, Wenjing; Li, Shiguang; Wu, Min; Xie, Teng; He, Yong; Huang, Xiaoqi; Hu, Junmei; Bi, Feng; Li, Tao; Gong, Qiyong

    2015-01-01

    Although previous studies have reported deficits in the gray matter volume of schizophrenic patients, it remains unclear whether these deficits occur at the onset of the disease, before treatment, and whether they are progressive over the duration of untreated disease. Furthermore, the gray matter volume represents the combinations of cortical thickness and surface area; these features are believed to be influenced by different genetic factors. However, cortical thickness and surface area in antipsychotic-naive first-episode schizophrenic patients have seldom been investigated. Here, the cortical thicknesses and surface areas of 128 antipsychotic-naive first-episode schizophrenic patients were compared with 128 healthy controls. The patients exhibited significantly lower cortical thickness, primarily in the bilateral prefrontal and parietal cortex, and increased thickness in the bilateral anterior temporal lobes, left medial orbitofrontal cortex, and left cuneus. Furthermore, decreased cortical thickness was related to positive schizophrenia symptoms but not to the severity of negative symptoms and the untreated disease duration. No significant difference of surface area was observed between the 2 groups. Thus, without the confounding factors of medication and illness progression, this study provides further evidence to support anatomical deficits in the prefrontal and parietal cortex early in course of the illness. The increased thicknesses of the bilateral anterior temporal lobes may represent a compensatory factor or may be an early-course neuronal pathology caused by preapoptotic osmotic changes or hypertrophy. Furthermore, these anatomical deficits are crucial to the pathogenesis of positive symptoms and relatively stable instead of progressing during the early stages of the disease. PMID:24353097

  15. Molecular epidemiology and disease severity of human respiratory syncytial virus in Vietnam.

    PubMed

    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

  16. 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

  17. Breathing pattern and carbon dioxide retention in severe chronic obstructive pulmonary disease.

    PubMed Central

    Gorini, M.; Misuri, G.; Corrado, A.; Duranti, R.; Iandelli, I.; De Paola, E.; Scano, G.

    1996-01-01

    BACKGROUND: The factors leading to chronic hypercapnia and rapid shallow breathing in patients with severe chronic obstructive pulmonary disease (COPD) are not completely understood. In this study the interrelations between chronic carbon dioxide retention, breathing pattern, dyspnoea, and the pressure required for breathing relative to inspiratory muscle strength in stable COPD patients with severe airflow obstruction were studied. METHODS: Thirty patients with COPD in a clinically stable condition with forced expiratory volume in one second (FEV1) of < 1 litre were studied. In each patient the following parameters were assessed: (1) dyspnoea scale rating, (2) inspiratory muscle strength by measuring minimal pleural pressure (PPLmin), and (3) tidal volume (VT), flow, pleural pressure swing (PPLsw), total lung resistance (RL), dynamic lung elastance (ELdyn), and positive end expiratory alveolar pressure (PEEPi) during resting breathing. RESULTS: Arterial carbon dioxide tension (PaCO2) related directly to RL/PPLmin, and ELdyn/PPLmin, and inversely to VT and PPLmin. There was no relationship between PaCO2 and functional residual capacity (FRC), total lung capacity (TLC), or minute ventilation. PEEPi was similar in eucapnic and hypercapnic patients. Expressing PaCO2 as a combined function of VT and PPLmin (stepwise multiple regression analysis) explained 71% of the variance in PaCO2. Tidal volume was directly related to inspiratory time (TI), and TI was inversely related to the pressure required for breathing relative to inspiratory muscle strength (PPLsw, %PPLmin). There was an association between the severity of dyspnoea and both the increase in PPLsw (%PPLmin) and the shortening in TI. CONCLUSIONS: The results indicate that, in stable patients with COPD with severe airflow obstruction, hypercapnia is associated with shallow breathing and inspiratory muscle weakness, and rapid and shallow breathing appears to be linked to both a marked increase in the pressure

  18. CCL2 Responses to Mycobacterium tuberculosis Are Associated with Disease Severity in Tuberculosis

    PubMed Central

    Hasan, Zahra; Cliff, Jacqueline M.; Dockrell, Hazel M.; Jamil, Bushra; Irfan, Muhammad; Ashraf, Mussarat; Hussain, Rabia

    2009-01-01

    Background Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. Methodology We investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, n = 16). Secretion of CCL2, IFNγ, IL10 and CCL3, and mRNA expression of CCL2, TNFα, CCL3 and CXCL8 were determined. Results M. tuberculosis- and BCG- induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01) as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023), while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005) patients. M. tuberculosis –induced IFNγ was greater in L-ETB than PTB (p = 0.04), while BCG-induced IFNγ was greater in L-ETB as compared with D-ETB patients (p = 0.036). TNFα mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02) and BCG (p = 0.03). Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups. Conclusions The increased CCL2 and TNFα in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease. PMID

  19. Case report: Severe hemolytic disease of the fetus and newborn due to anti-C+G.

    PubMed

    Jernman, Riina; Stefanovic, Vedran; Korhonen, Anu; Haimila, Katri; Sareneva, Inna; Sulin, Kati; Kuosmanen, Malla; Sainio, Susanna

    2015-01-01

    Anti-G is commonly present with anti-D and/or anti-C and can confuse serological investigations. in general, anti-G is not considered a likely cause of severe hemolytic disease of the fetus and newborn (HDFN), but it is important to differentiate it from anti-D in women who should be administered anti-D immunoglobulin prophylaxis. We report one woman with three pregnancies severely affected by anti-C+G requiring intrauterine treatment and a review of the literature. In our case, the identification of the correct antibody was delayed because the differentiation of anti-C+G and anti-D+C was not considered important during pregnancy since the father was D-. In addition, anti-C+G and anti-G titer levels were not found to be reliable as is generally considered in Rh immunization. Severe HDFN occurred at a maternal anti-C+G antibody titer of S and anti-G titer of 1 in comparison with the critical titer level of 16 or more in our laboratory. close collaboration between the immunohematology laboratory and the obstetric unit is essential. In previously affected families, early assessment for fetal anemia is required even when titers are low. PMID:26829179

  20. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients

    PubMed Central

    Obed, Aiman; Stern, Steffen; Jarrad, Anwar; Lorf, Thomas

    2015-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed. PMID:25892898

  1. 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

  2. New norms new policies: Did the Adelaide Thinkers in Residence scheme encourage new thinking about promoting well-being and Health in All Policies?

    PubMed

    Baum, Fran; Lawless, Angela; MacDougall, Colin; Delany, Toni; McDermott, Dennis; Harris, Elizabeth; Williams, Carmel

    2015-12-01

    Health systems have long been criticised for focussing on curing rather than preventing disease. This paper examines to what extent the Adelaide Thinkers in Residence (ATiR) scheme contributed to the change in norms whereby promoting well-being and a strategy to achieve this - Health in All Policies (HiAP)--was adopted by the South Australian (SA) State Government from 2007. The data presented in this paper are drawn from a five year (2012-2016) detailed mixed methods case study of the SA HiAP initiative which involved document analysis, interviews and workshops with public servants and political actors. We adapt the framework used by Finnemore and Sikkink (1998) which explains how norm changes can lead to political changes in international affairs. We also use Kingdon's concept of policy entrepreneurs to determine whether these ideas moved to an implementable initiative with the help of both a specific ATiR program on HiAP and the broader TiR scheme which promoted a series of innovations relevant to health. The process involved the ATiR reinforcing the work of local norm entrepreneurs with that of powerful external policy entrepreneurs, adapting the discourse about the value of prevention and promoting well-being so that it fitted with the dominant economic one. The powerful organisational platform of the ATiR, which was under the Department of the Premier and Cabinet and linked to the South Australian Strategic Plan (SASP) was used to advance these ideas. The case study offers important lessons for other jurisdictions on how to shift policy to encourage intersectoral approaches to health. PMID:26520058

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

    PubMed Central

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

    2016-01-01

    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. PMID:26493179

  4. 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. PMID:27043052

  5. A Rare Case of Parkinson's Disease with Severe Neck Pain Owing to Crowned Dens Syndrome

    PubMed Central

    Takahashi, Teruyuki; Tamura, Masato; Osabe, Keiichi; Tamiya, Takashi; Miki, Kenji; Yamaguchi, Mai; Akira, Kanno; Kamei, Satoshi; Takasu, Toshiaki

    2014-01-01

    Background Pain is regarded as one of the most common nonmotor symptoms in Parkinson's disease (PD). In particular, musculoskeletal pain has been reported as the most common type of PD-associated pain. Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Case Presentation This report describes the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity, gait disturbance and neck pain. Laboratory examination revealed marked elevations of white blood cells (10,100/µl) and C-reactive protein (CRP; 8.63 mg/dl). She was primarily diagnosed with severe and untreated PD, corresponding to Hoehn and Yahr scale score IV, with musculoskeletal pain and urinary tract infection. The patient was treated with antiparkinsonism drugs, antibiotic agents and nonsteroidal anti-inflammatory drugs, but they had only limited effects. Cervical plain computed tomography (CT) scanning detected remarkable crown-like calcification surrounding the odontoid process. Based on CT findings, the patient was diagnosed as having CDS with PD, and was immediately treated with corticosteroid. The severe neck rigidity with pain and the serum CRP level (0.83 mg/dl) of the patient were drastically improved within a week by the additional corticosteroid therapy. Conclusion Severe neck rigidity and bradykinesia in this patient might have strengthened the chondrocalcinosis around the odontoid process. Cervical plain CT scan is necessary and useful for the definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for musculoskeletal pain related to rigidity and bradykinesia in PD. PMID:24926265

  6. Th-U-total Pb geochronology of authigenic monazite in the Adelaide rift complex, South Australia, and implications for the age of the type Sturtian and Marinoan glacial deposits

    NASA Astrophysics Data System (ADS)

    Mahan, K. H.; Wernicke, B. P.; Jercinovic, M. J.

    2010-01-01

    The Adelaide rift complex in South Australia contains the type sections for Sturtian and Marinoan glacial deposits. The litho- and chemo-stratigraphy of these deposits play a central role in evaluating global Neoproterozoic ice age hypotheses and Rodinia supercontinent reconstructions, but reliable depositional age constraints have been extremely limited. We report results of in situ Th-U-total Pb (electron microprobe) dating of detrital and authigenic monazite in two samples from the Umberatana Group (Sturtian Holowilena Ironstone and pre-Marinoan Enorama Shale) in the Central Flinders Ranges. Several texturally and chemically distinct detrital and authigenic populations are recognized. Detrital dates range from 1600 Ma to 760 Ma and most relate to well-known orogenic or igneous events in surrounding cratonic regions. Authigenic monazite grew in three or more pulses ranging from 680 Ma to 500 Ma. The date of 680 ± 23 Ma (2 σ) for the earliest generation of authigenic monazite in sandstone from the Enorama Shale (1) provides an estimate for the age of the base of the Trezona carbon isotopic anomaly just beneath the Marinoan glacial deposits, (2) provides an absolute minimum age constraint on the underlying Sturtian glacial deposits, and (3) supports proposed correlations between type Marinoan deposits and precisely dated glacial deposits in Namibia and China, which bracket the presumed Marinoan equivalents between 655 and 635 Ma. This age is inconsistent with a Re-Os isochron age of 643 ± 2.4 Ma (2 σ) on shales near the bottom of the Sturtian-Marinoan interglacial succession, stratigraphically > 3000 m below the Enorama Shale sample, and militate against the hypothesis that the type Marinoan is correlative with the 580 Ma Gaskiers glaciation. Monazite growth near 600 Ma and again at about 500 Ma probably represent hydrothermal fluid-flow events, the latter of which also corresponds to the well-known Delamerian Orogeny during which the Adelaide sediments were

  7. 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

  8. 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

  9. Prolonged Breastfeeding Is Associated With Lower Risk Of Severe Hand, Foot And Mouth Disease In Chinese Children.

    PubMed

    Li, Yaping; Deng, Huiling; Li, Mei; Wang, Wenjun; Jia, Xiaoli; Gao, Ning; Dang, Shuangsuo

    2016-03-01

    To assess whether breastfeeding duration can affect risk of severe hand, foot and mouth disease (HFMD) later in childhood, we retrospectively analyzed demographic, environmental and breastfeeding data on 603 children with severe HFMD and 1036 children with mild HFMD. Multivariate analysis showed that breastfeeding for 6-12 months significantly reduced the risk of severe HFMD, as did breastfeeding for >12 months. PMID:26650113

  10. Relationship Between Beta Cell Dysfunction and Severity of Disease Among Critically Ill Children

    PubMed Central

    Liu, Ping-Ping; Lu, Xiu-Lan; Xiao, Zheng-Hui; Qiu, Jun; Zhu, Yi-Min

    2016-01-01

    Abstract Although beta cell dysfunction has been proved to predict prognosis among humans and animals, its prediction on severity of disease remains unclear among children. The present study was aimed to examine the relationship between beta cell dysfunction and severity of disease among critically ill children. This prospective study included 1146 critically ill children, who were admitted to Pediatric Intensive Care Unit (PICU) of Hunan Children's Hospital from November 2011 to August 2013. Information on characteristics, laboratory tests, and prognostic outcomes was collected. Homeostasis model assessment (HOMA)-β, evaluating beta cell function, was used to divide all participants into 4 groups: HOMA-β = 100% (group I, n = 339), 80% ≤ HOMA-β < 100% (group II, n = 71), 40% ≤ HOMA-β < 80% (group III, n = 293), and HOMA-β < 40% (group IV, n = 443). Severity of disease was assessed using the worst Sequential Organ Failure Assessment (SOFA) score, Pediatric Risk of Mortality (PRISM) III score, incidence of organ damage, septic shock, multiple organ dysfunction syndrome (MODS), mechanical ventilation (MV) and mortality. Logistic regression analysis was used to evaluate the risk of developing poor outcomes among patients in different HOMA-β groups, with group I as the reference group. Among 1146 children, incidence of HOMA-β < 100% was 70.41%. C-peptide and insulin declined with the decrement of HOMA-β (P < 0.01). C-reactive protein and procalcitonin levels, rather than white blood cell, were significantly different among 4 groups (P < 0.01). In addition, the worst SOFA score and the worst PRISMIII score increased with declined HOMA-β. For example, the worst SOFA score in group I, II, III, and IV was 1.55 ± 1.85, 1.71 ± 1.93, 1.92 ± 1.63, and 2.18 ± 1.77, respectively. Furthermore, patients with declined HOMA-β had higher risk of developing septic shock, MODS, MV, and mortality, even after adjusting age

  11. Severe iron deficiency anaemia as a manifestation of silent coeliac disease: case report and literature review.

    PubMed

    Paul, Siba P; Taylor, T M; Barnard, Penny

    2010-01-01

    Coeliac disease (CD) occurs in individuals sensitive to gluten protein contained in wheat products. It affects at least 1:100 children and may present with extra-intestinal manifestations such as iron deficiency anaemia, short stature and delay in puberty. A case of severe iron deficiency anaemia as a manifestation of CD is described here. There is a need to raise awareness among health professionals about CD and its extra-intestinal presentations. Suspicion of CD should lead to antibody screening tests and positive results should be followed by an intestinal biopsy for a definitive diagnosis. Involvement of a paediatric dietitian is vital in the management of CD and lifelong adherence to a gluten-free diet is necessary. We hope this article leaves the reader with a heightened awareness about CD and will lead to appropriate early referral to the paediatric services. PMID:20518373

  12. ERTS-1 data collection systems used to predict wheat disease severities

    NASA Technical Reports Server (NTRS)

    Kanemasu, E. T.; Schimmelpfennig, H.; Chin Choy, E.; Eversmeyer, M. G.; Lenhert, D.

    1974-01-01

    The feasibility of using the data collection system on Earth Technology Satellite-1 to predict wheat leaf rust severity and resulting yield loss was tested. Ground-based data-collection platforms (DCPs), placed in two commercial wheat fields, transmitted to the satellite such meteorological information as maximum and minimum temperature, relative humidity, and hours of free moisture. Meteorological data received from the two DCPs from April 23 to 29 were used to estimate the disease progress curve. Values from the curve were used to predict the percentage decrease in wheat yields resulting from leaf rust. Actual decrease in yield obtained by applying a zinc and maneb spray to control leaf rust, and then comparing yields of the controlled (healthy) and the noncontrolled (rusted) areas. In each field, a 9% decrease in yield was predicted by the DCP-derived data; actual decreases were 12% and 9%.

  13. ERTS-1 data collection systems used to predict wheat disease severities. [Riley County, Kansas

    NASA Technical Reports Server (NTRS)

    Kanemasu, E. T.; Schimmelpfenning, H.; Choy, E. C.; Eversmeyer, M. G.; Lenhert, D.

    1974-01-01

    The author has identified the following significant results. The feasibility of using the data collection system on ERTS-1 to predict wheat leaf rust severity and resulting yield loss was tested. Ground-based data collection platforms (DCP'S), placed in two commercial wheat fields in Riley County, Kansas, transmitted to the satellite such meteorological information as maximum and minimum temperature, relative humidity, and hours of free moisture. Meteorological data received from the two DCP'S from April 23 to 29 were used to estimate the disease progress curve. Values from the curve were used to predict the percentage decrease in wheat yields resulting from leaf rust. Actual decrease in yield was obtained by applying a zinc and maneb spray (5.6 kg/ha) to control leaf rust, then comparing yields of the controlled (healthy) and the noncontrolled (rusted) areas. In each field a 9% decrease in yield was predicted by the DCP-derived data; actual decreases were 12% and 9%.

  14. Severe heart failure, dilated cardiomyopathy and pulmonary haemosiderosis in coeliac disease: report of two cases.

    PubMed

    Poddar, Banani; Shava, Upender; Srivastava, Anshu; Kapoor, Aditya

    2014-05-01

    Coeliac disease (CD) is a chronic inflammatory, multi-system disorder with protean manifestations which has been linked to various auto-immune-mediated disorders. Dilated cardiomyopathy (DCM) is a rare extra-intestinal manifestation that is being recognised increasingly in patients with CD. Two cases of CD are described, an 18-year-old boy and a 13-year-old girl, both of whom presented with rapid onset of congestive heart failure and severe left ventricular systolic dysfunction. Upper limb venous thrombosis and recurrent haemoptysis secondary to pulmonary haemosiderosis in the second case were the other unusual features. The importance of CD screening of patients with DCM and pulmonary haemosiderosis is emphasised. PMID:24090525

  15. Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B.

    PubMed

    Lehmann, T; Beyeler, C; Lämmle, B; Hunziker, T; Vock, P; Olah, A J; Dahinden, C; Gerber, N J

    1996-09-01

    We describe a 33-year old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell population in different tissues. PMID:8810675

  16. Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.

    PubMed Central

    Ruttledge, M. H.; Andermann, A. A.; Phelan, C. M.; Claudio, J. O.; Han, F. Y.; Chretien, N.; Rangaratnam, S.; MacCollin, M.; Short, P.; Parry, D.; Michels, V.; Riccardi, V. M.; Weksberg, R.; Kitamura, K.; Bradburn, J. M.; Hall, B. D.; Propping, P.; Rouleau, G. A.

    1996-01-01

    The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22 has revealed a wide variety of different mutations in NF2 individuals. These patients display a marked variability in clinical presentation, ranging from very severe disease with numerous tumors at a young age to a relatively mild condition much later in life. To investigate whether this phenotypic heterogeneity is determined by the type of mutation in NF2, we have collected clinical information on 111 NF2 cases from 73 different families on whom we have performed mutation screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds revealed 36 different putative disease-causing mutations. These include 26 proposed protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion. Seventeen of these mutations are novel, whereas the remaining 19 have been described previously in other NF2 individuals or sporadic tumors. When individuals harboring protein-truncating mutations are compared with cases with single codon alterations, a significant correlation (P < .001) with clinical outcome is observed. Twenty-four of 28 patients with mutations that cause premature truncation of the NF2 protein, schwannomin, present with severe phenotypes. In contrast, all 16 cases from three families with mutations that affect only a single amino acid have mild NF2. These data provide conclusive evidence that a phenotype/genotype correlation exists for certain NF2 mutations. PMID:8755919

  17. 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. PMID:27267344

  18. The burden of illness in patients with moderate to severe chronic obstructive pulmonary disease in Canada

    PubMed Central

    Maleki-Yazdi, M Reza; Kelly, Suzanne M; Lam, Sy S; Marin, Mihaela; Barbeau, Martin; Walker, Valery

    2012-01-01

    INTRODUCTION: No recent Canadian studies with physician- and spirometry-confirmed diagnosis of chronic obstructive pulmonary disease (COPD) that assessed the burden of COPD have been published. OBJECTIVE: To assess the costs associated with maintenance therapy and treatment for acute exacerbations of COPD (AECOPD) over a one-year period. METHODS: Respirologists, internists and family practitioners from across Canada enrolled patients with an established diagnosis of moderate to severe COPD (Global initiative for chonic Obstructive Lung Disease stages 2 and 3) confirmed by postbronchodilator spirometry. Patient information and health care resources related to COPD maintenance and physician-documented AECOPD over the previous year were obtained by chart review and patient survey. RESULTS: A total of 285 patients (59.3% male; mean age 70.4 years; mean pack years smoked 45.6; mean duration of COPD 8.2 years; mean postbronchodilator forced expiratory volume in 1 s 58.0% predicted) were enrolled at 23 sites across Canada. The average annual COPD-related cost per patient was $4,147. Across all 285 patients, maintenance costs were $2,475 per patient, of which medications accounted for 71%. AECOPD treatment costs were $1,673 per patient, of which hospitalizations accounted for 82%. Ninety-eight patients (34%) experienced a total of 157 AECOPD. Treatment of these AECOPD included medications and outpatient care, 19 emergency room visits and 40 hospitalizations (mean length of stay 8.9 days). The mean cost per AECOPD was $3,036. DISCUSSION: The current costs associated with moderate and severe COPD are considerable and will increase in the future. Appropriate use of medications and strategies to prevent hospitalizations for AECOPD may reduce COPD-related costs because these were the major cost drivers. PMID:23061077

  19. Altered mean platelet volume in patients with polymyositis and its association with disease severity

    PubMed Central

    Peng, Y.-F.; Huang, Y.-X.; Wei, Y.-S.

    2016-01-01

    Polymyositis (PM) is an autoimmune disease characterized by chronic inflammation in skeletal muscle. Mean platelet volume (MPV), a marker in the assessment of systemic inflammation, is easily measured by automatic blood count equipment. However, to our knowledge, there are no data in the literature with respect to MPV levels in PM patients. Therefore, in this study we aimed to investigate MPV levels in patients with PM. This study included 92 newly diagnosed PM patients and 100 healthy individuals. MPV levels were found to be significantly lower compared with healthy controls (10.3±1.23 vs 11.5±0.74 fL, P<0.001). Interestingly, MPV was found to be positively correlated with manual muscle test (MMT) score and negatively correlated with erythrocyte sedimentation rate (ESR) in patients with PM (r=0.239, P=0.022; r=−0.268, P=0.010, respectively). In addition, MPV was significantly lower in active PM patients compared with inactive PM patients (9.9±1.39 vs 10.6±0.92 fL, P=0.010). MPV was independently associated with PM in multivariate regression analyses, when controlling for hemoglobin and ESR (OR=0.312, P=0.031, 95%CI=0.108 to 0.899). The ROC curve analysis for MPV in estimating PM patients resulted in an area under the curve of 0.800, with sensitivity of 75.0% and specificity of 67.4%. Our results suggest that MPV is inversely correlated with disease activity in patients with PM. MPV might be a useful tool for rapid assessment of disease severity in PM patients. PMID:27191605

  20. Peripheral artery disease is associated with severe impairment of vascular function.

    PubMed

    Kiani, Soroosh; Aasen, Jonathan G; Holbrook, Monika; Khemka, Abhishek; Sharmeen, Farhana; LeLeiko, Rebecca M; Tabit, Corey E; Farber, Alik; Eberhardt, Robert T; Gokce, Noyan; Vita, Joseph A; Hamburg, Naomi M

    2013-04-01

    Patients with peripheral artery disease (PAD) have higher cardiovascular event rates than patients with established coronary artery disease (CAD) and abnormal endothelial function predicts cardiovascular risk in PAD and CAD. We investigated the hypothesis that PAD is associated with a greater degree of impairment in vascular function than CAD. We used several non-invasive tests to evaluate endothelial function in 1320 men and women with combined PAD and CAD (n = 198), PAD alone (n = 179), CAD alone (n = 466), or controls aged > 45 years without CAD or PAD (n = 477). Patients with PAD had lower brachial artery flow-mediated dilation (5.1 ± 3.9% PAD and CAD, 5.9 ± 4.4% PAD alone) compared to patients with CAD alone (7.0 ± 4.5%) and no PAD or CAD (8.1 ± 5.1%, p < 0.0001). In multivariable models adjusting for clinical covariates and the presence of CAD, PAD remained associated with lower flow-mediated dilation (p < 0.0001). PAD was associated also with lower nitroglycerin-mediated dilation and reactive hyperemia. Patients with both PAD and CAD had a lower digital pulse amplitude tonometry (PAT) ratio in unadjusted models but not in adjusted models. Flow-mediated dilation was modestly associated with PAT ratio in patients with atherosclerotic disease (r = 0.23, p < 0.0001) but not among control participants (r = 0.008, p = 0.93). Our findings indicate that patients with PAD have greater impairment of vasodilator function and are consistent with the possibility that endothelial dysfunction may contribute to adverse cardiovascular prognosis in PAD. PMID:23509089

  1. Peripheral artery disease is associated with severe impairment of vascular function

    PubMed Central

    Kiani, Soroosh; Aasen, Jonathan G; Holbrook, Monika; Khemka, Abhishek; Sharmeen, Farhana; LeLeiko, Rebecca M; Tabit, Corey E; Farber, Alik; Eberhardt, Robert T; Gokce, Noyan; Vita, Joseph A; Hamburg, Naomi M

    2013-01-01

    Patients with peripheral artery disease (PAD) have higher cardiovascular event rates than patients with established coronary artery disease (CAD) and abnormal endothelial function predicts cardiovascular risk in PAD and CAD. We investigated the hypothesis that PAD is associated with a greater degree of impairment in vascular function than CAD. We used several non-invasive tests to evaluate endothelial function in 1320 men and women with combined PAD and CAD (n = 198), PAD alone (n = 179), CAD alone (n = 466), or controls aged > 45 years without CAD or PAD (n = 477). Patients with PAD had lower brachial artery flow-mediated dilation (5.1 ± 3.9% PAD and CAD, 5.9 ± 4.4% PAD alone) compared to patients with CAD alone (7.0 ± 4.5%) and no PAD or CAD (8.1 ± 5.1%, p < 0.0001). In multivariable models adjusting for clinical covariates and the presence of CAD, PAD remained associated with lower flow-mediated dilation (p < 0.0001). PAD was associated also with lower nitroglycerin-mediated dilation and reactive hyperemia. Patients with both PAD and CAD had a lower digital pulse amplitude tonometry (PAT) ratio in unadjusted models but not in adjusted models. Flow-mediated dilation was modestly associated with PAT ratio in patients with atherosclerotic disease (r = 0.23, p < 0.0001) but not among control participants (r = 0.008, p = 0.93). Our findings indicate that patients with PAD have greater impairment of vasodilator function and are consistent with the possibility that endothelial dysfunction may contribute to adverse cardiovascular prognosis in PAD. PMID:23509089

  2. TaqIB and severity of coronary artery disease in the Turkish population: a pilot study.

    PubMed

    Kaman, Dilara; İlhan, Necip; İlhan, Nevin; Akbulut, Mehmet

    2015-01-01

    The cholesteryl ester transfer protein (CETP) plays a crucial role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration. In this case-control study, we analyzed the genotype frequencies of CETP Taq1B polymorphisms in coronary artery disease patients (CAD; n=210) and controls (n=100). We analyzed the role of the CETP Taq1B variant in severity of CAD, and its association with plasma lipids and CETP concentration. DNA was extracted from 310 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis. Lipid concentrations were measured by an auto analyzer and CETP level by a commercial enzyme-linked immunosorbent assay (ELISA) kit. In our study population, the B2 allele frequency was higher in control subjects than patients with single, double or triple vessel disease. B2B2 genotype carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype in controls (51.93±9.47versus 45.34±9.93; p<0.05) and in CAD patients (45.52±10.81 versus 40.38±9.12; p<0.05). B2B2 genotype carriers had a significantly lower CETP concentration than those with the B1B1 genotype in controls (1.39±0.58 versus 1.88±0.83; p< 0.05) and in CAD patients (2.04±1.39versus 2.81±1.68; p< 0.05). Our data suggest that the B2 allele is associated with higher concentrations of HDL-C and lower concentrations of CETP, which confer a protective effect on coronary artery disease. PMID:25725138

  3. Circulating Angiogenic Factors as Biomarkers of Disease Severity and Bacterial Burden in Pulmonary Tuberculosis

    PubMed Central

    Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Nair, Dina; Babu, Subash

    2016-01-01

    Background Angiogenesis and lymphangiogenesis are classical features of granuloma formation in pulmonary tuberculosis (PTB). In addition, the angiogenic factor—VEGF-A is a known biomarker for PTB. Aims/Methodology To examine the association of circulating angiogenic factors with PTB, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3in individuals with PTB, latent TB (LTB) or no TB infection (NTB). Results Circulating levels of VEGF-A, VEGF-C andVEGF-R2 were significantly higher in PTB compared to LTB or NTB individuals. Moreover, the levels of VEGF-A, VEGF-C and VEGF-R2 were significantly higher in PTB with bilateral and/or cavitary disease. The levels of these factors also exhibited a significant positive relationship with bacterial burdens in PTB. ROC analysis revealed VEGF-A and VEGF-R2 as markers distinguishing PTB from LTB or NTB. Finally, the circulating levels of all the angiogenic factors examined were significantly reduced following successful chemotherapy. Conclusion Therefore, our data demonstrate that PTB is associated with elevated levels of circulating angiogenic factors, possibly reflecting vascular and endothelial dysfunction. In addition, some of these circulating angiogenic factors could prove useful as biomarkers to monitor disease severity, bacterial burden and therapeutic responses. PMID:26727122

  4. MRI Shows More Severe Hippocampal Atrophy and Shape Deformation in Hippocampal Sclerosis Than in Alzheimer's Disease

    PubMed Central

    Zarow, C.; Wang, L.; Chui, H. C.; Weiner, M. W.; Csernansky, J. G.

    2011-01-01

    While hippocampal atrophy is a key feature of both hippocampal sclerosis (HS) and Alzheimer's disease (AD), the pathology underlying this finding differs in these two conditions. In AD, atrophy is due primarily to loss of neurons and neuronal volume as a result of neurofibrillary tangle formation. While the etiology of HS is unknown, neuron loss in the hippocampus is severe to complete. We compared hippocampal volume and deformations from premortem MRI in 43 neuropathologically diagnosed cases of HS, AD, and normal controls (NC) selected from a longitudinal study of subcortical ischemic vascular disease (IVD Program Project). HS cases (n = 11) showed loss of neurons throughout the rostral-caudal extent of the hippocampus in one or both hemispheres. AD cases (n = 24) met NIA-Reagan criteria for high likelihood of AD. Normal control cases (n = 8) were cognitively intact and showed no significant AD or hippocampal pathology. The mean hippocampal volumes were significantly lower in HS versus AD groups (P < .001). Mean shape deformations in the CA1 and subiculum differed significantly between HS versus AD, HS versus NC, and AD versus NC (P < .0001). Additional study is needed to determine whether these differences will be meaningful for clinical diagnosis of individual cases. PMID:21547227

  5. A Novel Soluble Form of Tim-3 Associated with Severe Graft-versus-Host Disease

    PubMed Central

    Hansen, John A.; Hanash, Samir M.; Tabellini, Laura; Baik, Chris; Lawler, Richard L.; Grogan, Bryan M.; Storer, Barry; Chin, Alice; Johnson, Melissa; Wong, Chee-Hong; Zhang, Qing; Martin, Paul J.; McDonald, George B.

    2014-01-01

    The T cell Ig and mucin domain 3 (Tim-3) receptor has been implicated as a negative regulator of adaptive immune responses. We have utilized a proteomic strategy to identify novel proteins associated with graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Mass spectrometry analysis of plasma from subjects with mid-gut and upper-gut GVHD compared with those without GVHD identified increased levels of a protein identified with high confidence as Tim-3. A follow-up validation study using an immunoassay to measure Tim-3 levels in individual plasma samples from 127 patients demonstrated significantly higher plasma Tim-3 concentrations in patients with the more severe mid-gut GVHD, compared with those with upper-gut GVHD (P = .005), patients without GVHD (P = .002), and normal controls (P < .0001). Surface expression of Tim-3 was increased on CD8+ T cells from patients with grade 2 to 4 acute GVHD (P = .01). Mass spectrometry–based profiling of plasma from multiple subjects diagnosed with common diseases provided evidence for restricted release of soluble Tim-3 in the context of GVHD. These findings have mechanistic implications for the development of novel strategies for targeting the Tim-3 immune regulatory pathway as an approach to improving control of GVHD. PMID:23791624

  6. 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. PMID:26497564

  7. Markers of cerebral small vessel disease and severity of depression in the general population.

    PubMed

    Direk, Nese; Perez, Heidi Saavedra; Akoudad, Saloua; Verhaaren, Benjamin F J; Niessen, Wiro J; Hofman, Albert; Vernooij, Meike W; Ikram, M Arfan; Tiemeier, Henning

    2016-07-30

    The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non-specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology. PMID:27254084

  8. 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. PMID:26621477

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

    PubMed Central

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

    2000-01-01

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

  10. Severe hepatocellular disease in mice lacking one or both CaaX prenyltransferases[S

    PubMed Central

    Yang, Shao H.; Chang, Sandy Y.; Tu, Yiping; Lawson, Gregory W.; Bergo, Martin O.; Fong, Loren G.; Young, Stephen G.

    2012-01-01

    Protein farnesyltransferase (FTase) and protein geranylgeranyltransferase-I (GGTase-I) add 15- or 20-carbon lipids, respectively, to proteins that terminate with a CaaX motif. These posttranslational modifications of proteins with lipids promote protein interactions with membrane surfaces in cells, but the in vivo importance of the CaaX prenyltransferases and the protein lipidation reactions they catalyze remain incompletely defined. One study concluded that a deficiency of FTase was inconsequential in adult mice and led to little or no tissue pathology. To assess the physiologic importance of the CaaX prenyltransferases, we used conditional knockout alleles and an albumin–Cre transgene to produce mice lacking FTase, GGTase-I, or both enzymes in hepatocytes. The hepatocyte-specific FTase knockout mice survived but exhibited hepatocellular disease and elevated transaminases. Mice lacking GGTase-I not only had elevated transaminases but also had dilated bile cannaliculi, hyperbilirubinemia, hepatosplenomegaly, and reduced survival. Of note, GGTase-I–deficient hepatocytes had a rounded shape and markedly reduced numbers of actin stress fibers. Hepatocyte-specific FTase/GGTase-I double-knockout mice closely resembled mice lacking GGTase-I alone, but the disease was slightly more severe. Our studies refute the notion that FTase is dispensable and demonstrate that GGTase-I is crucial for the vitality of hepatocytes. PMID:22039581

  11. MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson's Disease

    PubMed Central

    Schlesinger, Ilana; Eran, Ayelet; Sinai, Alon; Erikh, Ilana; Nassar, Maria; Goldsher, Dorith; Zaaroor, Menashe

    2015-01-01

    Background. Thalamotomy is effective in alleviating tremor in Parkinson's disease (PD). Methods. Seven PD patients, mean age 59.4 ± 9.8 years (range, 46–74) with a mean disease duration of 5.4 ± 2.8 years (range, 2–10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity in all patients immediately following treatment. Total UPDRS decreased from 37.4 ± 12.2 to 18.8 ± 11.1 (p = 0.007) and PDQ-39 decreased from 42.3 ± 16.4 to 21.6 ± 10.8 (p = 0.008) following MRgFUS. These effects were sustained (mean follow-up 7.3 months). Adverse events during MRgFUS included headache (n = 3), dizziness (n = 2), vertigo (n = 4), and lip paresthesia (n = 1) and following MRgFUS were hypogeusia (n = 1), unsteady feeling when walking (n = 1, resolved), and disturbance when walking tandem (n = 1, resolved). Conclusions. Thalamotomy using MRgFUS is safe and effective in PD patients. Large randomized studies are needed to assess prolonged efficacy and safety. PMID:26421209

  12. National Institutes of Health (NIH) Chronic GVHD Staging in Severely Affected Patients: Organ and Global Scoring Correlate with Established Indicators of Disease Severity and Prognosis

    PubMed Central

    Baird, K.; Steinberg, S.M.; Grkovic, L.; Pulanic, D.; Cowen, E.W.; Mitchell, S.A.; Williams, K.M.; Datiles, M.B.; Bishop, R.; Bassim, C.W.; Mays, J.W.; Edwards, D.; Cole, K.; Avila, D.N.; Taylor, T.; Urban, A.; Joe, G.O.; Comis, L.E.; Berger, A.; Stratton, P.; Zhang, D.; Shelhamer, J.H.; Gea-Banacloche, J.C.; Sportes, C.; Fowler, D.H.; Gress, R.E.; Pavletic, S.Z.

    2013-01-01

    Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute (NCI) cross-sectional chronic Graft-versus-Host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures including the 2005 NIH Consensus Project cGVHD severity score. The purpose of this study is to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in order to standardize clinician evaluation and staging of cGVHD. 125 of 189 patients met criteria for severe cGVHD on the NIH global score and 62 had moderate disease, with a median of 4 (range 1–8) involved organs. Clinician average NIH organ score and the corresponding organ scores performed 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 Lee Scale, SF-36 Physical Component Scale (PCS), 2 minutes walk, grip strength, range of motion and Human Activity Profile (HAP). Joints/fascia, skin, and lung involvement impacted function and quality of life most significantly and showed highest number of correlations with outcome measures. The final Cox model showing factors jointly predictive for survival contained the time from cGVHD diagnosis (>49 vs. ≤49 months, HR=0.23; p=0.0011), absolute eosinophil count of (0–0.5 vs. >0.5 cells/µL, HR=3.95; p=0.0006) at the time of NIH evaluation, and NIH lung score (3 vs. 0–2, HR=11.02; p <0.0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. Strong association with subspecialist evaluation suggests that NIH organs and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex sub-specialist exams. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall

  13. Simple blood tests as predictive markers of disease severity and clinical condition in patients with venous insufficiency.

    PubMed

    Karahan, Oguz; Yavuz, Celal; Kankilic, Nazim; Demirtas, Sinan; Tezcan, Orhan; Caliskan, Ahmet; Mavitas, Binali

    2016-09-01

    Chronic venous insufficiency (CVI) is a progressive inflammatory disease. Because of its inflammatory nature, several circulating markers were investigated for predicting disease progression. We aimed to investigate simple inflammatory blood markers as predictors of clinical class and disease severity in patients with CVI. Eighty patients with CVI were divided into three groups according to clinical class (grade 1, 2 and 3) and score of disease severity (mild, moderate and severe). The basic inflammatory blood markers [neutrophil, lymphocyte, mean platelet volume (MPV), white blood cell (WBC), platelet, albumin, D-dimer, fibrinogen, fibrinogen to albumin ratio, and neutrophil to lymphocyte ratio] were investigated in each group. Serum neutrophil, lymphocyte, MPV, platelet count, D-dimer and neutrophil to lymphocyte ratio levels were similar among the groups (P > 0.05). Although the serum WBC levels were significant in the clinical severity groups (P < 0.05), it was useless to separate each severity class. However, albumin, fibrinogen and the fibrinogen to albumin ratio were significant predictors of clinical class and disease severity. Especially, the fibrinogen to albumin ratio was detected as an independent indicator for a clinical class and disease severity with high sensitivity and specificity (75% sensitivity and 87.5% specificity for clinical class and 90% sensitivity and 88.3% specificity for disease severity). Serum fibrinogen and albumin levels can be useful parameters to determine clinical class and disease severity in patients with CVI. Moreover, the fibrinogen to albumin ratio is a more sensitive and specific predictor of the progression of CVI. PMID:26650463

  14. 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

  15. Assessment of the severity of Ebola virus disease in Sierra Leone in 2014-2015.

    PubMed

    Wong, J Y; Zhang, W; Kargbo, D; Haque, U; Hu, W; Wu, P; Kamara, A; Chen, Y; Kargbo, B; Glass, G E; Yang, R; Cowling, B J; Liu, C

    2016-05-01

    The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6-75·5] and 68·9% (95% CrI 66·2-71·6), respectively. Risks of death were higher in the youngest (0-4 years) and oldest (⩾60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone. PMID:27029911

  16. Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease.

    PubMed

    Kubisch, Christian; Schoser, Benedikt G H; von Düring, Monika; Betz, Regina C; Goebel, Hans-Hilmar; Zahn, Susanne; Ehrbrecht, Antje; Aasly, Jan; Schroers, Anja; Popovic, Nikola; Lochmüller, Hanns; Schröder, J Michael; Brüning, Thomas; Malin, Jean-Pierre; Fricke, Britta; Meinck, Hans-Michael; Torbergsen, Torberg; Engels, Hartmut; Voss, Bruno; Vorgerd, Matthias

    2003-04-01

    Heterozygous missense mutations in the caveolin-3 gene (CAV3) cause different muscle disorders. Most patients with CAV3 alterations present with rippling muscle disease (RMD) characterized by signs of increased muscle irritability without muscle weakness. In some patients, CAV3 mutations underlie the progressive limb-girdle muscular dystrophy type 1C (LGMD1C). Here, we report two unrelated patients with novel homozygous mutations (L86P and A92T) in CAV3. Both presented with a more severe clinical phenotype than usually seen in RMD. Immunohistochemical and immunoblot analyses of muscle biopsies showed a strong reduction of caveolin-3 in both homozygous RMD patients similar to the findings in heterozygous RMD. Electron microscopy studies showed a nearly complete absence of caveolae in the sarcolemma in all RMD patients analyzed. Additional plasma membrane irregularities (small plasmalemmal discontinuities, subsarcolemmal vacuoles, abnormal papillary projections) were more pronounced in homozygous than in heterozygous RMD patients. A stronger activation of nitric oxide synthase was observed in both homozygous patients compared with heterozygous RMD. Like in LGMD1C, dysferlin immunoreactivity is reduced in RMD but more pronounced in homozygous as compared with heterozygous RMD. Thus, we further extend the phenotypic variability of muscle caveolinopathies by identification of a severe form of RMD associated with homozygous CAV3 mutations. PMID:12666119

  17. Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease: An Observational Study.

    PubMed

    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

    2016-06-01

    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

  18. Augmentation of Autoantibodies by Helicobacter pylori in Parkinson's Disease Patients May Be Linked to Greater Severity.

    PubMed

    Suwarnalata, Gunasekaran; Tan, Ai Huey; Isa, Hidayah; Gudimella, Ranganath; Anwar, Arif; Loke, Mun Fai; Mahadeva, Sanjiv; Lim, Shen-Yang; Vadivelu, Jamuna

    2016-01-01

    Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity. PMID:27100827

  19. 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

  20. Tensin2-deficient mice on FVB/N background develop severe glomerular disease

    PubMed Central

    UCHIO-YAMADA, Kozue; MONOBE, Yoko; AKAGI, Ken-ichi; YAMAMOTO, Yoshie; OGURA, Atsuo; MANABE, Noboru

    2016-01-01

    Tensin2 (Tns2) is an essential component for the maintenance of glomerular basement membrane (GBM) structures. Tns2-deficient mice were previously shown to develop mild glomerular injury on a DBA/2 background, but not on a C57BL/6J or a 129/SvJ background, suggesting that glomerular injury by the deletion of Tns2 was strongly dependent on the genetic background. To further understand the mechanisms for the onset and the progression of glomerular injury by the deletion of Tns2, we generated Tns2-deficient mice on an FVB/N (FVB) strain, which is highly sensitive to glomerular disease. Tns2-deficient mice on FVB (FVBGN) developed severe nephrotic syndrome, and female FVBGN mice died within 8 weeks. Ultrastructural analysis revealed that FVBGN mice exhibited severe glomerular defects with mesangial process invasion of glomerular capillary tufts, lamination and thickening of the GBM and subsequent podocyte foot process effacement soon after birth. Aberrant laminin components containing α1, α2 and β1 chains, which are normally expressed in the mesangium, accumulated in the GBM of FVBGN, suggesting that these components originated from mesangial cells that invaded glomerular capillary tufts. Compared to Tns2-deficient mice on the other backgrounds in previous reports, FVBGN mice developed earlier onset of glomerular defects and rapid progression of renal failure. Thus, this study further extended our understanding of the possible genetic background effect on the deterioration of nephrotic syndrome by Tns2 deficiency. PMID:26854109

  1. Tensin2-deficient mice on FVB/N background develop severe glomerular disease.

    PubMed

    Uchio-Yamada, Kozue; Monobe, Yoko; Akagi, Ken-Ichi; Yamamoto, Yoshie; Ogura, Atsuo; Manabe, Noboru

    2016-06-01

    Tensin2 (Tns2) is an essential component for the maintenance of glomerular basement membrane (GBM) structures. Tns2-deficient mice were previously shown to develop mild glomerular injury on a DBA/2 background, but not on a C57BL/6J or a 129/SvJ background, suggesting that glomerular injury by the deletion of Tns2 was strongly dependent on the genetic background. To further understand the mechanisms for the onset and the progression of glomerular injury by the deletion of Tns2, we generated Tns2-deficient mice on an FVB/N (FVB) strain, which is highly sensitive to glomerular disease. Tns2-deficient mice on FVB (FVBGN) developed severe nephrotic syndrome, and female FVBGN mice died within 8 weeks. Ultrastructural analysis revealed that FVBGN mice exhibited severe glomerular defects with mesangial process invasion of glomerular capillary tufts, lamination and thickening of the GBM and subsequent podocyte foot process effacement soon after birth. Aberrant laminin components containing α1, α2 and β1 chains, which are normally expressed in the mesangium, accumulated in the GBM of FVBGN, suggesting that these components originated from mesangial cells that invaded glomerular capillary tufts. Compared to Tns2-deficient mice on the other backgrounds in previous reports, FVBGN mice developed earlier onset of glomerular defects and rapid progression of renal failure. Thus, this study further extended our understanding of the possible genetic background effect on the deterioration of nephrotic syndrome by Tns2 deficiency. PMID:26854109

  2. Clinical and microbiological characteristics of severe Streptococcus pyogenes disease in Europe.

    PubMed

    Luca-Harari, Bogdan; Darenberg, Jessica; Neal, Shona; Siljander, Tuula; Strakova, Lenka; Tanna, Asha; Creti, Roberta; Ekelund, Kim; Koliou, Maria; Tassios, Panayotis T; van der Linden, Mark; Straut, Monica; Vuopio-Varkila, Jaana; Bouvet, Anne; Efstratiou, Androulla; Schalén, Claes; Henriques-Normark, Birgitta; Jasir, Aftab

    2009-04-01

    In an attempt to compare the epidemiology of severe Streptococcus pyogenes infection within Europe, prospective data were collected through the Strep-EURO program. Surveillance for severe cases of S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe by using a standardized case definition and questionnaire. Patient data as well as bacterial isolates were collected and characterized by T and M/emm typing, and selected strains were analyzed for the presence of superantigen genes. Data were analyzed to compare the clinical and microbiological patterns of the infections across the participating countries. A total of 4,353 isolates were collected from 5,521 cases with severe S. pyogenes infections who were identified. A wide diversity of M/emm types (n = 104) was found among the S. pyogenes clinical isolates, but the M/emm type distribution varied broadly between participating countries. The 10 most predominant M/emm types were M/emm type 1 (M/emm1), M/emm28, M/emm3, M/emm89, M/emm87, M/emm12, M/emm4, M/emm83, M/emm81, and M/emm5, in descending order. A correlation was found between some specific disease manifestations, the age of the patients, and the emm types. Although streptococcal toxic shock syndrome and necrotizing fasciitis were caused by a large number of types, they were particularly associated with M/emm1 and M/emm3. The emm types included in the 26-valent vaccine under development were generally well represented in the present material; 16 of the vaccine types accounted for 69% of isolates. The Strep-EURO collaborative program has contributed to enhancement of the knowledge of the spread of invasive disease caused by S. pyogenes within Europe and encourages future surveillance by the notification of cases and the characterization of strains, which are important for vaccination strategies and other health care issues. PMID:19158266

  3. Clinical and Microbiological Characteristics of Severe Streptococcus pyogenes Disease in Europe▿

    PubMed Central

    Luca-Harari, Bogdan; Darenberg, Jessica; Neal, Shona; Siljander, Tuula; Strakova, Lenka; Tanna, Asha; Creti, Roberta; Ekelund, Kim; Koliou, Maria; Tassios, Panayotis T.; van der Linden, Mark; Straut, Monica; Vuopio-Varkila, Jaana; Bouvet, Anne; Efstratiou, Androulla; Schalén, Claes; Henriques-Normark, Birgitta; Jasir, Aftab

    2009-01-01

    In an attempt to compare the epidemiology of severe Streptococcus pyogenes infection within Europe, prospective data were collected through the Strep-EURO program. Surveillance for severe cases of S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe by using a standardized case definition and questionnaire. Patient data as well as bacterial isolates were collected and characterized by T and M/emm typing, and selected strains were analyzed for the presence of superantigen genes. Data were analyzed to compare the clinical and microbiological patterns of the infections across the participating countries. A total of 4,353 isolates were collected from 5,521 cases with severe S. pyogenes infections who were identified. A wide diversity of M/emm types (n = 104) was found among the S. pyogenes clinical isolates, but the M/emm type distribution varied broadly between participating countries. The 10 most predominant M/emm types were M/emm type 1 (M/emm1), M/emm28, M/emm3, M/emm89, M/emm87, M/emm12, M/emm4, M/emm83, M/emm81, and M/emm5, in descending order. A correlation was found between some specific disease manifestations, the age of the patients, and the emm types. Although streptococcal toxic shock syndrome and necrotizing fasciitis were caused by a large number of types, they were particularly associated with M/emm1 and M/emm3. The emm types included in the 26-valent vaccine under development were generally well represented in the present material; 16 of the vaccine types accounted for 69% of isolates. The Strep-EURO collaborative program has contributed to enhancement of the knowledge of the spread of invasive disease caused by S. pyogenes within Europe and encourages future surveillance by the notification of cases and the characterization of strains, which are important for vaccination strategies and other health care issues. PMID:19158266

  4. Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life

    PubMed Central

    Lawson, Rachael A.; Yarnall, Alison J.; Duncan, Gordon W.; Khoo, Tien K.; Breen, David P.; Barker, Roger A.; Collerton, Daniel; Taylor, John-Paul; Burn, David J.

    2014-01-01

    Background Poor quality of life (QoL) is a feature of people with Parkinson's disease (PD) who develop dementia. The relationship between mild cognitive impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the impact of varying severities of cognitive impairment on QoL in a cohort of non-demented patients with early PD. Method Patients with newly diagnosed PD (n = 219) and age and sex matched healthy controls (n = 99) completed a schedule of neuropsychological tests, in addition to scales assessing QoL (PDQ-39), depression, sleep, neuropsychiatric symptoms and a clinical examination. The Movement Disorder Society criteria were used to define and classify PD-MCI. Results Participants with PD-MCI were significantly older than those with normal cognition, had more severe motor symptoms, scored higher for depression and had poorer quality of life. Logistic regression showed that mild cognitive impairment, independent of other factors, was an indicator of poorer QoL. Using cognitive performance 2.0 standard deviations (SD) below normative data as a cut-off to define PD-MCI, there was a significant difference in QoL scores between patients with PD-MCI and those classified as having normal cognition. Subjects with less severe mild cognitive impairment did not exhibit significant differences in QoL. Conclusions PD-MCI is a significant, independent factor contributing to poorer QoL in patients with newly diagnosed PD. Those classified with greatest impairment (2.0 SD below normal values) have lower QoL. This has implications for clinical practice and future interventions targeting cognitive impairments. PMID:25074728

  5. Understanding antimicrobial stewardship: Disease severity treatment thresholds and antimicrobial alternatives among organic and conventional calf producers.

    PubMed

    Habing, Greg; Djordjevic, Catherine; Schuenemann, Gustavo M; Lakritz, Jeff

    2016-08-01

    Reductions in livestock antimicrobial use (AMU) can be achieved through identification of effective antimicrobial alternatives as well as accurate and stringent identification of cases requiring antimicrobial therapy. Objective measurements of selectivity that incorporate appropriate case definitions are necessary to understand the need and potential for reductions in AMU through judicious use. The objective of this study was to measure selectivity using a novel disease severity treatment threshold for calf diarrhea, and identify predictors of more selective application of antimicrobials among conventional dairy producers. A second objective of this study was to describe the usage frequency and perceptions of efficacy of common antimicrobial alternatives among conventional and organic producers. The cross-sectional survey was mailed to Michigan and Ohio, USA dairy producers and contained questions on AMU attitudes, AMU practices, veterinary-written protocols, and antimicrobial alternatives. The treatment threshold, defined based on the case severity where the producer would normally apply antimicrobials, was identified with a series of descriptions with increasing severity, and ordinal multivariable logistic regression was used to determine the association between the treatment threshold and individual or herd characteristics. The response rate was 49% (727/1488). Overall, 42% of conventional producers reported any veterinary-written treatment protocol, and 27% (113/412) of conventional producers had a veterinary-written protocol for the treatment of diarrhea that included a case identification. The majority (58%, 253/437) of conventional producers, but a minority (7%) of organic producers disagreed that antibiotic use in agriculture led to resistant bacterial infections in people. Among conventional producers, the proportion of producers applying antimicrobials for therapy increased from 13% to 67% with increasing case severity. The treatment threshold was low

  6. 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

  7. TREM-1 Deficiency Can Attenuate Disease Severity without Affecting Pathogen Clearance

    PubMed Central

    Weber, Benjamin; Schuster, Steffen; Zysset, Daniel; Rihs, Silvia; Dickgreber, Nina; Schürch, Christian; Riether, Carsten; Siegrist, Mark; Schneider, Christoph; Pawelski, Helga; Gurzeler, Ursina; Ziltener, Pascal; Genitsch, Vera; Tacchini-Cottier, Fabienne; Ochsenbein, Adrian; Hofstetter, Willy; Kopf, Manfred; Kaufmann, Thomas; Oxenius, Annette; Reith, Walter; Saurer, Leslie; Mueller, Christoph

    2014-01-01

    Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock or microbial sepsis have so far mostly relied on the administration of TREM-1 fusion proteins or peptides representing part of the extracellular domain of TREM-1. However, binding of these agents to the yet unidentified TREM-1 ligand could also impact signaling through alternative receptors. More importantly, controversial results have been obtained regarding the requirement of TREM-1 for microbial control. To unambiguously investigate the role of TREM-1 in homeostasis and disease, we have generated mice deficient in Trem1. Trem1−/− mice are viable, fertile and show no altered hematopoietic compartment. In CD4+ T cell- and dextran sodium sulfate-induced models of colitis, Trem1−/− mice displayed significantly attenuated disease that was associated with reduced inflammatory infiltrates and diminished expression of pro-inflammatory cytokines. Trem1−/− mice also exhibited reduced neutrophilic infiltration and decreased lesion size upon infection with Leishmania major. Furthermore, reduced morbidity was observed for influenza virus-infected Trem1−/− mice. Importantly, while immune-associated pathologies were significantly reduced, Trem1−/− mice were equally capable of controlling infections with L. major, influenza virus, but also Legionella pneumophila as Trem1+/+ controls. Our results not only demonstrate an unanticipated pathogenic impact of TREM-1 during a viral and parasitic infection, but also indicate that therapeutic blocking of TREM-1 in distinct inflammatory disorders holds considerable promise by blunting excessive inflammation while preserving the capacity

  8. 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

  9. Increased fibrin formation and impaired fibrinolytic capacity in severe chronic kidney disease.

    PubMed

    Mörtberg, Josefin; Blombäck, Margareta; Wallén, Åkan; He, Shu; Jacobson, Stefan H; Spaak, Jonas

    2016-06-01

    Chronic kidney disease (CKD) is associated with a concurrent increased risk of thrombosis and bleeding. We aimed to investigate whether CKD is associated with increased fibrin formation, impaired fibrin degradation, or both. Twenty-one patients with CKD stage 4 (CKD 4), 15 haemodialysis patients, and 13 controls (C) without kidney disease were studied. We used a global assay to determine fibrin formation and degradation in plasma. Fibrin turbidity was measured over time to obtain a value of the coagulation activation profile (Cp) and the fibrinolysis activation profile (Fp), and the amount of fibrin formed, termed fibrin optical density sum (fibrin OD-sum). We used scanning electron microscopy (SEM) to visualize the fibrin network. Plasminogen activator inhibitor type-1 antigen, thrombin-activatable fibrinolysis inhibitor activity, fibrinogen, von Willebrand factor, antithrombin, albumin, and C-reactive protein were measured in plasma. Fibrin OD-sum was significantly elevated in haemodialysis patients [312 a.u.; 278-435 (median; interquartile range); P < 0.0013] and in CKD 4 (293 a.u.; 169-434; P = 0.0119) compared with controls (115 a.u.; 82-234). SEM showed a tight fibrin network in haemodialysis and CKD 4 patients. Fp was lower in the haemodialysis group than in controls (P = 0.030). Plasminogen activator inhibitor type-1 was lower in haemodialysis patients (P = 0.034). Thrombin-activatable fibrinolysis inhibitor activity, Cp, antithrombin, and C-reactive protein did not differ between groups. Fibrinogen was significantly elevated and albumin decreased in both haemodialysis and CKD 4 patients compared with controls. Von Willebrand factor was elevated in haemodialysis patients compared with controls (P = 0.010). The prothrombotic state in severe CKD is characterized by impaired fibrinolysis in association with increased fibrin formation despite normal levels of endogenous fibrinolysis inhibitors. PMID:26650459

  10. 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. PMID:27026106

  11. Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations.

    PubMed

    Wiethoff, Sarah; Hersheson, Joshua; Bettencourt, Conceicao; Wood, Nicholas W; Houlden, Henry

    2016-08-01

    The autosomal recessive spinocerebellar ataxias are an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. SYNE1 was originally discovered in 2007 as the causal gene underlying autosomal recessive spinocerebellar ataxia 1, a disease clinically thought to manifest with mainly pure cerebellar ataxia. Since the original report SYNE1 mutations have also been identified in families with motor neuronopathy and arthrogryposis but few families have been screened as the gene is very large at 146 exons in length. We screened 196 recessive and sporadic ataxia patients for mutations in SYNE1 using next generation sequencing in order to assess its frequency and extend the clinicogenetic spectrum. We identified four novel truncating mutations spread throughout the SYNE1 gene from three families living in London that originated from England, Turkey and Sri Lanka. The phenotype was mainly pure cerebellar ataxia in two families, cognitive decline was present in all three families, axonal neuropathy in one family and marked spasticity in the Turkish family, with a range of disease severities. Searching for genotype-phenotype correlations in the SYNE1 gene, defects located near the 3' prime end of the gene are more frequently associated with motor neuron or neuromuscular involvement so far. Our data indicate SYNE1 mutations are not an uncommon cause of recessive ataxia with or without additional clinical features in patients from various ethnicities. The use of next generation sequencing allows the rapid analysis of large genes and will likely reveal more SYNE1 associated cases and further expand genotype-phenotype correlations. PMID:27178001

  12. A spatial model for predicting effects of climate change on Swiss needle cast disease severity in the Pacific Northwest

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Swiss needle cast disease of Douglas-fir is caused by the ascomycete fungus Phaeocryptopus gaeumannii. Symptoms of the disease are foliage chlorosis and premature needle abscission due to occlusion of stomata by the ascocarps of the pathogen, resulting in impaired needle gas exchange. Severe defol...

  13. 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

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

    PubMed

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

    2003-01-01

    The Severe Acute Respiratory Syndrome (SARS) is the first severe and easily transmissible disease to emerge in the 21st century. It is caused by the infection with a coronavirus, a single strand RNA capsulated virus, recently found in a small mammalian, the masked palm civet. It is likely to represent the source of human infection. The first cases of SARS have been reported in the Chinese province of Guangdong and, since then, probable cases have been reported world wide. The clinical picture is characterized by nonspecific symptoms such as fever, cough or dyspnea in patients affected by air-space opacities (unifocal involvement in the 54.6% of cases) or distress respiratory syndrome and linked to a recent exposure to a SARS case or to a travel/residence in an affected area. The empirical therapy is based on broad-spectrum antibiotics, steroids and ribavirin, but susceptibility testing have failed to demonstrate direct anti-viral activity of ribavirin against SARS-related coronavirus in vitro. The exposure to respiratory droplets and the contact with biologic fluids (respiratory and gastrointestinal secretions) represent the most efficient transmission modality of the SARS-related coronavirus. Hand hygiene is the most simple and cost effective measure of infection control to prevent contagion, and the use of airborne, contact and droplet precaution is strictly recommended to all health care workers taking care of such patients. The spread of SARS, to less developed country with limited resource for public health programs, represent the emerging alarming threat in the new global scenario. PMID:12868234

  16. Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial

    PubMed Central

    Hitchings, Andrew W; Lai, Dilys; Jones, Paul W; Baker, Emma H

    2016-01-01

    Background Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. Methods This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. Results 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. Conclusion Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. Trial registration number ISRCTN66148745 and NCT01247870. PMID:26917577

  17. Relationship between Eating Disturbance and Dementia Severity in Patients with Alzheimer’s Disease

    PubMed Central

    Kai, Kyoko; Hashimoto, Mamoru; Amano, Koichiro; Tanaka, Hibiki; Fukuhara, Ryuji; Ikeda, Manabu

    2015-01-01

    Background Eating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer’s disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD. Methods A total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed. Results Overall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; “Appetite change” was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of “change of eating habits and food preference” were highest, and in the severe stage “swallowing disturbance” became critical. Conclusion In AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered. PMID:26266531

  18. Long-term result of autologous cultivated oral mucosal epithelial transplantation for severe ocular surface disease.

    PubMed

    Prabhasawat, Pinnita; Ekpo, Pattama; Uiprasertkul, Mongkol; Chotikavanich, Suksri; Tesavibul, Nattaporn; Pornpanich, Kanograt; Luemsamran, Panitee

    2016-09-01

    The present study aimed to investigate the clinical outcomes of autologous cultivated oral mucosal epithelial transplantation (COMET) on human amniotic membrane (AM) for corneal limbal stem cell deficiency (LSCD). In this prospective, noncomparative case series, 20 eyes (18 patients) with bilateral severe ocular surface disease were chosen to undergo COMET on human AM. The primary outcome was clinical success, and the secondary outcomes were the best-corrected visual acuity difference, corneal opacification, symblepharon formation, and complications. The mean patient age was 48.2 ± 15.5 years. The mean follow-up time was 31.9 ± 12.1 months (range 8-50 months). All except one eye exhibited complete epithelialization within the first postoperative week. A successful clinical outcome, defined as a stable ocular surface without epithelial defects, a clear cornea without fibrovascular tissue invasion at the pupillary area, and no or mild ocular surface inflammation, was obtained in 15 of 20 eyes (75 %). The clinical success rate at 1 year was 79.3 %, and that at 4 years (end of follow-up) was 70.5 %. Fourteen of 20 (70 %) eyes exhibited improvement in visual acuity after COMET, and some required subsequent cataract surgery (2 eyes), penetrating keratoplasty (3 eyes), or keratoprosthesis implantation (1 eye). Preoperative symblepharon was eliminated in most eyes (8 of 13, 61.5 %) after COMET combined with eyelid reconstruction when needed. The only complication was corneal perforation (1 eye) induced by a severe eyelid abnormality; treatment with a tectonic corneal graft was successful. COMET can successfully restore ocular surface damage in most eyes with corneal LSCD. PMID:27507558

  19. 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

  20. 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

  1. Growth Patterns of Clostridium difficile - Correlations with Strains, Binary Toxin and Disease Severity: A Prospective Cohort Study.

    PubMed

    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

  2. Association of Human Immune Response to Aedes aegypti Salivary Proteins with Dengue Disease Severity

    PubMed Central

    Machain-Williams, Carlos; Mammen, Mammen P; Zeidner, Nordin S; Beaty, Barry J; Prenni, Jessica E.; Nisalak, Ananda

    2011-01-01

    SUMMARY Dengue viruses (DENV; family Flaviviridae, genus Flavivirus) are transmitted by Aedes aegypti mosquitoes and can cause dengue fever (DF), a relatively benign disease, or more severe dengue haemorrhagic fever (DHF). Arthropod saliva contains proteins delivered into the bite wound that can modulate the host haemostatic and immune responses to facilitate the intake of a blood meal. The potential effects on DENV infection of previous exposure to Ae. aegypti salivary proteins have not been investigated. We collected Ae. aegypti saliva, concentrated the proteins, and fractionated them by non-denaturing polyacrylamide gel electrophoresis (PAGE). By use of immunoblots we analysed reactivity with the mosquito salivary proteins (MSP) of sera from 96 Thai children diagnosed with secondary DENV infections leading either to DF or DHF, or with no DENV infection, and found that different proportions of each patient group had serum antibodies reactive to specific Ae. aegypti salivary proteins. Our results suggest that prior exposure to MSP might play a role in the outcome of DENV infection in humans. PMID:21995849

  3. Balloon expandable transcatheter heart valves for native mitral valve disease with severe mitral annular calcification.

    PubMed

    Guerrero, Mayra; Urena, Marina; Pursnani, Amit; Wang, Dee D; Vahanian, Alec; O'Neill, William; Feldman, Ted; Himbert, Dominique

    2016-06-01

    Patients with mitral annular calcification (MAC) have high surgical risk for mitral valve replacement due to associated comorbidities and technical challenges related to calcium burden, precluding surgery in many patients. Transcatheter mitral valve replacement (TMVR) with the compassionate use of balloon expandable aortic transcatheter heart valves has been used in this clinical scenario. The purpose of this review was to summarize the early experience including successes and failures reported. TMVR might evolve into an acceptable alternative for selected patients with severe MAC who are not candidates for conventional mitral valve surgery. However, this field is at a very early stage and the progress will be significantly slower than the development of transcatheter aortic valve replacement due to the complexity of the mitral valve anatomy and its pathology. Optimizing patient selection process by using multimodality imaging tools to accurately measure the mitral valve annulus and evaluate the risk of left ventricular outflow tract obstruction is essential to minimize complications. Strategies for treating and preventing left ventricular outflow tract obstruction are being tested. Similarly, carefully selecting candidates avoiding patients at the end of their disease process, might improve the overall outcomes. PMID:27094423

  4. Severe nose bleeding after intake of acetylsalicylic acid: von Willebrand disease type 2A. Case 9.

    PubMed

    von der Weid, N X; Mansouri Taleghani, B; Wuillemin, W A

    2003-08-01

    This case report of a school boy with a history of severe and repeated episodes of epistaxis presents a short overview of the clinical and laboratory findings which lead to confirm the suspected diagnosis of von Willebrand disease (vWD). Suspicion of defective primary haemostasis should arise when unusual (because of their number or duration) mucosal bleeds appear in an otherwise normal and healthy patient. Because of its definitive inhibitory effect on platelet aggregation, acetylsalicylic acid (more than other non-steroidal anti-inflammatory drugs exerting unselective inhibition of cyclooxygenase) is a strong factor in triggering or sustaining the bleeding disorders in these patients. Among the congenital disorder of primary haemostasis, vWD is by far the most frequent one. The difficulties of laboratory diagnosis of vWD are stressed; the promises and pitfalls of new in vitro methods for measuring primary haemostasis (PFA-100 analyzer) are discussed. An accurate diagnosis of the specific type of vWD is of critical importance for correct patient management as well as for genetic counseling. PMID:12923584

  5. Epicardial Adipose Tissue Has a Unique Transcriptome that is Modified in Severe Coronary Artery Disease

    PubMed Central

    McAninch, Elizabeth A.; Fonseca, Tatiana L.; Poggioli, Raffaella; Panos, Anthony L.; Salerno, Tomas A.; Deng, Youping; Li, Yan; Bianco, Antonio C.; Iacobellis, Gianluca

    2016-01-01

    Objective To explore the transcriptome of epicardial adipose tissue (EAT) as compared to subcutaneous adipose tissue (SAT) and its modifications in a small number of patients with coronary artery disease (CAD) versus valvulopathy. Design and Methods SAT and EAT samples were obtained during elective cardiothoracic surgeries. The transcriptome of EAT was evaluated using an unbiased, whole-genome approach as compared to SAT in subjects with CAD (n=6) and without CAD (n=5), where the patients without CAD had cardiac valvulopathy. Results Relative to SAT, EAT is a highly inflammatory tissue enriched with genes involved in endothelial function, coagulation, immune signaling, potassium transport and apoptosis. EAT is lacking in expression of genes involved in protein metabolism, TGF-beta signaling, and oxidative stress. Although underpowered, in subjects with severe CAD, there is an expression trend suggesting widespread downregulation of EAT encompassing a diverse group of gene sets related to intracellular trafficking, proliferation/transcription regulation, protein catabolism, innate immunity/lectin pathway and ER stress. Conclusions The EAT transcriptome is unique when compared to SAT. In the setting of CAD versus valvulopathy, there is possible alteration of the EAT transcriptome with gene suppression. This pilot study explores the transcriptome of EAT in CAD and valvulopathy, providing new insight into its physiologic and pathophysiologic roles. PMID:25959145

  6. Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-Pr specificity.

    PubMed

    Shapiro, Roman; Chin-Yee, Ian; Lam, Selay

    2015-11-01

    Severe cold agglutinin disease with hemodynamic compromise requires rapid stabilization of the autoimmune hemolytic anemia as a bridge to the immunosuppressive effect of rituximab. Herein, we describe eculizumab treatment of severe complement-mediated hemolysis in a patient whose hemodynamic status deteriorated in spite of supportive blood transfusions and therapeutic plasma exchange. PMID:26576277

  7. Dose response relation to oral theophylline in severe chronic obstructive airways disease.

    PubMed Central

    Chrystyn, H.; Mulley, B. A.; Peake, M. D.

    1988-01-01

    OBJECTIVE--To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline. DESIGN--Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data. This was followed by random assignment to four consecutive two month treatment periods--placebo and low, medium, and high dose, as assessed by serum concentrations of theophylline. Respiratory function and exercise performance was assessed at the end of each two month period. SETTING--Chest unit in district hospital. PATIENTS--Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited; 33 aged 53-73 years completed the study. INTERVENTIONS--Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted, when 400 mg was given. Targets for the steady state serum theophylline concentrations were 5-10 mg/l in the low dose period, 10-15 mg/l in the medium dose, and 15-20 mg/l in the high dose period. ENDPOINTS--Respiratory function as measured by forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate, slow vital capacity, and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived. Exercise performance assessed by six minute walking test and diary cards using visual analogue scale. MEASUREMENTS AND MAIN RESULTS--The forced expiratory volume in one second, forced vital capacity, and peak expiratory flow rate changed only slightly (about 13%) over the range of doses. There was a linear dose dependent fall of trapped gas volume from 1.84 l (SE 0.157) to 1.42 l (0.152), 1.05 l (0.128), and 0.67 l (0.102) during the placebo and low, medium, and high dose treatment periods. Mean walking distance

  8. Relationship between QT/QS2 ratio and angiographic severity of coronary heart disease.

    PubMed

    Cuomo, S; Acanfora, D; Papa, M; Covelluzzi, F; Tedeschi, C; Furgi, G; Rengo, F; De Caprio, L

    1988-08-01

    The relationship between QT/QS2 ratio and angiographic severity of coronary heart disease (CHD) was determined in 99 patients who underwent coronary arteriography because of chest pain. Sixteen control patients with normal coronary arteriograms and normal left ventricular function and 83 patients with angiographic evidence of CHD were studied. QT/QS2 ratio and systolic time intervals were calculated from poligraphic recordings taken at rest. In control subjects QT/QS2 ratio was significantly shorter (0.91 +/- 0.04) than in patients with double (0.95 +/- 0.07; p less than 0.05 versus control subjects) and triple vessel coronary artery disease (0.95 +/- 0.05; p less than 0.05 versus control subjects). QT/QS2 ratio was significantly higher (p less than 0.01) in patients with 3 areas or more of left ventricular abnormal wall motion (LV AWM) (0.98 +/- 0.05) than in patients with none (0.92 +/- 0.06) or just 1-2 areas (0.93 +/- 0.06) of LV AWM. Multiple regression analysis revealed no relation between the number of coronary stenoses and QT/QS2 (t = 0.86; p = NS), while a relation was identified between the number of asynergic segments and QT/QS2 (t = 1.99; p less than 0.05). A significant correlation was found between QT/QS2 and PEP/LVET (r = 0.39; p less than 0.001). Setting the upper normal limit at 2 standard deviations from the mean of control subjects (QT/QS2 = 0.99), QT/QS2 criterion yielded a 30% sensitivity, a 94% specificity and a 96% predictive accuracy in diagnosing CHD. We conclude that in CHD patients QT/QS2 ratio is influenced by the extension of LV AWM. Although a low sensitivity may limit its use, a QT/QS2 value higher than 0.99 in a patient with chest pain strongly suggests CHD and thus this criterion may be diagnostically useful. PMID:3243415

  9. Risk factors of direct heat-related hospital admissions during the 2009 heatwave in Adelaide, Australia: a matched case–control study

    PubMed Central

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

    2016-01-01

    Objective The extreme heatwave of 2009 in South Australia dramatically increased morbidity, with a 14-fold increase in direct heat-related hospitalisation in metropolitan Adelaide. Our study aimed to identify risk factors for the excess morbidity. Design A matched case–control study of risk factors was conducted. Setting Patients and matched community controls were interviewed to gather data on demographics, living environment, social support, health status and behaviour changes during the heatwave. Participants Cases were all hospital admissions with heat-related diagnoses during the 5-day heatwave in 2009. Controls were randomly selected from communities. Outcome measures Descriptive analyses, simple and multiple conditional logistic regressions were performed. Adjusted ORs (AORs) were estimated. Results In total, 143 hospital patients and 143 matched community controls were interviewed, with a mean age of 73 years (SD 21), 96% European ethnicity, 63% retired, 36% with high school or higher education, and 8% institutional living. The regression model indicated that compared with the controls, cases were more likely to have heart disease (AOR=13.56, 95% CI 1.27 to 144.86) and dementia (AOR=26.43, 95% CI 1.99 to 350.73). The protective factors included higher education level (AOR=0.48, 95% CI 0.23 to 0.99), having air-conditioner in the bedroom (AOR=0.12, 95% CI 0.02 to 0.74), having an emergency button (AOR=0.09, 95% CI 0.01 to 0.96), using refreshment (AOR=0.10, 95% CI 0.01 to 0.84), and having more social activities (AOR=0.11, 95% CI 0.02 to 0.57). Conclusions Pre-existing heart disease and dementia significantly increase the risk of direct heat-related hospitalisations during heatwaves. The presence of an air-conditioner in the bedroom, more social activities, a higher education level, use of emergency buttons and refreshments reduce the risk during heatwaves. PMID:27256088

  10. Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease

    PubMed Central

    De Cassan, Chiara; Savarino, Edoardo; Marson, Piero; Tison, Tiziana; Hatem, Giorgia; Sturniolo, Giacomo Carlo; D’Incà, Renata

    2014-01-01

    AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity. METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients’ charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points. RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively). CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics. PMID:25493030

  11. The association of human leukocyte antigen polymorphisms with disease severity and latency period in patients with silicosis

    PubMed Central

    2014-01-01

    Background Denim sandblasting may cause silicosis as a result of free crystalline silica inhalation. Its pathogenesis remains unclear, but autoimmunity may play a role in the development of silicosis. The present study aimed to investigate the relationships between human leukocyte antigen (HLA) and the severity and latency period of silicosis. Methods 48 silicotic patients in the Eastern part of Turkey were classified according to their latency period and disease severity. The distribution of HLAs according to disease severity and latency period was assessed. Results A23 (7.5%), B49 (7.5%), and B51 (25%) were more common in the mild group than in the severe group, and B55 (8.9%) and DR4 (17.9%) were more common in the severe group than in the mild one. Only B51 was significantly more common in the mild group than in the severe one (25%, n = 10 vs. 7.1%, n = 4; p = 0.016). Conclusions This study suggests that HLA antigens may play a particular role in the severity of silica-induced lung disease, but there was no association between HLA and progression time of the disease. PMID:24646632

  12. Severe nocturnal and postexercise hypoxia in children and adolescents with sickle cell disease.

    PubMed

    Halphen, Isabelle; Elie, Caroline; Brousse, Valentine; Le Bourgeois, Muriel; Allali, Slimane; Bonnet, Damien; de Montalembert, Mariane

    2014-01-01

    Hypoxia is a common feature in children with sickle cell disease (SCD) that is inconsistently associated with painful crises and acute chest syndrome. To assess the prevalence and risk factors of hypoxia, we recorded daytime, nocturnal, and postexercise pulse oximetry (SpO2) values in 39 SCD patients with a median age of 10.8 years. Median daytime SpO2 was 97% (range, 89%-100%), and 36% of patients had daytime hypoxia defined as SpO2<96%. Median nocturnal SpO2 was 94.7% (range, 87.7%-99.5%), 50% of patients had nocturnal hypoxia defined as SpO2≤93%, and 11(37%) patients spent more than 10% of their total sleep time with SpO2<90%. Median postexercise SpO2 was 94% (range, 72%-100%) and 44.7% of patients had postexercise hypoxia defined as an SpO2 decrease ≥3% after a 6-minute walk test. Among patients with normal daytime SpO2, 35% had nocturnal and 42% postexercise hypoxia. Compared to 9 patients without daytime, nocturnal, or postexercise hypoxia, 25 patients with hypoxia under at least one of these three conditions had greater anemia severity (P = 0.01), lower HbF levels (P = 0.04), and higher aspartate aminotransferase levels (P = 0.03). Males predominated among patients with postexercise hypoxia (P = 0.004). Hypoxia correlated neither with painful crises nor with acute chest syndrome. Of 32 evaluable patients, 6 (18.8%) had a tricuspid regurgitation velocity ≥2.6 m/s, and this feature was associated with anemia (P = 0.044). Median percentage of the predicted distance covered during a 6-minute walk test was 86% [46-120]; the distance was negatively associated with LDH (P = 0.044) and with a past history of acute chest syndrome (P = 0.009). In conclusion, severe episodes of nocturnal and postexercise hypoxia are common in children with SCD, even those with normal daytime SpO2. PMID:24878576

  13. Relation of filling pattern to diastolic function in severe left ventricular disease.

    PubMed Central

    Ng, K S; Gibson, D G

    1990-01-01

    M mode and Doppler echocardiograms, apex cardiograms, and phonocardiograms were recorded in 50 patients with severe ventricular disease of varying aetiology to examine how left ventricular filling is disturbed by cavity dilatation. The size of the left ventricular cavity was increased in all with a mean (SD) transverse diameter of 7.2 (0.8) cm at end diastole and 6.3 (0.8) cm at end systole. All were in sinus rhythm and 35 had functional mitral regurgitation. In nine patients, in whom filling period was less than 170 ms, transmitral flow showed only a single peak, representing summation. In the remainder there was a strikingly bimodal distribution of filling pattern. In 12 the ventricle filled dominantly with atrial systole (A fillers). Isovolumic relaxation was long (75 (35) ms) and wall motion incoordinate; mitral regurgitation was present in only one. In most (29) the left ventricle filled predominantly during early diastole (E fillers). Mitral regurgitation, which was present in 26, was much more common than in the A fillers, while the isovolumic relaxation time (10 (24) ms) was much shorter and the normal phase relations between flow velocity and wall motion were lost. In 24 E fillers no atrial flow was detected. In four there was no evidence of any mechanical activity, suggesting "atrial failure". In 20, either the apex cardiogram or the mitral echogram showed an A wave, implying that atrial contraction had occurred but had failed to cause transmitral flow, showing that ventricular filling was fundamentally disturbed in late diastole. A series of discrete abnormalities of filling, beyond those shown by Doppler alone, could thus be detected in this apparently homogeneous patient group by a combination of non-invasive methods. The presence and nature of these abnormalities may shed light on underlying physiological disturbances. Images PMID:2337492

  14. Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese Nonalcoholic Steatohepatitis Patients

    PubMed Central

    Huang, Jee-Fu; Yeh, Ming-Lun; Yu, Ming-Lung; Huang, Chung-Feng; Dai, Chia-Yen; Hsieh, Ming-Yen; Hsieh, Meng-Hsuan; Huang, Ching-I; Lin, Zu-Yau; Chen, Shinn-Chern; Hsiao, Pi-Jung; Shin, Shyi-Jang; Chuang, Wan-Long

    2015-01-01

    Background & Aims Asians are more susceptible to non-alcoholic steatohepatitis (NASH) as well as metabolic disorder than other ethnicities. We aimed to assess the interaction between metabolic factors and fibrosis in Taiwanese NASH patients. Methods A total of 130 biopsy-proven Taiwanese NASH patients (94 males, age = 43.0 ± 13.0 years) were consecutively enrolled. Their demographic, metabolic profiles and histopathological manifestations were analyzed. Results Twenty-four (18.5%) NASH patients were non-obese. Thirty-three (25.4%) patients had significant fibrosis (F2) or more: 22 (16.9%) patients were of F2, whilst 11 (8.5%) patients were of advanced fibrosis (F3-4). The prevalence of metabolic syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively. There was a significant inverse correlation between hyperuricemia and fibrosis stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively (P = 0.01, linear trend). Multivariate logistic regression analysis showed that a decreased serum albumin level (OR = 40.0, 95% CI = 4.5–300, P = 0.001) and normal uric acid level (OR = 5.6, 95% CI = 1.5–21.7, P = 0.01) were the significant factors associated with significant fibrosis. Conclusions Hyperuricemia inversely predicts fibrosis stages. Females might carry a more disease severity than males in Taiwanese NASH patients. PMID:26441244

  15. Lung disease severity, chronic inflammation, iron deficiency, and erythropoietin response in adults with cystic fibrosis.

    PubMed

    Fischer, R; Simmerlein, R; Huber, R M; Schiffl, H; Lang, S M

    2007-12-01

    Chronic lung disorders are usually associated with a hypoxia driven increase in red cell mass. However, patients with cystic fibrosis (CF) often have normal or decreased haemoglobin levels. The present prospective observational study in cystic fibrosis patients was performed to determine which factors were involved in alterations in the hematopoetic response to corresponding arterial oxygen pressure. Sixty adult patients (age 21-51) with stable CF were included. They all had vitamin A, D, E, and K but no vitamin B12 supplementation. Twenty-five patients were on oral Fe(2+) (100 mg/day). Resting arterial blood gases, lung function, complete blood counts, parameters of iron status, CRP, sputum microbiology and serum erythropoietin were measured at recruitment and after 3 and 6 months. Patients had varying degrees of pulmonary functional impairment and 9% were hypoxemic (arterial oxygen pressure <60 mm Hg). Low-grade systemic inflammation (CRP > 0.5 mg/dl) was present in 40% of the patients, who all had bacterial colonization. None of the patient had erythrocytosis and 12 patients had anemia. There was no significant difference in iron status between patients with or without chronic iron supplementation and erythropoietin levels were normal. During the 6 months observation period no significant changes occurred. The patients exhibited an impaired erythropoietic response to hypoxemia with normal or low hematocrit in spite of chronic lung disease which might be caused by chronic inflammation associated with CF. Linear multivariate regression analysis revealed CRP levels but neither iron substitution, nor erythropoietin levels nor lung function parameters as independent determinant of haemoglobin levels. CF may be associated with anemia of variable severity as expression of the chronic inflammation present in these patients. The therapeutic consequences are to treat the underlying inflammation rather than to supplement iron. PMID:17948283

  16. [Oral diseases recorded in several ancient pulse-taking books unearthed in Mawangdui and Zhangjiashan].

    PubMed

    Li, X J; Zhu, L

    2016-03-01

    The earliest known records of oral ulcer, periodontitis and its accompanying lesions were seen in the manuscripts, Bing hou(Syndrome of Disease) and Yin yang mai si hou(Fatal Syndrome of Yin Yang Channels), the ancient pulse-taking books from Mawangdui and Zhangjiashan. In the manuscripts Zu bi shi yi mai jiu jing(11-Channel Moxibustion Classic of Foot and Arm) and Yin yang shi yi mai jiu jing(11-Channel Moxibustion Classic of Yin and Yang), there were the earliest content about mandibular and neck diseases, tongue diseases, tooth diseases and mouth diseases described based on the locations along the channel pathways, and preliminary clinical records of diagnosis and treatment of some oral diseases, reflecting the achievements of stomatology in the pre-Qin period and Oin as well as Han Dynasty. PMID:27255193

  17. Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.

    PubMed

    Matsumura-Kimoto, Yayoi; Inamoto, Yoshihiro; Tajima, Kinuko; Kawajiri, Akihisa; Tanaka, Takashi; Hirakawa, Tsuneaki; Ino, Kazuko; Asao, Yu; Tamogami, Hiroyuki; Kono, Chika; Takeda, Wataru; Okinaka, Keiji; Fuji, Shigeo; Kurosawa, Saiko; Kim, Sung-Won; Tanosaki, Ryuji; Yamashita, Takuya; Fukuda, Takahiro

    2016-06-01

    This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses. PMID:26968790

  18. 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

  19. 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.

  20. Impact of Different Potato Psyllid Populations on Zebra Chip Disease Incidence, Severity, and Potato Yield

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zebra chip (ZC) is an emerging and damaging potato disease that is causing millions of dollars in losses to the potato industry in the southwestern United States, Mexico, and Central America. ZC plant symptoms resemble those caused by potato purple top and psyllid yellows diseases. Tubers produced b...

  1. 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...

  2. 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...

  3. Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis

    PubMed Central

    Cook, Katherine W.; Crooks, James; Hussain, Khiyam; O’Brien, Kate; Braitch, Manjit; Kareem, Huner; Constantinescu, Cris S.; Robinson, Karen; Gran, Bruno

    2015-01-01

    Recent research has demonstrated that infection with the bacterial pathogen Helicobacter pylori is less common amongst patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). We aimed to compare the prevalence of H. pylori amongst MS patients and healthy controls, and also investigated the impact of this infection on an animal model for MS, experimental autoimmune encephalomyelitis (EAE). The H. pylori status of 71 MS patients and 42 healthy controls was determined by serology. Groups of C57BL/6 mice were infected with H. pylori, or given diluent alone as a placebo, prior to inducing EAE. Clinical scores were assessed for all mice, and spleens and spinal cord tissue were harvested. CD4+ T cell subsets were quantified by flow cytometry, and T cell proliferation assays were performed. In MS patients the seroprevalence of H. pylori was half that of healthy controls (p = 0.018). Over three independent experiments, prior H. pylori infection had a moderate effect in reducing the severity of EAE (p = 0.012). In line with this, the antigen-specific T cell proliferative responses of infected animals were significantly reduced (p = 0.001), and there was a fourfold reduction in the number of CD4+ cells in the CNS. CD4+ populations in both the CNS and the spleens of infected mice also contained greatly reduced proportions of IFNγ+, IL-17+, T-bet+, and RORγt+ cells, but the proportions of Foxp3+ cells were equivalent. There were no differences in the frequency of splenic CD4+cells expressing markers of apoptosis between infected and uninfected animals. H. pylori was less prevalent amongst MS patients. In mice, the infection exerted some protection against EAE, inhibiting both Th1 and Th17 responses. This could not be explained by the presence of increased numbers of Foxp3+ regulatory T cells, or T cell apoptosis. This is the first direct experimental evidence showing that H. pylori may provide protection against

  4. Characterizing and estimating rice brown spot disease severity using stepwise regression, principal component regression and partial least-square regression.

    PubMed

    Liu, Zhan-yu; Huang, Jing-feng; Shi, Jing-jing; Tao, Rong-xiang; Zhou, Wan; Zhang, Li-Li

    2007-10-01

    Detecting plant health conditions plays a key role in farm pest management and crop protection. In this study, measurement of hyperspectral leaf reflectance in rice crop (Oryzasativa L.) was conducted on groups of healthy and infected leaves by the fungus Bipolaris oryzae (Helminthosporium oryzae Breda. de Hann) through the wavelength range from 350 to 2,500 nm. The percentage of leaf surface lesions was estimated and defined as the disease severity. Statistical methods like multiple stepwise regression, principal component analysis and partial least-square regression were utilized to calculate and estimate the disease severity of rice brown spot at the leaf level. Our results revealed that multiple stepwise linear regressions could efficiently estimate disease severity with three wavebands in seven steps. The root mean square errors (RMSEs) for training (n=210) and testing (n=53) dataset were 6.5% and 5.8%, respectively. Principal component analysis showed that the first principal component could explain approximately 80% of the variance of the original hyperspectral reflectance. The regression model with the first two principal components predicted a disease severity with RMSEs of 16.3% and 13.9% for the training and testing dataset, respectively. Partial least-square regression with seven extracted factors could most effectively predict disease severity compared with other statistical methods with RMSEs of 4.1% and 2.0% for the training and testing dataset, respectively. Our research demonstrates that it is feasible to estimate the disease severity of rice brown spot using hyperspectral reflectance data at the leaf level. PMID:17910117

  5. Low nutrient intake among adult women and patients with severe tuberculosis disease in Uganda: a cross-sectional study

    PubMed Central

    2012-01-01

    Background Information regarding dietary nutrient intake during tuberculosis disease is lacking. We established the relationship between disease severity or wasting during pulmonary tuberculosis and nutrient intake. Methods In a cross-sectional study of 131 adults with or without pulmonary tuberculosis were screened for human immune-deficiency virus (HIV), wasting, disease severity using 13 item validated clinical TBscore, and 24-hour dietary intake recall. Results Of the 131 participants, 61 were males and 70 females. Overall men and women had similar age. In average 24-hour nutrient intake, the following nutrients: energy, protein, total fat, carbohydrate, calcium, vitamin A, and folate were low among patients with severe tuberculosis disease. Patients with moderate-to-severe clinical TBscore had lower average energy intake than patients with mild TBscores (6.11 vs. 9.27 MJ, respectively) (p<0.05). The average 24-hour nutrient intakes between wasted and non-wasted tuberculosis patients were comparable. Nutrient intake among men was higher when compared to women regardless of wasting and severity of tuberculosis. Among those with wasting, men had higher average energy intake than women (8.87 vs. 5.81 MJ, respectively) (p<0.05). Among patients with mild disease, men had higher average energy intake than women with mild disease (12.83 vs. 7.49 kcal, respectively) (p<0.001). Conclusions Findings suggest that severity of pulmonary tuberculosis and female gender had reduced nutrient intake. Early tuberculosis diagnosis and nutritional support may be important in management of tuberculosis patients. PMID:23217171

  6. Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults?

    PubMed

    Chu, Andrew S; Chopra, Kapil B; Perlmutter, David H

    2016-07-01

    The classical form of alpha-1-antitrypsin deficiency (A1ATD) is known to cause liver disease in children and adults, but there is relatively little information about the risk of severe, progressive liver disease and the need for liver transplantation. To better understand how newly evolving pharmacological, genetic, and cellular therapies may be targeted according to risk for progressive liver disease, we sought to determine the age distribution of A1ATD as a cause of severe liver disease, as defined by the need for liver transplantation. Using 3 US liver transplantation databases for the period 1991-2012, we found 77.2% of 1677 liver transplants with a reported diagnosis of A1ATD were adults. The peak age range was 50-64 years. Using 2 of the databases which included specific A1AT phenotypes, we found that many of these adults who undergo liver transplantation with A1ATD as the diagnosis are heterozygotes and have other potential causes of liver disease, most notably obesity and ethanol abuse. However, even when these cases are excluded and only ZZ and SZ phenotypes are considered, severe liver disease requiring transplantation is more than 2.5 times as likely in adults. The analysis also showed a markedly increased risk for males. In the pediatric group, almost all of the transplants are done in children less than 5 years of age. In conclusion, A1ATD causes progressive liver disease most commonly in adults with males in the highest risk category. In the pediatric group, children less than 5 years of age are highest in risk. These results suggest that A1ATD most commonly causes liver disease by mechanisms similar to age-dependent degenerative diseases and more rarely in children by powerful modifiers. Liver Transplantation 22 886-894 2016 AASLD. PMID:26946192

  7. PROGESTERONE TREATMENT REDUCES DISEASE SEVERITY AND INCREASES IL-10 IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

    PubMed Central

    Yates, M.A; Li, Y.; Chlebeck, P.; Proctor, T.; Vandenbark, A.A.; Offner, H.

    2010-01-01

    Ovarian hormones, including progesterone, are known to have immunomodulatory and neuroprotective effects which may alter the disease course of experimental autoimmune encephalomyelitis (EAE). In the current study, we examined the treatment potential of progesterone beginning at the onset of EAE symptoms. Progesterone treated animals showed reduced peak disease scores and cumulative disease indices, and decreased inflammatory cytokine secretion (IL-2 and IL-17). In addition, increased production of IL-10 was accompanied by increased numbers of CD19+ cells and an increase in CD8+ cells. Decreased chemokine and chemokine receptor expression in the spinal cord also contributed to decreased lesions in the spinal cord. PMID:20153059

  8. A retrospective, cross-sectional study reveals that women with CRSwNP have more severe disease than men.

    PubMed

    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

    2015-03-01

    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

  9. 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

  10. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

    PubMed Central

    Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young; Sohn, Kyung Mok; Kim, Yuri; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Ji-Yeob; Inn, Kyung-Soo; Kim, Jin-Hwan; Moon, Jae Young; Choi, Myung-Sik; Cho, Nam-Hyuk; Kim, Yeon-Sook

    2016-01-01

    Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS. PMID:27146253

  11. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.

    PubMed

    Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young; Sohn, Kyung Mok; Kim, Yuri; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Ji-Yeob; Inn, Kyung-Soo; Kim, Jin-Hwan; Moon, Jae Young; Choi, Myung-Sik; Cho, Nam-Hyuk; Kim, Yeon-Sook

    2016-01-01

    Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS. PMID:27146253

  12. 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

  13. Familial Cushing's disease with severe weight loss occurring in late childhood.

    PubMed

    Cameron, F J; Warne, G L

    1997-02-01

    We describe a rare case of familial Cushing's disease occurring in a 7-year-old boy, and 19 years of follow up. Our patient first presented soon after his maternal aunt had been treated for Cushing's disease. The clinical presentation was made complicated by the development of an intercurrent eating disorder resembling anorexia nervosa. This resulted in marked weight loss, and even though serum and urinary cortisol levels were elevated, many of the clinical stigmata of Cushing's disease were absent. Eating disorders are relatively uncommon in boys, and in this case there was an organic cause for the abnormal behaviour. This case shows, furthermore, that even the obesity of Cushing's disease can be overcome by the combination of diet and exercise. PMID:9069050

  14. Neuropsychiatric aspects of adult-onset Tay-Sachs disease: two case reports with several new findings.

    PubMed

    Hurowitz, G I; Silver, J M; Brin, M F; Williams, D T; Johnson, W G

    1993-01-01

    Deficiency of hexosaminidase A causes the GM2 gangliosidosis known as Tay-Sachs disease. It is now known that this condition has several late-onset variants that cause numerous neuropsychiatric disturbances. Early recognition is important because treatment with phenothiazines and heterocyclic antidepressants may worsen the course. The authors report two cases with several new findings, including prominent psychiatric symptoms without psychosis early in the course of the illness. PMID:8428133

  15. Severe Sarcoidosis.

    PubMed

    Kouranos, Vasileios; Jacob, Joe; Wells, Athol U

    2015-12-01

    In sarcoidosis, reduction in mortality and the prevention of disability due to major organ involvement are treatment goals. Thus, it is important to recognize severe disease and identify patients at higher risk of progression to severe disease. In this article, fibrotic lung disease and cardiac sarcoidosis are reviewed as the major contributors to sarcoidosis mortality and morbidity. In the absence of a standardized definition of severe pulmonary disease, a multidisciplinary approach to clinical staging is suggested, based on symptoms, pulmonary function tests, and imaging findings at presentation, integrated with the duration of disease and longitudinal disease behavior during early follow-up. PMID:26593144

  16. Increased Coronary Artery Disease Severity in Black Women Undergoing Coronary Bypass Surgery

    PubMed Central

    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.

    2015-01-01

    Abstract 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 Ptrend = 0.0021). A similar trend was not observed between black and white male CABG patients (adjusted Ptrend = 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. PMID:25700324

  17. EFFECTS OF ENHANCED ULTRAVIOLET-B RADIATION ON YIELD, AND DISEASE INCIDENCE AND SEVERITY FOR WHEAT UNDER FIELD CONDITIONS

    EPA Science Inventory

    The influence of enhanced UV-B radiation (280-320 nm) on wheat (Triticum aestivum cv. 'Florida 301') yield, and disease incidence and severity was investigated for two growing seasons under field conditions. Three levels of UV-B enhancement, simulating 8,12 and 16% stratospheric ...

  18. 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

  19. 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 ...

  20. Unknown syndrome: mental retardation with postaxial polydactyly, congenital absence of hair, severe seborrhoeic dermatitis, and Perthes' disease of the hip.

    PubMed

    Garrett, C; Tripp, J H

    1988-04-01

    We report a six year old male with mental retardation, postaxial polydactyly and syndactyly, atrichia congenita totalis, severe seborrhoeic dermatitis, recurrent staphylococcal skin sepsis, and Perthes' disease of the hip. His birth may have resulted from an incestuous mating. PMID:2966861

  1. Transaortic Intra-Aortic Balloon Pump Catheter Insertion through a Separate Saphenous Vein Graft in Patients with Severe Aortoiliac Disease

    PubMed Central

    Toktas, Faruk; Surer, Suleyman

    2014-01-01

    Background. Intra-aortic balloon pump (IABP) is the most widely used mechanical assist device for hemodynamic support in high risk patients undergoing cardiac surgery. The aim of our study was to confirm whether transaortic route is a suitable alternative to allow IABP insertion in patients with severe aortoiliac diseases. Methods. This study included 7 consecutive patients undergoing coronary artery bypass grafting for severe coronary artery disease associated with severe aortoiliac disease. These patients could not be weaned from cardiopulmonary bypass and required the IABP support, which were placed through the ascending aorta. IABP catheter was inserted indirectly through a separate saphenous vein graft anastomosed to the ascending aorta by an end-to-side manner under a partial occluding clamp and advanced to the desired position in the descending thoracic aorta and exteriorly brought into the subcutaneous tissues in the jugulum. Results. The procedure was successfully performed in all the patients. The mean duration of IABP support was 54.0 ± 13.4 hours. There were no in-hospital mortality and complications related to transaortic route. IABP removal did not require repeat sternotomy. At postoperative 6th month, multislice CT examination showed thrombotic occlusion at the remnant of the saphenous vein graft. Conclusions. This technique is a simple, reliable, and reproducible option in patients with severe aortoiliac disease in whom retrograde femoral route is not possible. PMID:24516360

  2. 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...

  3. 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...

  4. 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…

  5. Use of liver breath tests to assess severity of nonalcoholic fatty liver disease.

    PubMed

    Furnari, Manuele; Savarino, Vincenzo; Giannini, Edoardo G

    2014-01-01

    As the prevalence of obesity and insulin-resistance continues to increase in the general population, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions, thus becoming one of the leading causes of chronic liver disease worldwide. It may present as simple steatosis (NAFL) or steatohepatitis (NASH), which in turn may develop fibrosis and ultimately cirrhosis. Conventional biochemical liver test and radiological investigations are not able to provide reliable information on liver functional reserve, and liver biopsy remains the gold standard to stage NAFLD, differentiate simple steatosis from NASH, and grade fibrosis. However, liver biopsy has some limitations, and is not preferred by patients due to its invasiveness. Thus, non-invasive assessment of disease stage by using liver breath tests - which are based on hepatic clearance of non-radioactive stable (13)C-labelled drugs - may be of interest to stage disease and assess patients prognosis due to good accuracy and repeatability. These substrates are orally administered and are cleaved by enzymes specifically located in the liver thus reflecting either the microsomal, cytosolic, or mitochondrial functions. (13)C-Breath Tests have been initially oriented to differentiate broad categories of patients and more recently to refine stage differentiation in patients with early stages of liver disease. In NAFLD patients, (13)C-BTs were able to distinguish simple steatosis from NASH and had good correlation with both histological fibrosis stage and biochemical markers of fibrogenesis. Although promising results have been achieved in this field, their use in clinical practice is still restricted to a specialized niche. However, concordant data from literature conferred to (13)C-Breath Tests a potential role in providing punctual and longitudinal evaluation of patients, identifying those patients where liver biopsy may selectively be performed to stage disease, monitoring and predicting therapeutic

  6. Exposure to ozone reduces influenza disease severity and alters distribution of influenza viral antigens in murine lungs.

    PubMed

    Wolcott, J A; Zee, Y C; Osebold, J W

    1982-09-01

    Exposure to ambient levels of ozone (0.5 ppm) was shown to alter the pathogenesis of respiratory infection after aerosol infection of mice with influenza A virus. A semiquantitative method for determination of the sites of virus replication by direct immunofluorescence indicated that exposure to ozone reduced the involvement of respiratory epithelium in the infectious process and resulted in a less widespread infection of the alveolar parenchyma. Furthermore, the ozone-mediated alteration in viral antigen distribution was consistent with significantly reduced influenza disease mortality and prolonged survival time, but only when the oxidant was present during the course of infection. Reduced disease severity in ozone-exposed animals appeared to be independent of peak pulmonary virus titers, pulmonary interferon titers, and pulmonary and serum-neutralizing antibody titers. These studies suggested that the distribution of influenza virus in the murine lung was a key factor in disease severity. PMID:6182839

  7. [Anxiety and polymorphism Val66Met of BDNF gene--predictors of depression severity in ischemic heart disease].

    PubMed

    Golimbet, V E; Volel', B A; Kopylov, F Iu; Dolzhikov, A V; Korovaitseva, G I; Kasparov, S V; Isaeva, M I

    2015-01-01

    In a framework of search for early predictors of depression in patients with ischemic heart disease (IHD) we studied effect of molecular-genetic factors (polymorphism of brain-derived neirotrophic factor--BDNF), personality traits (anxiety, neuroticism), IHD severity, and psychosocial stressors on manifestations of depression in men with verified diagnosis of IHD. Severity of depression was assessed by Hamilton Depression Rating Scale 21-item (HAMD 21), anxiety and neuroticism were evaluated by the Spielberger State-Trait Anxiety Inventory and "Big Five" questionnaire, respectively. It wa shown that personal anxiety and ValVal genotype of BDNF gene appeared to be predictors of moderate and severe depression. PMID:26050483

  8. 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

    2016-01-01

    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

  9. 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

  10. 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

  11. Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity

    PubMed Central

    Fedeles, Sorin V.; So, Jae-Seon; Shrikhande, Amol; Lee, Seung Hun; Gallagher, Anna-Rachel; Barkauskas, Christina E.; Somlo, Stefan; Lee, Ann-Hwee

    2015-01-01

    The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in humans; however, it is not clear how altered SEC63 influences disease manifestations. In mice, loss of SEC63 induces cyst formation both in liver and kidney as the result of reduced polycystin-1 (PC1). Here we report that inactivation of SEC63 induces an unfolded protein response (UPR) pathway that is protective against cyst formation. Specifically, using murine genetic models, we determined that SEC63 deficiency selectively activates the IRE1α-XBP1 branch of UPR and that SEC63 exists in a complex with PC1. Concomitant inactivation of both SEC63 and XBP1 exacerbated the polycystic kidney phenotype in mice by markedly suppressing cleavage at the G protein–coupled receptor proteolysis site (GPS) in PC1. Enforced expression of spliced XBP1 (XBP1s) enhanced GPS cleavage of PC1 in SEC63-deficient cells, and XBP1 overexpression in vivo ameliorated cystic disease in a murine model with reduced PC1 function that is unrelated to SEC63 inactivation. Collectively, the findings show that SEC63 function regulates IRE1α/XBP1 activation, SEC63 and XBP1 are required for GPS cleavage and maturation of PC1, and activation of XBP1 can protect against polycystic disease in the setting of impaired biogenesis of PC1. PMID:25844898

  12. 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...

  13. 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...

  14. 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 toward the…

  15. 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 ...

  16. 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. PMID:25909431

  17. Plasma Concentration of Parasite DNA as a Measure of Disease Severity in Falciparum Malaria

    PubMed Central

    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.

    2015-01-01

    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. PMID:25344520

  18. A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

    PubMed Central

    Disson, Olivier; Brigitte, Madly; Guivel-Benhassine, Florence; Touret, Yasmina; Barau, Georges; Cayet, Nadège; Schuffenecker, Isabelle; Desprès, Philippe; Arenzana-Seisdedos, Fernando; Michault, Alain

    2008-01-01

    Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of C