The influence of parental factors on therapist adherence in multi-systemic therapy.

PubMed

Ellis, Mesha L; Weiss, Bahr; Han, Susan; Gallop, Robert

2010-08-01

Therapist treatment adherence has received a great deal of attention in recent years, in part because of its relation to treatment outcomes. Although certain therapist behaviors have been found to be associated with treatment outcomes, little is known about client factors impacting on therapists' ability to adhere to treatment protocols. In this study, we evaluated effects of parental beliefs, psychopathology, and interaction styles on therapists' adherence to Multi-systemic Therapy (MST) principles. Eighty-two parents participating in a clinical trial of MST completed baseline measures assessing psychopathology, family functioning, and treatment expectations. Analyses indicated that parental perceptions of therapist adherence were established within the first 4 weeks of treatment, and that parental psychopathology, motivation, expectations, and child rearing practices were related to parental ratings of therapist adherence. Results were essentially unchanged when controlling for parental positive response style. Clinical and research implications of the findings are discussed.

Therapists' and Clients' Perceptions of Bonding as Predictors of Outcome in Multisystemic Therapy®.

PubMed

Glebova, Tatiana; Foster, Sharon L; Cunningham, Phillippe B; Brennan, Patricia A; Whitmore, Elizabeth A

2017-12-08

This longitudinal study examined whether strength of and balance in self-reported caregiver, youth, and therapist emotional bonds in mid- and late treatment predicted outcomes in Multisystemic Therapy of adolescent behavior problems in a sample of 164 caregiver-youth dyads. Strength of and balance in bonds related to outcome in different ways, depending on the source of the report and time. Results showed a limited association between family members' emotional connection with the therapist and treatment outcome, whereas therapists' perceptions of bond with the caregiver showed highly significant associations across time. Caregiver-therapist agreement on emotional connection at both time points predicted therapist evaluation of treatment success and successful termination, but this was largely explained by therapists' level of alliance. Balance in bonds with the therapist between caregiver and youth had no significant associations with any outcome. The study major limitations such as examining only one component of alliance and possible implications are discussed. © 2017 Family Process Institute.

Adolescent Physiological and Behavioral Patterns of Emotion Dysregulation Predict Multisystemic Therapy Response.

PubMed

Winiarski, D Anne; Schechter, Julia C; Brennan, Patricia A; Foster, Sharon L; Cunningham, Phillippe B; Whitmore, Elizabeth A

2017-09-01

This study examined whether physiological and behavioral indicators of emotion dysregulation assessed over the course of Multisystemic Therapy (MST) were related to treatment response. Participants were 180 ethnically diverse adolescents ( n =120 males), ranging in age from 12 to 17 years. Treatment response was assessed through therapist report and official arrest records. Changes in cortisol reactivity and changes in scores on a behavioral dysregulation subscale of the Child Behavior Checklist were used as indicators of emotion dysregulation. Hierarchical linear modeling analyses examined whether a less favorable treatment response was associated with cortisol reactivity measures (a) collected early in treatment and (b) over the course of treatment, as well as with behavioral reports of emotion dysregulation reported (c) early in treatment, and (d) over the course of treatment. Sex was explored as a moderator of these associations. Results indicated that both cortisol and behavioral indices of emotion dysregulation early in treatment and over the course of therapy predicted treatment responsiveness. This relationship was moderated by sex: girls were more likely to evidence a pattern of increasing emotion regulation prior to successful therapy response. The results lend further support to the notion of incorporating emotion regulation techniques into treatment protocols for delinquent behavior.

Stress, Cortisol, and Externalizing Behavior in Adolescent Males: An Examination in the Context of Multisystemic Therapy

ERIC Educational Resources Information Center

Schechter, Julia C.; Brennan, Patricia A.; Cunningham, Phillippe B.; Foster, Sharon L.; Whitmore, Elizabeth

2012-01-01

Stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation have been associated with externalizing behavior in adolescence, but few studies have examined these factors in a treatment context. This study investigated the relationship between stress, cortisol, and externalizing behavior among 120 adolescent males (mean age = 15) receiving…

Effects of Topiramate in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Shapira, Nathan A.; Lessig, Mary C.; Lewis, Mark H.; Goodman, Wayne K.; Driscoll, Daniel J.

2004-01-01

Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was…

Intensive Quality Assurance of Therapist Adherence to Behavioral Interventions for Adolescent Substance Use Problems

ERIC Educational Resources Information Center

Holth, Per; Torsheim, Torbjorn; Sheidow, Ashli J.; Ogden, Terje; Henggeler, Scott W.

2011-01-01

This study was a cross-cultural replication of a study that investigated therapist adherence to behavioral interventions as a result of an intensive quality assurance system which was integrated into Multisystemic Therapy (MST). Thirty-three therapists and eight supervisors were block randomized to either an Intensive Quality Assurance or a…

MST with Conduct Disordered Youth in Sweden: Costs and Benefits after 2 Years

ERIC Educational Resources Information Center

Olsson, Tina M.

2010-01-01

Objectives: The purpose of this study was to investigate the costs and benefits associated with multisystemic therapy (MST) for conduct disordered youth, 2 years following intake. Methods: The study employed a secondary analysis of 156 youth enrolled in a randomized trial assessing the psychosocial and behavioral outcomes of MST. Results: MST cost…

Multisystemic Therapy Improves the Patient-Provider Relationship in Families of Adolescents with Poorly Controlled Insulin Dependent Diabetes

PubMed Central

Carcone, April Idalski; Ellis, Deborah A.; Chen, Xinguang; Naar-King, Sylvie; Cunningham, Phillippe B.; Moltz, Kathleen

2015-01-01

Objective The purpose of this study was to determine if Multisystemic Therapy (MST), an intensive, home and community-based family treatment, significantly improved patient-provider relationships in families where youth had chronic poor glycemic control. Methods One hundred forty-six adolescents with type 1 or 2 diabetes in chronic poor glycemic control (HbA1c ≥ 8%) and their primary caregivers were randomly assigned to MST or a telephone support condition. Caregiver perceptions of their relationship with the diabetes multidisciplinary medical team were assessed at baseline and treatment termination with the Measure of Process of Care-20. Results At treatment termination, MST families reported significant improvement on the Coordinated and Comprehensive Care scale and marginally significant improvement on the Respectful and Supportive Care scale. Improvements on the Enabling and Partnership and Providing Specific Information scales were not significant. Conclusions Results suggest MST improves the ability of the families and the diabetes treatment providers to work together. PMID:25940767

Common and Specific Factors Approaches to Home-Based Treatment: I-FAST and MST

ERIC Educational Resources Information Center

Lee, Mo Yee; Greene, Gilbert J.; Fraser, J. Scott; Edwards, Shivani G.; Grove, David; Solovey, Andrew D.; Scott, Pamela

2013-01-01

Objectives: This study examined the treatment outcomes of integrated families and systems treatment (I-FAST), a moderated common factors approach, in reference to multisystemic therapy (MST), an established specific factor approach, for treating at risk children and adolescents and their families in an intensive community-based setting. Method:…

Current and future prospects in the management of granulomatosis with polyangiitis (Wegener’s granulomatosis)

PubMed Central

Tarzi, Ruth M; Pusey, Charles D

2014-01-01

Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis) is a multisystem autoimmune condition associated with anti-neutrophil cytoplasm antibodies. Management of GPA can be complex, owing to the sometimes fulminant and multisystem nature of the presentation, the age demographics of the affected population, and a significant incidence of disease relapse. In this paper, we discuss how some of the challenges in the management of GPA have been and continue to be addressed including: reducing the toxicity of induction therapy; developing biomarkers to determine who can safely stop maintenance immunosuppression; improving the efficacy of maintenance therapy for relapsing patients; managing localized disease; and management of disease and treatment-associated comorbidity. Consideration is also given to emerging therapeutics in the treatment of GPA. PMID:24790453

Long-Term Youth Criminal Outcomes in MST Transport: The Impact of Therapist Adherence and Organizational Climate and Structure

ERIC Educational Resources Information Center

Schoenwald, Sonja K.; Chapman, Jason E.; Sheidow, Ashli J.; Carter, Rickey E.

2009-01-01

This study investigated relations among therapist adherence to an evidence-based treatment for youth with serious antisocial behavior (i.e., Multisystemic Therapy), organizational climate and structure, and youth criminal charges on average 4 years posttreatment. Participants were 1,979 youth and families treated by 429 therapists across 45…

Empirically Supported Family-Based Treatments for Conduct Disorder and Delinquency in Adolescents

ERIC Educational Resources Information Center

Henggeler, Scott W.; Sheidow, Ashli J.

2012-01-01

Several family-based treatments of conduct disorder and delinquency in adolescents have emerged as evidence-based and, in recent years, have been transported to more than 800 community practice settings. These models include multisystemic therapy, functional family therapy, multidimensional treatment foster care, and, to a lesser extent, brief…

Juvenile delinquency treatment and prevention: a literature review.

PubMed

May, Jessica; Osmond, Kristina; Billick, Stephen

2014-09-01

In the last three decades there has been ample research to demonstrate that instituting Multisystemic Therapy for serious juvenile offenders, keeping them in the community with intensive intervention, can significantly reduce recidivism. When there is recidivism, it is less severe than in released incarcerated juveniles. Multisystemic Therapy provides 24 h available parental guidance, family therapy, individual therapy, group therapy, educational support and quite importantly a change of peer group. In New York City, there is the new mandate through the Juvenile Justice Initiative to implement interventions to keep juvenile offenders in the community rather than sending them to be incarcerated. However, this paper aims to examine how teaching prosocial values in early childhood can reduce the incidence of first-time juvenile delinquency. Programs such as the Perry School Project will be discussed to demonstrate that although somewhat expensive, these innovative programs nonetheless are quite cost-effective as the cost to society of adjudication, incarceration and victim damages are significantly greater. Along with teaching prosocial 0020 values, there has been renewed interest in early identification of youth at risk for developing Antisocial Personality Disorder. An update is given on the status of both promising approaches in early intervention to prevent serious juvenile delinquency and hence adult criminality.

Predicting early positive change in multisystemic therapy with youth exhibiting antisocial behaviors.

PubMed

Tiernan, Kristine; Foster, Sharon L; Cunningham, Phillippe B; Brennan, Patricia; Whitmore, Elizabeth

2015-03-01

This study examined individual and family characteristics that predicted early positive change in the context of Multisystemic Therapy (MST). Families (n = 185; 65% male; average youth age 15 years) receiving MST in community settings completed assessments at the outset of treatment and 6-12 weeks into treatment. Early positive changes in youth antisocial behavior were assessed using the caregiver report on the Child Behavior Checklist Externalizing Behaviors subscale and youth report on the Self-Report Delinquency Scale. Overall, families showed significant positive changes by 6-12 weeks into treatment; these early changes were maintained into midtreatment 6-12 weeks later. Families who exhibited clinically significant gains early in treatment were more likely to terminate treatment successfully compared with those who did not show these gains. Low youth internalizing behaviors and absence of youth drug use predicted early positive changes in MST. High levels of parental monitoring and low levels of affiliation with deviant peers (mechanisms known to be associated with MST success) were also associated with early positive change. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Lupus erythematosus

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

Tuffanelli, D.L.

1981-02-01

Lupus erythematosus (LE) is a multisystem disease. Genetic predisposition, altered immunity, hormones, drugs, viruses, and ultraviolet light all may play a role in etiology. A wide range of cutaneous lesions occur, and variants such as subacute cutaneous LE, complement-deficient LE, and neonatal LE have recently been emphasized. Management of the LE patient, including appropriate diagnostic studies and therapy relevant to the dermatologist, is discussed in the review.

Mediators of change for multisystemic therapy with juvenile sexual offenders.

PubMed

Henggeler, Scott W; Letourneau, Elizabeth J; Chapman, Jason E; Borduin, Charles M; Schewe, Paul A; McCart, Michael R

2009-06-01

The mediators of favorable multisystemic therapy (MST) outcomes achieved at 12 months postrecruitment were examined within the context of a randomized effectiveness trial with 127 juvenile sexual offenders and their caregivers. Outcome measures assessed youth delinquency, substance use, externalizing symptoms, and deviant sexual interest/risk behaviors; hypothesized mediators included measures of parenting and peer relations. Data were collected at pretreatment, 6 months postrecruitment, and 12 months postrecruitment. Consistent with the MST theory of change and the small extant literature in this area of research, analyses showed that favorable MST effects on youth antisocial behavior and deviant sexual interest/risk behaviors were mediated by increased caregiver follow-through on discipline practices as well as decreased caregiver disapproval of and concern about the youth's bad friends during the follow-up. These findings have important implications for the community-based treatment of juvenile sexual offenders. Copyright 2009 APA

Outcomes from Wraparound and Multisystemic Therapy in a Center for Mental Health Services System-of-Care Demonstration Site

ERIC Educational Resources Information Center

Stambaugh, Leyla Faw; Mustillo, Sarah A.; Burns, Barbara J.; Stephens, Robert L.; Baxter, Beth; Edwards, Dan; DeKraai, Mark

2007-01-01

This study examined outcomes for 320 youth in a Center for Mental Health Services system-of-care demonstration site. Youth received wraparound-only (n = 213), MST-only (n = 54), or wraparound + MST (n = 53). Participants were 12 years old on average and mostly White (90%), and 75% were Medicaid-eligible. Service use and functional and clinical…

An independent randomized clinical trial of multisystemic therapy with non-court-referred adolescents with serious conduct problems.

PubMed

Weiss, Bahr; Han, Susan; Harris, Vicki; Catron, Thomas; Ngo, Victoria K; Caron, Annalise; Gallop, Robert; Guth, Carol

2013-12-01

Adolescent conduct problems exact serious social as well as personal costs, and effective treatments are essential. One of the most widely disseminated and effective programs for the treatment of serious conduct problems in adolescents is Multisystemic Therapy (MST). However, most evaluations of MST have involved the developers of MST. The purpose of the present study was to conduct an independent evaluation of MST, with non-court-referred adolescents with conduct problems. Participants were 164 adolescents ages 11-18 years who were recruited from self-contained behavior intervention classrooms in public schools. Adolescents and their families were randomly assigned to receive MST or services as usual. Outcome measures assessed conduct problems, school functioning, and court records of criminal behavior. Participants were followed for 18 months after baseline using parent, adolescent, and teacher reports; arrest data were collected for 2.5 years postbaseline. Two of 4 primary outcome measures focused on externalizing problems showed significant treatment effects favoring MST. Several secondary and intervention targets pertaining to family functioning and parent psychopathology showed positive effects of MST, and no negative effects were identified. Results provide some further support for the effectiveness of MST, although smaller effect sizes than previous studies also suggest the complexity of successful dissemination, particularly to non-court-referred populations.

Multisystemic Therapy and Functional Family Therapy Compared on their Effectiveness Using the Propensity Score Method.

PubMed

Eeren, Hester V; Goossens, Lucas M A; Scholte, Ron H J; Busschbach, Jan J V; van der Rijken, Rachel E A

2018-01-09

Multisystemic Therapy (MST) and Functional Family Therapy (FFT) have overlapping target populations and treatment goals. In this study, these interventions were compared on their effectiveness using a quasi-experimental design. Between October, 2009 and June, 2014, outcome data were collected from 697 adolescents (mean age 15.3 (SD 1.48), 61.9% male) assigned to either MST or FFT (422 MST; 275 FFT). Data were gathered during Routine Outcome Monitoring. The primary outcome was externalizing problem behavior (Child Behavior Checklist and Youth Self Report). Secondary outcomes were the proportion of adolescents living at home, engaged in school or work, and who lacked police contact during treatment. Because of the non-random assignment, a propensity score method was used to control for observed pre-treatment differences. Because the risk-need-responsivity (RNR) model guided treatment assignment, effectiveness was also estimated in youth with and without a court order as an indicator of their risk level. Looking at the whole sample, no difference in effect was found with regard to externalizing problems. For adolescents without a court order, effects on externalizing problems were larger after MST. Because many more adolescents with a court order were assigned to MST compared to FFT, the propensity score method could not balance the treatment groups in this subsample. In conclusion, few differences between MST and FFT were found. In line with the RNR model, higher risk adolescents were assigned to the more intensive treatment, namely MST. In the group with lower risk adolescents, this more intensive treatment was more effective in reducing externalizing problems.

Acute diffuse alveolar haemorrhage accompanied by gastrointestinal bleeding in a patient with serious systemic lupus erythematosus: A case report.

PubMed

Du, Jing; Wang, Ying; Li, Yan-Chun; Wang, Tong-Tong; Zhou, Yong-Lie; Ying, Zhen-Hua

2018-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding. Although intensive treatment was administered, the patient deteriorated rapidly and had a progressive decline in oxygen saturation followed by diffuse alveolar haemorrhage and acute left heart failure. Inotropic therapy, mechanical ventilation, blood transfusion, CRRT, antibiotics, intravenous glucocorticoids and other support therapies were initiated and gradually the patient's vital signs stabilized and haemoptysis subsided. This case report emphasises that complications of SLE can occur at any stage of the disease, especially in patients with active SLE. Therefore, it is important for clinicians to be aware of the rare presentations of SLE and its complex management. For multisystem dysfunction, early intensive treatment with high dose corticosteroids and cyclophosphamide is advocated.

Artificial Gravity: Will it Preserve Bone Health on Long-Duration Missions?

NASA Technical Reports Server (NTRS)

Davis-Street, Janis; Paloski, William H.

2005-01-01

Prolonged microgravity exposure disrupts bone, muscle, and cardiovascular homeostasis, sensory-motor coordination, immune function, and behavioral performance. Bone loss, in particular, remains a serious impediment to the success of exploration-class missions by increasing the risks of bone fracture and renal stone formation for crew members. Current countermeasures, consisting primarily of resistive and aerobic exercise, have not yet proven fully successful for preventing bone loss during long-duration spaceflight. While other bone-specific countermeasures, such as pharmacological therapy and dietary modifications, are under consideration, countermeasure approaches that simultaneously address multiple physiologic systems may be more desirable for exploration-class missions, particularly if they can provide effective protection at reduced mission resource requirements (up-mass, power, crew time, etc). The most robust of the multi-system approaches under consideration, artificial gravity (AG), could prevent all of the microgravity-related physiological changes from occurring. The potential methods for realizing an artificial gravity countermeasure are reviewed, as well as selected animal and human studies evaluating the effects of artificial gravity on bone function. Future plans for the study of the multi-system effects of artificial gravity include a joint, cooperative international effort that will systematically seek an optimal prescription for intermittent AG to preserve bone, muscle, and cardiovascular function in human subjects deconditioned by 6 degree head-down-tilt-bed rest. It is concluded that AG has great promise as a multi-system countermeasure, but that further research is required to determine the appropriate parameters for implementation of such a countermeasure for exploration-class missions.

Immunoglobulin G4-related acquired hemophilia: A case report

PubMed Central

Li, Xiaoyan; Duan, Wei; Zhu, Xiang; Xu, Jianying

2016-01-01

Acquired hemophilia A (AHA) is a relatively rare and life-threatening bleeding disorder whose pathogenesis is not completely understood. The present study reports a rare case of immunogubulin (IgG)4-related AHA with multisystemic involvement. A 55-year old male patient presented with symptoms of bronchial asthma and multiple subdermal hematomas. Chest computed tomography showed multiple diffuse nodular lesions with thickening of bronchovascular bundles, and scattered high-density spots in both lung lobes. Laboratory investigations showed increased activated partial prothrombin time (120.0 sec), a markedly decreased factor VIII (FVIII) activity (0.5%), a high-titer of FVIII inhibitor (27.2 Bethesda units/ml) and a marked increase in serum IgG4 (>4.03 g/l) level. Left inguinal lymph node biopsy revealed capsular thickening with marked lymphoplasmacytic infiltration, occlusive phlebitis and irregular fibrosis. Immunostaining revealed numerous IgG4-positive plasma cells (>100 cells/human plasma fibronectin) in the nodular lesions, with an IgG4/IgG ratio of >40%. The symptoms were markedly alleviated following corticosteroid therapy. The current study presents the first reported case of a rare IgG4-related AHA that presented with unusual clinical features and multisystemic involvement. The patient responded well to corticosteroid therapy. Documentation of such rare cases will help in characterizing the pathogenesis, and prompt recognition and timely treatment of this rare disorder. PMID:28105131

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

PubMed Central

Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

2013-01-01

Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

Toward Evidence-Based Transport of Evidence-Based Treatments: MST as an Example

ERIC Educational Resources Information Center

Schoenwald, Sonja K.

2008-01-01

This article describes the journey toward evidence-based transport and implementation in usual care settings of Multisystemic Therapy (MST) for youth with drug abuse and behavioral problems (Henggeler, Schoenwald, Borduin, Rowland, & Cunningham, 1998). Research and experience informing the design of the MST transport strategy, progress in…

From Diagnosis, to Life Saving Therapy, to Hollywood: The Journey of John Crowley

ERIC Educational Resources Information Center

Apel, Laura

2010-01-01

In February of 2000, "Exceptional Parent" introduced readers to the Crowley family. The author profiled John, Aileen, and their three children: Megan, Patrick, and John Jr. They told "Exceptional Parent" that in 1998 both Megan and Patrick were diagnosed with Pompe disease, a progressive, multisystemic, debilitating, and often fatal muscular…

Psychopathy as predictor and moderator of multisystemic therapy outcomes among adolescents treated for antisocial behavior.

PubMed

Manders, Willeke A; Deković, Maja; Asscher, Jessica J; van der Laan, Peter H; Prins, Pier J M

2013-10-01

The aim of the present study was to determine whether psychopathic traits act as a predictor and/or moderator of the effectiveness of Multisystemic Therapy (MST). The sample included N = 256 adolescents (188 boys and 68 girls) referred for conduct problems, randomized to MST or Treatment As Usual (TAU). The mean age was 16 years (SD = 1.31). Assessments were carried out before and immediately after treatment (6 months later). Three psychopathic traits (callous/unemotional traits, narcissism, and impulsiveness) were assessed with parent reports. Adolescents and parents were informants on externalizing problems. MST was more effective than TAU in decreasing externalizing problems for the "lower callous/unemotional" and "lower narcissism" group, but not for the "high callous/unemotional" and "high narcissism" group (moderators). Impulsiveness was found to predict more post-treatment externalizing problems rated by adolescents (predictor), but not more post-treatment externalizing problems rated by parents. These findings point out the clinical relevance of adequately assessing psychopathic traits in adolescents referred for treatment of antisocial behaviour, and identifying those adolescents who show high levels of these traits. It is important to tailor MST specifically to meet the needs of juveniles with high levels of callous/unemotional traits and high levels of narcissism to obtain the same level of effectiveness as with juveniles scoring lower on these traits.

Implementation of Evidence-Based Models in Social Work Practice: Practitioners' Perspectives on an MST Trial in Sweden

ERIC Educational Resources Information Center

Gustle, Lars-Henry; Hansson, Kjell; Sundell, Knut; Andree-Lofholm, Cecilia

2008-01-01

The implementation of new treatment methods in social work practice is warranted. Moreover, little is known about professionals' attitudes toward the introduction of evidence-based practices into their communities. Therefore, this article reports on the implementation of a Swedish research project that evaluated Multisystemic Therapy (MST). All…

Bridging the Gap between Science and Practice: The Effective Nationwide Transport of MST Programs in Norway

ERIC Educational Resources Information Center

Ogden, Terje; Christensen, Bernadette; Sheidow, Ashli J.; Holth, Per

2008-01-01

The successful nationwide transport and evaluation of Multisystemic Therapy (MST) programs in Norway is described. This description is provided within the context of the nation's movement towards the adoption of evidence-based practices (EBPs) during the past decade, the conduct of a multisite randomized clinical trial to examine the effectiveness…

Changes in Maternal Depression Are Associated with MST Outcomes for Adolescents with Co-Occurring Externalizing and Internalizing Problems

ERIC Educational Resources Information Center

Grimbos, Teresa; Granic, Isabela

2009-01-01

The efficacy of Multisystemic therapy (MST) in treating adolescent aggression has been established, however, not all youth and their families benefit from MST. One reason for this treatment variability could be the failure to distinguish between different aggressive subtypes with different risk factors, developmental prognoses and treatment needs.…

An Adult with Polyneuropathy and Hypogonadism due to Poems Syndrome.

PubMed

Zaidi, Saba; Sattar, Sidra; Asumal, Khealani Bhojo

2017-10-01

POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein myeloma and skin changes), is a rare disease which occurs in the setting of plasma cell dyscrasias. We describe a case of an adult lady who presented with gradual onset weakness of all four limbs and multisystem involvement characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism. The patient responded well to combination therapy of thalidomide, melphalan and dexamethasone. Eight months after the therapy, she noted decreased paresthesias and increased strength. She had reduced edema and ascites.

AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome.

PubMed

Di Meo, I; Marchet, S; Lamperti, C; Zeviani, M; Viscomi, C

2017-10-01

Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No treatment is currently available for this condition. Mice lacking Ndufs4, encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) recapitulates the main findings of complex I (cI)-related LS, including severe multisystemic cI deficiency and progressive neurodegeneration. In order to develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or young Ndufs4 -/- mice. We found that IV administration alone was only able to correct the cI deficiency in peripheral organs, whereas ICV administration partially corrected the deficiency in the brain. However, both treatments failed to improve the clinical phenotype or to prolong the lifespan of Ndufs4 -/- mice. In contrast, combined IV and ICV treatments resulted, along with increased cI activity, in the amelioration of the rotarod performance and in a significant prolongation of the lifespan. Our results indicate that extraneurological organs have an important role in LS pathogenesis and provide an insight into current limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem disorders. These findings warrant future investigations to develop new vectors able to efficiently target multiple organs.

Resolution of Hydronephrosis in a Patient With Mucopolysaccharidosis Type II With Enzyme Replacement Therapy.

PubMed

Nishiyama, Kei; Imai, Takashi; Ohkubo, Kazuhiro; Sanefuji, Masafumi; Takada, Hidetoshi

2017-03-01

Mucopolysaccharidosis type II (MPS II) is caused by deficiency of lysosomal enzyme iduronate-2-sulfatase. Insufficient activity of the enzyme results in accumulation of glycosaminoglycans leading to progressive multisystem pathologies. MPS II is less likely to be complicated by kidney and urinary tract problems. We report a boy with MPS II, who developed left hydronephrosis. His hydronephrosis improved after starting enzyme replacement therapy. It was suggested that MPS II was closely associated with the pathogenesis of hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Promoting the Implementation of an Evidence-Based Intervention for Adolescent Marijuana Abuse in Community Settings: Testing the Use of Intensive Quality Assurance

ERIC Educational Resources Information Center

Henggeler, Scott W.; Sheidow, Ashli J.; Cunningham, Phillippe B.; Donohue, Bradley C.; Ford, Julian D.

2008-01-01

The development and evaluation of effective strategies for transporting evidence-based practices to community-based clinicians has become a research and policy priority. Using multisystemic therapy programs as a platform, an experimental design examined the capacity of an Intensive Quality Assurance (IQA) system to promote therapist implementation…

Part II: Multisystemic Therapy--Addressing Racial Disparity and Its Effectiveness with Families from Diverse Racial and Ethnic Backgrounds

ERIC Educational Resources Information Center

Painter, Kirstin; Scannapieco, Maria

2009-01-01

Disparities in health and mental health care delivered to racial and ethnic minorities became a focus of national policy following reports of the Institute of Medicine (IOM, 2002) and the Surgeon General (USDHHS, 2001). The Surgeon General (USDHHS, 2001) reported racial and ethnic minorities experience disparities in availability and quality of…

Mediators of Treatment Effects in a Randomized Clinical Trial of Multisystemic Therapy-Health Care in Adolescents With Poorly Controlled Asthma: Disease Knowledge and Device Use Skills.

PubMed

Ellis, Deborah A; King, Pamela; Naar-King, Sylvie

2016-06-01

Determine whether Multisystemic Therapy-Health Care (MST-HC) improved asthma knowledge and controller device use skills among African-American youth with poorly controlled asthma and whether any improvements mediated changes in illness management. A randomized controlled trial was conducted with 170 adolescents with moderate to severe asthma. Families were randomized to MST-HC or attention control. Data were collected at baseline and 6 and 12 months after intervention completion. In linear mixed models, adolescents in the MST-HC group had increases in asthma knowledge; asthma knowledge was unchanged for attention control. Controller device use skills increased for adolescents in the MST-HC group, while skills declined for attention control. Both knowledge and skills mediated the relationship between intervention condition and changes in illness management. Tailored, home-based interventions that include knowledge and skills building components are one means by which illness management in African-American youth with poorly controlled asthma can be improved. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Economic Impact of the Statewide Implementation of an Evidence-Based Treatment: Multisystemic Therapy in New Mexico.

PubMed

Dopp, Alex R; Coen, Anita Saranga; Smith, Allison B; Reno, Jessica; Bernstein, David H; Kerns, Suzanne E U; Altschul, Deborah

2018-07-01

Several states have made considerable investments into large-scale implementation of evidence-based treatments (EBTs), yet little is known about key success indicators for these implementation efforts such as cost and sustainability. To that end, the present study examined the economic impact of statewide implementation of multisystemic therapy (MST; Henggeler, Schoenwald, Borduin, Rowland, & Cuningham, 2009), a family- and community-based behavioral EBT for serious juvenile offenders in New Mexico. Participants were 1,869 youth who received MST across 23 teams during the study period. We conducted a cost-benefit analysis using metrics from state data sources that compared the cost of MST to its benefits (i.e., avoided expenses from pre- to posttreatment) in two domains: (a) behavioral health services (i.e., Medicaid claims) and (b) juvenile crime (i.e., taxpayer expenses, tangible and intangible expenses to crime victims). MST costs were based on Medicaid claims, which were reimbursed at an enhanced billing rate that was intended to cover expenses for both clinical and implementation (e.g., training, quality assurance) activities. Results suggest that implementation of MST in New Mexico over the 7-year study period may have produced net benefits, through 2 years posttreatment, of more than $4,643 per youth in avoided behavioral health claims and $15,019 per youth through reductions in juvenile crime. Stated differently, every dollar that New Mexico spent on MST appeared to have returned $3.34 for a total benefit of $64.2 million over the course of the study. We discuss implications of these findings for policymakers, administrators, and researchers who are interested in increasing the sustainability of complex EBTs in community settings. Copyright © 2018. Published by Elsevier Ltd.

Economic evaluation of multisystemic therapy for young people at risk for continuing criminal activity in the UK.

PubMed

Cary, Maria; Butler, Stephen; Baruch, Geoffrey; Hickey, Nicole; Byford, Sarah

2013-01-01

To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England. A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending. 108 adolescents, aged 11-17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI -£5,838 to £8,283). The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research.

An Evaluation of Multisystemic Therapy with Australian Families.

PubMed

Porter, Mark; Nuntavisit, Leartluk

2016-12-01

This study aims to evaluate the effectiveness of the Multisystemic Therapy (MST) intervention for Australian families invloved with the Specialist Child and Adolescent Mental Health Service (CAMHS). This program was implemented within the Western Australian Department of Health in 2005, and has continually operated two small clinical teams within the Perth metropolitan area since then. This intervention was specifically chosen to improve service access, engagement, and intervention with vulnerable families having young persons with a history of significant and enduring behavioural problems. The study reports on data collected from July 2007 to July 2013 which includes baseline, post-treatment, 6-month, and 12-month follow-up. There were 153 MST families participating in the research at all time points (71% male; 11% Australian Aboriginal; average youth age was 13.6 years). Caregivers completed a set of questionnaires including Child Behaviour Checklist, Parenting Styles and Dimensions Questionnaire, and Depression, Anxiety and Stress Scale. One-way repeated measure ANOVA were used to measure changes over time. Significant caregiver-reported improvements in all measures were reported at post-treatment, and most improvements were maintained at the follow-up periods of 6 and 12 months post-intervention. These preliminary outcomes demonstrate that the 4-5 month MST intervention significantly reduces behavioural problems and emotional difficulties in young Australians and these improvements are generally maintained by caregivers over time. Primary caregivers reported improved skills and mental health functioning that were also maintained over the follow-up period. A proposed randomised controlled trial of the program will address potential placebo and selection bias effects.

Social context, parental monitoring, and multisystemic therapy outcomes.

PubMed

Robinson, Brittany A; Winiarski, D Anne; Brennan, Patricia A; Foster, Sharon L; Cunningham, Phillippe B; Whitmore, Elizabeth A

2015-03-01

Multisystemic therapy (MST) and other evidence-based treatments targeting juvenile delinquency have been well substantiated in the literature. Although these treatments have been demonstrated to be effective overall at reducing juvenile delinquency, it is well known that they do not benefit all treated youth. Research has yet to examine the potential influence of contextual factors, such as socioeconomic status (SES) and neighborhood characteristics, on treatment outcomes, particularly as they influence parental monitoring, which is often a focus of interventions targeting juvenile delinquency. A primary goal of these treatments is to help parents develop the requisite skills to adequately monitor and discipline their children; however, this goal may be compromised by contextual factors affecting parental effectiveness and, ultimately, treatment efficacy. The objective of this study was to explore the role of SES and neighborhood factors in moderating the effects of parental monitoring across treatment. Using hierarchical linear modeling (HLM), we analyzed these contextual and family predictors of response to MST treatment within a sample of 185 youth (65.4% male) ages 12-18 (M = 15.35; SD = 1.28). Neighborhood factors interacted with parental monitoring, such that monitoring predicted decreases in externalizing behavior only for youth residing in better neighborhoods. In contrast, SES was unrelated to changes in externalizing behaviors in response to MST. Taken together, these results demonstrate a need for further understanding the potential role of the youth's larger social context in predicting MST outcomes. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy.

PubMed

Héritier, Sébastien; Emile, Jean-François; Barkaoui, Mohamed-Aziz; Thomas, Caroline; Fraitag, Sylvie; Boudjemaa, Sabah; Renaud, Florence; Moreau, Anne; Peuchmaur, Michel; Chassagne-Clément, Catherine; Dijoud, Frédérique; Rigau, Valérie; Moshous, Despina; Lambilliotte, Anne; Mazingue, Françoise; Kebaili, Kamila; Miron, Jean; Jeziorski, Eric; Plat, Geneviève; Aladjidi, Nathalie; Ferster, Alina; Pacquement, Hélène; Galambrun, Claire; Brugières, Laurence; Leverger, Guy; Mansuy, Ludovic; Paillard, Catherine; Deville, Anne; Armari-Alla, Corinne; Lutun, Anne; Gillibert-Yvert, Marion; Stephan, Jean-Louis; Cohen-Aubart, Fleur; Haroche, Julien; Pellier, Isabelle; Millot, Frédéric; Lescoeur, Brigitte; Gandemer, Virginie; Bodemer, Christine; Lacave, Roger; Hélias-Rodzewicz, Zofia; Taly, Valérie; Geissmann, Frédéric; Donadieu, Jean

2016-09-01

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). In children with LCH, BRAF(V600E) mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy. © 2016 by American Society of Clinical Oncology.

Feasibility of Adapting Multisystemic Therapy to Improve Illness Management Behaviors and Reduce Asthma Morbidity in High Risk African American Youth: A Case Series

ERIC Educational Resources Information Center

Naar-King, Sylvie; Ellis, Deborah; Kolmodin, Karen; Cunningham, Phillippe; Secord, Elizabeth

2009-01-01

African-American adolescents have the highest rates of asthma morbidity and mortality, yet there are few successful behavioral interventions to improve illness management for this group. Mental health providers have an opportunity to expand their services and impact by targeting adolescents with poor asthma management. We describe the adaptation…

Langerhans cell histiocytosis of skull: a retrospective study of 18 cases.

PubMed

Zhang, Xiang-Heng; Zhang, Ji; Chen, Zheng-He; Sai, Ke; Chen, Yin-Sheng; Wang, Jian; Ke, Chao; Guo, Chen-Chen; Chen, Zhong-Ping; Mou, Yong-Gao

2017-04-01

The present study presents 18 cases of Chinese patients harboring a Langerhans cell histiocytosis (LCH) of the skull. Eighteen consecutive patients were diagnosed as LCH of the skull and confirmed pathologically between March 2002 and February 2014. In the present study, the patients of LCH without skull involvement were excluded. According to disease extent at diagnosis, the 18 LCH patients with skull involvement were divided into three groups: (I) unifocal-monosystem group, including ten cases with solitary skull lesion; (II) multifocal-monosystem group, including two cases with multiple bone lesions and no extra-skeletal involvement; (III) multisystem group, including six cases with LCH lesions involving both skeletal and extra-skeletal system. In unifocal-monosystem group, excision of the skull lesion was performed in eight of ten cases, a low dosage of local radiotherapy and a purposeful observation was accept by the remaining two cases of this group after biopsy respectively. In multifocal-monosystem group, both of the two cases were received chemotherapy. In multi-system group, all the six cases were managed with systemic chemotherapy, after their diagnoses of LCH were confirmed. The mean age at the time of diagnosis was 9.4 years. There was a male predominance in this disease male/female ratio was 3.5:1. In our cases, a skull mass with or without tenderness was the most common chief complaint (13 cases, 72.2%), and frontal bone was the most frequent affected locations of skull (6 cases, 33.3%). In unifocal-monosystem group, nine of ten remained free from LCH, the remain one lesion recurred 22 months after his surgical excision. In multifocal-monosystem group, a complete response (CR) was obtained in one of them, and a stable disease (SD) of multiple osseous lesions was obtained in another one. In the multi-system group, a CR in four cases and a partial response (PR) in one case were obtained, and a progressive disease (PD) was observed in the remaining one. The unifocal-monosystem of LCH of the skull is a clinicopathological entity with a good outcome, and resection, irradiation or purposeful observation are also can be been utilized as the choice of treatment. For the multifocal bone lesions and multisystem lesions of LCH, chemotherapy is an effective treatment as a systemic therapy. There is no enough publication literature to determine guidelines or indications for managing this disease.

AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome

PubMed Central

Di Meo, I; Marchet, S; Lamperti, C; Zeviani, M; Viscomi, C

2017-01-01

Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No treatment is currently available for this condition. Mice lacking Ndufs4, encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) recapitulates the main findings of complex I (cI)-related LS, including severe multisystemic cI deficiency and progressive neurodegeneration. In order to develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or young Ndufs4−/− mice. We found that IV administration alone was only able to correct the cI deficiency in peripheral organs, whereas ICV administration partially corrected the deficiency in the brain. However, both treatments failed to improve the clinical phenotype or to prolong the lifespan of Ndufs4−/− mice. In contrast, combined IV and ICV treatments resulted, along with increased cI activity, in the amelioration of the rotarod performance and in a significant prolongation of the lifespan. Our results indicate that extraneurological organs have an important role in LS pathogenesis and provide an insight into current limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem disorders. These findings warrant future investigations to develop new vectors able to efficiently target multiple organs. PMID:28753212

Test of “Facilitation” vs. “Proximal Process” Moderator Models for the Effects of Multisystemic Therapy on Adolescents with Severe Conduct Problem

PubMed Central

Weiss, Bahr; Han, Susan S.; Tran, Nam T.; Gallop, Robert; Ngo, Victoria K.

2014-01-01

The present study identified moderators of Multisystemic Therapy’s (MST) effects on adolescent conduct problems, considering “facilitation” and “proximal process” moderation models. The sample included 164 adolescents (mean age=14.6 years; 83% male) randomly assigned to receive MST or services as usual; parent, youth, and teacher reports of adolescent functioning were obtained. A number of significant moderators were identified. Proximal process moderation patterns were identified (e.g., families with parents with lower levels of adaptive child discipline skills gained more from MST), but the majority of significant interactions showed a facilitation moderation pattern with, for instance, higher levels of adaptive functioning in families and parents appearing to facilitate MST (i.e., greater benefits from MST were found for these families). This facilitation pattern may reflect such families being more capable of and/or more motivated to use the resources provided by MST. It is suggested that factors consistently identified as facilitation moderators may serve as useful foci for MST’s strength-based levers of change approach. Other implications of these findings for individualized treatment also are discussed. PMID:25387903

Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine.

PubMed

Alwan, Wisam; Nestle, Frank O

2015-01-01

Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.

Intensive Quality Assurance of Therapist Adherence to Behavioral Interventions for Adolescent Substance Use Problems.

PubMed

Holth, Per; Torsheim, Torbjørn; Sheidow, Ashli J; Ogden, Terje; Henggeler, Scott W

2011-01-01

This study was a crosscultural replication of a study that investigated therapist adherence to behavioral interventions as a result of an intensive quality assurance system which was integrated into Multisystemic Therapy. Thirty-three therapists and eight supervisors participated in the study and were block randomized to either an Intensive Quality Assurance or a Workshop Only condition. Twenty-one of these therapists treated 41 cannabis-abusing adolescents and their families. Therapist adherence and youth drug screens were collected during a five-month baseline period prior to the workshop on contingency management and during 12 months post workshop. The results replicated the previous finding that therapist adherence to the cognitive-behavioral interventions, but not to contingency management, showed a strong positive difference in trend in favor of the intensive quality assurance condition. While the clinical impact of such quality assurance may be delayed and remains to be demonstrated, cannabis abstinence increased as a function of time in therapy, and was more likely with stronger therapy adherence to contingency management, but did not differ across quality assurance interventions.

Placement and Delinquency Outcomes Among System-Involved Youth Referred to Multisystemic Therapy: A Propensity Score Matching Analysis.

PubMed

Vidal, Sarah; Steeger, Christine M; Caron, Colleen; Lasher, Leanne; Connell, Christian M

2017-11-01

Multisystemic therapy (MST) was developed to help youth with serious social, emotional, and behavioral problems. Research on the efficacy and effectiveness of MST has shown positive outcomes in different domains of development and functioning among various populations of youth. Nonetheless, even with a large body of literature investigating the treatment effects of MST, few studies have focused on the effectiveness of MST through large-scale dissemination efforts. Utilizing a large sample of youth involved in a statewide dissemination of MST (n = 740; 43% females; 14% Black; 29% Hispanic; 49% White; M age  = 14.9 years), propensity score matching was employed to account for baseline differences between the treatment (n = 577) and comparison (n = 163) groups. Treatment effects were examined based on three outcomes: out-of-home placement, adjudication, and placement in a juvenile training school over a 6-year period. Significant group differences remained after adjusting for baseline differences, with youth who received MST experiencing better outcomes in offending rates than youth who did not have an opportunity to complete MST due to non-clinical or administrative reasons. Survival analyses revealed rates of all three outcomes were approximately 40% lower among the treatment group. Overall, this study adds to the body of literature supporting the long-term effectiveness of MST in reducing offending among high-risk youth. The findings underscore the potential benefits of taking evidence-based programs such as MST to scale to improve the well-being and functioning of high-risk youth. However, strategies to effectively deliver the program in mental health service settings, and to address the specific needs of high-risk youth are necessary.

Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.

PubMed

Maier, Cheryl L; Gross, Phillip J; Dean, Christina L; Chonat, Satheesh; Ip, Andrew; McLemore, Morgan; El Rassi, Fuad; Stowell, Sean R; Josephson, Cassandra D; Fasano, Ross M

2018-06-01

Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission. Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy. © 2018 AABB.

Systemic lupus erythematosus: an update.

PubMed

Golder, Vera; Hoi, Alberta

2017-03-20

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease predominantly affecting women of childbearing age. New classification criteria for SLE have greater sensitivity and therefore improve the diagnostic certainty for some patients, especially those who may previously have been labelled as having undifferentiated symptoms. Uncontrolled disease activity leads to irreversible end-organ damage, which in turn increases the risk of premature death; early and sustained control of disease activity can usually be achieved by conventional immunosuppressant therapy. The development of biological therapy lags behind that for other rheumatic diseases, with belimumab being the only targeted therapy approved by the Therapeutic Goods Administration. "Treat-to-target" concepts are changing trial design and clinical practice, with evidence-based definition of response criteria in the form of remission and low disease activity now on the horizon. While new therapies are awaited, research should also focus on optimising the use of current therapy and improving the quality of care of patients with SLE.

Lyme Disease: What the Wilderness Provider Needs to Know.

PubMed

Forrester, Joseph D; Vakkalanka, J Priyanka; Holstege, Christopher P; Mead, Paul S

2015-12-01

Lyme disease is a multisystem tickborne illness caused by the spirochete Borrelia burgdorferi and is the most common vectorborne disease in the United States. Prognosis after initiation of appropriate antibiotic therapy is typically good if treated early. Wilderness providers caring for patients who live in or travel to high-incidence Lyme disease areas should be aware of the basic biology, epidemiology, clinical manifestations, and treatment of Lyme disease. Published by Elsevier Inc.

Treatment with agalsidase beta during pregnancy in Fabry disease.

PubMed

Politei, Juan M

2010-04-01

Fabry disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase A, which leads to excessive accumulation of glycosphingolipids in most tissues in the body, with life-threatening clinical consequences in the kidney, heart, and cerebrovascular system. Enzyme replacement therapy using exogenously produced alpha-galactosidase has been available for treatment of this multisystem progressive disease since 2001. Two different preparations of enzyme replacement therapy for Fabry disease are available outside of the USA: agalsidase alfa and agalsidase beta. Despite being X-linked, Fabry disease affects many female patients, and this report presents a successful pregnancy of a female patient receiving agalsidase beta.

Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study.

PubMed

Carroll, Judith E; Gruenewald, Tara L; Taylor, Shelley E; Janicki-Deverts, Denise; Matthews, Karen A; Seeman, Teresa E

2013-10-15

Childhood abuse increases adult risk for morbidity and mortality. Less clear is how this "toxic" stress becomes embedded to influence health decades later, and whether protective factors guard against these effects. Early biological embedding is hypothesized to occur through programming of the neural circuitry that influences physiological response patterns to subsequent stress, causing wear and tear across multiple regulatory systems. To examine this hypothesis, we related reports of childhood abuse to a comprehensive 18-biomarker measure of multisystem risk and also examined whether presence of a loving parental figure buffers against the impact of childhood abuse on adult risk. A total of 756 subjects (45.8% white, 42.7% male) participated in this ancillary substudy of the Coronary Artery Risk Development in Young Adults Study. Childhood stress was determined by using the Risky Families Questionnaire, a well-validated retrospective self-report scale. Linear regression models adjusting for age, sex, race, parental education, and oral contraceptive use found a significant positive relationship between reports of childhood abuse and multisystem health risks [B (SE) = 0.68 (0.16); P < 0.001]. Inversely, higher amounts of reported parental warmth and affection during childhood was associated with lower multisystem health risks [B (SE) = -0.40 (0.14); P < 0.005]. A significant interaction of abuse and warmth (P < 0.05) was found, such that individuals reporting low levels of love and affection and high levels of abuse in childhood had the highest multisystem risk in adulthood.

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

PubMed

West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life.

PubMed

Zhang, Huza; Chambers, William; Sciascia, Savino; Cuadrado, Maria J

2016-01-01

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.

Update on role of agalsidase alfa in management of Fabry disease

PubMed Central

Ramaswami, Uma

2011-01-01

Fabry disease (FD) is an X-linked lysosomal storage disorder that affects both men and women. The manifestations of this heterogeneous disease are multisystemic and progressive. Prior to the development of enzyme replacement therapy, the management and treatment for Fabry disease was largely nonspecific and supportive. Because enzyme replacement therapy became commercially available in 2001, a variety of clinical benefits in Fabry patients have been consistently reported, including improved renal pathology and cardiac function, and reduced severity of neuropathic pain and improved pain-related quality of life. This update focuses on published data on the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa, and gives a brief overview on some of the outstanding management issues in the treatment of this complex disease. PMID:21552486

Key issues in the management of patients with systemic lupus erythematosus: latest developments and clinical implications

PubMed Central

Jordan, Natasha; D’Cruz, David

2015-01-01

Systemic lupus erythematous (SLE) is a chronic multisystem disease with significant associated morbidity and mortality. A deeper understanding of the pathogenesis of SLE has led to the development of biologic agents, primarily targeting B cells and others inhibiting costimulatory molecules, type I interferons and cytokines such as interleukin-6. Several of these agents have been studied in clinical trials; some have shown promise while others have yielded disappointing results. Economic and regulatory issues continue to hamper the availability of such therapies for SLE patients. With increasing recognition that recurrent flares of disease activity lead to long-term damage accrual, one of the most important recent developments in patient management has been the concept of treat-to-target in SLE while minimizing patient exposure to excessive corticosteroid and other immunosuppressive therapy. This article reviews these key issues in SLE management, outlining recent developments and clinical implications for patients. PMID:26622325

Panhypopituitarism after multisystem trauma.

PubMed

Wiechecka, Joanna; Krzewska, Aleksandra; Droń, Izabela; Beń-Skowronek, Iwona

2013-01-01

The pituitary gland plays a key role in hormonal regulation in the organism, contributing to maintenance of balance of basic vital functions. To emphasise the need for assessment of pituitary function after head injury, as correct diagnosis and hormone replacement therapy prove to be a life-saving therapy accelerating the recovery process. A healthy, normally developing 9-year-old girl, a child of young and healthy parents, was struck by a falling tree. The results of severe head trauma included adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of damage to the anterior and posterior pituitary gland. Administration of hormone replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly improved the patient´s condition and facilitated effective rehabilitation. Determination of pituitary hormones in children after severe head injury should be an important part of diagnosis allowing identification of an early stage of acute hypopituitarism and acceleration of recovery through hormone replacement therapy.

Efficacy of multisystemic therapy in youths aged 10-17 with severe antisocial behaviour and emotional disorders: systematic review.

PubMed

Tan, Jia Xuan; Fajardo, Maria Lourdes Restrepo

2017-11-01

Antisocial behaviour and conduct disorders are the most common behavioural and mental health problems in children and young people globally. An efficacious intervention is needed to manage these antisocial behaviours that have costly consequences. Multisystemic Therapy (MST), an intensive home-based intervention for youths with psychosocial and behavioural problems, is recommended under National Institute for Health and Clinical Excellence guidelines for conduct disorder. However, reviews on the efficacy of MST are mixed. To review randomised controlled trials (RCTs) reporting efficacy of MST among youths presenting with antisocial behaviour and emotional disorder respectively. A systematic map term to subject heading search was conducted in PsycINFO, Embase, and Ovid Medline databases for articles up to November 2015. RCTs comparing MST vs.treatment as usual (TAU) in youths presenting with antisocial behaviour and emotional disorder were included. 12 RCTs ( n  = 1425) reported efficacy of MST vs. TAU in youths presenting with antisocial behaviour and emotional disorder. Clinically significant treatment effects of MST showed a reduction of antisocial behaviour which includes delinquency. MST, vs. psychiatric hospitalisation, was associated with a reduction of suicidal attempts in youths presenting with psychiatric emergencies. 4 studies showed that MST was less costly than TAU in the short term, with further analysis required for long-term cost-effectiveness. MST is an efficacious intervention for severe antisocial behaviours in reduction of delinquency and should be included in clinical practices. MST was shown to have a positive effect on emotional disorder but further research is needed to evaluate the efficacy of MST with emotional disorder. Further analysis is required to assess the services utilized for long-term cost effectiveness.

Ethnomedicine in healthcare systems of the world: a Semester at Sea pilot survey in 11 countries.

PubMed

Muleady-Mecham, Nancy E; Schley, Stephanie

2009-06-17

An understanding and appreciation for the varied healthcare systems in use throughout the world are increasingly vital for medical personnel as patient populations are now composed of ethnically diverse people with wide-ranging belief systems. While not a statistically valid survey, this pilot study gives a global overview of healthcare differences around the world. A pilot study of 459 individuals from 11 different countries around the world was administered by 33 students in the upper division course, People, Pathology, and World Medicine from Semester at Sea, Fall 2007, to ascertain trends in healthcare therapies. Open-ended surveys were conducted in English, through an interpreter, or in the native language. Western hospital use ranked highly for all countries, while ethnomedical therapies were utilized to a lesser degree. Among the findings, mainland China exhibited the greatest overall percentage of ethnomedical therapies, while the island of Hong Kong, the largest use of Western hospitals. The figures and trends from the surveys suggest the importance of understanding diverse cultural healthcare beliefs when treating individuals of different ethnic backgrounds. The study also revealed the increasingly complex and multisystem-based medical treatments being used internationally.

Advances in the diagnosis and treatment of cystic fibrosis.

PubMed

Martiniano, Stacey L; Hoppe, Jordana E; Sagel, Scott D; Zemanick, Edith T

2014-08-01

CF is a genetic, life-shortening, multisystem disease that is most commonly diagnosed through newborn screen performed in all 50 states in the United States. In the past, therapies for CF lung disease have primarily targeted the downstream effects of a dysfunctional CFTR protein. Newer CFTR modulator therapies, targeting the basic defect in CF, are available for a limited group of people with CF, and offer the hope of improved treatment options for many more people with CF in the near future. Best practice is directed by consensus clinical care guidelines from the CFF and is provided with a multidisciplinary approach by the team at the CF care center and the primary care office.

Wound Trauma Mediated Inflammatory Signaling Attenuates a Tissue Regenerative Response in MRL/MpJ Mice

DTIC Science & Technology

2010-01-01

multi-system organ failure, and remote organ injury at sites such as the lung, liver , small intestines, and brain, representing major causes of...inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound...healing, multi-system organ failure and increased mortality. Methods: In this study, we examined the impact of thermal injury -induced systemic

The Spectrum of Monogenic Autoinflammatory Syndromes: Understanding Disease Mechanisms and Use of Targeted Therapies

PubMed Central

Glaser, Rachel L.; Goldbach-Mansky, Raphaela

2009-01-01

Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases present clinically with episodes of seemingly unprovoked inflammation (fever, rashes, and elevation of acute phase reactants). Understanding the genetics has led to discovery of new molecules involved in recognizing exogenous and endogenous danger signals, and the inflammatory response to these stimuli. These advances have furthered understanding of innate inflammatory pathways and spurred collaborative research in rheumatology and infectious diseases. The pivotal roles of interleukin (IL)-1β in cryopyrin-associated periodic syndromes, tumor necrosis factor (TNF) in TNF receptor-associated periodic syndrome, and links to inflammatory cytokine dysregulation in other monogenic autoinflammatory diseases have resulted in effective therapies targeting proinflammatory cytokines IL-1β and TNF and uncovered other new potential targets for anti-inflammatory therapies. PMID:18606080

Therapeutic options for lymphangioleiomyomatosis (LAM): where we are and where we are going

PubMed Central

Steagall, Wendy K; Moss, Joel

2009-01-01

Lymphangioleiomyomatosis (LAM), a multisystem disease affecting predominantly premenopausal and middle-aged women, causes progressive respiratory failure due to cystic lung destruction and is associated with lymphatic and kidney tumors. In the past, the treatment of LAM comprised exclusively anti-estrogen and related hormonal therapies. These treatments, however, have not been proven effective. In this article, we discuss new findings regarding the molecular mechanisms involved in the regulation of LAM cell growth, which may offer opportunities to develop effective and targeted therapeutic agents. PMID:20948684

Recent Advances in the Immunopathogenesis of Systemic Lupus Erythematosus

PubMed Central

Bardana, Emil J.; Pirofsky, Bernard

1975-01-01

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease having definite etiologic associations with ethnic, genetic, viral and immunologic factors. Its pathologic hallmark, vasculitis, is currently felt to be the end result of an immune-complex mechanism. Several clinical and serologic variants of SLE are recognized including discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD) and drug-induced equivalents—such as procainamide-induced lupus (PIL). The distinguishing features of these variants as well as their prognosis and therapy are discussed in relation to recent developments in the immunopathogenesis of SLE. PMID:46657

The challenge of treating conduct disorder in low-resourced settings: rap music to the rescue.

PubMed

Evans, Dylan J

2010-12-01

Conduct disorder is one of the most frequent serious childhood problems that present for treatment in community clinic settings. Evidence-based treatments for conduct disorder are intensive and require considerable resources to implement. In low-resourced contexts it is often not feasible to implement evidence-based treatments in their current form, which poses significant challenges for clinicians attempting to treat children in these settings. This article explores these challenges using a case study of the treatment of a young adolescent boy with a short-term multisystem intervention where rap music was employed as a powerful tool to facilitate an empathic connection in therapy and as a projective technique to explore underlying emotional difficulties.

Do Extremely Violent Juveniles Respond Differently to Treatment?

PubMed Central

Asscher, Jessica J.; Deković, M.; Van den Akker, Alithe L.; Prins, Pier J. M.; Van der Laan, Peter H.

2016-01-01

This study increases knowledge on effectiveness of treatment for extremely violent (EV) youth by investigating their response to multisystemic therapy (MST). Using data of a randomized controlled trial on effectiveness of MST, we investigated differences in treatment response between EV youth and not extremely violent (NEV) youth. Pre- to post-treatment comparison indicated MST was equally effective for EV and NEV youth, whereas treatment as usual was not effective for either group. Growth curves of within-treatment changes indicated EV youth responded differently to MST than NEV youth. The within-treatment change was for EV youth non-linear: Initially, they show a deterioration; however, after one month, EV juveniles respond positively to MST, indicating longer lasting, intensive programs may be effective in treating extreme violence. PMID:27794135

CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome.

PubMed

Kosho, Tomoki

2016-02-01

Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) deficiency represents a specific form of Ehlers-Danlos syndrome (EDS) caused by recessive loss-of-function mutations in CHST14. The disorder has been independently termed "adducted thumb-clubfoot syndrome", "EDS, Kosho type", and "EDS, musculocontractural type". To date, 31 affected patients from 21 families have been described. Clinically, CHST14/D4ST1 deficiency is characterized by multiple congenital malformations (craniofacial features including large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low-set and rotated ears, high palate, long philtrum, thin upper lip vermilion, small mouth, and micro-retrognathia; multiple congenital contractures including adduction-flexion contractures and talipes equinovarus as well as other visceral or ophthalmological malformations) and progressive multisystem fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; pneumothorax or pneumohemothorax; large subcutaneous hematomas; and diverticular perforation). Etiologically, multisystem fragility is presumably caused by impaired assembly of collagen fibrils resulting from loss of dermatan sulfate (DS) in the decorin glycosaminoglycan side chain that promotes electrostatic binding between collagen fibrils. This is the first reported human disorder that specifically affects biosynthesis of DS. Its clinical characteristics indicate that CHST14/D4ST1 and, more fundamentally, DS, play a critical role in fetal development and maintenance of connective tissues in multiple organs. Considering that patients with CHST14/D4ST1 deficiency develop progressive multisystem fragility-related manifestations, establishment of a comprehensive and detailed natural history and health-care guidelines as well as further elucidation of the pathophysiology in view of future etiology-based therapy are crucial. © 2015 Japan Pediatric Society.

Current and emerging treatments for brain metastases.

PubMed

Lin, Jenny; Jandial, Rahul; Nesbit, Amanda; Badie, Behnam; Chen, Mike

2015-04-01

Brain metastasis in patients with cancer can be indicative of multisystem spread or lead to neurological demise if not locally controlled, and is associated with poor survival and high morbidity. Compared with metastasis to other areas of the body, brain metastasis possesses a unique biology that confers high resistance to systemic therapies. This phenomenon has been historically attributed to the inability of chemotherapeutic agents to pass through the blood-brain barrier. Recent studies challenge this premise, revealing other potentially targetable mechanism(s). Therapies that exploit recent advances in the understanding of brain metastasis are still in early stages of development. Encouragingly, and discovered by happenstance, some molecularly targeted drugs already appear to have efficacy against certain tumors and accompanying cerebral edema. In the meantime, conventional treatment modalities such as surgery and radiation have iteratively reached new levels of refinement. However, these achievements are somewhat muted by the emergence of magnetic resonance (MR)-guided laser interstitial thermal therapy, a minimally invasive neuroablative technique. On the horizon, MR-guided focused ultrasound surgery is similarly intriguing. Even in the absence of further advances, local control is frequently achieved with state-of-the-art therapies. Dramatic improvements will likely require sophisticated approaches that account for the particular effects of the microenvironment of the central nervous system on metastasis.

Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

PubMed

Littell, J H; Popa, M; Forsythe, B

2005-10-19

Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. To provide unbiased estimates of the impacts of MST on restrictive out-of-home living arrangements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. Electronic searches were made of bibliographic databases (including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies. Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance methods, and 95% confidence intervals were used. The most rigorous (intent-to-treat) analysis found no significant differences between MST and usual services in restrictive out-of-home placements and arrests or convictions. Pooled results that include studies with data of varying quality tend to favor MST, but these relative effects are not significantly different from zero. The study sample size is small and effects are not consistent across studies; hence, it is not clear whether MST has clinically significant advantages over other services. There is inconclusive evidence of the effectiveness of MST compared with other interventions with youth. There is no evidence that MST has harmful effects.

Can bipolar disorder be viewed as a multi-system inflammatory disease?

PubMed Central

Leboyer, Marion; Soreca, Isabella; Scott, Jan; Frye, Mark; Henry, Chantal; Tamouza, Ryad; Kupfer, David J.

2012-01-01

Background Patients with bipolar disorder are known to be at high risk of premature death. Comorbid cardio-vascular diseases are a leading cause of excess mortality, well above the risk associated with suicide. In this review, we explore comorbid medical disorders, highlighting evidence that bipolar disorder can be effectively conceptualized as a multi-systemic inflammatory disease. Methods We conducted a systematic PubMed search of all English-language articles recently published with bipolar disorder cross-referenced with the following terms: mortality and morbidity, cardio-vascular, diabetes, obesity, metabolic syndrome, inflammation, auto-antibody, retro-virus, stress, sleep and circadian rhythm. Results Evidence gathered so far suggests that the multi-system involvement is present from the early stages, and therefore requires proactive screening and diagnostic procedures, as well as comprehensive treatment to reduce progression and premature mortality. Exploring the biological pathways that could account for the observed link show that dysregulated inflammatory background could be a common factor underlying cardio-vascular and bipolar disorders. Viewing bipolar disorder as a multi-system disorder should help us to re-conceptualize disorders of the mind as “disorders of the brain and the body”. Limitations The current literature substantially lacks longitudinal and mechanistic studies, as well as comparison studies to explore the magnitude of the medical burden in bipolar disorder compared to major mood disorders as well as psychotic disorders. It is also necessary to look for subgroups of bipolar disorder based on their rates of comorbid disorders. Conclusions Comorbid medical illnesses in bipolar disorder might be viewed not only as the consequence of health behaviors and of psychotropic medications, but rather as an early manifestation of a multi-systemic disorder. Medical monitoring is thus a critical component of case assessment. Exploring common biological pathways of inflammation should help biomarkers discovery, ultimately leading to innovative diagnostic tools, new methods of prevention and personalized treatments. PMID:22497876

Treatment of multiple unresectable basal cell carcinomas from Gorlin-Goltz syndrome: a case report.

PubMed

Ojevwe, Fidelis O; Ojevwe, Cindy D; Zacny, James P; Dudek, Arkadiusz Z; Lin, Amy; Kohlitz, Patrick

2015-03-01

Nevoid basal cell carcinoma syndrome (NBCCS), which is also known by other names, including Gorlin-Goltz syndrome and multiple basal-cell carcinoma (BCC) syndrome, is a rare multi-systemic disease inherited in a dominant autosomal manner with complete penetrance and variable expressivity. The main clinical manifestations include multiple BCCs, odontogenic keratocysts of the jaw, hyperkeratosis of the palms and soles, skeletal abnormalities, intracranial calcifications and facial deformities. A 31-year-old male diagnosed with Gorlin-Goltz syndrome with multiple unresectable facial BCCs was treated with the Hedgehog inhibitor vismodegib. After one month of therapy on vismodegib, there were significant reductions in the size of multiple BCCs on the patient's face. The patient remains on this therapy. Hedgehog pathway inhibition is an effective strategy to treat unresectable BCCs from Gorlin-Goltz syndrome. Although vismodegib shows some promising clinical results in the early phase of its use, there are concerns of possible resistance developing within months. Duration of therapy, role of maintenance treatment and drug modification to reduce resistance need to be explored in future case studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Unary and binary multisystems; topologic classification of phase diagrams and relation to Euler's theorem on polyhedra.

USGS Publications Warehouse

Roseboom, E.H.; Zen, E.-A.

1982-01-01

A representation polyhedron summarizing the topology of a large number of possible nets previously devised by Zen (M.A. 18-167) is extended from n + 3 unary to n + 6 phase unary systems. A general way for constructing n + 4 phase nets is outlined. With the technique described, 62 multisystems are recognized, of which 26 contain all 16 possible divariant fields and represent the most nearly complete closed nets possible for a binary six-phase (n + 4) multisystem.-M.S.

Long-term youth criminal outcomes in MST transport: the impact of therapist adherence and organizational climate and structure.

PubMed

Schoenwald, Sonja K; Chapman, Jason E; Sheidow, Ashli J; Carter, Rickey E

2009-01-01

This study investigated relations among therapist adherence to an evidence-based treatment for youth with serious antisocial behavior (i.e., Multisystemic Therapy), organizational climate and structure, and youth criminal charges on average 4 years posttreatment. Participants were 1,979 youth and families treated by 429 therapists across 45 provider organizations. Results showed therapist adherence predicted significantly lower rates of youth criminal charges independently and in the presence of organizational variables. Therapist perceptions of job satisfaction and opportunities for growth and advancement relative to the organizational average predicted youth criminal charges, as did organizational average levels of participation in decision making. These associations washed out in the presence of adherence, despite the fact that job satisfaction and growth and advancement were associated with adherence.

The ARC organizational and community intervention strategy for implementing evidence-based children's mental health treatments.

PubMed

Glisson, Charles; Schoenwald, Sonja K

2005-12-01

This paper reviews the implications of organizational and community intervention research for the implementation of effective mental health treatments in usual community practice settings. The paper describes an organizational and community intervention model named ARC for Availability, Responsiveness and Continuity, that was designed to support the improvement of social and mental health services for children. The ARC model incorporates intervention components from organizational development, interorganizational domain development, the diffusion of innovation, and technology transfer that target social, strategic, and technological factors in effective children's services. This paper also describes a current NIMH-funded study that is using the ARC intervention model to support the implementation of an evidence-based treatment, Multisystemic Therapy (MST), for delinquent youth in extremely rural, impoverished communities in the Appalachian Mountains of East Tennessee.

Heart failure: not a single organ disease but a multisystem syndrome.

PubMed

Warriner, David; Sheridan, Paul; Lawford, Patricia

2015-06-01

Heart failure is not simply a single organ disease; rather it is a complex multi-system clinical syndrome, with impairment of endocrine, haematological, musculoskeletal, renal, respiratory and vascular systems, which influence morbidity and mortality.

All Might Have Won, But Not All Have the Prize: Optimal Treatment for Substance Abuse Among Adolescents with Conduct Problems

PubMed Central

Spas, Jayson; Ramsey, Susan; Paiva, Andrea L.; Stein, L.A.R.

2012-01-01

Considerable evidence from the literature on treatment outcomes indicates that substance abuse treatment among adolescents with conduct problems varies widely. Treatments commonly used among this population are cognitive-behavioral therapy (CBT), 12-step facilitation, multisystemic therapy (MST), psychoeducation (PE), and motivational interviewing (MI). This manuscript thoroughly and systematically reviews the available literature to determine which treatment is optimal for substance-abusing adolescents with conduct problems. Results suggest that although there are several evidence-based and empirically supported treatments, those that incorporate family-based intervention consistently provide the most positive treatment outcomes. In particular, this review further reveals that although many interventions have gained empirical support over the years, only one holds the prize as being the optimal treatment of choice for substance abuse treatment among adolescents with conduct problems. PMID:23170066

Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant recipient treated with cyclosporine A.

PubMed

Cavdar, C; Sifil, A; Sanli, E; Gülay, H; Camsari, T

1998-12-01

Since cyclosporine A (CsA) had been used in renal transplant recipients, important improvements in short-term and long-term graft survivals have been detected. In spite of these improvements CsA seems to have several adverse effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other organs and systems (skin, liver, nervous system, etc.) and causes, increased risks of infections and malignancies. Hypomagnesemia is one of the side effects of CsA therapy, but it is a rare condition in living related donor renal transplant recipients. It may also cause multi-system dysfunction, especially hypocalcemia and hypokalemia, which cannot be corrected without magnesium therapy. In addition, rhabdomyolysis was detected in animals, but it has not been reported in living related donor renal transplant recipients. In this case report, a living related donor renal transplant recipient who suffered from hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and discussed.

Downhill oesophageal variceal bleeding: A rare complication in Behçet's disease-related superior vena cava syndrome.

PubMed

Ennaifer, Rym; B'chir Hamzaoui, Saloua; Larbi, Thara; Romdhane, Hayfa; Abdallah, Maya; Bel Hadj, Najet; M'rad, Sander

2015-03-01

Behçet's disease (BD) is a multisystemic disorder that involves vessels of all sizes. Superior vena cava (SVC) thrombosis is a rare complication that can lead to the development of various collateral pathways. A 31-year-old man presented with SVC syndrome. He had a history of recurrent genital aphthosis. Computed tomography revealed extensive thrombosis of the right internal jugular, axillary, and subclavian veins with collateral circulation. The patient was diagnosed with BD, and he was started on anticoagulation and immunosuppressive therapy. One week later, he presented with haematemesis. Upper gastrointestinal endoscopy disclosed varices in the upper third of the oesophagus with stigmata of recent bleeding. Portal hypertension was ruled out. Anticoagulation therapy was discontinued. He was discharged on immunosuppressive therapy. Bleeding from downhill oesophageal varices should be suspected in any patient presenting with upper gastrointestinal bleeding and a history of SVC syndrome due to BD. Copyright © 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

PubMed Central

Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz

2012-01-01

Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957

Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease.

PubMed

Carrillo, Elena; Lomas, Amparo; Pinés, Pedro J; Lamas, Cristina

2017-01-01

Mutations in hepatocyte nuclear factor 1β gene ( HNF1B ) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations. HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history may not be present.Once diagnosis is made, treatment of diabetes with oral agents is worth trying, since the response can be sustained for a longer period than the one usually described. Oral treatment can help postpone insulinization and, once this is necessary, can help reduce the required doses.

Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature.

PubMed

Pisani, Antonio; Visciano, Bianca; Roux, Graciana Diez; Sabbatini, Massimo; Porto, Caterina; Parenti, Giancarlo; Imbriaco, Massimo

2012-11-01

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency of the hydrolytic enzyme alpha galactosidase A, with consequent accumulation of globotrioasoyl ceramide in cells and tissues of the body, resulting in a multi-system pathology including end organ failure. In the classical phenotype, cardiac failure, renal failure and stroke result in a reduced median life expectancy. The current causal treatment for Fabry disease is the enzyme replacement therapy (ERT): two different products, Replagal (agalsidase alfa) and Fabrazyme (agalsidase beta), have been commercially available in Europe for almost 10 years and they are both indicated for long-term treatment. In fact, clinical trials, observational studies and registry data have provided many evidences for safety and efficacy of ERT in improving symptoms of pain, gastrointestinal disturbances, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life. Few data are available on comparison of the two treatments and on the clinical course of the disease. This article reviews the published evidence for clinical efficacy of the two available enzyme preparations. Copyright © 2012 Elsevier Inc. All rights reserved.

Old treatments for new insights and strategies: proposed management in adults and children with alkaptonuria.

PubMed

Arnoux, Jean-Baptiste; Le Quan Sang, Kim-Hanh; Brassier, Anais; Grisel, Coraline; Servais, Aude; Wippf, Julien; Dubois, Sandrine; Sireau, Nicolas; Job-Deslandre, Chantal; Ranganath, Lakshminarayan; de Lonlay, Pascale

2015-09-01

Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2 dioxygenase. It results in an accumulation of homogentisate which oxidizes spontaneously to benzoquinone acetate, a highly oxidant compound, which polymerises to a melanin-like structure, in a process called ochronosis. Asymptomatic during childhood, this accumulation will lead from the second decade of life to a progressive and severe spondylo-arthopathy, associated with multisystem involvement: osteoporosis/fractures, stones (renal, prostatic, gall bladder, salivary glands), ruptures of tendons/muscle/ligaments, renal failure and aortic valve disease. The pathophysiological mechanisms of AKU remain poorly understood, but recent advances lead us to reconsider the treatment strategy in AKU patients. Besides the supporting therapies (pain killers, anti-inflammatory drugs, physiotherapy, joints replacements and others), specific therapies have been considered (anti-oxidant, low protein diet, nitisinone), but clinical studies have failed to prove efficiency on the rheumatological lesions of the disease. Here we propose a treatment strategy for children and adults with AKU, based on a review of the latest findings on AKU and lessons from other aminoacipathies, especially tyrosinemias.

Enzyme replacement therapy for Fabry disease: some answers but more questions.

PubMed

Alfadhel, Majid; Sirrs, Sandra

2011-01-01

Fabry disease (FD) is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT) has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.

Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?

PubMed

Villar, Jesús; Martínez, Domingo; Mosteiro, Fernando; Ambrós, Alfonso; Añón, José M; Ferrando, Carlos; Soler, Juan A; Montiel, Raquel; Vidal, Anxela; Conesa-Cayuela, Luís A; Blanco, Jesús; Arrojo, Regina; Solano, Rosario; Capilla, Lucía; Del Campo, Rafael; Civantos, Belén; Fernández, María Mar; Aldecoa, César; Parra, Laura; Gutiérrez, Andrea; Martínez-Jiménez, Chanel; González-Martín, Jesús M; Fernández, Rosa L; Kacmarek, Robert M

2018-06-01

Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. A secondary analysis from three prospective, multicenter, observational studies. A network of multidisciplinary ICUs. We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. None. We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p < 0.000001). Most deaths in acute respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.

Long-Term Youth Criminal Outcomes in MST Transport: The Impact of Therapist Adherence and Organizational Climate and Structure

PubMed Central

Schoenwald, Sonja K.; Chapman, Jason E.; Sheidow, Ashli J.; Carter, Rickey E.

2010-01-01

The current study investigated relations among therapist adherence to an evidence-based treatment for youth with serious antisocial behavior (i.e., Multisystemic Therapy), organizational climate and structure, and youth criminal charges on average 4 years post-treatment. Participants were 1979 youth and families treated by 429 therapists across 45 provider organizations. Results showed therapist adherence predicted significantly lower rates of youth criminal charges independently and in the presence of organizational variables. Therapist perceptions of job satisfaction and opportunities for growth and advancement relative to the organizational average predicted youth criminal charges, as did organizational average levels of participation in decision-making. These associations washed out in the presence of adherence, despite the fact that job satisfaction and growth and advancement were associated with adherence. PMID:19130360

A case report of neonatal thyrotoxicosis due to maternal autoimmune hyperthyroidism.

PubMed

Markham, Lori A; Stevens, Debra L

2003-12-01

A case of neonatal thyrotoxicosis secondary to maternal autoimmune hyperthyroidism is reported in an infant born at 34 weeks gestation who presented with tachycardia, jitteriness, diarrhea, and a small goiter. Propranolol and oxygen were used to treat high-output cardiac failure and transient persistent pulmonary hypertension. The infant's response to propylthiouracil therapy, gradual resolution of cardiac and systemic symptoms, and normaliziation of thyroid studies are described. Thyroid physiology and function and the special considerations in a premature infant are reviewed. An overview of maternal autoimmune hyperthyroidism and the implications for the developing fetus and neonate are presented. The risk factors for, and clinical presentation of, hyperthyroidism are outlined and treatment strategies highlighted. The nursing care of infants with hyperthyroidism is carefully described with an emphasis on the surveillance for and management of multisystem manifestations.

Confirming, Validating, and Norming the Factor Structure of Systemic Therapy Inventory of Change Initial and Intersession.

PubMed

Pinsof, William M; Zinbarg, Richard E; Shimokawa, Kenichi; Latta, Tara A; Goldsmith, Jacob Z; Knobloch-Fedders, Lynne M; Chambers, Anthony L; Lebow, Jay L

2015-09-01

Progress or feedback research tracks and feeds back client progress data throughout the course of psychotherapy. In the effort to empirically ground psychotherapeutic practice, feedback research is both a complement and alternative to empirically supported manualized treatments. Evidence suggests that tracking and feeding back progress data with individual or nonsystemic feedback systems improves outcomes in individual and couple therapy. The research reported in this article pertains to the STIC(®) (Systemic Therapy Inventory of Change)-the first client-report feedback system designed to empirically assess and track change within client systems from multisystemic and multidimensional perspectives in individual, couple, and family therapy. Clients complete the STIC Initial before the first session and the shorter STIC Intersession before every subsequent session. This study tested and its results supported the hypothesized factor structure of the six scales that comprise both STIC forms in a clinical outpatient sample and in a normal, random representative sample of the U.S. This study also tested the STIC's concurrent validity and found that its 6 scales and 40 of its 41 subscales differentiated the clinical and normal samples. Lastly, the study derived clinical cut-offs for each scale and subscale to determine whether and how much a client's score falls in the normal or clinical range. Beyond supporting the factorial and concurrent validity of both STIC forms, this research supported the reliabilities of the six scales (Omegahierarchical ) as well as the reliabilities of most subscales (alpha and rate-rerate). This article delineates clinical implications and directions for future research. © 2015 Family Process Institute.

The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey

PubMed Central

Turner, Martin R; Swash, Michael

2015-01-01

Recent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS. PMID:25644224

Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy.

PubMed

Briani, Chiara; Manara, Renzo; Lessi, Federica; Citton, Valentina; Zambello, Renato; Adami, Fausto

2012-05-01

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma vascular endothelial growth factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularization, and obstructive vessel remodeling without inflammatory signs pointing to a role of VEGF in the meningeal manifestations. Here, we report the dramatic pachymeningeal improvement in patients undergoing lenalidomide therapy. These findings support the therapeutic role of lenalidomide and might shed further light on the pathophysiology of the disease

Thyroid storm masked by hemodialysis and glucocorticoid therapy in a patient with rheumatoid arthritis.

PubMed

Sasaki, Yohei; Shimizu, Yoshio; Nakata, Junichiro; Kameda, Toshiaki; Muto, Masahiro; Ohsawa, Isao; Io, Hiroaki; Hamada, Chieko; Horikoshi, Satoshi; Tomino, Yasuhiko

2012-01-01

Thyroid function test values are generally at low levels in patients with end-stage kidney disease. Life-threatening thyrotoxicosis or thyroid storm is rare, especially in hemodialysis (HD) patients, and is characterized by multisystem involvement and a high mortality rate if not immediately recognized and treated. Here, we report a female patient with severe symptomatic thyroid storm, receiving long-term HD and glucocorticoid therapy. Methimazole at a dose of 15 mg per day, β-adrenergic blockade and HD succeeded in controlling the patient's condition by gradually adjusting the target dry weight for hyperthyroidism-induced weight loss. When she was discharged from the hospital, her dry weight was reduced from 47.2 to 39.2 kg. The management of patients with severe symptomatic thyroid storm on HD represents a rare scenario. It is essential to initiate the available treatments as early as possible to reduce its mortality.

Monitoring clinical progression with mitochondrial disease biomarkers

PubMed Central

Steele, Hannah E; Horvath, Rita; Lyon, Jon J; Chinnery, Patrick F

2017-01-01

Abstract Mitochondrial disorders are genetically determined metabolic diseases due to a biochemical deficiency of the respiratory chain. Given that multi-system involvement and disease progression are common features of mitochondrial disorders they carry substantial morbidity and mortality. Despite this, no disease-modifying treatments exist with clear clinical benefits, and the current best management of mitochondrial disease is supportive. Several therapeutic strategies for mitochondrial disorders are now at a mature preclinical stage. Some are making the transition into early-phase patient trials, but the lack of validated biomarkers of disease progression presents a challenge when developing new therapies for patients. This update discusses current biomarkers of mitochondrial disease progression including metabolomics, circulating serum markers, exercise physiology, and both structural and functional imaging. We discuss the advantages and disadvantages of each approach, and consider emerging techniques with a potential role in trials of new therapies. PMID:28969370

Urgent chemotherapy in hematological patients in the ICU.

PubMed

Moors, Ine; Pène, Frédéric; Lengline, Étienne; Benoit, Dominique

2015-12-01

Over the past decades, survival of critically ill hematological patients has dramatically improved, and these patients are more frequently referred to the ICU for intensive treatment, including a rising need for administering anticancer-therapy in this setting. The scarce literature on this subject provides evidence for feasibility of administering chemotherapy in the ICU, with expected ICU survival of 60-70%, and one in three patients surviving at least 1 year after discharge. We summarize the recent evidence concerning outcome, dosing and indications of chemotherapy in the ICU, and provide practical guidelines for some special oncological situations. Anticancer-therapy in the ICU is feasible and no longer futile as long as it is initiated in a selected, well-informed patient population with reasonable prognostic expectations. Accurate recognition of organ failure and early referral to the ICU for both supportive care and timely administration of chemotherapy is recommended before the development of multisystem organ failure.

Behçet's disease.

PubMed

Saadoun, David; Wechsler, Bertrand

2012-04-12

DEFINITION OF THE DISEASE: Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. BD seems to cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. European cases are often described, not exclusively in the migrant population. The clinical spectrum includes oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. The etiopathogenesis of the disease remains unknown, although genetic predisposition, environmental factors and immunological abnormalities have been implicated. Diagnosis is only based on clinical criteria. DIFFERRENTIAL DIAGNOSIS: It depends on the clinical presentation of BD, but sarcoidosis, multiple sclerosis, Crohn's disease, Takayasu's arteritis, polychondritis or antiphospholipid syndrome need to be considered. Treatment is symptomatic using steroids and immunomodulatory therapy. It is efficient depending on the rapidity of initiation, the compliance, and the duration of therapy. The prognosis is severe due to the ocular, neurological and arterial involvement.

Pazopanib therapy for cerebellar hemangioblastomas in von Hippel–Lindau disease

PubMed Central

Kim, Betty Y. S.; Jonasch, Eric

2016-01-01

von Hippel–Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). The most common tumors associated with this disease are histologically benign, slow-growing CNS hemangioblastomas affecting the retina, cerebellum, brainstem, spinal cord or nerve roots. With mean age at diagnosis of 30 years, CNS hemangioblastomas are usually the first manifestation of the disease. Ongoing clinical and radiological surveillance is required, with symptomatic lesions necessitating treatment. As tumor growth is inevitable during the lifetime of most VHL patients, and the multiplicity of tumors may preclude surgical cure, the search for effective therapies is ongoing. Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. Treatment initiation with daily oral pazopanib (800 mg/day) resulted in significant neurologic improvement and radiologic tumor volume reduction. PMID:22374327

Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae

PubMed Central

Brown, Rebecca J.; Rother, Kristina I.; Artman, Henry; Mercurio, Mary Gail; Wang, Roger; Looney, R. John; Cowen, Edward W.

2010-01-01

Background Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjögren syndrome A, and anti-Smith antibodies. Conclusions Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. PMID:19153345

Multisystemic Disease Modeling of Liver-Derived Protein Folding Disorders Using Induced Pluripotent Stem Cells (iPSCs).

PubMed

Leung, Amy; Murphy, George J

2016-01-01

Familial transthyretin amyloidosis (ATTR) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe detailed methodologies for the directed differentiation of protein folding disease-specific iPSCs into hepatocytes that produce mutant protein, and neural-lineage cells often targeted in disease. Methodologies are also described for the construction of multisystem models and drug screening using iPSCs.

A Progress Report on a Multi-Systems Theory of Communication Behavior.

ERIC Educational Resources Information Center

Grunig, James E.

Previous research is reviewed in which a multi-systems theory of communication behavior has been used to explain communication behavior of individuals and of several organization-related systems and subsystems. Recent research is then summarized which sought to develop conditional probabilities that communication behavior will occur in each of 16…

Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

PubMed

Littell, J H; Popa, M; Forsythe, B

2005-07-20

Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. To provide unbiased estimates of the impacts of MST on restrictive out-of-home living placements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. Electronic searches were made of bibliographic databases including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies.Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance methods, and 95% confidence intervals were used. Pooled results show no significant effects of MST on the likelihood or duration of restrictive out-of-home placements, proportion of youth who were arrested or convicted, or numbers of arrests/convictions within one-year post-intervention. There were no significant differences on drug tests or self-reported drug use at a 6-month follow-up. In analyses of post-treatment data for program completers, there were no significant between-group differences on self-reported delinquency, peer relations, youth behavior problems, youth psychiatric symptoms, parent psychiatric symptoms, or family functioning. There is little evidence of the superiority of MST over other interventions with youth. There is also no evidence that MST has harmful effects.

Evaluation of multisystemic therapy pilot services in Services for Teens Engaging in Problem Sexual Behaviour (STEPS-B): study protocol for a randomized controlled trial.

PubMed

Fonagy, Peter; Butler, Stephen; Baruch, Geoffrey; Byford, Sarah; Seto, Michael C; Wason, James; Wells, Charles; Greisbach, Jessie; Ellison, Rachel; Simes, Elizabeth

2015-11-02

Clinically effective and cost-effective methods for managing problematic sexual behaviour in adolescents are urgently needed. Adolescents who show problematic sexual behaviour have a range of negative psychosocial outcomes, and they and their parents can experience stigma, hostility and rejection from their community. Multisystemic therapy (MST) shows some evidence for helping to reduce adolescent sexual reoffending and is one of the few promising interventions available to young people who show problematic sexual behaviour. This paper describes the protocol for Services for Teens Engaging in Problem Sexual Behaviour (STEPS-B), a feasibility trial of MST for problem sexual behaviour (MST-PSB) in antisocial adolescents at high risk of out-of-home placement due to problematic sexual behaviour. Eighty participants and their families recruited from five London boroughs will be randomized to MST-PSB or management as usual with follow-up to 20 months post-randomization. The primary outcome is out-of-home placement at 20 months. Secondary outcomes include sexual and non-sexual offending rates and antisocial behaviours, participant well-being, educational outcomes and total service and criminal justice sector costs. Feasibility outcomes include mapping the clinical service pathways needed to recruit adolescents displaying problematic sexual behaviour, acceptability of a randomized controlled trial to the key systems involved in managing these adolescents, and acceptability of the research protocol to young people and their families. Data will be gathered from police computer records, the National Pupil Database and interviews and self-report measures administered to adolescents and parents and will be analysed on an intention-to-treat basis. The STEPS-B feasibility trial aims to inform policymakers, commissioners of services and professionals about the potential for implementing MST-PSB as an intervention for adolescents showing problem sexual behaviour. Should MST-PSB show potential, STEPS-B will determine what would be necessary to implement the programme more fully and at a scale that would warrant a full trial. ISRCTN28441235 (registered 25 January 2012).

Vitamin C: The next step in sepsis management?

PubMed

Teng, J; Pourmand, A; Mazer-Amirshahi, M

2018-02-01

Sepsis is a life-threatening medical condition, affecting approximately 26 million people worldwide every year. The disease is a continuum, marked by dysregulated inflammation and hemodynamic instability leading to shock, multi-system organ dysfunction, and death. Over the past decades, there has been a focus on the early identification and treatment of sepsis primarily with bundled and goal directed therapy. Despite these advances, morbidity and mortality has remained high, prompting investigation into novel therapies. Vitamin C is a water-soluble vitamin that plays a role in mediating inflammation through antioxidant activities and is also important in the synthesis of cortisol, catecholamines, and vasopressin, which are key mediators in the disease process. Emerging evidence provides cursory data in support of the administration of vitamin C in addition to standard therapy to ameliorate the effects of inflammation and improve hemodynamic stability in patients with sepsis and septic shock; however, further evidence is needed to support this practice. This review discusses the physiologic role of vitamin C as well as the recent literature and evidence for the use of vitamin C in patients presenting with sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

Monogenic Lupus.

PubMed

Lo, Mindy S

2016-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease known for its clinical heterogeneity. Over time, new insights into the complex genetic origin of SLE have started to explain some of this clinical variability. These findings, reviewed here, have also yielded important understanding in the immune mechanisms behind SLE pathogenesis. Several new monogenic disorders with lupus-like phenotype have been described. These can be organized into physiologic pathways that parallel mechanisms of disease in SLE. Examples include genes important for DNA damage repair (e.g., TREX1), nucleic acid sensing and type I interferon overproduction (e.g., STING, TREX1), apoptosis (FASLG), tolerance (PRKCD), and clearance of self-antigen (DNASE1L3). Further study of monogenic lupus may lead to better genotype/phenotype correlations in SLE. Eventually, the ability to understand individual patients according to their genetic profile may allow the development of more targeted and personalized approaches to therapy.

Mitochondrial DNA: impacting central and peripheral nervous systems

PubMed Central

Carelli, Valerio

2014-01-01

Because of their high-energy metabolism, neurons are highly dependent on mitochondria, which generate cellular ATP through oxidative phosphorylation. The mitochondrial genome encodes for critical components of the oxidative phosphorylation pathway machinery, and therefore mutations in mitochondrial DNA (mtDNA) cause energy production defects that frequently have severe neurological manifestations. Here, we review the principles of mitochondrial genetics and focus on prototypical mitochondrial diseases to illustrate how primary defects in mtDNA or secondary defects in mtDNA due to nuclear genome mutations can cause prominent neurological and multisystem features. In addition, we discuss the pathophysiological mechanisms underlying mitochondrial diseases, the cellular mechanisms that protect mitochondrial integrity, and the prospects for therapy. PMID:25521375

The Many Faces of Lupus

PubMed Central

El-Gabalawy, Hani

1990-01-01

Systemic lupus erythematosus is a multisystem disorder that presents itself in several different ways. Arthritis, dermatitis, nephritis, and pleuropericarditis are the most common features initially. Various hematologic and neuropsychiatric manifestations are also seen during the course of the disease. Anti-nuclear antibodies are the hallmark of lupus but are nonspecific and detectable in many other disorders. Once the diagnosis is established, the severity of the disease needs to be determined, in particular the extent of major organ involvement. The level of disease activity should be repeatedly estimated using clinical and laboratory parameters. Therapeutic decisions are based on disease severity and activity. Aggressive suppression of major organ inflammation and reduction of long-term toxicity are the main goals of therapy. PMID:21233973

Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes.

PubMed

Yadlapati, Sujani; Efthimiou, Petros

2016-01-01

Cryopyrin-associated periodic syndromes (CAPS) is a rare group of autoinflammatory disorders that includes familial cold autoinflammatory syndrome or FCAS, Muckle-wells syndrome or MWS, and neonatal-onset multisystem inflammatory disease or NOMID. CAPS is caused by a mutation in the NOD-like receptor family, pyrin domain containing 3 (NLRP3) gene. This ultimately leads to increased production of interleukin (IL)-1β. IL-1β is a biologically active member of the IL-1 family. It is not only a pro-inflammatory cytokine responsible for features such as fever, rash, and arthritis, but is also a major mediator in the central pathways of fatigue. Fatigue is a major component of CAPS and is associated with severely compromised quality of life. In clinical studies, fatigue was measured using functional assessment of chronic illness therapy-fatigue or FACIT-F and short form-36 or SF-36, physical component score instruments. These questionnaires can also be used to monitor improvement of fatigue following initiation of therapy. IL-1 inhibitors block the IL-1 signaling cascade, thereby preventing systemic inflammation in CAPS. The decrease in systemic inflammation is accompanied by improvement in fatigue.

Idiopathic inflammatory myositis.

PubMed

Tieu, Joanna; Lundberg, Ingrid E; Limaye, Vidya

2016-02-01

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Still's Disease in a Pediatric Patient after Liver Transplantation.

PubMed

Meza, Juan-Carlos; Muñoz-Buitrón, Evelyn; Bonilla-Abadía, Fabio; Cañas, Carlos Alberto; Tobón, Gabriel J

2013-01-01

Still's disease (SD) is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease model as a tool for vaccine testing under controlled conditions.

PubMed

McKillen, John; McNair, Irene; Lagan, Paula; McKay, Karen; McClintock, Julie; Casement, Veronica; Charreyre, Catherine; Allan, Gordon

2016-04-01

Snatch farrowed, colostrum deprived piglets were inoculated with different combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum, all animals were monitored and samples taken for serology, immunohistochemistry and qPCR. At 24 dpc all non-vaccinated animals remaining were exhibiting signs of post-weaning multi-systemic wasting syndrome which was confirmed by laboratory analysis. Details of the study, analysis of samples and performance of the candidate vaccines are described. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic ataxia telangiectasia porcine model phenocopies the multisystemic features of the human disease.

PubMed

Beraldi, Rosanna; Meyerholz, David K; Savinov, Alexei; Kovács, Attila D; Weimer, Jill M; Dykstra, Jordan A; Geraets, Ryan D; Pearce, David A

2017-11-01

Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in children is characterized by cerebellar degeneration, leading to motor impairment. Lung disease and cancer are the two most common causes of death in AT patients. Accelerated thymic involution may contribute to the cancer, and recurrent and/or chronic respiratory infections may be a contributing factor to lung disease in AT. AT patients have fertility issues, are highly sensitive to ionizing radiation and they present oculocutaneous telangiectasia. Current treatments only slightly ameliorate disease symptoms; therapy that alters or reverses the course of the disease has not yet been discovered. Previously, we have shown that ATM -/- pigs, a novel model of AT, present with a loss of Purkinje cells, altered cerebellar cytoarchitecture and motor coordination deficits. ATM -/- porcine model not only recapitulates the neurological phenotype, but also other multifaceted clinical features of the human disease. Our current study shows that ATM -/- female pigs are infertile, with anatomical and functional signs of an immature reproductive system. Both male and female ATM -/- pigs show abnormal thymus structure with decreased cell cycle and apoptosis markers in the gland. Moreover, ATM -/- pigs have an altered immune system with decreased CD8 + and increased natural killer and CD4 + CD8 + double-positive cells. Nevertheless, ATM -/- pigs manifest a deficient IgG response after a viral infection. Based on the neurological and peripheral phenotypes, the ATM -/- pig is a novel genetic model that may be used for therapeutic assessments and to identify pathomechanisms of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of the thrombin generation profile in systemic lupus erythematosus.

PubMed

Kern, A; Barabás, E; Balog, A; Burcsár, Sz; Kiszelák, M; Vásárhelyi, B

2017-03-01

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

[Complications and cause of death in mexican children with rocky mountain spotted fever].

PubMed

Martínez-Medina, Miguel Ángel; Rascón-Alcantar, Adela

Rocky Mountain spotted fever is a life threatening disease caused by Rickettsia rickettsia, characterized by multisystem involvement. We studied 19 dead children with Rocky Mountain spotted fever. All children who were suspected of having rickettsial infections were defined as having Rocky Mountain spotted fever by serology test and clinical features. Through the analysis of each case, we identified the clinical profile and complications associated to the death of a patient. In nine (69.2%) of 13 cases that died in the first three days of admission, the associated condition was septic shock. Others complications included respiratory distress causes by non-cardiogenic pulmonary edema, renal impairment, and multiple organ damage. The main cause of death in this study was septic shock. The fatality rate from Rocky Mountain spotted fever can be related to the severity of the infection, delay in diagnosis, and delay in initiation of antibiotic therapy. Pulmonary edema and cerebral edema can be usually precipitated by administration of excess intravenous fluids.

Aggressive behaviour in adolescent psychiatric settings: what are risk factors, possible interventions and implications for nursing practice? A literature review.

PubMed

Hage, S; Van Meijel, B; Fluttert, F; Berden, G F M G

2009-09-01

This study was aimed to identify the risk factors of aggressive behaviour in adolescents (1318 years), and to describe available intervention strategies. The findings are evaluated on the basis of their implications for nursing practice. Aggressive behaviour in adolescent psychiatric settings is a neglected research area. The consequences of aggressive behaviour on nurses, other patients and the therapeutic environment can be profound. For the development and implementation of innovative intervention strategies aimed at preventing aggressive behaviour in adolescent psychiatric patients, knowledge of risk factors and evidence-based interventions for aggressive behaviour are of the utmost importance. A systematic search of PubMed, Cinahl, PsychINFO and Cochrane Systematic Reviews (19912007) was employed. The risk factors for aggressive behaviour comprise personal and environmental risk factors. Some risk factors can be influenced by nursing intervention strategies. Available intervention programmes range from interpersonal skills training to massage therapy, parent management training, functional family therapy and multi-systemic therapy. The most effective programmes combine interpersonal skills training with parent management training. No specific nursing intervention programmes were found for dealing with aggressive behaviour in adolescent patients. Nursing staff can assist in achieving a systematic improvement in the treatment outcomes of existing intervention programmes for the prevention of aggression. There is a need for specific nursing intervention programmes to deal with aggressive behaviour in adolescent psychiatric settings.

Impact of a sodium carbonate spray combined with professional oral hygiene procedures in patients with Sjögren's syndrome: an explorative study.

PubMed

Gambino, Alessio; Broccoletti, Roberto; Cafaro, Adriana; Cabras, Marco; Carcieri, Paola; Arduino, Paolo G

2017-06-01

The aim of this study was to make an initial estimation on the effects of a sodium bicarbonate and xylitol spray (Cariex ® ), associated with non-surgical periodontal therapy, in participants with primary Sjögren's syndrome. Sjögren's syndrome (SS) is a multisystem autoimmune disease that predominantly involves salivary and lachrymal glands, with the clinical effect of dry eyes and mouth. A prospective cohort of 22 women and two men has been evaluated. They were randomized into three groups (eight patients each): Group A) those treated once with non-surgical periodontal therapy, education and motivation to oral hygiene, associated with the use of Cariex ® ; Group B) treated only with Cariex ® ; Group C) treated only with non-surgical periodontal therapy, education and motivation to oral hygiene. Clinical variables described after treatment were unstimulated whole salivary flow, stimulated whole salivary flow, salivary pH, reported pain (using Visual Analogue Scale) and the Periodontal Screening and Recording index. Salivary flow rate improved in all groups, but the difference was statistically significant only in those treated with Cariex ® , alone or in combination with periodontal therapy. Gingival status improved in participants who underwent periodontal non-surgical therapy while remained unchanged in those only treated with Cariex ® . Reported pain decreased in all groups, showing the best result in participants treated with periodontal therapy together with Cariex ® . We propose a practical approach for improving gingival conditions and alleviating oral symptoms in patients with SS. Future randomized and controlled trials are however required to confirm these results as well as larger population, and also assessing other parameters due to oral dryness, possible oral infections and more comprehensive periodontal indices. © 2016 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Current therapy and drug pipeline for the treatment of patients with acromegaly.

PubMed

Kumar, Sampath Satish; Ayuk, John; Murray, Robert D

2009-04-01

Acromegaly is a multisystem disease resulting from chronic exposure to supraphysiological levels of growth hormone (GH), and is associated with significant morbidity and excess mortality. The etiology is almost exclusively an underlying pituitary adenoma. Current therapeutic interventions include surgery, radiotherapy, and medical therapy. Despite surgery, around 50% of patients fail to achieve the biochemical targets shown to correlate with normalization of mortality rates. Radiotherapy is efficacious in controlling tumor growth and GH secretion; still, achievement of biochemical targets may take up to a decade and a number of safety issues have been raised with this treatment modality. Medical therapy, therefore, has an important role as adjuvant therapy in patients who fail to achieve control with surgery, or while awaiting the effects of radiotherapy to be realized. Furthermore, medical therapy is increasingly being used as primary therapy. Current medical therapies include dopaminergic agonists, somatostatin analogs, and GH receptor (GHR) antagonists. Dopaminergic agonists achieve biochemical targets in up to 30% of patients, and somatostatin analogs in around 60%. The currently available GHR antagonist pegvisomant effectively controls insulin-like growth factor-I levels in over 90% of patients; however, it has no effect on the tumor itself and has considerable financial implications. Research into optimizing the somatostatin and dopaminergic systems has led to promising advances in agonist development. Moieties with selectivity for various combinations of somatostatin receptor subtype receptors have been examined, along with molecules that additionally show high affinity for the dopaminergic D2 receptor. Of the molecules studied in vitro, only pasireotide (SOM230) and BIM-23A760 are currently undergoing further development. Other innovations to improve convenience of currently available drugs are also being investigated. Significant advances in under standing of the somatostatin and dopaminergic system have aided drug development. This may lead to new clinically available therapies enabling control of acromegaly in a larger proportion of patients, and at an earlier stage in their disease management.

Huntington's disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain.

PubMed

Rüb, U; Seidel, K; Heinsen, H; Vonsattel, J P; den Dunnen, W F; Korf, H W

2016-11-01

Huntington's disease (HD) is an autosomal dominantly inherited, and currently untreatable, neuropsychiatric disorder. This progressive and ultimately fatal disease is named after the American physician George Huntington and according to the underlying molecular biological mechanisms is assigned to the human polyglutamine or CAG-repeat diseases. In the present article we give an overview of the currently known neurodegenerative hallmarks of the brains of HD patients. Subsequent to recent pathoanatomical studies the prevailing reductionistic concept of HD as a human neurodegenerative disease, which is primarily and more or less exclusively confined to the striatum (ie, caudate nucleus and putamen) has been abandoned. Many recent studies have improved our neuropathological knowledge of HD; many of the early groundbreaking findings of neuropathological HD research have been rediscovered and confirmed. The results of this investigation have led to the stepwise revision of the simplified pathoanatomical and pathophysiological HD concept and culminated in the implementation of the current concept of HD as a multisystem degenerative disease of the human brain. The multisystem character of the neuropathology of HD is emphasized by a brain distribution pattern of neurodegeneration (i) which apart from the striatum includes the cerebral neo-and allocortex, thalamus, pallidum, brainstem and cerebellum, and which (ii) therefore, shares more similarities with polyglutamine spinocerebellar ataxias than previously thought. © 2016 International Society of Neuropathology.

[Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature].

PubMed

Riccio, Eleonora; Capuano, Ivana; Visciano, Bianca; Marchetiello, Cristina; Petrillo, Fortunato; Pisani, Antonio

2013-01-01

Anderson-Fabry disease is a hereditary X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha galactosidase A. It results in the accumulation of the glycosphingolypid globotrioasoyl ceramide (Gb3 in different cells and organs, resulting in a multi-system pathology including end organ failure. Patients with Fabry disease present clinically with cardiac, renal and neurological involvement; both life expectancy and quality of life are severely compromised. The current causal treatment for Fabry disease is enzyme replacement therapy (ERT), available since 2001. The two recombinant preparations available for ERT are agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). They have both been showed to have positive effect on kidney and heart, on the symptoms of pain and quality of life. Few data to date are available on comparison of the two preparations of ERT. This article reviews evidence of the literature and shows our personal experience about the safety and efficacy of ERT.

Behçet's disease

PubMed Central

2012-01-01

Definition of the disease Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. Epidemiology BD seems to cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. European cases are often described, not exclusively in the migrant population. Clinical description The clinical spectrum includes oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Etiology The etiopathogenesis of the disease remains unknown, although genetic predisposition, environmental factors and immunological abnormalities have been implicated. Diagnostic methods Diagnosis is only based on clinical criteria. Differrential diagnosis It depends on the clinical presentation of BD, but sarcoidosis, multiple sclerosis, Crohn’s disease, Takayasu’s arteritis, polychondritis or antiphospholipid syndrome need to be considered. Management Treatment is symptomatic using steroids and immunomodulatory therapy. It is efficient depending on the rapidity of initiation, the compliance, and the duration of therapy. Prognosis The prognosis is severe due to the ocular, neurological and arterial involvement. PMID:22497990

Is bronchoscopy an obsolete tool in cystic fibrosis? The role of bronchoscopy in cystic fibrosis and its clinical use

PubMed Central

2017-01-01

Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases. Though bronchoscopy has been used in conjunction with other modalities such as computed tomography and sputum induction providing a better understanding of the progression of the disease, it still remains valuable in the diagnosis and management of CF. PMID:29214071

Pheochromocytoma Multisystem Crisis Behaving Like Interstitial Pneumonia: An Autopsy Case

PubMed Central

Nomoto, Yohta; Kawano, Kiyoshi; Fujisawa, Naoki; Yoshida, Keiko; Yamashita, Tomoko; Makita, Naoki; Takeshita, Hiroaki; Kamimori, Kimio; Yanagi, Shiro; Yoshiyama, Minoru

2017-01-01

Pheochromocytoma multisystem crisis is a rare and life-threatening disease that is associated with numerous symptoms and which is also difficult to diagnose. We herein report an autopsy case of a 61-year-old man who died due to pheochromocytoma multisystem crisis. The patient complained of vomiting and breathlessness. Computed tomography showed a shadow-like region with a similar appearance to interstitial pneumonia. The patient was diagnosed with takotsubo cardiomyopathy induced by severe lung disease based on the results of echocardiography and coronary angiography. The patient was treated for interstitial pneumonia. However, his condition rapidly deteriorated and he died 6 hours after arrival. We were later informed of his extremely high catecholamine serum levels. We found pheochromocytoma with hemorrhage at autopsy. The patient's lungs showed acute passive congestion with edema and extravasation. PMID:28090043

Multisystemic Sarcoidosis Presenting as Pretibial Leg Ulcers.

PubMed

Wollina, Uwe; Baunacke, Anja; Hansel, Gesina

2016-09-01

Sarcoidosis is a multisystemic disease of unknown etiology. Up to 30% of patients develop cutaneous manifestations, either specific or nonspecific. Ulcerating sarcoidosis leading to leg ulcers is a rare observation that may lead to confusions with other, more common types of chronic leg ulcers. We report the case of a 45-year-old female patient with chronic multisystemic sarcoidosis presenting with pretibial leg ulcers. Other etiology could be excluded. Histology revealed nonspecific findings. Therefore, the diagnosis of nonspecific leg ulcers in sarcoidosis was confirmed. Treatment consisted of oral prednisolone and good ulcer care. Complete healing was achieved within 6 months. Sarcoidosis is a rare cause of leg ulcers and usually sarcoid granulomas can be found. Our patient illustrates that even in the absence of sarcoid granulomas, leg ulcers can be due to sarcoidosis. © The Author(s) 2016.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Key Elements of a Successful Multi-System Collaboration for School-Based Mental Health: In-Depth Interviews with District and Agency Administrators

ERIC Educational Resources Information Center

Powers, Joelle D.; Edwards, Jeffrey D.; Blackman, Kate F.; Wegmann, Kate M.

2013-01-01

The alarming number of youth with unmet mental health needs in the US is a significant social problem. The pilot school-based mental health project described here established an innovative multi-system partnership between an urban school district, a public mental health agency, and a local university to better meet the mental health needs of youth…

18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

PubMed

Eshghi, Naghmehossadat; Lundeen, Tamara F; MacKinnon, Lea; Avery, Ryan; Kuo, Phillip H

2018-05-01

An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

Longitudinal cystic fibrosis care.

PubMed

Antunovic, S S; Lukac, M; Vujovic, D

2013-01-01

Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis.

[Graft-versus-host disease, a rare complication of lung transplantation].

PubMed

Morisse-Pradier, H; Nove-Josserand, R; Philit, F; Senechal, A; Berger, F; Callet-Bauchu, E; Traverse-Glehen, A; Maury, J-M; Grima, R; Tronc, F; Mornex, J-F

2016-02-01

Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lyme neuroborreliosis.

PubMed

Koedel, Uwe; Pfister, Hans-Walter

2017-02-01

Lyme disease is a multistage and multisystem disease. Neurological manifestations [termed Lyme neuroborreliosis (LNB)] occur in about 10% of patients with Lyme disease. Diagnostics and treatment of early and late LNB are widely established. However, the management of persistent symptoms is still fraught with controversies, and therefore is the focus of this review. The incidence of Lyme disease seems to be much higher than previously assumed. Laboratory methods (namely serological tests) are essential for diagnosing LNB, but only when performed according to the guidelines of scientific medical societies. Most patients treated for LNB have good outcomes. However, some patients remain with nonspecific symptoms despite conventional therapy, a syndrome called posttreatment Lyme disease syndrome (PTLDS). IDSA has provided a formal definition of PTLDS, but its pathogenesis and even its existence remains to be clarified. Of note, there is evidence that these patients do not suffer from persistent Borrelia burgdorferi infection and do not benefit from additional antibiotic therapy. Acute and late LNB are well established disorders. The existence of PTLDS as a disease entity is still unclear and needs further investigation. Unorthodox alternative therapies advertised to patients with Lyme disease on the Internet are not proven to be effective and well tolerated.

Guidelines of care for the management of psoriasis and psoriatic arthritis Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies

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

Menter, A.; Korman, N.J.; Elmets, C.A.

2009-04-15

Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the Population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use ofmore » topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.« less

Extensive intramuscular manifestation of sarcoidosis with initially missed diagnosis and delayed therapy: a case report.

PubMed

Meyer, Niklaus; Sutter, Reto; Schirp, Udo; Gutzeit, Andreas

2017-08-24

Sarcoidosis is a multisystemic granulomatous disorder, which in nearly all cases involves the lungs and other organs. Isolated forms of sarcoidosis within the muscles, but without lung involvement, are extremely rare and can lead to delayed or even false diagnosis. A 52-year-old white, Swiss man presented with painful arm cramps and a history of symptoms over the previous 3 years. In the initial clinical investigation, our patient also showed edema in both legs without any other complaints. After performing an magnetic resonance imaging scan of his extremities and a positron emission tomography/computed tomography scan, diffuse myositis was described. The subsequent muscle biopsy provided the surprising diagnosis of muscle sarcoidosis, without involvement of the lungs or any other organ. After starting therapy with glucocorticoids, his symptoms improved immediately. Sarcoidosis is a common disorder, which in most cases affects the lungs. In this case report an isolated sarcoidosis is described without lung involvement, but with involvement of the muscles of the extremities and the trunk. Reported cases of sarcoidosis only involving skeletal muscle and without lung involvement are extremely rare. Radiologists should consider this presentation of sarcoidosis to avoid delayed diagnosis and therapy.

Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.

PubMed

Imbriaco, M; Pisani, A; Spinelli, L; Cuocolo, A; Messalli, G; Capuano, E; Marmo, M; Liuzzi, R; Visciano, B; Cianciaruso, B; Salvatore, M

2009-07-01

Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.

Multi-system influences on adolescent risky sexual behavior.

PubMed

Chen, Angela Chia-Chen; Thompson, Elaine Adams; Morrison-Beedy, Dianne

2010-12-01

We examined multi-system influences on risky sexual behavior measured by cumulative sexual risk index and number of nonromantic sexual partners among 4,465 single, sexually experienced adolescents. Hierarchical Poisson regression analyses were conducted with Wave I-II data from the National Longitudinal Study of Adolescent Health. Individual and family factors predicted both outcome measures. Neighborhood set predicted cumulative sexual risk index only, and peer factors predicted the number of nonromantic sexual partners only. School set did not predict either outcome. There were significant associations among risky sexual behavior, drug use, and delinquent behaviors. The results highlight the need for multifaceted prevention programs that address relevant factors related to family, peer and neighborhood influence as well as individual factors among sexually active adolescents. Copyright © 2010 Wiley Periodicals, Inc.

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PubMed

Messalli, G; Imbriaco, M; Avitabile, G; Russo, R; Iodice, D; Spinelli, L; Dellegrottaglie, S; Cademartiri, F; Salvatore, M; Pisani, A

2012-02-01

Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone

PubMed Central

Lawres, Lauren A.; Garg, Aprajita; Kumar, Vidya; Bruzual, Igor; Forquer, Isaac P.; Renard, Isaline; Virji, Azan Z.; Boulard, Pierre; Rodriguez, Eduardo X.; Allen, Alexander J.; Pou, Sovitj; Wegmann, Keith W.; Winter, Rolf W.; Nilsen, Aaron; Mao, Jialing; Preston, Douglas A.; Belperron, Alexia A.; Bockenstedt, Linda K.; Hinrichs, David J.; Riscoe, Michael K.; Doggett, J. Stone

2016-01-01

Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti. Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis. PMID:27270894

Biological treatments in Behçet's disease: beyond anti-TNF therapy.

PubMed

Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

The Role of Thromboelastography in Pediatric Patients with Sinusoidal Obstructive Syndrome Receiving Defibrotide.

PubMed

Gendreau, Joanna L; Knoll, Christine; Adams, Roberta H; Su, Leon L

2017-04-01

Sinusoidal obstructive syndrome (SOS) is a potentially fatal form of hepatic injury after hematopoietic stem cell transplantation. Patients can develop liver dysfunction, portal hypertension, ascites, coagulopathies, and multisystem organ failure. The mortality rate of severe SOS has been reported as high as 98% by day 100 after transplantation. Defibrotide, which is now approved for the treatment of SOS, has significantly decreased mortality. Defibrotide is a polynucleotide with profibrinolytic, anti-ischemic, and anti-inflammatory activity. These properties can increase the risk of life-threatening bleeding in this patient population. Previous protocols have suggested maintaining international normalized ratio ≤ 1.5, platelets > 30 k/uL, and fibrinogen ≥ 150 mg/dL to minimize this risk of bleeding. However, this can be challenging in fluid-sensitive patients with SOS. Thromboelastography (TEG) is a functional assay that evaluates the balance of procoagulant and anticoagulant proteins. In this series, TEG was used to guide defibrotide therapy as well as blood product transfusions in SOS patients with abnormal coagulation studies. Each patient recovered from SOS and had no bleeding complications. A randomized clinical trial is the next step in supporting the use of TEG in SOS patients with abnormal coagulation studies receiving defibrotide therapy. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Risks, Outcomes, and Evidence-Based Interventions for Girls in the US Juvenile Justice System.

PubMed

Leve, Leslie D; Chamberlain, Patricia; Kim, Hyoun K

2015-09-01

The proportion of the juvenile justice population that comprises females is increasing, yet few evidence-based models have been evaluated and implemented with girls in the juvenile justice system. Although much is known about the risk and protective factors for girls who participate in serious delinquency, significant gaps in the research base hamper the development and implementation of theoretically based intervention approaches. In this review, we first summarize the extant empirical work about the predictors and sequelae of juvenile justice involvement for girls. Identified risk and protective factors that correspond to girls' involvement in the juvenile justice system have been shown to largely parallel those of boys, although exposure rates and magnitudes of association sometimes differ by sex. Second, we summarize findings from empirically validated, evidence-based interventions for juvenile justice-involved youths that have been tested with girls. The interventions include Functional Family Therapy, Multisystemic Therapy, Multidimensional Family Therapy, and Treatment Foster Care Oregon (formerly known as Multidimensional Treatment Foster Care). We conclude that existing evidence-based practices appear to be effective for girls. However, few studies have been sufficiently designed to permit conclusions about whether sex-specific interventions would yield any better outcomes for girls than would interventions that already exist for both sexes and that have a strong base of evidence to support them. Third, we propose recommendations for feasible, cost-efficient next steps to advance the research and intervention agendas for this under-researched and underserved population of highly vulnerable youths.

Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease.

PubMed

Petit, A; Dadzie, O E

2013-10-01

We present an overview of the association between ethnicity and the clinical and epidemiological aspects of four multisystemic diseases: lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease. In particular, we highlight observed ethnic differences in cutaneous manifestations of these diseases. This article should help guide clinical management, as well as serve to highlight future areas for research. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Plastic Surgery Challenges in War Wounded II: Regenerative Medicine

PubMed Central

Valerio, Ian L.; Sabino, Jennifer M.; Dearth, Christopher L.

2016-01-01

Background: A large volume of service members have sustained complex injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). These injuries are complicated by contamination with particulate and foreign materials, have high rates of bacterial and/or fungal infections, are often composite-type defects with massive soft tissue wounds, and usually have multisystem involvement. While traditional treatment modalities remain a mainstay for optimal wound care, traditional reconstruction approaches alone may be inadequate to fully address the scope and magnitude of such massive complex wounds. As a result of these difficult clinical problems, the use of regenerative medicine therapies, such as autologous adipose tissue grafting, stem cell therapies, nerve allografts, and dermal regenerate templates/extracellular matrix scaffolds, is increased as adjuncts to traditional reconstructive measures. Basic and Clinical Science Advances: The beneficial applications of regenerative medicine therapies have been well characterized in both in vitro studies and in vivo animal studies. The use of these regenerative medicine techniques in the treatment of combat casualty injuries has been increasing throughout the recent war conflicts. Clinical Care Relevance: Military medicine has shown positive results when utilizing certain regenerative medicine modalities in treating complex war wounds. As a result, multi-institution clinical trials are underway to further evaluate these observations and reconstruction measures. Conclusion: Successful combat casualty wound care often requires a combination of traditional aspects of the reconstructive ladder/elevator with adoption of various regenerative medicine therapies. Due to the recent OIF/OEF conflicts, a high volume of combat casualties have benefited from adoption of regenerative medicine therapies and increased access to innovative clinical trials. Furthermore, many of these patients have had long-term follow-up to report on clinical outcomes that substantiate current treatment paradigms and concepts within regenerative medicine, reconstructive, and rehabilitation care. These results are applicable to not only combat casualty care but also to nonmilitary patients. PMID:27679752

How I manage patients with Fanconi anaemia.

PubMed

Dufour, Carlo

2017-07-01

Fanconi Anaemia is a rare, genetic heterogeneous multisystem disease that is the most common congenital syndrome of marrow failure. Twenty genes have been reported to cause the disease. Remarkable progress has been made over the last 20 years in the understanding of the genetic and pathophysiological mechanisms. Unfortunately, these advances have not been completely paralleled by advances in medical treatment, where the most important component remains stem cell transplantation. This therapy, although contributing to long-term negative effects, such as increased occurrence of late malignancies, is the only current option capable of prolonging the survival of patients. In spite of relevant recent progress in matched unrelated donor transplants, the largest studies with longer follow-up still show a superiority of matched sibling donor transplants with a success rate, in selected cohorts, of over 90%. This article reviews different aspects of the disease, including genetics, diagnosis and treatment options, with special focus on stem cell transplantation, comprehensive post-diagnosis management, decision-making processes and long-term follow-up. © 2017 John Wiley & Sons Ltd.

Reducing recidivism and symptoms in emerging adults with serious mental health conditions and justice system involvement.

PubMed

Davis, Maryann; Sheidow, Ashli J; McCart, Michael R

2015-04-01

The peak years of offending in the general population and among those with serious mental health conditions (SMHC) are during emerging adulthood. There currently are no evidence-based interventions for reducing offending behavior among 18-21 year olds, with or without SMHC. This open trial examined outcomes from an adaptation of Multisystemic Therapy (MST), an effective juvenile recidivism reduction intervention, modified for use with emerging adults with SMHC and recent justice system involvement. MST for emerging adults (MST-EA) targets MH symptoms, recidivism, problem substance use, and young adult functional capacities. All study participants (n = 41) were aged 17-20 and had a MH diagnosis and recent arrest or incarceration. Implementation outcomes indicated that MST-EA was delivered with strong fidelity, client satisfaction was high, and the majority of participants successfully completed the intervention. Research retention rates also were high. Pre-post-analyses revealed significant reductions in participants' MH symptoms, justice system involvement, and associations with antisocial peers.

Reducing Recidivism and Symptoms in Emerging Adults with Serious Mental Health Conditions and Justice System Involvement

PubMed Central

Davis, Maryann; Sheidow, Ashli J.; McCart, Michael R.

2014-01-01

The peak years of offending in the general population and among those with serious mental health conditions (SMHC) are during emerging adulthood. There currently are no evidence-based interventions for reducing offending behavior among 18–21 year olds, with or without SMHC. This open trial examined outcomes from an adaptation of Multisystemic Therapy (MST), an effective juvenile recidivism reduction intervention, modified for use with emerging adults with SMHC and recent justice system involvement. MST for emerging adults (MST-EA) targets MH symptoms, recidivism, problem substance use, and young adult functional capacities. All study participants (n=41) were aged 17–20 and had a MH diagnosis and recent arrest or incarceration. Implementation outcomes indicated that MST-EA was delivered with strong fidelity, client satisfaction was high, and the majority of participants successfully completed the intervention. Research retention rates also were high. Pre-post analyses revealed significant reductions in participants’ MH symptoms, justice-system involvement, and associations with antisocial peers. PMID:25023764

Cytomegalovirus Retinitis as a Presenting Feature of Multisystem Disorder: Dyskeratosis Congenita.

PubMed

Parchand, Swapnil; Barwad, Adarsh

2017-01-01

Cytomegalovirus (CMV) retinitis is an opportunistic infection commonly seen in disorders that affect the immune system of the body such as acquired immunodeficiency syndrome and hematological malignancies such as leukemia/lymphoma or organ transplantation. The occurrence of CMV retinitis in the absence of such condition should be thoroughly investigated, as it is a strong indicator of poor immune competence. We here report an interesting case of CMV retinitis as a presenting feature of rare multisystem disorde r "Dyskeratosis congenita."

Multisystem altruistic metadynamics—Well-tempered variant

NASA Astrophysics Data System (ADS)

Hošek, Petr; Kříž, Pavel; Toulcová, Daniela; Spiwok, Vojtěch

2017-03-01

Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

Multisystem altruistic metadynamics-Well-tempered variant.

PubMed

Hošek, Petr; Kříž, Pavel; Toulcová, Daniela; Spiwok, Vojtěch

2017-03-28

Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

Multi-System Effects of Daily Artificial Gravity Exposures in Humans Deconditioned by Bed Rest

NASA Technical Reports Server (NTRS)

Paloski, William H.

2007-01-01

We have begun to explore the utility of intermittent artificial gravity (AG) as a multi-system countermeasure to the untoward health and performance effects of adaptation to decreased gravity during prolonged space flight. The first study in this exploration was jointly designed by an international, multi-disciplinary team of scientists interested in standardizing an approach so that comparable data could be obtained from follow-on studies performed in multiple international locations. Fifteen rigorously screened male volunteers participated in the study after providing written informed consent. All were subjected to 21 days of 6deg head-down-tilt (HDT) bed rest. Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple observations were made of dependent measures in the bone, muscle, cardiovascular, sensory-motor, immune, and behavioral systems during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period. Comparisons between the treatment and control subjects demonstrated salutary effects of the AG exposure on aspects of the muscle and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Bone deconditioning was similar between the treatment and control groups, suggesting that the loading provided by this specific AG paradigm was insufficient to protect that system from deconditioning. Future work will be devoted to varying the loading duty cycle and/or coupling the AG loading with exercise to provide maximum physiological protection across all systems. Testing will also be extended to female subjects. The results of this study suggest that intermittent AG could be an effective multi-system countermeasure.

Heat shock protein 27 is involved in PCV2 infection in PK-15 cells.

PubMed

Liu, Jie; Zhang, Lili; Zhu, Xuejiao; Bai, Juan; Wang, Liming; Wang, Xianwei; Jiang, Ping

2014-08-30

Porcine circovirus type 2 (PCV2) has been identified as the etiologic agent which causing postweaning multisystemic wasting syndrome in swine farms in the world. Some quantitative proteomic studies showed that many proteins significantly changed in PCV2-infected cells. To explore the role of cellular chaperones during PCV2 infection, cytoprotective chaperone Hsp27 was analyzed in PCV2-infected PK-15 cells in this study. The results showed that Hsp27 could up-regulate and accumulate in phosphorylated forms in the nuclear zone during PCV2 replication. Suppression of Hsp27 phosphorylation with specific chemical inhibitors or downregulation of all forms of Hsp27 via RNA interference significantly reduced the virus replication. Meanwhile, over-expression of Hsp27 enhanced PCV2 genome replication and virion production. It indicated that Hsp27 was required for PCV2 production in PK-15 cells culture. It should be helpful for understanding the mechanism of replication and pathogenesis of PCV2 and development of novel antiviral therapies in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Childhood Ataxia: Clinical Features, Pathogenesis, Key Unanswered Questions, and Future Directions

PubMed Central

Ashley, Claire N.; Hoang, Kelly D.; Lynch, David R.; Perlman, Susan L.; Maria, Bernard L.

2013-01-01

Childhood ataxia is characterized by impaired balance and coordination primarily due to cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies. PMID:22859693

Comparing an Emotion- and a Behavior-Focused Parenting Program as Part of a Multsystemic Intervention for Child Conduct Problems.

PubMed

Duncombe, Melissa E; Havighurst, Sophie S; Kehoe, Christiane E; Holland, Kerry A; Frankling, Emma J; Stargatt, Robyn

2016-01-01

This study evaluated the effectiveness of a multisystemic early intervention that included a comparison of an emotion- and behavior-focused parenting program for children with emerging conduct problems. The processes that moderated positive child outcomes were also explored. A repeated measures cluster randomized group design methodology was employed with three conditions (Tuning in to Kids, Positive Parenting Program, and waitlist control) and two periods (preintervention and 6-month follow-up). The sample consisted of 320 predominantly Caucasian 4- to 9-year-old children who were screened for disruptive behavior problems. Three outcome measures of child conduct problems were evaluated using a parent (Eyberg Child Behavior Inventory) and teacher (Strengths and Difficulties Questionnaire) rating scale and a structured child interview (Home Interview With Child). Six moderators were assessed using family demographic information and a parent-rated measure of psychological well-being (Depression Anxiety and Stress Scales short form). The results indicated that the multisystemic intervention was effective compared to a control group and that, despite different theoretical orientations, the emotion- and behavior-focused parenting programs were equally effective in reducing child conduct problems. Child age and parent psychological well-being moderated intervention response. This effectiveness trial supports the use of either emotion- or behavior-focused parenting programs in a multisystemic early intervention and provides greater choice for practitioners in the selection of specific programs.

Finite-time consensus for controlled dynamical systems in network

NASA Astrophysics Data System (ADS)

Zoghlami, Naim; Mlayeh, Rhouma; Beji, Lotfi; Abichou, Azgal

2018-04-01

The key challenges in networked dynamical systems are the component heterogeneities, nonlinearities, and the high dimension of the formulated vector of state variables. In this paper, the emphasise is put on two classes of systems in network include most controlled driftless systems as well as systems with drift. For each model structure that defines homogeneous and heterogeneous multi-system behaviour, we derive protocols leading to finite-time consensus. For each model evolving in networks forming a homogeneous or heterogeneous multi-system, protocols integrating sufficient conditions are derived leading to finite-time consensus. Likewise, for the networking topology, we make use of fixed directed and undirected graphs. To prove our approaches, finite-time stability theory and Lyapunov methods are considered. As illustrative examples, the homogeneous multi-unicycle kinematics and the homogeneous/heterogeneous multi-second order dynamics in networks are studied.

Cardiac Sarcoidosis: Clinical Manifestations, Imaging Characteristics, and Therapeutic Approach

PubMed Central

Houston, Brian A; Mukherjee, Monica

2014-01-01

Sarcoidosis is a multi-system disease pathologically characterized by the accumulation of T-lymphocytes and mononuclear phagocytes into the sine qua non pathologic structure of the noncaseating granuloma. Cardiac involvement remains a key source of morbidity and mortality in sarcoidosis. Definitive diagnosis of cardiac sarcoidosis, particularly early enough in the disease course to provide maximal therapeutic impact, has proven a particularly difficult challenge. However, major advancements in imaging techniques have been made in the last decade. Advancements in imaging modalities including echocardiography, nuclear spectroscopy, positron emission tomography, and magnetic resonance imaging all have improved our ability to diagnose cardiac sarcoidosis, and in many cases to provide a more accurate prognosis and thus targeted therapy. Likewise, therapy for cardiac sarcoidosis is beginning to advance past a “steroids-only” approach, as novel immunosuppressant agents provide effective steroid-sparing options. The following focused review will provide a brief discussion of the epidemiology and clinical presentation of cardiac sarcoidosis followed by a discussion of up-to-date imaging modalities employed in its assessment and therapeutic approaches. PMID:25452702

Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues.

PubMed

Classen, Joseph; Koschel, Jiri; Oehlwein, Christian; Seppi, Klaus; Urban, Peter; Winkler, Christian; Wüllner, Ullrich; Storch, Alexander

2017-08-01

Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

Are Developmentally-Exposed C57BL/6 Mice Insensitive to Suppression of TDAR by PFOA?

EPA Science Inventory

Perfluorooctanoic acid (PFOA) is an environmentally persistent fluorinated compound that is present in biological samples worldwide and associated with multisystem toxicity in laboratory animal models. Several studies have reported suppression of T-cell-dependent antibody respons...

Modeling multisystem biological risk in young adults: The Coronary Artery Risk Development in Young Adults Study.

PubMed

Seeman, Teresa; Gruenewald, Tara; Karlamangla, Arun; Sidney, Steve; Liu, Kiang; McEwen, Bruce; Schwartz, Joseph

2010-01-01

Although much prior research has focused on identifying the roles of major regulatory systems in health risks, the concept of allostatic load (AL) focuses on the importance of a more multisystems view of health risks. How best to operationalize allostatic load, however, remains the subject of some debate. We sought to test a hypothesized metafactor model of allostatic load composed of a number of biological system factors, and to investigate model invariance across sex and ethnicity. Biological data from 782 men and women, aged 32-47, from the Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000. These include measures of blood pressure, metabolic parameters (glucose, insulin, lipid profiles, and waist circumference), markers of inflammation (interleukin-6, C-reactive protein, and fibrinogen), heart rate variability, sympathetic nervous system activity (12-hr urinary norepinephrine and epinephrine) and hypothalamic-pituitary-adrenal axis activity (diurnal salivary free cortisol). A "metafactor" model of AL as an aggregate measure of six underlying latent biological subfactors was found to fit the data, with the metafactor structure capturing 84% of variance of all pairwise associations among biological subsystems. There was little evidence of model variance across sex and/or ethnicity. These analyses extend work operationalizing AL as a multisystems index of biological dysregulation, providing initial support for a model of AL as a metaconstruct of inter-relationships among multiple biological regulatory systems, that varies little across sex or ethnicity.

Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness.

PubMed

Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

2014-12-01

To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease.

Gastrointestinal Behçet's disease: A review

PubMed Central

Skef, Wasseem; Hamilton, Matthew J; Arayssi, Thurayya

2015-01-01

Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet’s disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time. PMID:25852265

Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome)

PubMed Central

Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro

2017-01-01

Myotonic dystrophy, or Steinert's disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient's need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient's quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases. PMID:28642828

Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome).

PubMed

Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro; Grippaudo, Cristina

2017-01-01

Myotonic dystrophy, or Steinert's disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient's need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient's quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases.

Biological and targeted therapies of systemic lupus erythematosus: evidence and the state of the art.

PubMed

Mok, Chi Chiu

2017-07-01

Systemic lupus erythematosus (SLE) is a multi-systemic disease characterized by an unpredictable disease course and periods of remission and flare, leading to organ damage and mortality. Novel biological agents are being developed (targeting the lymphocytes, accessory molecules and cytokines) that aim to enhance the therapeutic efficacy when combined with standard therapies. Areas covered: This article updates recent data on the use of biological and targeted therapies in SLE. Expert commentary: B cells remain the main target of development of novel therapeutics in SLE. Similar to the intravenous preparation, subcutaneous belimumab has been shown to be superior to placebo when added to the standard of care in SLE. However, two phase III trials of epratuzumab and blisibimod did not meet their primary endpoints. Recent data on the inhibition of type I interferons (anifrolumab) appear promising. Newer calcineurin inhibitors and combination strategies using conventional immunosuppressive agents are being tested in lupus nephritis. Finally, international groups are developing consensus definitions on disease remission and low disease activity state to explore the benefits of the treat-to-target strategy in SLE. Hopefully, the armamentarium for the treatment of SLE can be expanded in the near future, so that the longevity and quality of life of patients can be further improved.

Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

PubMed Central

Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

2017-01-01

Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

Adalimumab for treatment of severe Behçet's uveitis: a retrospective long-term follow-up study.

PubMed

Interlandi, Emanuela; Leccese, Pietro; Olivieri, Ignazio; Latanza, Loredana

2014-01-01

Behçet's disease (BD) is a chronic multisystem inflammatory disorder associated to uveitis that may represent a serious sight-threatening condition. The purpose of the present study is to assess the effectiveness of adalimumab as new strategic therapeutic approach in patients affected by severe Behçet's uveitis. Clinical data from twelve selected patients (22 eyes) were retrospectively analysed. All patients received 40 mg of adalimumab subcutaneously, once every 2 weeks, in addition to traditional immunosuppressive on-going therapy and eight of them were switched to adalimumab after failure of infliximab therapy. Primary outcome measures included ocular inflammatory activity, frequency of uveitis attacks and steroid-sparing effect. Secondary outcomes were changes of best-corrected visual acuity (BCVA), impact on traditional immunosuppressive therapy and occurrence of adalimumab-related side effects. Mean age of patients (11 males and 1 female) at the onset of disease was 24.34 years (±8.62 SD). Ocular involvement resulted bilateral in 83% of cases and mainly consisted in panuveitis (68% of eyes). After mean follow-up of 21 months (±9.63 SD) all patients but one (92%) achieved uveitis remission with BCVA improvement at least in one eye. Average uveitis attacks decreased from 2 to 0,42 during adalimumab (p<0.001) and daily-steroid dose was tapered in all adalimumab responders up to suspension in seven of them. No patient developed related side effects during adalimumab administration. Our results demonstrate that adalimumab is a very effective and safe option for treatment of patients with severe and resistant Behçet's uveitis, providing an appropriate and long-term control of ocular inflammation.

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder?

PubMed Central

Isaacs, Jeremy D; Dean, Andrew F; Shaw, Christopher E; Al‐Chalabi, Ammar; Mills, Kerry R; Leigh, P Nigel

2007-01-01

Sensory involvement is thought not to be a feature of amyotrophic lateral sclerosis (ALS). However, in the setting of a specialist motor neuron disease clinic, we have identified five patients with sporadic ALS and a sensory neuropathy for which an alternative cause could not be identified. In three individuals, sensory nerve biopsy was performed, demonstrating axonal loss without features of an alternative aetiology. These findings support the hypothesis that ALS is a multisystem neurodegenerative disorder that may occasionally include sensory neuropathy among its non‐motor features. PMID:17575021

Cross-system comparisons elucidate disturbance complexities and generalities

Treesearch

Debra P.C. Peters; Ariel E. Lugo; F. Stuart Chapin; Steward T.A. Pickett; Michael Duniway; Adrian V. Rocha; Frederick J. Swanson; Christine Laney; Julia Jones

2011-01-01

Given that ecological effects of disturbance have been extensively studied in many ecosystems, it is surprising that few quantitative syntheses across diverse ecosystems have been conducted. Multi-system studies tend to be qualitative because they focus on disturbance types that are difficult to measure in an ecologically relevant way. In addition, synthesis of...

THE DEVELOPMENTAL IMMUNOTOXICITY OF DIBUTYLTIN DICHLORIDE IN SPRAGUE-DAWLEY RATS

EPA Science Inventory

Methyl- and butyltin compounds used as stabilizers in polyvinyl chloride (PVC) pipe production are of concern as they leach from supply pipes into drinking water and have been associated with multisystem toxicity. This study assessed immune function in Sprague-Dawley (CD) rats d...

Pain control methods in use and perceived effectiveness by patients with Ehlers-Danlos syndrome: a descriptive study.

PubMed

Arthur, Karen; Caldwell, Karen; Forehand, Samantha; Davis, Keith

2016-01-01

The purpose of this study was to assess the pain control methods in use by patients who have Ehlers-Danlos Syndrome (EDS), a group of connective tissue disorders, and their perceived effectiveness. This descriptive study involved 1179 adults diagnosed with EDS who completed an anonymous on-line survey. The survey consisted of demographics information, the Patient Reported Outcomes Measurement Information System (PROMIS) Pain-Behavior, PROMIS Pain-Interference, and Neuro QOL Satisfaction with Social Roles and Activities scales, as well as a modified version of the Pain Management Strategies Survey. Respondents reported having to seek out confirmation of their EDS diagnosis with multiple healthcare providers, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Patients with EDS experience higher levels of pain interference and lower satisfaction with social roles and activities compared to national norms. Among the treatment modalities in this study, those perceived as most helpful for acute pain control were opioids, surgical interventions, splints and braces, avoidance of potentially dangerous activities and heat therapy. Chronic pain treatments rated as most helpful were opioids, splints or braces and surgical interventions. For methods used for both acute and chronic pain, those perceived as most helpful were opioids, massage therapies, splints or braces, heat therapy and avoiding potentially dangerous activities. EDS is a complex, multi-systemic condition that can be difficult to diagnose and poses challenges for healthcare practitioners who engage with EDS patients in holistic care. Improved healthcare provider knowledge of EDS is needed, and additional research on the co-occurring diagnoses with EDS may assist in comprehensive pain management for EDS patients. Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders associated with defective production of collagen, which can dramatically reduce musculoskeletal functioning by symptoms of joint laxity and frequent dislocations eventually leading to disability. Respondents to an on-line survey reported having to seek out confirmation of their EDS diagnosis with multiple physicians, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Participants with EDS reported the most helpful methods for managing acute pain were opioids, surgical interventions, splints and braces, heat therapy, nerve blocks and physical therapy, while chronic pain was treated most effectively with opioids, heat therapy, splints or braces and surgical interventions.

ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum.

PubMed

Bertamino, Marta; Severino, Mariasavina; Grossi, Alice; Rusmini, Marta; Tortora, Domenico; Gandolfo, Carlo; Pederzoli, Silvia; Malattia, Clara; Picco, Paolo; Striano, Pasquale; Ceccherini, Isabella; Di Rocco, Maja

2018-04-12

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by fragmented and mineralized elastic fibers in the mid-dermis of the skin, eye, digestive tract and cardiovascular system. Clinical presentation includes typical skin lesions, ocular angioid streaks, and multisystem vasculopathy. The age of onset varies considerably from infancy to old age, but the diagnosis is usually made in young adults due to frequent absence of pathognomonic skin and ocular manifestations in early childhood. We report two children with PXE presenting with isolated multisystem vasculopathy and early-onset stroke. In the first patient, diagnosis was delayed until typical dermatologic alterations appeared; in the second patient, next-generation sequencing (NGS) study led to early diagnosis and specific follow-up, underlying the crucial role in idiopathic pediatric stroke of early genetic testing using NGS-based panels. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Behçet’s syndrome: providing integrated care

PubMed Central

Esatoglu, Sinem Nihal; Kutlubay, Zekayi; Ucar, Didar; Hatemi, Ibrahim; Uygunoglu, Ugur; Siva, Aksel; Hatemi, Gulen

2017-01-01

Behçet’s syndrome (BS) is a multisystem vasculitis that presents with a variety of mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system involvement. Although it occurs worldwide, it is especially prevalent in the Far East and around the Mediterranean Sea. Male gender and younger age at disease onset are associated with a more severe disease course. The management of BS depends on the severity of symptoms. If untreated, morbidity and mortality are considerably high in patients with major organ involvement. Multidisciplinary patient care is essential for the management of BS, as it is for other multisystem diseases. Rheumatologists, dermatologists, ophthalmologists, neurologists, cardiovascular surgeons and gastroenterologists are members of the multidisciplinary team. In this study, we reviewed the epidemiology, etiology, diagnostic criteria sets, clinical findings and treatment of BS and highlighted the importance of the multidisciplinary team in the management of BS. PMID:28860798

hnRNPA2B1 and hnRNPA1 mutations are rare in patients with "multisystem proteinopathy" and frontotemporal lobar degeneration phenotypes.

PubMed

Le Ber, Isabelle; Van Bortel, Inge; Nicolas, Gael; Bouya-Ahmed, Kawtar; Camuzat, Agnès; Wallon, David; De Septenville, Anne; Latouche, Morwena; Lattante, Serena; Kabashi, Edor; Jornea, Ludmila; Hannequin, Didier; Brice, Alexis

2014-04-01

hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Risks, Outcomes, and Evidence-based Interventions for Girls in the U.S. Juvenile Justice System

PubMed Central

Leve, Leslie D.; Chamberlain, Patricia; Kim, Hyoun K.

2015-01-01

The proportion of the juvenile justice population that is comprised of females is increasing, yet few evidence-based models have been evaluated and implemented with girls in the juvenile justice system. Although much is known about the risk and protective factors for girls who participate in serious delinquency, significant gaps in the research base hamper the development and implementation of theoretically based intervention approaches. In this review, we first summarize the extant empirical work about the predictors and sequelae of juvenile justice involvement for girls. Identified risk and protective factors that correspond to girls’ involvement in the juvenile justice system have been shown to largely parallel those of boys, although exposure rates and magnitudes of association sometimes differ by sex. Second, we summarize findings from empirically validated, evidence-based interventions for juvenile justice–involved youths that have been tested with girls. The interventions include Functional Family Therapy, Multisystemic Therapy, Multidimensional Family Therapy, and Treatment Foster Care Oregon (formerly known as Multidimensional Treatment Foster Care). We conclude that existing evidence-based practices appear to be effective for girls. However, few studies have been sufficiently designed to permit conclusions about whether sex-specific interventions would yield any better outcomes for girls than would interventions that already exist for both sexes and that have a strong base of evidence to support them. Third, we propose recommendations for feasible, cost-efficient next steps to advance the research and intervention agendas for this under-researched, under-served population of highly vulnerable youths. PMID:26119215

Lyme disease: why the controversy?

PubMed

Beaman, M H

2016-12-01

Some Australians have become convinced of the existence of locally acquired Lyme disease (LD). The history of LD, since its recognition in the early 1970s, is reviewed as a model for investigative approaches to unknown syndromes. Australian Management Guidelines for LD include the requirement for diagnostic testing by National Association of Testing Authorities-accredited laboratories using Therapeutic Goods Administration-licensed tests, which result in the efficient diagnosis of LD in overseas travellers. Despite this, patients who have not left Australia pay many thousands of dollars for non-specialist consultations and testing at overseas laboratories. Unproven long-term therapy with multiple antibiotics has resulted in serious complications, including allergies, line sepsis, pancreatitis and pseudomembranous colitis. Studies have shown that LD vectors are not found in Australia, and Lyme Borrelia has not been found in Australian vectors, animals or patients with autochthonous illnesses. I propose that (i) A non-controversial name for the chronic syndrome should be adopted, 'Australian Multisystem Disorder'. (ii) Research funding should enable the development of a consensus case definition and studies of the epidemiology of this syndrome with laboratory investigations to identify an aetiology and surrogate markers of disease. Prospective, randomised treatment studies could then be undertaken using ethical protocols. © 2016 Royal Australasian College of Physicians.

Research, Data, and Evidence-Based Treatment Use in State Behavioral Health Systems, 2001-2012.

PubMed

Bruns, Eric J; Kerns, Suzanne E U; Pullmann, Michael D; Hensley, Spencer W; Lutterman, Ted; Hoagwood, Kimberly E

2016-05-01

Empirical study of public behavioral health systems' use of data and their investment in evidence-based treatments (EBTs) is limited. This study describes trends in state-level EBT investment and research supports from 2001 to 2012. Data were from National Association for State Mental Health Program Directors Research Institute (NRI) surveys, which were completed by representatives of state mental health authorities (SMHAs). Multilevel models examined change over time related to state adoption of EBTs, numbers of clients served, and penetration rates for six behavioral health EBTs for adults and children: supported housing, supported employment, assertive community treatment, therapeutic foster care, multisystemic therapy, and functional family therapy. State supports related to research, evaluation, and information management were also examined. Increasing percentages of states reported funding an external research center, promoting the adoption of EBTs through provider contracts, and providing financial incentives for EBTs. Decreasing percentages of states reported promoting EBT adoption through stakeholder mobilization, monitoring fidelity, and specific budget requests. There was greater reported use of adult-focused EBTs (65%-80%) compared with youth-focused EBTs (25%-50%). Overall penetration rates of EBTs were low (1%-3%) and EBT adoption by states showed flat or declining trends. SMHAs' investment in data systems and use of research showed little change. SMHA investment in EBTs, implementation infrastructure, and use of research has declined. More systematic measurement and examination of these metrics may provide a useful approach for setting priorities, evaluating success of health reform efforts, and making future investments.

Lung Involvement in Systemic Sclerosis

PubMed Central

Hassoun, Paul M.

2011-01-01

Summary Scleroderma is a multisystem disease characterized by a severe inflammatory process and exuberant fibrosis. Lung involvement is a frequent complication and a leading cause of morbidity and mortality in this syndrome. Two major pulmonary syndromes are associated with scleroderma; a pulmonary vascular disorder evolving over time into relatively isolated pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD). Each syndrome, when present, is a cause of morbidity and significantly reduces survival of scleroderma patients when compared to patients free of lung complication. When pulmonary hypertension and ILD are combined, survival is further reduced. Current therapy appears to have no meaningful effect on either condition and, thus, there is a need for better understanding of underlying pathogenic mechanisms. This review focuses on clinical, diagnostic, and therapeutic features of PAH and ILD as well as other frequent but less debilitating lung complications of scleroderma. PMID:21195581

Cryopyrin-associated periodic syndromes: diagnosis and management.

PubMed

Miyamae, Takako

2012-04-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory disorders; many cases of CAPS are caused by mutations in the NLRP3 gene. In these conditions, interleukin (IL)-1 is overproduced, and this overproduction plays a major role in disease onset and progression. CAPS include three variants, ranging in order of increasing severity from familial cold autoinflammatory syndrome, previously termed familial cold urticaria, through Muckle-Wells syndrome, to chronic infantile neurologic cutaneous articular syndrome, also known as neonatal onset multisystemic inflammatory disease. Diagnosis of CAPS is initially based on clinical manifestations and medical history, and later confirmed genetically. CAPS should be suspected when characteristic skin lesions, typical periodic fever episodes, bone/joint manifestations, and CNS involvement are recognized. CAPS are life-long diseases, and early diagnosis and early treatment with IL-1-targeted therapies may improve prognosis.

Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

PubMed

Lee, Jason J; Pope, Janet E

2016-02-01

Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

Vemurafenib in Langerhans cell histiocytosis: report of a pediatric patient and review of the literature.

PubMed

Heisig, Anne; Sörensen, Jan; Zimmermann, Stefanie-Yvonne; Schöning, Stefan; Schwabe, Dirk; Kvasnicka, Hans-Michael; Schwentner, Raphaela; Hutter, Caroline; Lehrnbecher, Thomas

2018-04-24

Selective BRAF inhibitors such as vemurafenib have become a treatment option in patients with Langerhans cell Histiocytosis (LCH). To date, only 14 patients receiving vemurafenib for LCH have been reported. Although vemurafenib can stabilize the clinical condition of these patients, it does not seem to cure the patients, and it is unknown, when and how to stop vemurafenib treatment. We present a girl with severe multisystem LCH who responded only to vemurafenib. After 8 months of treatment, vemurafenib was tapered and replaced by prednisone and vinblastine, a strategy which has not been described to date. Despite chemotherapy, early relapse occurred, but remission was achieved by re-institution of vemurafenib. Further investigation needs to address the optimal duration of vemurafenib therapy in LCH and whether and which chemotherapeutic regimen may prevent disease relapse after cessation of vemurafenib.

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Pilot Study Overview

NASA Technical Reports Server (NTRS)

Paloski, William H.; Young, L. R.

2007-01-01

Efficient, effective, multi-system countermeasures will likely be required to protect the health, safety, and performance of crews aboard planned exploration-class space flight missions to Mars and beyond. To that end, NASA, DLR, and IMBP initiated a multi-center international project to begin systematically exploring the utility of artificial gravity (AG) as a multi-system countermeasure in ground based venues using test subjects deconditioned by bed rest. The goal of this project is to explore the efficacy of short-radius, intermittent AG as a countermeasure to bone, muscle, cardiovascular, and sensory-motor adaptations to hypogravity. This session reports the results from a pilot study commissioned to validate a standardized protocol to be used by all centers involved in the project. Subject selection criteria, medical monitoring requirements, medical care procedures, experiment control procedures, and standardized dependent measures were established jointly. Testing was performed on 15 rigorously screened male volunteers subjected to 21 days of 6deg HDT bed rest. (All provided written consent to volunteer after the nature of the study and its hazards were clearly explained to them.) Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple tests of multiple dependent measures were made in each of the primary physiological systems of interest during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period was complete. Analyses of these data (presented in other papers in this session) suggest the AG prescription had salutary effects on aspects of the bone, muscle, and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Furthermore, treatment subjects were able to tolerate 153/160 centrifuge sessions over the 21 day deconditioning protocol, suggesting that tolerance was unaffected by deconditioning. These positive results set the stage for full implementation of the planned multi-center international AG project. Future work will be devoted to developing optimization techniques for AG prescriptions (likely supplemented by exercise) to provide maximum physiological protection across all systems subject to space flight deconditioning in both men and women with minimum time and/or side effects. While a continuous AG solution (rotating vehicle) would likely be more efficient, this study suggests that intermittent AG could be an effective multi-system countermeasure.

Effects of family treatment on parenting beliefs among caregivers of youth with poorly controlled asthma.

PubMed

Ellis, Deborah A; King, Pamela; Naar-King, Sylvie; Lam, Phebe; Cunningham, Phillippe B; Secord, Elizabeth

2014-10-01

Caregiver involvement is critical in ensuring optimal adolescent asthma management. The study investigated whether multisystemic therapy (MST), an intensive home-based family therapy, was superior to family support for changing beliefs regarding asthma-related positive parenting among caregivers of African-American youth with poorly controlled asthma. The relationship between parenting beliefs and asthma management at the conclusion of the intervention was also assessed. A randomized controlled trial was conducted with 167 adolescents with moderate-to-severe, persistent, poorly controlled asthma and their primary caregivers. Families were randomly assigned to MST or family support (FS), a home-based family support condition. Data were collected at baseline and 7-month posttest. Changes in caregiver ratings of importance and confidence for engaging in asthma-related positive parenting were assessed through questionnaire. Illness management was assessed by the Family Asthma Management System Scale. Participation in MST was associated with more change in caregiver beliefs as compared with FS for both importance (t = 2.39, p = .02) and confidence (t = 2.04, p = .04). Caregiver beliefs were also significantly related to youth controller medication adherence at the conclusion of treatment (importance: r = .21, p = .01; confidence: r = .23, p = .004). Results support the effectiveness of MST for increasing parental beliefs in the value of asthma-related positive parenting behaviors and parental self-efficacy for these behaviors among families of minority adolescents with poorly controlled asthma.

Mitochondrial disorder caused Charles Darwin's cyclic vomiting syndrome.

PubMed

Finsterer, Josef; Hayman, John

2014-01-08

Charles Darwin (CD), "father of modern biology," suffered from multisystem illness from early adulthood. The most disabling manifestation was cyclic vomiting syndrome (CVS). This study aims at finding the possible cause of CVS in CD. A literature search using the PubMed database was carried out, and CD's complaints, as reported in his personal writings and those of his relatives, friends, colleagues, biographers, were compared with various manifestations of mitochondrial disorders (MIDs), known to cause CVS, described in the literature. Organ tissues involved in CD's disease were brain, nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral manifestations included episodic headache, visual disturbance, episodic memory loss, periodic paralysis, hysterical crying, panic attacks, and episodes of depression. Manifestations of polyneuropathy included numbness, paresthesias, increased sweating, temperature sensitivity, and arterial hypotension. Muscular manifestations included periods of exhaustion, easy fatigability, myalgia, and muscle twitching. Cardiac manifestations included episodes of palpitations and chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal seasickness, eructation, belching, and flatulence. Dermatological manifestations included painful lips, dermatitis, eczema, and facial edema. Treatments with beneficial effects to his complaints were rest, relaxation, heat, and hydrotherapy. CVS in CD was most likely due to a multisystem, nonsyndromic MID. This diagnosis is based upon the multisystem nature of his disease, the fact that CVS is most frequently the manifestation of a MID, the family history, the variable phenotypic expression between affected family members, the fact that symptoms were triggered by stress, and that only few symptoms could not be explained by a MID.

Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

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

Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela

2011-11-18

Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount ofmore » mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.« less

PSYCHOLOGICAL INTERVENTION IN TUBEROUS SCLEROSIS: A CASE REPORT

PubMed Central

Sharma, Puja; Rao, Kiran

2002-01-01

Tuberous sclerosis (TS) is characterized by the clinical triad of epilepsy, mental subnormality and adenoma sebaceum. TS is a multi-system disorder resulting in severe distress for the individuals and their family members. The present study illustrates an eclectic psychosocial management of a patient with TS and normal intelligence. PMID:21206610

Impact of Multisystem Health Care on Readmission and Follow-up Among Veterans Hospitalized for Chronic Obstructive Pulmonary Disease.

PubMed

Rinne, Seppo T; Elwy, Anashua R; Bastian, Lori A; Wong, Edwin S; Wiener, Renda S; Liu, Chuan-Fen

2017-07-01

Chronic obstructive pulmonary disease (COPD) is one of the most common causes of readmission at Veterans Affairs (VA) hospitals. Previous studies demonstrate worse outcomes for veterans with multisystem health care, though the impact of non-VA care on COPD readmissions is unknown. To examine the association of use of non-VA outpatient care with 30-day readmission and 30-day follow-up among veterans admitted to the VA for COPD. This is a retrospective cohort study using VA administrative data and Medicare claims. In total, 20,472 Medicare-eligible veterans who were admitted to VA hospitals for COPD during October 1, 2008 and September 30, 2011. We identified the source of outpatient care during the year before the index hospitalization as VA-only, dual-care (VA and Medicare), and Medicare-only. Outcomes of interest included any-cause 30-day readmission, COPD-specific 30-day readmission and follow-up visit within 30 days of discharge. We used mixed-effects logistic regression, controlling for baseline severity of illness, to examine the association between non-VA care and postdischarge outcomes. There was no association between non-VA care and any-cause readmission. We did identify an increased COPD-specific readmission risk with both dual-care [odds ratio (OR)=1.20; 95% confidence interval (CI), 1.02-1.40] and Medicare-only (OR=1.41; 95% CI, 1.15-1.75). Medicare-only outpatient care was also associated with significantly lower rates of follow-up (OR=0.81; 95% CI, 0.72-0.91). Differences in disease-specific readmission risk may reflect differences in disease management between VA and non-VA providers. Further research is needed to understand how multisystem care affects coordination and other measures of quality for veterans with COPD.

Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness

PubMed Central

Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

2014-01-01

Objective To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). Methods We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. Results In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. Interpretation We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease. PMID:25574476

Dynamics of particulate organic matter composition in coastal systems: Forcing of spatio-temporal variability at multi-systems scale

NASA Astrophysics Data System (ADS)

Liénart, Camilla; Savoye, Nicolas; David, Valérie; Ramond, Pierre; Rodriguez Tress, Paco; Hanquiez, Vincent; Marieu, Vincent; Aubert, Fabien; Aubin, Sébastien; Bichon, Sabrina; Boinet, Christophe; Bourasseau, Line; Bozec, Yann; Bréret, Martine; Breton, Elsa; Caparros, Jocelyne; Cariou, Thierry; Claquin, Pascal; Conan, Pascal; Corre, Anne-Marie; Costes, Laurence; Crouvoisier, Muriel; Del Amo, Yolanda; Derriennic, Hervé; Dindinaud, François; Duran, Robert; Durozier, Maïa; Devesa, Jérémy; Ferreira, Sophie; Feunteun, Eric; Garcia, Nicole; Geslin, Sandrine; Grossteffan, Emilie; Gueux, Aurore; Guillaudeau, Julien; Guillou, Gaël; Jolly, Orianne; Lachaussée, Nicolas; Lafont, Michel; Lagadec, Véronique; Lamoureux, Jézabel; Lauga, Béatrice; Lebreton, Benoît; Lecuyer, Eric; Lehodey, Jean-Paul; Leroux, Cédric; L'Helguen, Stéphane; Macé, Eric; Maria, Eric; Mousseau, Laure; Nowaczyk, Antoine; Pineau, Philippe; Petit, Franck; Pujo-Pay, Mireille; Raimbault, Patrick; Rimmelin-Maury, Peggy; Rouaud, Vanessa; Sauriau, Pierre-Guy; Sultan, Emmanuelle; Susperregui, Nicolas

2018-03-01

In costal systems, particulate organic matter (POM) results from a multiplicity of sources having their respective dynamics in terms of production, decomposition, transport and burial. The POM pool experiences thus considerable spatial and temporal variability. In order to better understand this variability, the present study employs statistical multivariate analyses to investigate links between POM composition and environmental forcings for a panel of twelve coastal systems distributed along the three maritime regions of France and monitored weekly to monthly for 1 to 8 years. At multi-system scale, two main gradients of POC composition have been identified: a 'Continent-Ocean' gradient associated with hydrodynamics, sedimentary dynamics and depth of the water column, and a gradient of trophic status related to nutrient availability. At local scale, seasonality of POC composition appears to be station-specific but still related to part of the above-mentioned forcings. A typology of systems was established by coupling spatial and temporal variability of POC composition. Four groups were highlighted: (1) the estuarine stations where POC composition is dominated by terrestrial POM and driven by hydrodynamics and sedimentary processes, (2) the oligotrophic systems, characterized by the contribution of diazotrophs due to low nutrient availability, and the marine meso/eutroph systems whose POC composition is (3) either deeply dominated by phytoplankton or (4) dominated by phytoplankton but where the contribution of continental and benthic POC is not negligible and is driven by hydrodynamics, sedimentary processes and the height of the water column. Finally, the present study provides several insights into the different forcings to POM composition and dynamics in temperate coastal systems at local and multi-system scales. This work also presents a methodological approach that establishes statistical links between forcings and POM composition, helping to gain more objectively insight of forcings.

An introduction to the multisystem model of knowledge integration and translation.

PubMed

Palmer, Debra; Kramlich, Debra

2011-01-01

Many nurse researchers have designed strategies to assist health care practitioners to move evidence into practice. While many have been identified as "models," most do not have a conceptual framework. They are unidirectional, complex, and difficult for novice research users to understand. These models have focused on empirical knowledge and ignored the importance of practitioners' tacit knowledge. The Communities of Practice conceptual framework allows for the integration of tacit and explicit knowledge into practice. This article describes the development of a new translation model, the Multisystem Model of Knowledge Integration and Translation, supported by the Communities of Practice conceptual framework.

Cross-sectional Imaging Review of Tuberous Sclerosis.

PubMed

Krishnan, Anant; Kaza, Ravi K; Vummidi, Dharshan R

2016-05-01

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder characterized by development of hamartomas in the brain, abdomen, and thorax. It results from a mutation in one of 2 tumor suppressor genes that activates the mammalian target of rapamycin pathway. This article discusses the origins of the disorder, the recently updated criteria for the diagnosis of TSC, and the cross-sectional imaging findings and recommendations for surveillance. Familiarity with the diverse radiological features facilitates diagnosis and helps in treatment planning and monitoring response to treatment of this multisystem disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

A case of vascular Ehlers-Danlos Syndrome with a cardiomyopathy and multi-system involvement.

PubMed

Lan, Nick Si Rui; Fietz, Michael; Pachter, Nicholas; Paul, Vincent; Playford, David

Ehlers-Danlos Syndrome comprises a heterogeneous group of heritable connective tissue disorders resulting from various gene mutations. We present an unusual case of vascular Ehlers-Danlos Syndrome with distinctive physical characteristics and a cardiomyopathy with features suggesting isolated left ventricular non-compaction. The cardiac features represent the first report of a cardiomyopathy associated with a mutation in the COL3A1 gene. This case also illustrates the multi-system nature of Ehlers-Danlos Syndrome and the complexity of managing patients with the vascular subtype. Copyright © 2018 Elsevier Inc. All rights reserved.

Gasoline immersion injury

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

Simpson, L.A.; Cruse, C.W.

1981-01-01

Chemical burns and pulmonary complications are the most common problems encountered in the patient immersed in gasoline. Our patient demonstrated a 46-percent total-body-surface area, partial-thickness chemical burn. Although he did not develop bronchitis or pneumonitis, he did display persistent atelectasis, laryngeal edema, and subsequent upper airway obstruction. This had not previously been reported in gasoline inhalation injuries. Hydrocarbon hepatitis secondary to the vascular endothelial damage is apparently a reversible lesion with no reported long-term sequelae. Gasoline immersion injuries may be a series multisystem injury and require the burn surgeon to take a multisystem approach to its diagnosis and treatment.

Descriptive summary of an outbreak of porcine post-weaning multisystemic wasting syndrome (PMWS ) in New Zealand.

PubMed

Neumann, E J; Dobbinson, S S A; Welch, E B M; Morris, R S

2007-12-01

Investigations were conducted to determine the cause of an acute, multi-farm outbreak of porcine respiratory disease that included diarrhoea and subsequent loss of body condition in affected pigs. A definition for post-weaning multisystemic wasting syndrome (PMWS) including both clinical and pathological features, previously developed for the pig industry in New Zealand, was applied to the current outbreak. In addition to self-reporting by owners of affected farms, local veterinarians, disease and epidemiology consultants, and animal health officials from the Ministry of Agriculture and Forestry (MAF) were involved in conducting farm visits and submission of diagnostic specimens. Pathogens known to be endemic in the pig industry in New Zealand as well as likely exotic diseases were excluded as causative agents of the outbreak. Clinical signs including dyspnoea, diarrhoea, and rapid loss of body condition were consistent with the New Zealand case definition for PMWS. Interstitial pneumonia, pulmonary oedema, generalised lymph-node enlargement, and presence of porcine circovirus type 2 (PCV2) inclusion bodies were consistently identified in affected pigs. Classical swine fever virus (CSFv), Porcine reproductive and respiratory syndrome virus (PRRSv), and Influenza virus were ruled out, using molecular and traditional virological techniques. Spread of the disease between farms was hypothesised to be facilitated by locally migrating flocks of black-backed seagulls. The original source of the disease incursion was not identified. Based on the consistent presence of circovirus-associated lesions in lymphoid tissues in combination with generalised enlargement of lymph nodes, histiocytic interstitial pneumonia, clinical wasting, and poor response to antibiotic therapy, a diagnosis of PMWS was made. PMWS should be considered in the differential diagnoses of sudden onset of respiratory dyspnoea, diarrhoea, and rapid loss of body condition in young pigs in New Zealand pig herds.

Musculoskeletal involvement in sarcoidosis*, **

PubMed Central

Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

2014-01-01

Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

Cortisol and salivary alpha-amylase trajectories following a group social-evaluative stressor with adolescents.

PubMed

Katz, Deirdre A; Peckins, Melissa K

2017-12-01

Intraindividual variability in stress responsivity and the interrelationship of multiple neuroendocrine systems make a multisystem analytic approach to examining the human stress response challenging. The present study makes use of an efficient social-evaluative stress paradigm - the Group Public Speaking Task for Adolescents (GPST-A) - to examine the hypothalamic-pituitary-adrenocortical (HPA)-axis and Autonomic Nervous System (ANS) reactivity profiles of 54 adolescents with salivary cortisol and salivary alpha-amylase (sAA). First, we account for individuals' time latency of hormone concentrations between individuals. Second, we use a two-piece multilevel growth curve model with landmark registration to examine the reactivity and recovery periods of the stress response separately. This analytic approach increases the models' sensitivity to detecting trajectory differences in the reactivity and recovery phases of the stress response and allows for interindividual variation in the timing of participants' peak response following a social-evaluative stressor. The GPST-A evoked typical cortisol and sAA responses in both males and females. Males' cortisol concentrations were significantly higher than females' during each phase of the response. We found no gender difference in the sAA response. However, the rate of increase in sAA as well as overall sAA secretion across the study were associated with steeper rates of cortisol reactivity and recovery. This study demonstrates a way to model the response trajectories of salivary biomarkers of the HPA-axis and ANS when taking a multisystem approach to neuroendocrine research that enables researchers to make conclusions about the reactivity and recovery phases of the HPA-axis and ANS responses. As the study of the human stress response progresses toward a multisystem analytic approach, it is critical that individual variability in peak latency be taken into consideration and that accurate modeling techniques capture individual variability in the stress response so that accurate conclusions can be made about separate phases of the response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

2018-03-18

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Exploring the Critical Dialogical Process: Psychological and Physical Spaces Creating Conditions Conducive to Multi-System Collective Action in Higher Education

ERIC Educational Resources Information Center

Pittman-Adkins, Pamela

2015-01-01

Purpose: The purpose of this study is to explore physical and psychological elements conducive to engaging educators from K-12 and higher education in meaningful exchanges that lead to collective action. Research Design: Through a qualitative case study of two higher education sites focused on advancing academically-based service learning…

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

PubMed Central

Finsterer, Josef; Frank, Marlies

2016-01-01

Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy. Rare GI manifestations of MIDs include dry mouth, paradontosis, tracheoesophageal fistula, stenosis of the duodeno-jejunal junction, atresia or imperforate anus, liver cysts, pancreas lipomatosis, pancreatic cysts, congenital stenosis or obstruction of the GI tract, recurrent bowel perforations with intra-abdominal abscesses, postprandial abdominal pain, diverticulosis, or pneumatosis coli. Diagnosing GI involvement in MIDs is not at variance from diagnosing GI disorders due to other causes. Treatment of mitochondrial GI disease includes noninvasive or invasive measures. Therapy is usually symptomatic. Only for myo-neuro-gastro-intestinal encephalopathy is a causal therapy with autologous stem-cell transplantation available. It is concluded that GI manifestations of MIDs are more widespread than so far anticipated and that they must be recognized as early as possible to initiate appropriate diagnostic work-up and avoid any mitochondrion-toxic treatment. PMID:28286566

A Multi-Systemic School-Based Approach for Addressing Childhood Aggression

ERIC Educational Resources Information Center

Runions, Kevin

2008-01-01

School-based approaches to addressing aggression in the early grades have focused on explicit curriculum addressing social and emotional processes. The current study reviews research on the distinct modes of aggression, the status of current research on social and emotional processing relevant to problems of aggression amongst young children, as…

Stress Reactivity of Six-Year-Old Children Involved in Challenging Tasks

ERIC Educational Resources Information Center

Sajaniemi, Nina; Suhonen, Eira; Kontu, Elina; Lindholm, Harri; Hirvonen, Ari

2012-01-01

The aim of this study was to investigate whether the preschool activities challenge the stress regulative system in children. We used a multi-system approach to evaluate the underlying processes of stress responses and measured both cortisol and [alpha]-amylase responses after emotionally and cognitively challenging tasks followed by a recovery…

A Case Study of Early Development in Smith-Magenis Syndrome

ERIC Educational Resources Information Center

Fidler, Deborah J.; Philofsky, Amy D.; Hepburn, Susan L.

2006-01-01

The aim of this article is to provide an in-depth description of early development in a young child with Smith-Magenis syndrome (SMS). SMS is a multisystem, neurodevelopmental genetic disorder associated with mental retardation that predisposes individuals to a distinct pattern of maladaptive behaviors and other neuropsychological impairments.…

Evaluating Multisystemic Efforts to Impact Disproportionality through Key Decision Points

ERIC Educational Resources Information Center

Derezotes, Dennette; Richardson, Brad; King, Connie Bear; Kleinschmit-Rembert, Julia; Pratt, Betty

2008-01-01

Working in four communities, Casey Foundation/Center for the Study of Social Policy (CSSP) Alliance on Racial Equity (the Alliance) have developed a Racial Equity Scorecard for measuring disproportionality at key decision points for use in impacting disproportionality in the child welfare system. The four communities include King County,…

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

PubMed Central

Safdar, Adeel; Bourgeois, Jacqueline M.; Ogborn, Daniel I.; Little, Jonathan P.; Hettinga, Bart P.; Akhtar, Mahmood; Thompson, James E.; Melov, Simon; Mocellin, Nicholas J.; Kujoth, Gregory C.; Prolla, Tomas A.; Tarnopolsky, Mark A.

2011-01-01

A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. PMID:21368114

Developing a multi-systemic fall prevention model, incorporating the physical environment, the care process and technology: a systematic review.

PubMed

Choi, Young-Seon; Lawler, Erin; Boenecke, Clayton A; Ponatoski, Edward R; Zimring, Craig M

2011-12-01

This paper reports a review that assessed the effectiveness and characteristics of fall prevention interventions implemented in hospitals. A multi-systemic fall prevention model that establishes a practical framework was developed from the evidence. Falls occur through complex interactions between patient-related and environmental risk factors, suggesting a need for multifaceted fall prevention approaches that address both factors. We searched Medline, CINAHL, PsycInfo and the Web of Science databases for references published between January 1990 and June 2009 and scrutinized secondary references from acquired papers. Due to the heterogeneity of interventions and populations, we conducted a quantitative systematic review without a meta-analysis and used a narrative summary to report findings. From the review, three distinct characteristics of fall prevention interventions emerged: (1) the physical environment, (2) the care process and culture and (3) technology. While clinically significant evidence shows the efficacy of environment-related interventions in reducing falls and fall-related injuries, the literature identified few hospitals that had introduced environment-related interventions in their multifaceted fall intervention strategies. Using the multi-systemic fall prevention model, hospitals should promote a practical strategy that benefits from the collective effects of the physical environment, the care process and culture and technology to prevent falls and fall-related injuries. By doing so, they can more effectively address the various risk factors for falling and therefore, prevent falls. Studies that test the proposed model need to be conducted to establish the efficacy of the model in practice. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

Mitochondrial disorder caused Charles Darwin’s cyclic vomiting syndrome

PubMed Central

Finsterer, Josef; Hayman, John

2014-01-01

Background Charles Darwin (CD), “father of modern biology,” suffered from multisystem illness from early adulthood. The most disabling manifestation was cyclic vomiting syndrome (CVS). This study aims at finding the possible cause of CVS in CD. Methods A literature search using the PubMed database was carried out, and CD’s complaints, as reported in his personal writings and those of his relatives, friends, colleagues, biographers, were compared with various manifestations of mitochondrial disorders (MIDs), known to cause CVS, described in the literature. Results Organ tissues involved in CD’s disease were brain, nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral manifestations included episodic headache, visual disturbance, episodic memory loss, periodic paralysis, hysterical crying, panic attacks, and episodes of depression. Manifestations of polyneuropathy included numbness, paresthesias, increased sweating, temperature sensitivity, and arterial hypotension. Muscular manifestations included periods of exhaustion, easy fatigability, myalgia, and muscle twitching. Cardiac manifestations included episodes of palpitations and chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal seasickness, eructation, belching, and flatulence. Dermatological manifestations included painful lips, dermatitis, eczema, and facial edema. Treatments with beneficial effects to his complaints were rest, relaxation, heat, and hydrotherapy. Conclusion CVS in CD was most likely due to a multisystem, nonsyndromic MID. This diagnosis is based upon the multisystem nature of his disease, the fact that CVS is most frequently the manifestation of a MID, the family history, the variable phenotypic expression between affected family members, the fact that symptoms were triggered by stress, and that only few symptoms could not be explained by a MID. PMID:24453499

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

PubMed

Kis, Erika; Baltás, Eszter; Kinyó, Agnes; Varga, Erika; Nagy, Nikoletta; Gyulai, Rolland; Kemény, Lajos; Oláh, Judit

2012-11-01

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

Medulloblastoma in a toddler with Gorlin syndrome.

PubMed

Al-Rahawan, Mohamad G; Trevino, Sorleen; Jacob, Roy; Murray, Jeffrey C; Al-Rahawan, Mohamad M

2018-04-01

Gorlin syndrome (GS) is a rare hereditary multisystem disorder caused by mutations in PTCH1, PTCH2 , or SUFU . It is characterized by multiple anomalies and an increased risk of developing various tumors. Basal cell carcinoma is most common, and medulloblastoma (MB) is especially frequent in patients with SUFU mutations. MB treatment often includes radiation therapy in patients older than 3 years; however, such treatment is very toxic to patients with GS. Most reported cases of MB in patients with GS present after GS is diagnosed. We report a male toddler with multicentric posterior fossa tumor and calcifications along the falx cerebri, suggesting MB and GS. Pathology revealed nodular MB. His testing confirmed a germline SUFU mutation. His tumor resolved with three induction cycles of chemotherapy, but he died of respiratory failure due to infection at 20 months of age. Overlooking calcifications along the falx cerebri in children with MB can induce significant morbidity.

Celiac disease and non-celiac gluten sensitivity

PubMed Central

Lebwohl, Benjamin; Ludvigsson, Jonas F

2015-01-01

Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population. PMID:26438584

Critical appraisal of canakinumab in the treatment of adults and children with cryopyrin-associated periodic syndrome (CAPS)

PubMed Central

Toker, Ori; Hashkes, Philip J

2010-01-01

The cryopyrin-associated syndromes (CAPS) include three autosomal-dominant syndromes, that are caused by a mutation in the NLRP3 gene on chromosome 1, encoding the cryopyrin protein. These syndromes, familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multisystem inflammatory disease, are characterized by urticaria-like rash, fever, central nervous system inflammation, an arthropathy and a risk of the development of amyloidosis in a respectively escalating degree of severity between the various syndromes. Recently the role of cryopyrin in the regulation of interleukin (IL)-1 production and activation was described and anti IL-1 therapies were found to be very effective in treating these syndromes. There are several types of anti IL-1 medications based on different mechanisms of antagonizing IL-1. This paper focuses on the efficacy and safety of canakinumab, a long-acting humanized anti IL-1 antibody, in treating these syndromes. PMID:20531965

Cryopyrin-associated periodic syndromes and the eye.

PubMed

Oberg, Thomas J; Vitale, Albert T; Hoffman, Robert O; Bohnsack, John F; Warner, Judith E

2013-08-01

To describe the ophthalmologic findings in two patients with Muckle-Wells Syndrome, a phenotype of the Cryopyrin Associated Periodic Syndromes (CAPS) spectrum. There is currently sparse ophthalmic literature regarding the ocular manifestations of CAPS. We hope to increase awareness of this spectrum of diseases and the importance of proper treatment amongst eye care professionals. Interventional Case Series. Patient 1 experienced resolution of aseptic meningitis, papilledema, and anterior uveitis following treatment with anikinra. Patient 2 experienced resolution of panuveitis following treatment with anikinra. The severe ocular manifestations of the most severe CAPS phenotype, Chronic Infantile Neurological Cutaneous and Articular Syndrome/Neonatal Onset Multisystem Inflammatory Disease Syndrome (CINCA/NOMID) have been previously described. There is increasing evidence that patients may experience similar ocular disease with the milder phenotype of Muckle-Wells Sydnrome. There is also increasing evidence that appropriate therapy can have a profound effect on patient prognosis.

[HIV infection in France in 2012: reality, risks and challenges for a chronic multisystem disease].

PubMed

Blot, M; Piroth, L

2012-06-01

Thirty years after the discovery of HIV and 15 years since the advent of Highly Active Antiretroviral Therapy (HAART), the features of HIV infection have evolved and need a new approach, which is both more comprehensive and specialized. Indeed, the burden of a chronic disease with multiple determining features has replaced the rapidly fatal infection of the past, which was almost exclusively related to the effects of immunosuppression. Physicians have to be concerned with "new risks" associated with treatment side effects; the consequences of ongoing inflammation and ageing of the HIV-infected population. These include metabolic, cardiovascular, neurocognitive and renal disease as well as lipodystrophy and malignancy. Antiretroviral treatment has been a major step forward, subject to accessibility, tolerance and adherence, but it has not solved all the problems associated with this infection, as it becomes a chronic illness. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Mitochondrial disorders: Challenges in diagnosis & treatment

PubMed Central

Khan, Nahid Akhtar; Govindaraj, Periyasamy; Meena, Angamuthu Kannan; Thangaraj, Kumarasamy

2015-01-01

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment. PMID:25857492

ENT manifestations of alkaptonuria: report on a case series.

PubMed

Steven, R A; Kinshuck, A J; McCormick, M S; Ranganath, L R

2015-10-01

Alkaptonuria is an inborn error of metabolism. It is a multisystem disease with characteristic ENT manifestations. This paper reports, for the first time, the ENT findings in a cohort of alkaptonuria patients. Patients attending the National Centre for Alkaptonuria (Royal Liverpool and Broadgreen University Hospitals NHS Trust) underwent a full ENT assessment. Eighteen of the 20 patients (90 per cent) had an ENT sign or symptom. These included discolouration of the pinna, cerumen, nasal septum and pharynx. Discolouration of cerumen may occur before 30 years of age and may therefore be an important early clinical sign. Further audiological assessment of patients is needed to clarify if an association exists between alkaptonuria and hearing loss. Alkaptonuria is a condition that could present to the otolaryngologist. Successful early diagnosis and referral to a specialist centre is essential so that patients can be offered disease-modifying therapy.

Cerebral vein thrombosis in a four year old with Behçet's disease.

PubMed

Hacihamdioglu, Duygu Ovunc; Demiriz, Murat; Sobaci, Gungor; Kocaoglu, Murat; Demirkaya, Erkan; Gok, Faysal

2014-01-01

Behçet's disease (BD) is a multisystem disorder. The main pathology in BD is vasculitis that involves arteries and veins of all calibers. Central nervous system involvement occurs in 5-10% of patients. Increased morbidity and mortality is rarely observed in children. The mean age at onset in pediatric BD is approximately 7 years. Neurologic involvement in BD is usually observed after 3-6 years. We report the case of a four-year-old Turkish boy with BD with sagittal sinus thrombosis treated with infliximab. The patient presented papilledema without neurologic signs. Although long-term efficacy evaluations are needed in this case, infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis. This is the youngest case of BD with sagittal sinus thrombosis reported so far. Copyright © 2012 Elsevier España, S.L. All rights reserved.

A comprehensive team approach to the management of patients with Prader-Willi syndrome.

PubMed

Eiholzer, Urs; Whitman, Barbara Y

2004-09-01

Prader-Willi syndrome (PWS) is a genetic disorder characterized by extreme obesity accompanied by other, multisystem clinical manifestations encompassing both physical and behavioral/cognitive abnormalities. The multi-dimensional problems of patients with PWS cannot be treated with a single intervention and benefit from a team approach to management to optimize outcomes. Childhood stature below target height and reduced final height are some defining characteristics of PWS, and compelling evidence from growth hormone (GH) treatment trials suggests that hypothalamic GH deficiency exists. Treatment with GH has been shown to increase height velocity in children with PWS, decrease weight-for-height index values and body fat mass, and have a positive effect on lean body mass during at least the first year of therapy. In addition to medical concerns, the behavioral manifestations, including an uncorrectable deficit in appetite control, and cognitive limitations associated with PWS, require long-term multidisciplinary management.

Rat-bite fever in children: case report and review.

PubMed

Ojukwu, Ifeoma C; Christy, Cynthia

2002-01-01

We report 2 cases of rat-bite fever (RBF), a multisystem zoonosis, in children and review the literature. RBF is caused by I of 2 Gram-negative organisms: Streptobacillus moniliformis or, less commonly, Spirillum minus. Both of our cases developed in school-aged girls with a history of rat exposure who presented with a multisystem illness consisting of fever, petechial and purpuric rash, arthralgia and polyarthritis. Both responded promptly to antibiotic treatment. An additional 10 cases from a MEDLINE review (1960-2000) are reviewed. RBF must be included in the differential diagnosis of febrile patients with rashes and a history of exposure to rats.

Treatment of juvenile xanthogranuloma.

PubMed

Stover, Daniel G; Alapati, Srilatha; Regueira, Osvaldo; Turner, Curtis; Whitlock, James A

2008-07-01

Juvenile xanthogranuloma (JXG) is generally a benign, self-limited histiocytic disorder of the skin. We report two cases of multisystem JXG presenting with clinical features more commonly seen in Langerhans cell histiocytosis (LCH), including diabetes insipidus and lytic bony lesions. Histologically, the skin lesions demonstrated a histiocytic dermal infiltrate that stained for CD-68, but S-100 and CD1a stains were negative. Treatment according to LCH-based chemotherapy regimens resulted in prompt resolution of symptoms. A literature review of multisystem JXG cases treated with chemotherapy suggests that symptomatic patients can successfully be treated with LCH-based regimens that include both corticosteroids and vinca alkaloids. (c) 2008 Wiley-Liss, Inc.

Envisioning an America Without Sexual Orientation Inequities in Adolescent Health

PubMed Central

Birkett, Michelle; Greene, George J.; Hatzenbuehler, Mark L.; Newcomb, Michael E.

2014-01-01

This article explicates a vision for social change throughout multiple levels of society necessary to eliminate sexual orientation health disparities in youths. We utilized the framework of Bronfenbrenner’s ecological theory of development, a multisystemic model of development that considers direct and indirect influences of multiple levels of the environment. Within this multisystem model we discuss societal and political influences, educational systems, neighborhoods and communities, romantic relationships, families, and individuals. We stress that continued change toward equity in the treatment of lesbian, gay, and bisexual youths across these levels will break down the barriers for these youths to achieve healthy development on par with their heterosexual peers. PMID:24328618

Nursing Integration and Innovation Across a Multisystem Enterprise: Priorities for Nurse Leaders.

PubMed

Pappas, Sharon; McCauley, Linda

There is no escaping the fact that the ability to skillfully influence change is a requirement for nurse leaders. This need is intensified as the national health care system reforms and as the morphology of health care systems continues to change, especially in academic health care systems. The purpose of this article was 2-fold. The first objective was to relay the experience of the integration of nursing practice, education, and research within an academic health care system. The second was to, through this story of integration, expose the uniqueness and importance of nurse leader roles influencing innovation across a multisystem enterprise to fulfill the organization's mission.

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

PubMed

Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

2016-12-01

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

PubMed Central

Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

2009-01-01

In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

PubMed Central

Tortarolo, Massimo; Lo Coco, Daniele; Veglianese, Pietro; Vallarola, Antonio; Giordana, Maria Teresa; Marcon, Gabriella; Beghi, Ettore; Poloni, Marco; Strong, Michael J.; Iyer, Anand M.; Aronica, Eleonora

2017-01-01

Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFα levels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFα toxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg) whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFα is considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFα in ALS in the light of its multisystem nature. PMID:29081600

Pressure for drug development in lysosomal storage disorders - a quantitative analysis thirty years beyond the US orphan drug act.

PubMed

Mechler, Konstantin; Mountford, William K; Hoffmann, Georg F; Ries, Markus

2015-04-18

Lysosomal storage disorders are a heterogeneous group of approximately 50 monogenically inherited orphan conditions. A defect leads to the storage of complex molecules in the lysosome, and patients develop a complex multisystemic phenotype of high morbidity often associated with premature death. More than 30 years ago the Orphan Drug Act of 1983 passed the United States legislation intended to facilitate the development of drugs for rare disorders. We directed our efforts in assessing which lysosomal diseases had drug development pressure and what distinguished those with successful development and approvals from diseases not treated or without orphan drug designation. Analysis of the FDA database for orphan drug designations through descriptive and comparative statistics. Between 1983 and 2013, fourteen drugs for seven conditions received FDA approval. Overall, orphan drug status was designated 70 times for 20 conditions. Approved therapies were enzyme replacement therapies (N = 10), substrate reduction therapies (N = 1), small molecules facilitating lysosomal substrate transportation (N = 3). FDA approval was significantly associated with a disease prevalence higher than 0.5/100,000 (p = 0.00742) and clinical development programs that did not require a primary neurological endpoint (p = 0.00059). Orphan drug status was designated for enzymes, modified enzymes, fusion proteins, chemical chaperones, small molecules leading to substrate reduction, or facilitating subcellular substrate transport, stem cells as well as gene therapies. Drug development focused on more common diseases. Primarily neurological diseases were neglected. Small clinical trials with either somatic or biomarker endpoints were successful. Enzyme replacement therapy was the most successful technology. Four factors played a key role in successful orphan drug development or orphan drug designations: 1) prevalence of disease 2) endpoints 3) regulatory precedent, and 4) technology platform. Successful development seeded further innovation.

Examining Therapist Comfort in Delivering Family Therapy in Home and Community Settings: Development and Evaluation of the Therapist Comfort Scale

PubMed Central

Glebova, Tatiana; Foster, Sharon L.; Cunningham, Phillippe B.; Brennan, Patricia A.; Whitmore, Elizabeth

2015-01-01

This study reports on the development and psychometric properties of a new measure assessing therapist comfort in the home treatment context, and the relationship between therapist comfort, related process variables, and therapist characteristics. Data were drawn from a longitudinal evaluation of 185 families treated by 51 therapists using Multisystemic Therapy (MST). Therapist comfort was measured at four time points. Psychometric evaluation indicated that the measure was internally and temporally consistent. Examination of the measure’s validity indicated that therapists’ feelings of safety and comfort during the provision of home-based treatment were associated with family neighborhood characteristics and family socioeconomic factors. Furthermore, the therapist’s reported level of alliance (as measured by the Emotional Bonding subscale of the Working Alliance Inventory) was related to her/his feeling of comfort. Analyses also indicated that therapists with greater belief in the clinical utility of the MST model felt more comfortable when delivering MST. Together the results suggest that economically disadvantaged families treated in home and community settings may be most at risk for erosions in the therapeutic relationship over time as a function of lower therapist comfort. Because therapist comfort was associated with therapeutic alliance - a factor found to be associated with clinical outcomes across studies and treatment models - findings imply that psychotherapists should regularly examine their own level of comfort, especially when providing services in non-traditional settings, and that therapist comfort should be routinely assessed as part of clinical supervision and training. PMID:22181024

Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease

PubMed Central

Doerfler, Phillip A.; Todd, Adrian G.; Clément, Nathalie; Falk, Darin J.; Nayak, Sushrusha; Herzog, Roland W.; Byrne, Barry J.

2016-01-01

Pompe disease is a progressive neuromuscular disorder caused by lysosomal accumulation of glycogen from a deficiency in acid alpha-glucosidase (GAA). Replacement of the missing enzyme is available by repeated protein infusions; however, efficacy is limited by immune response and inability to restore enzymatic function in the central nervous system. An alternative therapeutic option is adeno-associated virus (AAV)-mediated gene therapy, which results in widespread gene transfer and prolonged transgene expression. Both enzyme replacement therapy (ERT) and gene therapy can elicit anti-GAA immune reactions that dampen their effectiveness and pose life-threatening risks to patient safety. To modulate the immune responses related to gene therapy, we show that a human codon-optimized GAA (coGAA) driven by a liver-specific promoter (LSP) using AAV9 is capable of promoting immune tolerance in a Gaa−/− mouse model. Copackaging AAV9-LSP-coGAA with the tissue-restricted desmin promoter (AAV9-DES-coGAA) demonstrates the necessary cell autonomous expression in cardiac muscle, skeletal muscle, peripheral nerve, and the spinal cord. Simultaneous high-level expression in liver led to the expansion of GAA-specific regulatory T-cells (Tregs) and induction of immune tolerance. Transfer of Tregs into naïve recipients prevented pathogenic allergic reactions after repeated ERT challenges. Copackaged AAV9 also attenuated preexisting humoral and cellular immune responses, which enhanced the biochemical correction. Our data present a therapeutic design in which simultaneous administration of two copackaged AAV constructs may provide therapeutic benefit and resolve immune reactions in the treatment of multisystem disorders. PMID:26603344

Assessing the Benefit-Risk Profile for Pediatric Implantable Auditory Prostheses.

PubMed

Fisher, Laurel M; Martinez, Amy S; Richmond, Frances J; Krieger, Mark D; Wilkinson, Eric P; Eisenberg, Laurie S

2017-01-01

Children with congenital cochleovestibular abnormalities associated with profound hearing loss have few treatment options if cochlear implantation does not yield benefit. An alternative is the auditory brainstem implant (ABI). Regulatory authority device approvals currently include a structured benefit-risk assessment. Such an assessment, for regulatory purposes or to guide clinical decision making, has not been published, to our knowledge, for the ABI and may lead to the design of a research program that incorporates regulatory authority, family, and professional input. Much structured benefit-risk research has been conducted in the context of drug trials; here we apply this approach to device studies. A qualitative framework organized benefit (speech recognition, parent self-report measures) and risk (surgery- and device-related) information to guide the selection of candidates thought to have potential benefit from ABI. Children with cochleovestibular anatomical abnormalities are challenging for appropriate assessment of candidacy for a cochlear implant or an ABI. While the research is still preliminary, children with an ABI appear to slowly obtain benefit over time. A team of professionals, including audiological, occupational, and educational therapy, affords maximum opportunity for benefit. Pediatric patients who have abnormal anatomy and are candidates for an implantable auditory prosthetic require an individualized, multisystems review. The qualitative benefit-risk assessment used here to characterize the condition, the medical need, potential benefits, risks, and risk management strategies has revealed the complex factors involved. After implantation, continued team support for the family during extensive postimplant therapy is needed to develop maximum auditory skill benefit.

Closing the Gap: Principal Perspectives on an Innovative School-Based Mental Health Intervention

ERIC Educational Resources Information Center

Blackman, Kate F.; Powers, Joelle D.; Edwards, Jeffrey D.; Wegmann, Kate M.; Lechner, Ethan; Swick, Danielle C.

2016-01-01

Mental health needs among children in the United States have significant consequences for children and their families, as well as the schools that serve them. This qualitative study evaluated the second year of an innovative school-based mental health project that created a multi-system partnership between an urban school district, a public mental…

Improving Academic Achievement of Students with Problematic Attendance by Implementing a Multisystemic School-Based Model

ERIC Educational Resources Information Center

Kay, James Edward

2010-01-01

This study addressed the problem of poor attendance adversely affecting grades and learning. Current school policies do not address problematic attendance for all school-aged children, perpetuating trends of academic failure. The research objective was to determine if unexcused absences had a greater negative impact on a high-stakes test compared…

[Juvenile xanthogranuloma: 3 cases report and literature review].

PubMed

Liu, Zi-qin; Liu, Rong; Shi, Xiao-dong; Li, Jing-xian; Zou, Ji-zhen

2011-09-01

To report the clinical characteristics and treatment of 3 patients with juvenile xanthogranuloma (JXG). A retrospective review of the medical records of 3 patients with JXG. JXG was characterized by solitary or multiple yellowish cutaneous nodules, or eye involvement . It could also affect pituitary. JXG was easily misdiagnosed as Langerhans cell histiocytosis (LCH). Treatment for JXG was surgical excision of a solitary skin lesion and some cases might be, spontaneous regression. In cases with multisystem involvement, chemotherapy regimens used to treat LCH may be effective. JXG is one of the more common non-Langerhans histiocytic proliferations and is frequently seen in infants and children. LCH-like chemotherapy is effective for patients with symptomatic multisystem JXG.

The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study.

PubMed

Scheper, Mark C; Nicholson, Lesley L; Adams, Roger D; Tofts, Louise; Pacey, Verity

2017-12-01

The objective of the manuscript was to describe the natural history of complaints and disability in children diagnosed with joint hypermobility syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT) and to identify the constructs that underlie functional decline. One hundred and one JHS/EDS-HT children were observed over 3 years and assessed at three time points on the following: functional impairments, quality of life, connective tissue laxity, muscle function, postural control and musculoskeletal and multi-systemic complaints. Cluster analysis was performed to identify subgroups in severity. Clinical profiles were determined for these subgroups, and differences were assessed by multivariate analysis of covariance. Mixed linear regression models were used to determine the subsequent trajectories. Finally, an exploratory factor analysis was used to uncover the underlying constructs of functional impairment. Three clusters of children were identified in terms of functional impairment: mild, moderately and severely affected. Functional impairment at baseline was predictive of worsening trajectories in terms of reduced walking distance and decreased quality of life (P ⩽ 0.05) over 3 years. Multiple interactions between the secondary outcomes were observed, with four underlying constructs identified. All four constructs (multi-systemic effects, pain, fatigue and loss of postural control) contributed significantly to disability (P ⩽ 0.046). Children diagnosed with JHS/EDS-HT who have a high incidence of multi-systemic complaints (particularly, orthostatic intolerance, urinary incontinence and diarrhoea) and poor postural control in addition to high levels of pain and fatigue at baseline are most likely to have a deteriorating trajectory of functional impairment and, accordingly, warrant clinical prioritization. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Artificial Gravity as a Multi-System Countermeasure for Exploration Class Space Flight Missions

NASA Technical Reports Server (NTRS)

Paloski, William H.; Dawson, David L. (Technical Monitor)

2000-01-01

NASA's vision for space exploration includes missions of unprecedented distance and duration. However, during 30 years of human space flight experience, including numerous long-duration missions, research has not produced any single countermeasure or combination of countermeasures that is completely effective. Current countermeasures do not fully protect crews in low-Earth orbit, and certainly will not be appropriate for crews journeying to Mars and back over a three-year period. The urgency for exploration-class countermeasures is compounded by continued technical and scientific successes that make exploration class missions increasingly attractive. The critical and possibly fatal problems of bone loss, cardiovascular deconditioning, muscle weakening, neurovestibular disturbance, space anemia, and immune compromise may be alleviated by the appropriate application of artificial gravity (AG). However, despite a manifest need for new countermeasure approaches, concepts for applying AG as a countermeasure have not developed apace. To explore the utility of AG as a multi-system countermeasure during long-duration, exploration-class space flight, eighty-three members of the international space life science and space flight community met earlier this year. They concluded unanimously that the potential of AG as a multi-system countermeasure is indeed worth pursuing, and that the requisite AG research needs to be supported more systematically by NASA. This presentation will review the issues discussed and recommendations made.

Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases.

PubMed

Afrin, Lawrence B; Pöhlau, Dieter; Raithel, Martin; Haenisch, Britta; Dumoulin, Franz L; Homann, Juergen; Mauer, Uwe M; Harzer, Sabrina; Molderings, Gerhard J

2015-11-01

Neurologists and psychiatrists frequently encounter patients whose central and/or peripheral neurologic and/or psychiatric symptoms (NPS) are accompanied by other symptoms for which investigation finds no unifying cause and for which empiric therapy often provides little to no benefit. Systemic mast cell activation disease (MCAD) has rarely been considered in the differential diagnosis in such situations. Traditionally, MCAD has been considered as just one rare (neoplastic) disease, mastocytosis, generally focusing on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, MC activation syndrome (MC), has been recognized, featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. There also has developed greater appreciation for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic themes--including very wide arrays of central and peripheral NPS. Significantly helpful treatment--including for neuropsychiatric issues--usually can be identified once MCAD is accurately diagnosed. We describe MCAD's pathogenesis, presentation (focusing on NPS), and therapy, especially vis-à-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

[Corticosteroid therapy in Henoch-Schönlein gastritis].

PubMed

Pavlović, Momcilo; Radlović, Nedeljko; Leković, Zoran; Berenji, Karolina; Novak, Arpad

2007-01-01

Henoch-Schönlein purpura (HSP) is the most common vascular disease of childhood. It is a multisystem disease most commonly affecting the skin,joints, gastrointestinal tract, and kidneys, but other organs may be affected, too. Gastrointestinal involvement occurs in approximately 65-90% of patients, ranging from mild symptoms such as abdominal pain, nausea, and vomiting, to more severe manifestations such as gastrointestinal bleeding and intussusception. In most cases, HSP spontaneously resolves without treatment. The use of corticosteroids is controversial and usually reserved for severe systemic manifestations. Some authors suggest that the abdominal pain and gastrointestinal hemorrhage of HSP may respond to steroids, with some suggesting that there is a benefit in their use and describing a regimen. This is a case report of HSP in a fourteen-year-old boy with abdominal pain and hematemesis. Upper endoscopy showed an edematous and erythematous change in the body of the stomach and purpuric lesions in the duodenum, while multiple erosions were found in the antral area. Parenteral corticosteroid therapy with gastric acid secretion inhibitor administration led to regression of gastrointestinal symptoms on the seventh day, with relapses on the fourth and sixth day. Peroral administration of corticosteroids and gradual decrease of daily doses started on the eighth day of abdominal symptoms. New purpuric skin rashes appeared during six weeks. Corticosteroid therapy with gastric acid secretion inhibitors showed a positive effect in our patient with a severe form of HSP accompanied by abdominal pain and gastrointestinal hemorrhage.

Neuroimaging to Investigate Multisystem Involvement and Provide Biomarkers in Amyotrophic Lateral Sclerosis

PubMed Central

Pradat, Pierre-François; El Mendili, Mohamed-Mounir

2014-01-01

Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS). Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS. PMID:24949452

Evaluation and management of esophageal manifestations in systemic sclerosis.

PubMed

Denaxas, Konstantinos; Ladas, Spyros D; Karamanolis, George P

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

Evaluation and management of esophageal manifestations in systemic sclerosis

PubMed Central

Denaxas, Konstantinos; Ladas, Spyros D.; Karamanolis, George P.

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities. PMID:29507463

Recurrent symptomatic ischemic stroke in a 46-year-old African male revealing Angio-Behçet with severe cardiovascular involvement.

PubMed

Marie, Ba Djibril; Aminata, Diack; Cherif, Mboup Mouhamed; Daouda, Fall Moussa

2017-03-01

Behçet'sdisease (BD) is a chronic, multisystem vasculitis. It is categorized under variable vessel vasculitis in the new Chapel Hill nomenclature as it involves blood vessels of any type and size. It is characterized by relapsing aphthous ulcers commonly occurring in the oral mucosa and genitalia with ocular involvement. Other organ systems may be involved any time throughout the course of the disease. The exact cause is unknown. However, combination of genetic and environmental factors is likely to play a role. Cardiac involvement may occur in the form of intracardiac thrombus, endocarditis, myocarditis, pericarditis, endomyocardial fibrosis, coronary arteritis, myocardial infarction, and valvular disease. We present a case of Angio-Behçet in a 46-year-old African male with severe cardiovascular involvement including pulmonary artery hypertension (PAH), right ventricular failure and left ventricular diastolic dysfunction diagnosed after 2 episodes of symptomatic ischemic stroke resulting from complete occlusion of the right internal carotid artery (ICA) up to its intracranial portion. Immunosuppressive and anticoagulant therapies have induced improvement in cardiac manifestations. Nevertheless, prompt recognition of the primarily vascular manifestation of BD without mucocutaneous manifestations was responsible for considerable delay that did not afford surgical therapy for the carotid occlusion.

The family empowerment program: an interdisciplinary approach to working with multi-stressed urban families.

PubMed

Cleek, Elizabeth N; Wofsy, Matt; Boyd-Franklin, Nancy; Mundy, Brian; Howell Lcsw, Tamika J

2012-06-01

The family empowerment program (FEP) is a multi-systemic family therapy program that partners multi-stressed families with an interdisciplinary resource team while remaining attached to a "traditional" mental health clinic. The rationale for this model is that far too often, families presenting at community mental health centers struggle with multiple psychosocial forces, for example problems with housing, domestic violence, child care, entitlements, racism, substance abuse, and foster care, as well as chronic medical and psychiatric illnesses, that exacerbate symptoms and impact traditional service delivery and access to effective treatment. Thus, families often experience fragmented care and are involved with multiple systems with contradictory and competing agendas. As a result, services frequently fail to harness the family's inherent strengths. The FEP partners the family with a unified team that includes representatives from Entitlements Services, Family Support and Parent Advocacy, and Clinical Staff from the agency's Outpatient Mental Health Clinic practicing from a strength-based family therapy perspective. The goal of the FEP is to support the family in achieving their goals. This is accomplished through co-construction of a service plan that addresses the family's needs in an efficient and coherent manner-emphasizing family strengths and competencies and supporting family self-sufficiency. © FPI, Inc.

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

PubMed

Picker-Minh, Sylvie; Mignot, Cyril; Doummar, Diane; Hashem, Mais; Faqeih, Eissa; Josset, Patrice; Dubern, Béatrice; Alkuraya, Fowzan S; Kraemer, Nadine; Kaindl, Angela M

2016-04-29

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

Cohesin and Human Disease

PubMed Central

Liu, Jinglan; Krantz, Ian D.

2016-01-01

Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases. PMID:18767966

Developmental origins of infant stress reactivity profiles: A multi-system approach.

PubMed

Rash, Joshua A; Thomas, Jenna C; Campbell, Tavis S; Letourneau, Nicole; Granger, Douglas A; Giesbrecht, Gerald F

2016-07-01

This study tested the hypothesis that maternal physiological and psychological variables during pregnancy discriminate between theoretically informed infant stress reactivity profiles. The sample comprised 254 women and their infants. Maternal mood, salivary cortisol, respiratory sinus arrhythmia (RSA), and salivary α-amylase (sAA) were assessed at 15 and 32 weeks gestational age. Infant salivary cortisol, RSA, and sAA reactivity were assessed in response to a structured laboratory frustration task at 6 months of age. Infant responses were used to classify them into stress reactivity profiles using three different classification schemes: hypothalamic-pituitary-adrenal (HPA)-axis, autonomic, and multi-system. Discriminant function analyses evaluated the prenatal variables that best discriminated infant reactivity profiles within each classification scheme. Maternal stress biomarkers, along with self-reported psychological distress during pregnancy, discriminated between infant stress reactivity profiles. These results suggest that maternal psychological and physiological states during pregnancy have broad effects on the development of the infant stress response systems. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 578-599, 2016. © 2016 Wiley Periodicals, Inc.

Acute lower gastrointestinal bleeding.

PubMed

Jocić, Tatiana; Latinović Bošnjak, Olgica; Hadnađev, Ljiljana; Damjanov, Dragomir; Savić, Željka; Orlić, Tihomir

2014-01-01

Acute lower gastrointestinal bleeding accounts for approximately 20% of all acute gastrointestinal hemorrhages, and they are the most common urgent cases in gastroenterology. The aim of this study was to determine the most common etiology, efficacy in diagnostics and therapy, and the outcome in patients with acute lower gastrointestinal bleeding. Data were collected from the medical records of 86 patients who had been hospitalized for acute lower gastrointestinal bleeding in 2009 at the Ward of Gastroenterology and Hepatology, Clinical Centre of Vojvodina. The average age of the patients was 70.4 years (ranging from 37 to 88), and the largest number of patients 41/86 (47.7%) were between the ages 71 and 80. Colon diverticulosis was the most common cause of bleeding, and it occurred in 21 patients from the study sample (24.4%), and the other causes were malignant tumors (12/86, i.e. 13.9%), polyps (10/86, i.e. 11.6%), anorectal diseases (7/86, i.e. 8.3%/0) and colitis (8/86, i.e. 9.3%). No diagnostic procedures were performed in 15 patients (17.4%) due to their poor medical condition and comorbidities. The total mortality rate was 6/86 (6.9%), and the largest number of deaths occurred (5/86 i.e. 5.8%) due to a multisystem organ failure and underlying diseases which were not associated with acute lower gastrointestinal bleeding. Uncontrolled bleeding was the cause of death in only 1 patient (1.2%). Acute lower gastrointestinal bleeding is most commonly found in the older population, whose age, comorbidities, and ongoing therapy have impact on bleeding lesions, diagnostic and therapeutic modalities and the outcomes of bleeding. Endoscopic procedures are still the gold standard in diagnostics.

Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

PubMed

Arbour, Richard B

2013-01-01

Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological criteria. These processes begin far earlier in the continuum of injury, at the moment of terminal brain stem herniation. As such, aggressive, mechanism-based care, including hormonal replacement therapy, becomes clinically appropriate before formal brain death declaration to support cardiopulmonary stability following terminal brain stem herniation.

Update on critical care for acute spinal cord injury in the setting of polytrauma.

PubMed

Yue, John K; Winkler, Ethan A; Rick, Jonathan W; Deng, Hansen; Partow, Carlene P; Upadhyayula, Pavan S; Birk, Harjus S; Chan, Andrew K; Dhall, Sanjay S

2017-11-01

Traumatic spinal cord injury (SCI) often occurs in patients with concurrent traumatic injuries in other body systems. These patients with polytrauma pose unique challenges to clinicians. The current review evaluates existing guidelines and updates the evidence for prehospital transport, immobilization, initial resuscitation, critical care, hemodynamic stability, diagnostic imaging, surgical techniques, and timing appropriate for the patient with SCI who has multisystem trauma. Initial management should be systematic, with focus on spinal immobilization, timely transport, and optimizing perfusion to the spinal cord. There is general evidence for the maintenance of mean arterial pressure of > 85 mm Hg during immediate and acute care to optimize neurological outcome; however, the selection of vasopressor type and duration should be judicious, with considerations for level of injury and risks of increased cardiogenic complications in the elderly. Level II recommendations exist for early decompression, and additional time points of neurological assessment within the first 24 hours and during acute care are warranted to determine the temporality of benefits attributable to early surgery. Venous thromboembolism prophylaxis using low-molecular-weight heparin is recommended by current guidelines for SCI. For these patients, titration of tidal volumes is important to balance the association of earlier weaning off the ventilator, with its risk of atelectasis, against the risk for lung damage from mechanical overinflation that can occur with prolonged ventilation. Careful evaluation of infection risk is a priority following multisystem trauma for patients with relative immunosuppression or compromise. Although patients with polytrauma may experience longer rehabilitation courses, long-term neurological recovery is generally comparable to that in patients with isolated SCI after controlling for demographics. Bowel and bladder disorders are common following SCI, significantly reduce quality of life, and constitute a focus of targeted therapies. Emerging biomarkers including glial fibrillary acidic protein, S100β, and microRNAs for traumatic SCIs are presented. Systematic management approaches to minimize sources of secondary injury are discussed, and areas requiring further research, implementation, and validation are identified.

Spotlight on agalsidase beta in Fabry disease.

PubMed

Keating, Gillian M; Simpson, Dene

2007-01-01

Agalsidase beta (Fabrazyme) is a recombinant human alpha-galactosidase A enzyme approved for intravenous use in the treatment of Fabry disease. Fabry disease is a progressive, multisystemic, potentially life-threatening disorder caused by a deficiency of alpha-galactosidase A. This deficiency results in accumulation of glycosphingolipids, particularly globotriaosylceramide (GL-3), in the lysosomes of various tissues. This accumulation is the underlying driver of disease progression. Agalsidase beta provides an exogenous source of alpha-galactosidase A. Intravenous agalsidase beta is effective and well tolerated in patients with Fabry disease. In a phase III trial, agalsidase beta was shown to clear GL-3 from various target cells and, in a subsequent extension of this trial, prevent GL-3 reaccumulation. In a post-approval trial, agalsidase beta was shown to provide significant clinical benefit by reducing the risk of a major clinical event. Thus, agalsidase beta represents an important advance in the treatment of Fabry disease, and agalsidase beta therapy should be strongly considered in patients with Fabry disease who are suitable candidates.

Agalsidase Beta: a review of its use in the management of Fabry disease.

PubMed

Keating, Gillian M; Simpson, Dene

2007-01-01

Agalsidase beta (Fabrazyme) is a recombinant human alpha-galactosidase A enzyme approved for intravenous use in the treatment of Fabry disease. Fabry disease is a progressive, multisystemic, potentially life threatening disorder caused by a deficiency of alpha-galactosidase A. This deficiency results in accumulation of glycosphingolipids, particularly globotriaosylceramide (GL-3), in the lysosomes of various tissues. This accumulation is the underlying driver of disease progression. Agalsidase beta provides an exogenous source of alpha-galactosidase A.Intravenous agalsidase beta is effective and well tolerated in patients with Fabry disease. In a phase III trial, agalsidase beta was shown to clear GL-3 from various target cells and, in a subsequent extension of this trial, prevent GL-3 reaccumulation. In a post-approval trial, agalsidase beta was shown to provide significant clinical benefit by reducing the risk of a major clinical event. Thus, agalsidase beta represents an important advance in the treatment of Fabry disease, and agalsidase beta therapy should be strongly considered in patients with Fabry disease who are suitable candidates.

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report

PubMed Central

PAPA, ANDREA ANTONIO; RAGO, ANNA; PETILLO, ROBERTA; D’AMBROSIO, PAOLA; SCUTIFERO, MARIANNA; FEO, MARISA DE; MAIELLO, CIRO; PALLADINO, ALBERTO

2017-01-01

Steinert’s disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

New directions for patient-centred care in scleroderma: the Scleroderma Patient-centred Intervention Network (SPIN)

PubMed Central

Thombs, Brett D.; Jewett, Lisa R.; Assassi, Shervin; Baron, Murray; Bartlett, Susan J.; Costa Maia, Angela; El-Baalbaki, Ghassan; Furst, Daniel E.; Gottesman, Karen; Haythornthwaite, Jennifer A.; Hudson, Marie; Ann Impens, PhD; Korner, Annett; Leite, Catarina; Mayes, Maureen D.; Malcarne, Vanessa L.; Motivala, Sarosh J.; Mouthon, Luc; Nielson, Warren R.; Plante, Diane; Poiraudeau, Serge; Poole, Janet L.; Pope, Janet; Sauve, Maureen; Steele, Russell J.; Suarez-Almazor, Maria E.; Taillefer, Suzanne; van den Ende, Cornelia H.; Erin Arthurs, BSc; Bassel, Marielle; Delisle, Vanessa; Milette, Katherine; Leavens, Allison; Razykov, Ilya; Khanna, Dinesh

2014-01-01

Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc. PMID:22244687

Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

PubMed

Di Siena, Sara; Campolo, Federica; Gimmelli, Roberto; Di Pietro, Chiara; Marazziti, Daniela; Dolci, Susanna; Lenzi, Andrea; Nussenzweig, Andre; Pellegrini, Manuela

2018-02-22

Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease.

Neurosarcoidosis associated with intracerebral haemorrhage: a challenge in diagnosis and management.

PubMed

Maskery, Mark Peter; Cooper, Paul N; Pace, Adrian

2018-06-01

Sarcoidosis is an idiopathic multisystem granulomatous disorder of unknown cause. Nervous system involvement (central and/or peripheral) is uncommon, developing in 5%-10%. The presenting symptoms are variable, reflecting the level of involvement, and frequently fluctuate and progress. Diagnosing neurosarcoidosis in people with previously confirmed systemic disease may be relatively straightforward, but diagnosing primary neurosarcoidosis is challenging. Managing neurosarcoidosis is primarily consensus based; corticosteroid is its mainstay, alongside corticosteroid-sparing agents and emerging novel therapies. We describe a 39-year-old woman who presented with cranial neuropathy. Serial imaging, cerebrospinal fluid sampling and tissue biopsy gave a diagnosis of probable neurosarcoidosis. Her clinical course was complicated by intracerebral haemorrhage following intravenous corticosteroids for neurological relapse. This is a very rare complication of neurosarcoidosis; we discuss its possible causes and suggest ways to reduce its risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation.

PubMed

Chuquilin, Miguel; Govindarajan, Raghav; Peck, Dawn; Font-Montgomery, Esperanza

2016-09-01

Leigh syndrome is a mitochondrial disease caused by mutations in different genes, including ATP6A for which no known therapy is available. We report a case of adult-onset Leigh syndrome with response to immunotherapy. A twenty year-old woman with baseline learning difficulties was admitted with progressive behavioral changes, diplopia, headaches, bladder incontinence, and incoordination. Brain MRI and PET scan showed T2 hyperintensity and increased uptake in bilateral basal ganglia, respectively. Autoimmune encephalitis was suspected and she received plasmapheresis with clinical improvement. She was readmitted 4 weeks later with dysphagia and aspiration pneumonia. Plasmapheresis was repeated with resolution of her symptoms. Given the multisystem involvement and suggestive MRI changes, genetic testing was done, revealing a homoplasmic T9176C ATPase 6 gene mtDNA mutation. Monthly IVIG provided clinical improvement with worsening when infusions were delayed. Leigh syndrome secondary to mtDNA T9176C mutations could have an autoimmune mechanism that responds to immunotherapy.

Management of a rare presentation of Vogt-Koyanagi-Harada disease in human immunodeficiency virus/acquired immunodeficiency disease syndrome patient.

PubMed

Priya, D; Sudharshan, S; Biswas, Jyotirmay

2017-05-01

Vogt-Koyanagi-Harada (VKH), a multisystem autoimmune bilateral panuveitis with systemic manifestations, is uncommon in immunocompromised patients such as human immunodeficiency virus (HIV)/acquired immunodeficiency disease syndrome (AIDS). We report a rare presentation of VKH in a 45-year-old HIV-positive female on highly active antiretroviral therapy (HAART) who presented with a history of recurrent panuveitis. A diagnosis of probable VKH was made based on ocular and systemic signs and symptoms. She was treated with topical and systemic steroids with close monitoring of CD4 counts and viral loads. After inflammation control, complicated cataract was managed surgically under perioperative steroid cover. VKH in HIV/AIDS has not been reported earlier. This case shows that significant inflammation can be seen even in HIV/AIDS patients on HAART with VKH in spite of moderate CD4 counts. Management is a challenge considering the systemic risks with long-term use of steroids.

Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy.

PubMed

Yogasundaram, Haran; Kim, Daniel; Oudit, Omar; Thompson, Richard B; Weidemann, Frank; Oudit, Gavin Y

2017-07-01

Anderson-Fabry disease (AFD) is an X-linked recessive, multisystem disease of lysosomal storage. A mutation in the gene encoding the hydrolase enzyme α-galactosidase A results in its deficiency, or complete absence of activity. Subsequent progressive intracellular accumulation of glycosphingolipids, predominantly globotriaosylceramide, in various tissues, results in progressive organ dysfunction and failure, most commonly affecting the kidneys, nervous system, skin, eyes, vascular endothelium, and the heart. Cardiac involvement in AFD represents a leading cause of morbidity and mortality. Globotriaosylceramide accumulation affects cardiomyocytes, smooth muscle cells, vascular endothelial cells, and fibroblasts leading to various pathologies including valvular regurgitation, conduction disease and arrhythmias, coronary microvascular dysfunction, and right and left ventricular hypertrophy (LVH) leading to early diastolic dysfunction and late-stage systolic impairment. Diagnosis is on the basis of decreased plasma α-galactosidase activity in men and positive genetic testing in women. Contemporary large-scale screening studies have revealed a prevalence of 1%-5% in patients with unexplained LVH in multiple cohorts. Cardiac magnetic resonance imaging, with its unique tissue characterization capabilities, is the most important imaging modality to assess for cardiomyopathy in patients with AFD. Enzyme replacement therapy is indicated in AFD patients with significant organ involvement, and has been shown to clear sphingolipids from endothelial cells in other organs, as well as to reduce left ventricular mass as early as 6 months after starting treatment. There is increasing evidence that enzyme replacement therapy might be more effective if given at earlier stages of disease, before the development of LVH and myocardial fibrosis. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Histologic patterns of thymic involvement in Langerhans cell proliferations: a clinicopathologic study and review of the literature.

PubMed

Picarsic, Jennifer; Egeler, R Maarten; Chikwava, Kudakwashe; Patterson, Kathleen; Jaffe, Ronald

2015-01-01

Thymic involvement by Langerhans cell histiocytosis (LCH) has been described mainly in isolated case reports. A description of the histopathologic patterns of LCH proliferations in the thymus, together with therapeutic implications, has not, to our knowledge, been previously addressed. The pathology consultation files at Children's Hospital of Pittsburgh of the University of Pennsylvania Medical Center were reviewed for cases of thymic involvement by LCH. Relevant cases in the literature were also reviewed, and the histopathology and clinical course of those cases were collected. Nine consultation cases of thymic involvement were reviewed, together with 23 cases in the literature, which provided adequate pathologic description and ancillary confirmation (n  =  32), revealing 4 distinct pathologic groups. Group 1 showed microscopic collection of hyperplastic LCH-like cells in incidental thymectomies of patients without LCH disease, requiring no further treatment (n  =  7; 22%). Group 2 showed solitary and/or cystic LCH of the thymus with gland disruption, and at least 3 cases resolved without systemic therapy (n  =  10; 31%). Group 3 showed more variable thymic involvement in multisystemic LCH disease, with either a medullary restricted pattern or more diffuse gland involvement, requiring adjuvant therapy and having a higher mortality rate (n  =  13; 41%). Group 4 showed a mixed histiocytic lesion with a concurrent LCH and juvenile xanthogranuloma-like proliferation (n  =  2; 6%). Thymic involvement in LCH is quite rare. Based on our cases and those in the literature, we propose 4 distinct pathologic groups of thymic involvement in Langerhans cell proliferations with relevance for diagnosis and treatment.

A new mouse model to explore therapies for preeclampsia.

PubMed

Ahmed, Abdulwahab; Singh, Jameel; Khan, Ysodra; Seshan, Surya V; Girardi, Guillermina

2010-10-27

Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.

International Rare Histiocytic Disorders Registry (IRHDR)

ClinicalTrials.gov

2018-04-18

Rare Histiocytic Disorders (RHDs); Juvenile Xanthogranuloma (JXG); Reticulohistiocytoma (Epithelioid Histiocytoma); Xanthoma Disseminatum (XD); Multicentric Reticulohistiocytosis (MRH); Systemic Juvenile Xanthogranuloma; Erdheim-Chester Disease (ECD); Multi-system Rosai-Dorfman Disease (RDD)

Effect of a Gonadotrophin-Releasing Hormone Analogue on Lung Function in Lymphangioleiomyomatosis

PubMed Central

Harari, Sergio; Cassandro, Roberto; Chiodini, Jacopo; Taveira-DaSilva, Angelo M.; Moss, Joel

2010-01-01

Background Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. Methods Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. Results Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. Conclusions Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density. PMID:18071009

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

PubMed

Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

2015-04-01

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.

Psychological interventions for parents of children and adolescents with chronic illness

PubMed Central

Eccleston, Christopher; Palermo, Tonya M; Fisher, Emma; Law, Emily

2012-01-01

Background Psychological therapies have been developed for parents of children and adolescents with a chronic illness. Such therapies include parent only or parent and child/adolescent, and are designed to treat parent behaviour, parent mental health, child behaviour/disability, child mental health, child symptoms and/or family functioning. No comprehensive, meta-analytic reviews have been published in this area. Objectives To evaluate the effectiveness of psychological therapies that include coping strategies for parents of children/adolescents with chronic illnesses (painful conditions, cancer, diabetes mellitus, asthma, traumatic brain injury, inflammatory bowel diseases, skin diseases or gynaecological disorders). The therapy will aim to improve parent behaviour, parent mental health, child behaviour/disability, child mental health, child symptoms and family functioning. Search methods We searched CENTRAL, MEDLINE, EMBASE and PsyclNFO for randomised controlled trials (RCTs) of psychological interventions that included parents of children and adolescents with a chronic illness. The initial search was from inception of these databases to June 2011 and we conducted a follow-up search from June 2011 to March 2012. We identified additional studies from the reference list of retrieved papers and from discussion with investigators. Selection criteria Included studies were RCTs of psychological interventions that delivered treatment to parents of children and adolescents (under 19 years of age) with a chronic illness compared to active control, wait list control or treatment as usual. We excluded studies if the parent component was a coaching intervention, the aim of the intervention was health prevention/promotion, the comparator was a pharmacological treatment, the child/adolescent had an illness not listed above or the study included children with more than one type of chronic illness. Further to this, we excluded studies when the sample size of either comparator group was fewer than 10 at post-treatment. Data collection and analysis We included 35 RCTs involving a total of 2723 primary trial participants. Two review authors extracted data from 26 studies. We analysed data using two categories. First, we analysed data by each medical condition across all treatment classes at two time points (immediately post-treatment and the first available follow-up). Second, we analysed data by each treatment class (cognitive behavioural therapy (CBT), family therapy (FT), problem solving therapy (PST) and multisystemic therapy (MST)) across all medical conditions at two time points (immediately post-treatment and the first available follow-up). We assessed treatment effectiveness on six possible outcomes: parent behaviour, parent mental health, child behaviour/disability, child mental health, child symptoms and family functioning. Main results Across all treatment types, psychological therapies that included parents significantly improved child symptoms for painful conditions immediately post-treatment. Across all medical conditions, cognitive behavioural therapy (CBT) significantly improved child symptoms and problem solving therapy significantly improved parent behaviour and parent mental health immediately post-treatment. There were no other effects at post-treatment or follow-up. The risk of bias of included studies is described. Authors' conclusions There is no evidence on the effectiveness of psychological therapies that include parents in most outcome domains of functioning, for a large number of common chronic illnesses in children. There is good evidence for the effectiveness of including parents in psychological therapies that reduce pain in children with painful conditions. There is also good evidence for the effectiveness of CBT that includes parents for improving the primary symptom complaints when available data were included from chronic illness conditions. Finally, there is good evidence for the effectiveness of problem solving therapy delivered to parents on improving parent problem solving skills and parent mental health. All effects are immediately post-treatment. There are no significant findings for any treatment effects in any condition at follow-up. PMID:22895990

21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of the glomeruli of the kidney), lupus nephritis (kidney disease associated with a multisystem autoimmune disease, systemic lupus erythematosus), as well as several skin diseases, e.g., dermititis...

Multimorbidity and healthcare utilisation among high-cost patients in the US Veterans Affairs Health Care System

PubMed Central

Zulman, Donna M; Pal Chee, Christine; Wagner, Todd H; Yoon, Jean; Cohen, Danielle M; Holmes, Tyson H; Ritchie, Christine; Asch, Steven M

2015-01-01

Objectives To investigate the relationship between multimorbidity and healthcare utilisation patterns among the highest cost patients in a large, integrated healthcare system. Design In this retrospective cross-sectional study of all patients in the U.S. Veterans Affairs (VA) Health Care System, we aggregated costs of individuals’ outpatient and inpatient care, pharmacy services and VA-sponsored contract care received in 2010. We assessed chronic condition prevalence, multimorbidity as measured by comorbidity count, and multisystem multimorbidity (number of body systems affected by chronic conditions) among the 5% highest cost patients. Using multivariate regression, we examined the association between multimorbidity and healthcare utilisation and costs, adjusting for age, sex, race/ethnicity, marital status, homelessness and health insurance status. Setting USA VA Health Care System. Participants 5.2 million VA patients. Measures Annual total costs; absolute and share of costs generated through outpatient, inpatient, pharmacy and VA-sponsored contract care; number of visits to primary, specialty and mental healthcare; number of emergency department visits and hospitalisations. Results The 5% highest cost patients (n=261 699) accounted for 47% of total VA costs. Approximately two-thirds of these patients had chronic conditions affecting ≥3 body systems. Patients with cancer and schizophrenia were less likely to have documented comorbid conditions than other high-cost patients. Multimorbidity was generally associated with greater outpatient and inpatient utilisation. However, increased multisystem multimorbidity was associated with a higher outpatient share of total costs (1.6 percentage points per affected body system, p<0.01) but a lower inpatient share of total costs (−0.6 percentage points per affected body system, p<0.01). Conclusions Multisystem multimorbidity is common among high-cost VA patients. While some patients might benefit from disease-specific programmes, for most patients with multimorbidity there is a need for interventions that coordinate and maximise efficiency of outpatient services across multiple conditions. PMID:25882486

Rapamycin and Chloroquine: The In Vitro and In Vivo Effects of Autophagy-Modifying Drugs Show Promising Results in Valosin Containing Protein Multisystem Proteinopathy

PubMed Central

Nalbandian, Angèle; Llewellyn, Katrina J.; Nguyen, Christopher; Yazdi, Puya G.; Kimonis, Virginia E.

2015-01-01

Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can now be included as disorders that can potentially be ameliorated by rapalogs. PMID:25884947

21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... factor B aids in the diagnosis of several kidney diseases, e.g., chronic glomerulonephritis (inflammation of the glomeruli of the kidney), lupus nephritis (kidney disease associated with a multisystem...

Toxic epidermal necrolysis and hemophagocytic lymphohistiocytosis: a case report and literature review

PubMed Central

Sniderman, Jonathan D S; Cuvelier, Geoff D E; Veroukis, Stasa; Hansen, Gregory

2015-01-01

Key Clinical Message Diagnostic criteria for hemophagocytic lymphohistiocytosis should be reviewed early in critically ill patients with toxic epidermal necrolysis, multisystem dysfunction, and a deteriorating clinical trajectory. PMID:25767712

SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations.

PubMed

Zarate, Yuri A; Fish, Jennifer L

2017-02-01

The SATB2-associated syndrome is a recently described syndrome characterized by developmental delay/intellectual disability with absent or limited speech development, craniofacial abnormalities, behavioral problems, dysmorphic features, and palatal and dental abnormalities. Alterations of the SATB2 gene can result from a variety of different mechanisms that include contiguous deletions, intragenic deletions and duplications, translocations with secondary gene disruption, and point mutations. The multisystemic nature of this syndrome demands a multisystemic approach and we propose evaluation and management guidelines. The SATB2-associated syndrome registry has now been started and that will allow gathering further clinical information and refining the provided surveillance recommendations. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Refining the multisystem view of the stress response: Coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict

PubMed Central

Powers, Sally I.; Granger, Douglas A.

2013-01-01

This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period (“matched phase coordination”), and association between overall levels of cortisol and sAA in response to conflict (“average level coordination”). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. PMID:23684904

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

PubMed Central

Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

2012-01-01

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

PubMed

Miyahira, Andrea K; Kissick, Haydn T; Bishop, Jennifer L; Takeda, David Y; Barbieri, Christopher E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2015-03-01

The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. © 2014 Wiley Periodicals, Inc.

A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.

PubMed

Bossart, Katharine N; Zhu, Zhongyu; Middleton, Deborah; Klippel, Jessica; Crameri, Gary; Bingham, John; McEachern, Jennifer A; Green, Diane; Hancock, Timothy J; Chan, Yee-Peng; Hickey, Andrew C; Dimitrov, Dimiter S; Wang, Lin-Fa; Broder, Christopher C

2009-10-01

Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.

Hypomelanosis of Ito: neurological and psychiatric pictures in developmental age.

PubMed

Parisi, L; Di Filippo, T; Roccella, M

2012-02-01

Hypomelanosis of Ito (HOI) is a multisystem neurocutaneous disorder. In the described cases, cutaneous manifestations (unilateral or bilateral streaks and swirls of hypomelanosis with regular and confluent borders) and extracutaneous abnormalities are often associated. Extracutaneous abnormalities involve the musculoskeletal system (scoliosis, vertebral anomalies, cranial-facial malformations) and other organs, as well as the central nervous system (CNS). The most significant anomalies of the CNS are psychomotor retardation and cognitive deficit. Autism, epilepsy, language disorders, cerebral malformations (neural migration disorders, cerebral hypoplasia, cortical atrophy, agenesis of the corpus callosum) are sometimes present. Numerous abnormal chromosomal patterns have been observed. HOI is usually a sporadic disorder; though autosomal dominant transmission has been suggested, recessive and X-linked inheritance patterns have also been reported. This study describes five children with HOI presenting with various features of the clinical spectrum of the syndrome. Some of these cases were referred for psychomotor therapy as part of an integrated neuropsychologic and psychomotor treatment support program. In this view, psychomotor treatment aims to promote the emotional-relational component, to overcome rigid divisions, and to integrate learning-related cognitive aspects with psychodynamic concepts. Finally, the goals of psychological and social support are to help the parents accept their child's handicap, understand the child's behavior, plan future pregnancies, and foster an environment for their child's integration.

Genetics Home Reference: neonatal onset multisystem inflammatory disease

MedlinePlus

... a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has ... is direct-to-consumer genetic testing? What are genome editing and CRISPR-Cas9? What is precision medicine? ...

[Sarcoidosis of the female genital tract].

PubMed

Šefčíková, A; Turková, M; Žurková, M

To present the findings of sarcoidosis on female genital tract. Review. Department of Obstetric and Gynecology, Silesian Hospital Opava. Overview of published findings from case studies. Sarcoidosis is a multisystem granulomatous disorder of unclear cause. It typically involves the lymph nodes of mediastinum, predominantly billateral and/or pulmonary infiltrates. We find extrapulmonary involvement in 30-50% of cases. Sarcoidosis of the female reproductive system is a rare, it represent less than 1% cases of sarcoidosis. Lesions there may affect any organ, including the vulva, vagina, cervix, uterus, fallopian tube and ovary, but also for example placenta and breast. There is also recorded the incidence of multiple localization on female genitalia. Since sarcoidosis of this area is so rare, often proceeds asymptomatic and recognized only as an incidental finding, there are mention only the case histories in literature yet.Clinical symptoms may be non-specific, often imitating a tumor, or tend to be specific, depending on the localization of disability such as perineal pain, pain in the scar after the previous birth trauma, persistent pruritus, itching, irritation, dyspareunia, menstrual cycle disorders, menorrhagia, metrorrhagia, postmenopausal bleeding, amenorrhoe, abdominal pain, endometrial polypoid lesions, recurrent or persistent serometra or discharge. The diagnosis is made up of histologically - we are demonstrating noncaseating granulomas.The therapy is difficult, there are no available official guidelines. If the lesions are clinically silent, we can observed them because they may spontaneously disappear. If we are embarking on medical therapy, we start from a local application, and if this is unsuccessful then we approach the systemic administration. Corticosteroids are the drug of choice. If we diagnose the sarcoidosis of the female genital organs we must exclude systemic disease of sarcoidosis. The prognosis of disease is good.

Circulating cell-free BRAFV600E as a biomarker in children with Langerhans cell histiocytosis.

PubMed

Héritier, Sébastien; Hélias-Rodzewicz, Zofia; Lapillonne, Hélène; Terrones, Nathalie; Garrigou, Sonia; Normand, Corinne; Barkaoui, Mohamed-Aziz; Miron, Jean; Plat, Geneviève; Aladjidi, Nathalie; Pagnier, Anne; Deville, Anne; Gillibert-Yvert, Marion; Moshous, Despina; Lefèvre-Utile, Alain; Lutun, Anne; Paillard, Catherine; Thomas, Caroline; Jeziorski, Eric; Nizard, Philippe; Taly, Valérie; Emile, Jean-François; Donadieu, Jean

2017-08-01

The BRAF V600E mutation is reported in half of patients with Langerhans cell histiocytosis (LCH). This study investigated the detection of the BRAF V600E allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAF V600E -mutated LCH were investigated to detect ccf BRAF V600E at diagnosis (n = 48) and during follow-up (n = 17) using a picolitre-droplet digital PCR assay. At diagnosis, ccf BRAF V600E was positive in 15/15 (100%) patients with risk-organ positive multisystem (RO+ MS) LCH, 5/12 (42%) of patients with RO- MS LCH and 3/21 (14%) patients with single-system (SS) LCH (P < 0·001, Fisher's exact test). The positive BRAF V600E load was higher for RO+ patients (mean, 2·90%; range, 0·04-11·4%) than for RO- patients (mean, 0·16%; range, 0·01-0·39) (P = 0·003, Mann-Whitney U test). After first-line vinblastine-steroid induction therapy, 7/7 (100%) of the non-responders remained positive for ccf BRAF V600E compared to 2/4 (50%) of the partial-responders and 0/4 of the complete responders (P = 0·002, Fisher's exact test). Six children treated with vemurafenib showed a clinical response that was associated with a decrease in the ccf BRAF V600E load at day 15. Thus, ccf BRAF V600E is a promising biomarker for monitoring the response to therapy for children with RO+ MS LCH or RO- LCH resistant to first-line chemotherapy. © 2017 John Wiley & Sons Ltd.

Multipurpose fare media : developments and issues

DOT National Transportation Integrated Search

1997-06-01

This TCRP digest presents the interim findings of TCRP Project A-14, Potential of Multipurpose Fare Media," conducted by Multisystems, Inc., in collaboration with Dove Associates. Inc., and Mundle & Associates, Inc.Included in the digest are (1) a...

Beyond cervical lipomas: myoclonus, gait disorder and multisystem involvement leading to mitochondrial disease.

PubMed

López-Blanco, Roberto; Rojo-Sebastián, Ana; Torregrosa-Martínez, Maria Henedina; Blazquez, Alberto

2017-06-19

Madelung's disease (benign symmetric lipomatosis) is a rare syndrome in which there are multiple lipomas around the neck, upper limbs and trunk in the context of chronic alcoholism. We report on a female patient with lipomas and slightly progressive myoclonus, neuropathy, myopathy, ataxia and respiratory systemic involvement (labelled in the past as Madelung's disease). Multisystem involvement and family history of lipomas led to the development of mitochondrial genetic tests, which can assess two concurrent mitochondrial mutations: the m.8344A>G mutation in MT-TK gene, related MERRF (myoclonic epilepsy with ragged-red fibre) phenotype and m.14484T>C mutation in the MT-ND6 gene responsible for Leber hereditary optic neuropathy phenotype. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Multisystemic Listeriosis in a Common Brushtail Possum (Trichosurus vulpecula) and Two Common Ringtail Possums (Pseudocheirus peregrinus).

PubMed

Sangster, C R

2016-05-01

A single free-ranging common brushtail possum (Trichosurus vulpecula) and 2 captive sibling common ringtail possums (Pseudocheirus peregrinus)from a zoological facility in Sydney, Australia, were diagnosed with multisystemic listeriosis. The brushtail was found dead in an animal enclosure while the ringtails presented with signs of cardiovascular collapse and died shortly thereafter. All 3 animals were culture positive forListeria monocytogenesand demonstrated focal suppurative lesions within the brainstem in addition to fulminant disease in other areas of the thorax and/or abdomen. Listeriosis in phalangeriformes species has rarely been reported, and brainstem lesions have not previously been described. It is speculated that access to the brainstem by the organism may have occurred hematogenously or via retrograde migration along cranial nerves. Sources of infection and the possibility of transmission between animals are also discussed. © The Author(s) 2015.

Core Clinical Phenotypes in Myotonic Dystrophies

PubMed Central

Wenninger, Stephan; Montagnese, Federica; Schoser, Benedikt

2018-01-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) represent the most frequent multisystemic muscular dystrophies in adulthood. They are progressive, autosomal dominant diseases caused by an abnormal expansion of an unstable nucleotide repeat located in the non-coding region of their respective genes DMPK for DM1 and CNBP in DM2. Clinically, these multisystemic disorders are characterized by a high variability of muscular and extramuscular symptoms, often causing a delay in diagnosis. For both subtypes, many symptoms overlap, but some differences allow their clinical distinction. This article highlights the clinical core features of myotonic dystrophies, thus facilitating their early recognition and diagnosis. Particular attention will be given to signs and symptoms of muscular involvement, to issues related to respiratory impairment, and to the multiorgan involvement. This article is part of a Special Issue entitled “Beyond Borders: Myotonic Dystrophies—A European Perception.”

SIL1-related Marinesco-Sjoegren syndrome (MSS) with associated motor neuronopathy and bradykinetic movement disorder.

PubMed

Byrne, Susan; Dlamini, Nomazulu; Lumsden, Daniel; Pitt, Matthew; Zaharieva, Irina; Muntoni, Francesco; King, Andrew; Robert, Leema; Jungbluth, Heinz

2015-07-01

Marinesco-Sjoegren syndrome (MSS) is a recessively inherited multisystem disorder caused by mutations in SIL1 and characterized by cerebellar atrophy with ataxia, cataracts, a skeletal muscle myopathy, and variable degrees of developmental delay. Pathogenic mechanisms implicated to date include mitochondrial, nuclear envelope and lysosomal-autophagic pathway abnormalities. Here we present a 5-year-old girl with SIL1-related MSS and additional unusual features of an associated motor neuronopathy and a bradykinetic movement disorder preceding the onset of ataxia. These findings suggest that an associated motor neuronopathy may be part of the phenotypical spectrum of SIL1-related MSS and should be actively investigated in genetically confirmed cases. The additional observation of a bradykinetic movement disorder suggests an intriguing continuum between neurodevelopmental and neurodegenerative multisystem disorders intricately linked in the same cellular pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying Effective Components of Child Maltreatment Interventions: A Meta-analysis.

PubMed

van der Put, Claudia E; Assink, Mark; Gubbels, Jeanne; Boekhout van Solinge, Noëlle F

2018-06-01

There is a lack of knowledge about specific components that make interventions effective in preventing or reducing child maltreatment. The aim of the present meta-analysis was to increase this knowledge by summarizing findings on effects of interventions for child maltreatment and by examining potential moderators of this effect, such as intervention components and study characteristics. Identifying effective components is essential for developing or improving child maltreatment interventions. A literature search yielded 121 independent studies (N = 39,044) examining the effects of interventions for preventing or reducing child maltreatment. From these studies, 352 effect sizes were extracted. The overall effect size was significant and small in magnitude for both preventive interventions (d = 0.26, p < .001) and curative interventions (d = 0.36, p < .001). Cognitive behavioral therapy, home visitation, parent training, family-based/multisystemic, substance abuse, and combined interventions were effective in preventing and/or reducing child maltreatment. For preventive interventions, larger effect sizes were found for short-term interventions (0-6 months), interventions focusing on increasing self-confidence of parents, and interventions delivered by professionals only. Further, effect sizes of preventive interventions increased as follow-up duration increased, which may indicate a sleeper effect of preventive interventions. For curative interventions, larger effect sizes were found for interventions focusing on improving parenting skills and interventions providing social and/or emotional support. Interventions can be effective in preventing or reducing child maltreatment. Theoretical and practical implications are discussed.

The evolving role of the total artificial heart in the management of end-stage congenital heart disease and adolescents.

PubMed

Ryan, Thomas D; Jefferies, John L; Zafar, Farhan; Lorts, Angela; Morales, David L S

2015-01-01

Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease.

IMMUNOTOXICITY OF INDIVIDUAL ORGANOTIN COMPOUNDS IN SPRAGUE-DAWLEY RATS

EPA Science Inventory

Organotins, used as stabilizers for polyvinyl chloride pipe, leach into drinking water from supply pipes and may cause multisystem toxicity, including immunotoxicity. We assessed immune function in Sprague-Dawley rats exposed to dibutyltin dichloride (DBTC) or dimethyltin dichlor...

Reversible pulmonary hypertension in Whipple disease: a case report with clinicopathological implications, and literature review.

PubMed

Lyle, Pamela L; Weber, Robert D; Bogarin, Javier; Kircher, Tobias

2009-01-01

Whipple disease is a rare multisystemic disorder of infectious aetiology caused by Tropheryma whipplei. Pulmonary hypertension is a rare association for which the underlying pathophysiological mechanism is unclear. Our patient was a 54-year-old man with a 1-year history of progressive polyarticular arthritis, and worsening respiratory and gastrointestinal symptoms. Pulmonary artery catheterisation demonstrated moderate-to-severe pulmonary hypertension. Duodenal biopsies, with electron microscopy, were diagnostic of Whipple disease. Involvement by Whipple disease was also evident in the stomach, bone marrow and pulmonary pleura. A 2-week course of intravenous ceftriaxone was initiated and this was followed by a 1-year course of trimethoprim/sulfamethoxazole (160/800), once daily. Nine months into antibiotic treatment, a repeat echocardiogram showed normalisation of the size and function of the cardiac chambers, including the right atrium and right ventricle. There was complete resolution of the severe tricuspid insufficiency and pulmonary hypertension. Whipple disease is not generally considered as a possible cause of pulmonary hypertension but such awareness is important given that it may be potentially reversible with antibiotic therapy.

Reversible pulmonary hypertension in Whipple disease: a case report with clinicopathological implications, and literature review

PubMed Central

Lyle, Pamela L; Weber, Robert D; Bogarin, Javier; Kircher, Tobias

2009-01-01

Whipple disease is a rare multisystemic disorder of infectious aetiology caused by Tropheryma whipplei. Pulmonary hypertension is a rare association for which the underlying pathophysiological mechanism is unclear. Our patient was a 54-year-old man with a 1-year history of progressive polyarticular arthritis, and worsening respiratory and gastrointestinal symptoms. Pulmonary artery catheterisation demonstrated moderate-to-severe pulmonary hypertension. Duodenal biopsies, with electron microscopy, were diagnostic of Whipple disease. Involvement by Whipple disease was also evident in the stomach, bone marrow and pulmonary pleura. A 2-week course of intravenous ceftriaxone was initiated and this was followed by a 1-year course of trimethoprim/sulfamethoxazole (160/800), once daily. Nine months into antibiotic treatment, a repeat echocardiogram showed normalisation of the size and function of the cardiac chambers, including the right atrium and right ventricle. There was complete resolution of the severe tricuspid insufficiency and pulmonary hypertension. Whipple disease is not generally considered as a possible cause of pulmonary hypertension but such awareness is important given that it may be potentially reversible with antibiotic therapy. PMID:21686934

Nuclear Imaging in Sarcoidosis.

PubMed

Piekarski, Eve; Benali, Khadija; Rouzet, François

2018-05-01

Sarcoidosis is a multisystem granulomatosis which may result in a wide variety of clinical and biological presentations. Symptoms are often nonspecific, and incidental abnormal findings on chest radiography is rather common. Although sarcoidosis resolves favorably in most cases, some localizations can provoke functional impairment or even impact on patients' prognosis. The diagnosis is based on a pathological hallmark which is the non-necrotizing epithelioid-cell rich granuloma. Owing to the ability to detect inflammation throughout the body with a high sensibility, FDG-PET/CT gained a central role in sarcoidosis because it can suggest the diagnosis in certain clinical context, guide biopsy, evaluate the extent of the disease, help assess the prognosis, and monitor immunosuppressive therapy. This review will briefly describe clinical and typical findings of conventional imaging according to organ involvement, in order to highlight the additional information provided by nuclear imaging. In the future, we can expect to further improve diagnostic performance of imaging in some indications through the availability of more specific radiopharmaceuticals and the wider use of combined PET/MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

Update on the Medical Management of Gastrointestinal Behçet's Disease

PubMed Central

Venerito, Vincenzo; Franceschini, Rossella; Lapadula, Giovanni; Galeazzi, Mauro; Frediani, Bruno; Iannone, Florenzo

2017-01-01

Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the “stigmata” of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet's disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. Consequently, the differential diagnosis is often a daunting task, albeit the presence of typical endoscopic and pathologic findings may be a valuable aid to the exact diagnosis. To date, there are no standardized medical treatments for GIBD; therefore therapy should be tailored to the single patient and based on the severity of the clinical features and their complications. This work provides a digest of all current experience and evidence about pharmacological agents suggested by the medical literature as having a potential role for managing the dreadful features of GIBD. PMID:28210071

[Langerhans cell histiocytosis in adults].

PubMed

Néel, A; Artifoni, M; Donadieu, J; Lorillon, G; Hamidou, M; Tazi, A

2015-10-01

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Update on Biologic Therapies for Systemic Lupus Erythematosus.

PubMed

Borba, Helena Hiemisch Lobo; Funke, Andreas; Wiens, Astrid; Utiyama, Shirley Ramos da Rosa; Perlin, Cássio Marques; Pontarolo, Roberto

2016-07-01

Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease driven by genetic, hormonal, and environmental factors. Despite the advances in diagnostic and therapeutic approaches in the last decades, SLE still leads to significant morbidity and increased mortality. Although a cure for SLE is still unknown, treatment is required to control acute disease exacerbation episodes (flares), decrease the frequency and severity of subsequent lupus flares, address comorbidities, and prevent end-organ damage. While conventional SLE pharmacotherapy may exhibit suboptimal efficacy and substantial toxicity, a growing knowledge of the disease pathogenesis enabled the research on novel therapeutic agents directed at specific disease-related targets. In this paper, we review the recent progress in the clinical investigation of biologic agents targeting B cells, T cells, cytokines, innate immunity, and other immunologic or inflammatory pathways. Although many investigational agents exhibited insufficient efficacy or inadequate safety in clinical trials, one of them, belimumab, fulfilled the efficacy and safety regulatory requirements and was approved for the treatment of SLE in Europe and the USA, which confirms that, despite all difficulties, advances in this field are possible.

Clinical manifestations and management of Gaucher disease.

PubMed

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R.

PubMed

Filippakis, Harilaos; Alesi, Nicola; Ogorek, Barbara; Nijmeh, Julie; Khabibullin, Damir; Gutierrez, Catherine; Valvezan, Alexander J; Cunningham, James; Priolo, Carmen; Henske, Elizabeth P

2017-06-13

Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL-R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and pointing toward the translational potential of these pathways for the therapy of TSC.

Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10.

PubMed

Bergamin, Carla S; Rolim, Luiz Clemente; Dib, Sergio A; Moisés, Regina S

2008-11-01

Maternally inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This subtype of diabetes is characterized by maternal transmission, young age at onset and bilateral hearing impairment. Besides diabetes and deafness, the main diagnostic features, a wide range of multisystemic symptoms may be associated with the A3243G mutation. Organs that are most metabolically active, such as muscles, myocardium, retina, cochlea, kidney and brain are frequently affected. Gastrointestinal tract symptoms are also common in patients with mitochondrial disease and constipation and diarrhea are the most frequent manifestations. However, there are few prior reports of intestinal pseudo obstruction in MIDD patients. Here we report the case of a patient with MIDD associated with the mtDNA A3243G mutation who developed chronic intestinal pseudo obstruction, and the introduction of Coenzyme Q10 as adjunctive therapy led to a solution of the pseudo obstruction.

A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review.

PubMed

Michalak, Agata; Cichoż-Lach, Halina; Prozorow-Król, Beata; Buk, Leszek; Dzida, Monika

2018-04-13

Epidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring. Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland. Management of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.

Thyrotoxic and pheochromocytoma multisystem crisis: a case report.

PubMed

Suzuki, Kodai; Miyake, Takahito; Okada, Hideshi; Yamaji, Fuminori; Kitagawa, Yuichiro; Fukuta, Tetsuya; Yasuda, Ryu; Tanaka, Yoshihito; Okamoto, Haruka; Nachi, Sho; Doi, Tomoaki; Yoshida, Takahiro; Kumada, Keisuke; Yoshida, Shozo; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji

2017-06-23

Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm). A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave's hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor. After retroperitoneal laparoscopic adrenalectomy on hospital day 33, his condition stabilized. He was discharged on hospital day 58. Since he required more intensive cardiovascular management for thyrotoxic crisis, beta blockade was increased under intensive care unit monitoring even though initial alpha blockade is recommended in pheochromocytoma. When these crises occur simultaneously, cardiovascular management can be very challenging.

Trauma caused by falling objects at construction sites.

PubMed

Atique, Sajid; Zarour, Ahmad; Siddiqui, Tariq; El-Menyar, Ayman; Maull, Kimball; Al Thani, Hassan; Latifi, Rifat

2012-09-01

Workplace-related injuries carry a significant health care challenge. The state of Qatar is developing rapidly, with much construction and an expanding industrial work force. This study aimed to assess the incidence and social impact of work-related injuries requiring hospitalization caused by falling objects at the construction sites. We performed a prospective study for all admissions, which resulted from falling objects between January 2008 and June 2010 at the only trauma center in the state of Qatar. Data were analyzed, and outcomes were described (mortality, length of hospital stay, and safety measures). Of the total injured patients (N = 4,302) admitted between January 2008 and June 2010, 185 (4%) had injuries caused purely by falling objects. Patients' mean age was 29 years, and 97% of the patients were men. All injuries occurred at construction sites. Most patients (86%) were brought by ambulance, and the reminder was brought by private vehicles. After initial evaluation and resuscitation, 120 patients (65%) were found to have a single-system injury, and 65 (35%) had multisystem injury. Operative interventions were required in 50% of the patients. Mean length of hospital stay varied from 6.5 days for single-system injuries to 19 days for multisystem injuries. Safety devices were used in 32 patients (17.3%). All of the 16 mortality cases (8.6%) were reported in multiple injuries. Traumatic injury caused by falling object represents a significant problem in a rapidly developing country. Many of these injuries could be prevented by following established safety guidelines. Epidemiologic study, level III.

New treatments targeting the basic defects in cystic fibrosis.

PubMed

Fajac, Isabelle; Wainwright, Claire E

2017-06-01

Cystic fibrosis (CF) is a monogenic autosomal recessive disorder affecting around 75,000 individuals worldwide. It is a multi-system disease but the main morbidity and mortality is caused by chronic lung disease. Due to newborn screening, a multidisciplinary approach to care and intensive symptomatic treatment, the prognosis has dramatically improved over the last decades and there are currently more adults than children in many countries. However, CF is still a very severe disease with a current median age of life expectancy in the fourth decade of life. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes the CFTR protein, a protein kinase A-activated ATP-gated anion channel that regulates the transport of electrolytes such as chloride and bicarbonate. More than 2000 mutations have been reported, although not all of these have functional consequences. An enormous research effort and progress has been made in understanding the consequences of these mutations on the CFTR protein structure and function, and this has led to the approval of two new drug therapies that are able to bind to defective CFTR proteins and partially restore their function. They are mutation-specific therapies and available at present for specific mutations only. They are the first personalized medicine for CF with a possible disease-modifying effect. A pipeline of other compounds is under development with different mechanisms of action. It is foreseeable that new combinations of compounds will further improve the correction of CFTR function. Other strategies including premature stop codon read-through drugs, antisense oligonucleotides that correct the basic defect at the mRNA level or gene editing to restore the defective gene as well as gene therapy approaches are all in the pipeline. All these strategies are needed to develop disease-modifying therapies for all patients with CF. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs

PubMed Central

Van Poucke, Mario; Stee, Kimberley; Bhatti, Sofie F M; Vanhaesebrouck, An; Bosseler, Leslie; Peelman, Luc J; Van Ham, Luc

2017-01-01

SeSAME/EAST syndrome is a multisystemic disorder in humans, characterised by seizures, sensorineural deafness, ataxia, developmental delay and electrolyte imbalance. It is exclusively caused by homozygous or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar syndrome in two families belonging to the Malinois dog breed, based on clinical, neurological, electrodiagnostic and histopathological examination. Genetic analysis detected a novel pathogenic KCNJ10 c.986T>C (p.(Leu329Pro)) variant that is inherited in an autosomal recessive way. This variant has an allele frequency of 2.9% in the Belgian Malinois population, but is not found in closely related dog breeds or in dog breeds where similar symptoms have been already described. The canine phenotype is remarkably similar to humans, including ataxia and seizures. In addition, in half of the dogs clinical and electrophysiological signs of neuromyotonia were observed. Because there is currently no cure and treatment is nonspecific and unsatisfactory, this canine translational model could be used for further elucidating the genotype/phenotype correlation of this monogenic multisystem disorder and as an excellent intermediate step for drug safety testing and efficacy evaluations before initiating human studies. PMID:27966545

Acute pancreatitis: a multisystem disease.

PubMed

Agarwal, N; Pitchumoni, C S

1993-06-01

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.

Refining the multisystem view of the stress response: coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict.

PubMed

Laurent, Heidemarie K; Powers, Sally I; Granger, Douglas A

2013-07-02

This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period ("matched phase coordination"), and association between overall levels of cortisol and sAA in response to conflict ("average level coordination"). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Constitutional Mutations in RTEL1 Cause Severe Dyskeratosis Congenita

PubMed Central

Walne, Amanda J.; Vulliamy, Tom; Kirwan, Michael; Plagnol, Vincent; Dokal, Inderjeet

2013-01-01

Dyskeratosis congenita (DC) and its phenotypically severe variant, Hoyeraal-Hreidarsson syndrome (HHS), are multisystem bone-marrow-failure syndromes in which the principal pathology is defective telomere maintenance. The genetic basis of many cases of DC and HHS remains unknown. Using whole-exome sequencing, we identified biallelic mutations in RTEL1, encoding a helicase essential for telomere maintenance and regulation of homologous recombination, in an individual with familial HHS. Additional screening of RTEL1 identified biallelic mutations in 6/23 index cases with HHS but none in 102 DC or DC-like cases. All 11 mutations in ten HHS individuals from seven families segregated in an autosomal-recessive manner, and telomere lengths were significantly shorter in cases than in controls (p = 0.0003). This group had significantly higher levels of telomeric circles, produced as a consequence of incorrect processing of telomere ends, than did controls (p = 0.0148). These biallelic RTEL1 mutations are responsible for a major subgroup (∼29%) of HHS. Our studies show that cells harboring these mutations have significant defects in telomere maintenance, but not in homologous recombination, and that incorrect resolution of T-loops is a mechanism for telomere shortening and disease causation in humans. They also demonstrate the severe multisystem consequences of its dysfunction. PMID:23453664

Prader-Willi Syndrome

ERIC Educational Resources Information Center

Kundert, Deborah King

2008-01-01

Although known for its distinctive food-related behaviors, Prader-Willi syndrome is a multisystem disorder with genetic, developmental, and behavioral features. Two separate and distinct eating disorders are noted: initial feeding difficulties and failure to thrive, and later overeating. Additional outcomes observed with this disorder include…

Evaluation of Phase II of the SmarTraveler advanced traveler information system : operational test

DOT National Transportation Integrated Search

1994-07-31

Under contract to the Massachusetts Highway Department, the Central Transportation : Planning Staff (technical staff to the Boston MPO) chose Multisystems, Inc. of : Cambridge, Massachusetts, to perform an evaluation of Phase II of the SmarTraveler :...

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial

PubMed Central

Tompkins, Bryon A; DiFede, Darcy L; Khan, Aisha; Landin, Ana Marie; Schulman, Ivonne Hernandez; Pujol, Marietsy V; Heldman, Alan W; Miki, Roberto; Goldschmidt-Clermont, Pascal J; Goldstein, Bradley J; Mushtaq, Muzammil; Levis-Dusseau, Silvina; Byrnes, John J; Lowery, Maureen; Natsumeda, Makoto; Delgado, Cindy; Saltzman, Russell; Vidro-Casiano, Mayra; Da Fonseca, Moisaniel; Golpanian, Samuel; Premer, Courtney; Medina, Audrey; Valasaki, Krystalenia; Florea, Victoria; Anderson, Erica; El-Khorazaty, Jill; Mendizabal, Adam; Green, Geoff; Oliva, Anthony A; Hare, Joshua M

2017-01-01

Abstract Background Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair. Methods This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion. Results No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy. Conclusion Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder. Clinical Trial Registration www.clinicaltrials.gov: CRATUS (#NCT02065245). PMID:28977399

Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI.

PubMed

Horovitz, Dafne D G; Magalhães, Tatiana S P C; Acosta, Angelina; Ribeiro, Erlane M; Giuliani, Liane R; Palhares, Durval B; Kim, Chong A; de Paula, Ana Carolina; Kerstenestzy, Marcelo; Pianovski, Mara A D; Costa, Maria Ione F; Santos, Francisca C; Martins, Ana Maria; Aranda, Carolina S; Correa Neto, Jordão; Holanda, Gervina Brady Moreira; Cardoso, Laércio; da Silva, Carlos A B; Bonatti, Renata C F; Ribeiro, Bethania F R; Rodrigues, Maria do Carmo S; Llerena, Juan C

2013-05-01

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age. Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated. A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved. The prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population. Copyright © 2013 Elsevier Inc. All rights reserved.

New horizons for cystic fibrosis treatment.

PubMed

Fajac, Isabelle; De Boeck, Kris

2017-02-01

Cystic fibrosis is an inherited multi-system disease associated with chronic lung infection, malabsorption, salt loss syndromes, male infertility and leading to numerous comorbidities. The landscape in cystic fibrosis care has changed markedly with currently more adult patients than children in many countries. Over 2000 different mutations in the CFTR gene have been reported and the majority are extremely rare. Understanding how CFTR mutations translate to disturbed synthesis or function of the CFTR protein has opened the way to 'personalized' treatments to correct the basic defect. The first 2 drugs have reached the clinic: a CFTR potentiator to augment CFTR channel function, and the combination of this potentiator with a corrector to increase CFTR expression at the cell membrane. To obtain robust correction of CFTR expression at the cell membrane, combinations of correctors with additive efficacy are under investigation. Other mutation type-specific treatments under clinical investigation are premature stop codon-read through drugs and antisense oligonucleotides that correct the basic defect at the mRNA level. Restoring the defective gene by gene editing can already be achieved ex vivo. Mutation agnostic treatments are explored as well: stabilizing CFTR expression at the cell membrane, circumventing the CFTR channel by blocking or activating other ion channels, and gene therapy. Combinations of these therapies can be anticipated. The pipeline of corrective strategies under clinical investigation is increasing continuously and a rising number of pharmaceutical companies are entering the field. Copyright © 2016 Elsevier Inc. All rights reserved.

Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap).

PubMed

Church, Leigh D; Savic, Sinisa; McDermott, Michael F

2008-12-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of inherited inflammatory disorders consisting of familial cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome). These rare disorders are associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NALP3 or cryopyrin, and inflammation driven by excessive production of the cytokine interleukin-1beta (IL-1beta). Amyloidosis is a serious complication with 25% of MWS patients developing amyloidosis, with occasional fatal consequences, whilst up to 20% of CINCA/NOMID patients die from various complications, before reaching the early adulthood. In some CINCA/NOMID adult survivors amyloidosis can also occur. Prior to the discovery of the CIAS1 gene mutations and the advent of IL-1 targeted therapy, treatment was aimed at suppressing inflammation, with limited success. The selective blockade of IL-1beta, with anakinra (IL-1 receptor antagonist), not only provided supportive evidence for the role of IL-1beta in CAPS, but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. In February, 2008, 'Orphan Drug' approval from the Food and Drug Administration (FDA) for rilonacept (IL-1 Trap/Arcalyst(), Regeneron Pharmaceuticals, Inc) was given for the treatment of two CAPS disorders, FCAS and MWS in adults and children 12 years and older, making rilonacept the first therapy approved for the treatment of CAPS.

Posterior reversible encephalopathy syndrome as a complication of Henoch-Schönlein purpura in a seven-year-old girl.

PubMed

Dos Santos, Daiane; Langer, Felipe Welter; Dos Santos, Tatiane; Rafael Tronco Alves, Giordano; Feiten, Marisa; Teixeira de Paula Neto, Walter

2017-02-01

Introduction Henoch-Schönlein purpura is a multisystem small vessel vasculitis. Neurologic manifestations are uncommon. Posterior reversible encephalopathy syndrome is a rare complication of Henoch-Schönlein purpura with typical clinical and neuroimaging findings that occurs most commonly in the setting of severe hypertension and renal injury. Case presentation A seven-year-old girl was admitted to our institution presenting with clinical and laboratory findings suggestive of Henoch-Schönlein purpura. Glucocorticoid therapy was initiated, but five days following her admission, she developed altered consciousness, seizures, arterial hypertension, and cortical blindness. Brain MRI scan revealed areas of vasogenic oedema in parieto-occipital lobes, consistent with posterior reversible encephalopathy syndrome. She was immediately initiated on antihypertensives and antiepileptics, which successfully improved her neurologic symptoms. Further laboratory work-up disclosed a rapidly progressive glomerulonephritis secondary to Henoch-Schönlein purpura that was the likely cause of her sudden blood pressure elevation. Immunosuppressive therapy was undertaken, and at one-year follow-up, the patient exhibited complete renal and neurologic recovery. Conclusion Posterior reversible encephalopathy syndrome is a severe complication of Henoch-Schönlein purpura. If promptly diagnosed and treated, children with Henoch-Schönlein purpura presenting with posterior reversible encephalopathy syndrome usually have a good prognosis. Clinicians should be familiar with the characteristic presentation of posterior reversible encephalopathy syndrome and be aware that hypertension and renal injury may predispose Henoch-Schönlein purpura patients to developing this complication.

Multimorbidity and healthcare utilisation among high-cost patients in the US Veterans Affairs Health Care System.

PubMed

Zulman, Donna M; Pal Chee, Christine; Wagner, Todd H; Yoon, Jean; Cohen, Danielle M; Holmes, Tyson H; Ritchie, Christine; Asch, Steven M

2015-04-16

To investigate the relationship between multimorbidity and healthcare utilisation patterns among the highest cost patients in a large, integrated healthcare system. In this retrospective cross-sectional study of all patients in the U.S. Veterans Affairs (VA) Health Care System, we aggregated costs of individuals' outpatient and inpatient care, pharmacy services and VA-sponsored contract care received in 2010. We assessed chronic condition prevalence, multimorbidity as measured by comorbidity count, and multisystem multimorbidity (number of body systems affected by chronic conditions) among the 5% highest cost patients. Using multivariate regression, we examined the association between multimorbidity and healthcare utilisation and costs, adjusting for age, sex, race/ethnicity, marital status, homelessness and health insurance status. USA VA Health Care System. 5.2 million VA patients. Annual total costs; absolute and share of costs generated through outpatient, inpatient, pharmacy and VA-sponsored contract care; number of visits to primary, specialty and mental healthcare; number of emergency department visits and hospitalisations. The 5% highest cost patients (n=261,699) accounted for 47% of total VA costs. Approximately two-thirds of these patients had chronic conditions affecting ≥3 body systems. Patients with cancer and schizophrenia were less likely to have documented comorbid conditions than other high-cost patients. Multimorbidity was generally associated with greater outpatient and inpatient utilisation. However, increased multisystem multimorbidity was associated with a higher outpatient share of total costs (1.6 percentage points per affected body system, p<0.01) but a lower inpatient share of total costs (-0.6 percentage points per affected body system, p<0.01). Multisystem multimorbidity is common among high-cost VA patients. While some patients might benefit from disease-specific programmes, for most patients with multimorbidity there is a need for interventions that coordinate and maximise efficiency of outpatient services across multiple conditions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Multisystem Temperature Equilibration and the Second Law

ERIC Educational Resources Information Center

Leff, Harvey S.

1977-01-01

Shows that the entropy change during the temperature equilibration of an isolated collection of systems which may exchange heat (but not work) energy is positive when the constant-volume heat capacity of each system is a non-negative function of the temperature. (MLH)

Novel multi-system functional gains via task specific training in spinal cord injured male rats.

PubMed

Ward, Patricia J; Herrity, April N; Smith, Rebecca R; Willhite, Andrea; Harrison, Benjamin J; Petruska, Jeffrey C; Harkema, Susan J; Hubscher, Charles H

2014-05-01

Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2010-01-01

Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion

PubMed Central

Carbonaro, Denise A.; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C.; Dorey, Frederick; Kellems, Rodney E.; Blackburn, Michael R.

2008-01-01

Adenosine deaminase (ADA)–deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose–dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy. PMID:18356486

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.

PubMed

Carbonaro, Denise A; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C; Dorey, Frederick; Kellems, Rodney E; Blackburn, Michael R; Kohn, Donald B

2008-06-15

Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose-dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

Physiologic Dysfunction Scores and Cognitive Function Test Performance in United States Adults

PubMed Central

Kobrosly, Roni W; Seplaki, Christopher L; Jones, Courtney M; van Wijngaarden, Edwin

2013-01-01

Objective To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. Methods We examined a summary score measuring physiological dysfunction, a multisystem measure of the body’s ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the third National Health and Nutrition Examination Survey (1988–1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. ‘Physiologic dysfunction’ scores summarizing measures of cardiovascular, immunologic, kidney, and liver function were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiological dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. Results We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% CI = (0.066, 0.348), p < 0.0001) that persisted after adjustment for all covariates (p = 0.03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = 0.37) or perceptual-motor ability (p = 0.33). Conclusions Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains. PMID:22155941

Service Usage Typologies in a Clinical Sample of Trauma-Exposed Adolescents: A Latent Class Analysis.

PubMed

Choi, Kristen R; Briggs, Ernestine C; Seng, Julia S; Graham-Bermann, Sandra A; Munro-Kramer, Michelle L; Ford, Julian D

2017-11-27

The purpose of this study is to describe typologies of service utilization among trauma-exposed, treatment-seeking adolescents and to examine associations between trauma history, trauma-related symptoms, demographics, and service utilization. Latent class analysis was used to derive a service utilization typologies based on 10 service variables using a sample of 3,081 trauma-exposed adolescents ages 12 to 16 from the National Child Traumatic Stress Network Core Dataset. Services used 30 days prior to the initial assessment from 5 sectors were examined (health care, mental health, school, social services, and juvenile justice). A 5-class model was selected based on statistical fit indices and substantive evaluation of classes: (a) High intensity/multisystem, 9.5%; (b) Justice-involved, 7.2%; (c) Low intensity/multisystem, 19.9%; (d) Social service and mental health, 19.9%; and (e) Low service usage/reference, 43.5%. The classes could be differentiated based on cumulative trauma, maltreatment history, PTSD, externalizing and internalizing symptoms, and age, gender, race/ethnicity and place of residence. This study provides new evidence about patterns of service utilization by trauma exposed, treatment seeking adolescents. Most of these adolescents appear to be involved with at least 2 service systems prior to seeking trauma treatment. Higher cumulative exposure to multiple types of trauma was associated with greater service utilization intensity and complexity, but trauma symptomatology was not. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A systematic review of allostatic load, health, and health disparities.

PubMed

Beckie, Theresa M

2012-10-01

The theoretical constructs of allostasis and allostatic load (AL) have contributed to our understanding of how constantly changing social and environmental factors impact physiological functioning and shape health and aging disparities, particularly along socioeconomic, gendered, racial, and ethnic lines. AL represents the cumulative dysregulation of biological systems with prolonged or poorly regulated allostatic responses. Nearly two decades of empirical research has focused on operationalizing the AL construct for examining the antecedents and health outcomes accompanying multisystem biological dysregulation. The purpose of this systematic review is to examine the empirical literature that quantifies the AL construct; the review also evaluates the social, environmental, and genetic antecedents of AL as well as its predictive utility for a variety of health outcomes. A total of 58 articles published between 1997 and 2012 were retrieved, analyzed, and synthesized. The results revealed considerable heterogeneity in the operationalization of AL and the measurement of AL biomarkers, making interpretations and comparisons across studies challenging. There is, however, empirical substantiation for the relationships between AL and socioeconomic status, social relationships, workplace, lifestyle, race/ethnicity, gender, stress exposure, and genetic factors. The literature also demonstrated associations between AL and physical and mental health and all-cause mortality. Targeting the antecedents of AL during key developmental periods is essential for improving public health. Priorities for future research include conducting prospective longitudinal studies, examining a broad range of antecedent allostatic challenges, and collecting reliable measures of multisystem dysregulation explicitly designed to assess AL, at multiple time points, in population-representative samples.

Capsular Polysaccharide Interferes With Biofilm Formation by Pasteurella Multocida Serogroup A

USDA-ARS?s Scientific Manuscript database

Pasteurella multocida is an important multihost animal and zoonotic pathogen that is capable of causing respiratory and multisystemic diseases, bacteremia,and bite wound infections. The glycosaminoglycan capsule of P. multocida is an essential virulence factor that protects the bacterium from host d...

Genetics and Hearing Loss: A Review of Stickler Syndrome.

ERIC Educational Resources Information Center

Nowak, Catherine Bearce

1998-01-01

Stickler syndrome is an autosomal dominant multisystem disease. The four most affected systems are craniofacial, skeletal, ocular, and auditory. The manifestations of Stickler syndrome vary considerably among affected individuals. Audiologists and speech-language pathologists should be familiar with the characteristics associated with Stickler…

From Pulmonary Embolism to Inflammatory Bowel Disease; Give Tunnel Vision up.

PubMed

Tajdini, Masih; Hosseini, Seyed Mohammad Reza

2016-01-01

Inflammatory bowel disease (IBD) is a multisystem disorder with gastrointestinal tract involvement. These patients have the higher risk for thromboembolic events compared to normal population. This report describes a unique case of pulmonary embolism as a first manifestation of inflammatory bowel disease.

Dental treatment for people with cystic fibrosis.

PubMed

Harrington, N; Barry, P J; Barry, S M

2016-06-01

To describe the nature and consequences of the multi-system genetic condition cystic fibrosis with a view to ensuring optimal dental treatment planning for these patients. A literature search was conducted to identify the key medical and dental manifestations of cystic fibrosis. These findings are discussed and utilised to create recommendations for treatment planning in patients with cystic fibrosis for the practising dental practitioner. Cystic fibrosis is a complex, lethal, multisystem autosomal recessive disorder resulting from mutations on chromosome 7 which result in dysfunction of an ion channel that sits on epithelial surfaces. Respiratory disease remains the leading cause of mortality. Survival has greatly increased in recent decades secondary to improved treatment and specialist care. Specific dental manifestations of the disease may result from the condition itself or complications of treatment. Modification of patient management may be necessary to provide optimum patient care. The pathophysiology and clinical manifestations are relevant to practicing dental practitioners and inform recommendations to be utilised to ensure optimal treatment planning for these patients.

Langerhans cell histiocytosis manifesting as recurrent simultaneous bilateral spontaneous pneumothorax in early infancy.

PubMed

Alavi, Samin; Ashena, Zahra; Paydar, Afshin; Hemmati, Nadereh

2007-12-01

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by infiltration of either single or multiple organs by a distinct cell type that is S-100 and CD1a positive and contains ultrastructural Birbeck granules on electron microscopy. Historically, LCH included four main clinical forms: Letter-Siwe disease, Hand-Schuller-Christian disease, eosinophilic granuloma (together grouped as histiocytosis) and Hashimoto-Pritzker disease. The writing group of the Histiocytotic Society in 1987 proposed the uniform term of 'Langerhans cell histiocytosis' to encompass all the aforementioned eponymous forms. Lung involvement occurs in up to half of all children with multisystem disease and usually parallels overall disease activity. Spontaneous pneumothorax (SP) occurs in approximately 10% of children with pulmonary disease and may be a fatal complication. Patients with pulmonary LCH are likely predisposed to the development of pneumothorax based on destructive changes in the lung parenchyma. Here, we report a case of multisystem LCH in which the patient presented at 2 months of age because of simultaneous bilateral pneumothorax.

Emergent multisystemic Enterococcus infection threatens endangered Christmas Island reptile populations

PubMed Central

Hall, Jane; Thompson, Paul; Eden, John-Sebastian; Srivastava, Mukesh; Tiernan, Brendan; Jenkins, Cheryl; Phalen, David

2017-01-01

Multisystemic infections with a morphologically unusual bacterium were first observed in captive critically endangered Lister’s geckos (Lepidodactylus listeri) on Christmas Island in October 2014. Since then the infection was identified in another captive critically endangered lizard species, the blue-tailed skink (Cryptoblepharus egeriae) and two species of invasive geckos; the four clawed gecko (Gehyra mutilata) and Asian house gecko (Hemidactylus frenatus), in a wide geographic range across the east side of the island. The Gram and periodic acid-Schiff positive cocci to diplococci have a propensity to form chains surrounded by a matrix, which ultrastructurally appears to be formed by fibrillar capsular projections. The bacterium was associated with severe and extensive replacement of tissues, but minimal host inflammatory response. Attempts to grow the organism in culture and in embryonated eggs were unsuccessful. Molecular characterisation of the organism placed it as a novel member of the genus Enterococcus. Disease Risk Analyses including this organism should now be factored into conservation management actions and island biosecurity. PMID:28727845

Encephalitozoonosis in two inland bearded dragons (Pogona vitticeps).

PubMed

Richter, B; Csokai, J; Graner, I; Eisenberg, T; Pantchev, N; Eskens, H U; Nedorost, N

2013-02-01

Microsporidiosis is reported rarely in reptiles. Sporadic multisystemic granulomatous disease of captive bearded dragons (Pogona vitticeps) has been associated with microsporidia showing Encephalitozoon-like morphology. Two such cases are described herein. Both animals displayed clinical signs suggestive of renal failure. Necropsy examination revealed granulomatous lesions in the liver and adrenal area in both animals, and in several other organs in one animal. The lesions were associated with intracellular protozoa consistent with microsporidia. Ultrastructural examination of the organisms revealed morphology similar to Encephalitozoon spp. Immunohistochemistry and chromogenic in-situ hybridization for Encephalitozoon cuniculi were positive in both animals. Nucleotide sequencing of the partial small subunit ribosomal RNA gene and the complete internal transcribed spacer (ITS) region revealed high similarity with published E. cuniculi sequences in both animals. However, the ITS region showed a GTTT-repeat pattern distinct from mammalian E. cuniculi strains. This may be a novel E. cuniculi strain associated with multisystemic granulomatous disease in bearded dragons. Copyright © 2012 Elsevier Ltd. All rights reserved.

A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury

PubMed Central

Jodele, Sonata; Laskin, Benjamin L; Dandoy, Christopher E.; Myers, Kasiani C.; El-Bietar, Javier; Davies, Stella M.; Goebel, Jens; Dixon, Bradley P.

2015-01-01

Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is now a well-recognized and potentially severe complication of HSCT that carries a high risk of death. In those who survive, TA-TMA may be associated with long-term morbidity and chronic organ injury. Recently, there have been new insights into the incidence, pathophysiology, and management of TA-TMA. Specifically, TA-TMA can manifest as a multi-system disease occurring after various triggers of small vessel endothelial injury, leading to subsequent tissue damage in different organs. While the kidney is most commonly affected, TA-TMA involving organs such as the lung, bowel, heart, and brain is now known to have specific clinical presentations. We now review the most up-to-date research on TA-TMA, focusing on the pathogenesis of endothelial injury, the diagnosis of TA-TMA affecting the kidney and other organs, and new clinical approaches to the management of this complication after HSCT. PMID:25483393

[BIPOLAR DISORDER AS A MULTI-SYSTEM ILLNESS].

PubMed

Fenchel, Daphna; Levkovitz, Yechiel; Kotler, Moshe

2017-12-01

Bipolar disorder is a chronic condition, characterized by high distress in patients and high suicide rates (30%). Most patients suffer from medical and other psychiatric comorbidities, which worsen the psychiatric symptoms and decrease the likelihood of remission. More than 70% of bipolar patients have cardio-metabolic symptoms, with higher rates compared to other psychiatric disorders. Cardiovascular disease is the major cause of high mortality rates in these patients, with 1.5-2 fold increased risk of mortality, compared to the general population without psychiatric symptoms. The rates of cardiovascular risk factors and their resulting increased mortality rates are similar to those found in schizophrenia. In addition to cardio-metabolic conditions, 50% of patients with bipolar disorder suffer from other medical symptoms, which are also associated with worse outcomes. Therefore, the current perspective is that bipolar disorder is not only a psychiatric disorder, but rather a multi-system illness, affecting the entire body. The optimal treatment for these patients should include diagnosis, monitoring and treatment of both psychiatric and physical symptoms, which would improve their prognosis.

Legionella pneumonia in the Niagara Region, Ontario, Canada: a case series.

PubMed

Cargnelli, Stephanie; Powis, Jeff; Tsang, Jennifer L Y

2016-12-01

Legionella pneumophila, a major cause of Legionnaires' disease, accounts for 2-15 % of all community-acquired pneumonia requiring hospitalization and up to 30 % of community-acquired pneumonia requiring intensive care unit admission. Early initiation of appropriate antimicrobial therapy is a crucial step in the prevention of morbidity and mortality. However, recognition of Legionnaires' disease continues to be challenging because of its nonspecific clinical features. We sought to describe hospitalized community-acquired Legionnaires' disease to increase awareness of this important and potentially lethal disease. A retrospective multicenter observational study was conducted with all patients with confirmed Legionnaires' disease in the Niagara Region of the Province of Ontario, Canada, from June to December 2013. From June to December 2013, there were 14 hospitalized cases of Legionnaires' disease in the Niagara Region. Of these, 86 % (12 patients) had at least one comorbidity and 71 % (10 patients) were cigarette smokers. In our cohort, Legionnaires' disease was diagnosed with a combination of a urinary Legionella antigen test and a Legionella real-time polymerase chain reaction assay. Delay in effective antimicrobial therapy in the treatment of Legionella infection led to clinical deterioration. The majority of patients had met systemic inflammatory response syndrome criteria with fever >38 °C (71 %), heart rate >90 beats per minute (71 %), and respiratory rate >20 breaths per minute (86 %). Eleven patients (79 %) required admission to the intensive care unit or step-down unit, and nine patients (64 %) required intubation. Clinical improvement after initiation of antimicrobials was protracted. Legionnaires' disease should be considered during the late spring and summer months in patients with a history of tobacco use and various comorbidities. Clinically, patients presented with severe, nonspecific, multisystem disease characterized by shortness of breath, abnormal vital signs, and laboratory derangements including hyponatremia, elevated creatine kinase, and evidence of organ dysfunction. In addition, antimicrobial therapy with newer macrolides or respiratory fluoroquinolones should be initiated for severe community-acquired pneumonia requiring intensive care unit admission, prior to laboratory confirmation of diagnosis, especially when a clinical suspicion of Legionella infection exists.

Further Insights in Trichothiodistrophy: A Clinical, Microscopic, and Ultrastructural Study of 20 Cases and Literature Review

PubMed Central

Ferrando, Juan; Mir-Bonafé, José M.; Cepeda-Valdés, Rodrigo; Domínguez, Anna; Ocampo-Candiani, Jorge; García-Veigas, Javier; Gómez-Flores, Minerva; Salas-Alanis, Julio C.

2012-01-01

Background: Trichothiodistrophy (TTD) is a rare autosomal recessive condition that is characterized by a specific congenital hair shaft dysplasia caused by deficiency of sulfur associated with a wide spectrum of multisystem abnormalities. In this article, we study clinical, microscopic, and ultrastructural findings of 20 patients with TTD with the aim to add further insights regarding to this rare condition. Additionally, analyses of our results are compared with those extracted from the literature in order to enhance its comprehensibility. Materials and Methods: Twenty cases of TTD were included: 7 from Mexico and 14 from Spain. Clinical, microscopic, scanning electron microscopy (SEM) studies and X-ray microanalysis (XrMa) were carried out in all of them. Genetic studies were performed in all seven Mexican cases. Patients with xeroderma pigmentosum and xeroderma pigmentosum/TTD-complex were excluded. Results: Cuticular changes and longitudinal crests of the hair shaft were demonstrated. These crests were irregular, disorganized, following the hair longest axis. Hair shaft sulfur deficiency was disposed discontinuously and intermittently rather than uniformly. This severe decrease of sulfur contents was located close to the trichoschisis areas. Only five patients did not show related disturbances. Micro-dolichocephaly was observed in five cases and represented the most frequent facial dysmorphism found. It is also remarkable that all patients with urologic malformations also combined diverse neurologic disorders. Moreover, three Mexican sisters demonstrated the coexistence of scarce pubic vellus hair, developmental delay, onychodystrophy, and maxillar/mandibullar hypoplasia. Conclusions: TTD phenotype has greatly varied from very subtle forms to severe alterations such as neurologic abnormalities, blindness, lamellar ichthyosis and gonadal malformations. Herein, a multisystem study should be performed mandatorily in patients diagnosed with TTD. PMID:23180925

The Cognitive and Behavioural Phenotype of Roifman Syndrome

ERIC Educational Resources Information Center

de Vries, P. J.; McCartney, D. L.; McCartney, E.; Woolf, D.; Wozencroft, D.

2006-01-01

Background: Roifman syndrome (OMIM 300258) is a multi-system disorder with a physical phenotype that includes B-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and characteristic facial dysmorphism. So far, six cases, all boys, have been reported in the literature. Roifman…

Constitutional mutations in RTEL1 cause severe dyskeratosis congenita.

PubMed

Walne, Amanda J; Vulliamy, Tom; Kirwan, Michael; Plagnol, Vincent; Dokal, Inderjeet

2013-03-07

Dyskeratosis congenita (DC) and its phenotypically severe variant, Hoyeraal-Hreidarsson syndrome (HHS), are multisystem bone-marrow-failure syndromes in which the principal pathology is defective telomere maintenance. The genetic basis of many cases of DC and HHS remains unknown. Using whole-exome sequencing, we identified biallelic mutations in RTEL1, encoding a helicase essential for telomere maintenance and regulation of homologous recombination, in an individual with familial HHS. Additional screening of RTEL1 identified biallelic mutations in 6/23 index cases with HHS but none in 102 DC or DC-like cases. All 11 mutations in ten HHS individuals from seven families segregated in an autosomal-recessive manner, and telomere lengths were significantly shorter in cases than in controls (p = 0.0003). This group had significantly higher levels of telomeric circles, produced as a consequence of incorrect processing of telomere ends, than did controls (p = 0.0148). These biallelic RTEL1 mutations are responsible for a major subgroup (∼29%) of HHS. Our studies show that cells harboring these mutations have significant defects in telomere maintenance, but not in homologous recombination, and that incorrect resolution of T-loops is a mechanism for telomere shortening and disease causation in humans. They also demonstrate the severe multisystem consequences of its dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Trauma operating room in conjunction with an air ambulance system: indications, interventions, and outcomes.

PubMed

Law, D K; Law, J K; Brennan, R; Cleveland, H C

1982-09-01

We report a retrospective study of 198 trauma patients brought directly to a trauma operating room by an air ambulance system. Despite rapid transport, expert prehospital resuscitation, and the capability of early surgical intervention, the overall mortality was high (57%). There was no significant salvage of patients arriving without pulse, blood pressure or cardiac activity. Optimal trauma care failed to show encouraging results in this preselected group of patients with predominantly blunt and multisystem injury. The justification and cost effectiveness of this system of trauma care is discussed.

Narrowing the wingless-2 mutation to a 227 Kb candidate region on chicken chromosome 12

USDA-ARS?s Scientific Manuscript database

Wingless-2 (wg-2) is an autosomal recessive mutation in chicken that results in an embryonic lethal condition. Affected individuals exhibit a multisystem syndrome characterized by absent wings, truncated legs, and craniofacial, kidney, and feather malformations. Previously, work focused on phenotype...

Treating Pediatric Obesity Using an Empirically Supported Treatment: A Case Report

ERIC Educational Resources Information Center

Cunningham, Phillippe B.; Ellis, Deborah A.; Naar-King, Sylvie

2010-01-01

Overweight and obesity are increasing dramatically in the United States of America, especially among children. Effective treatment of the multiple risk factors that promote youth obesity requires treatment approaches that are flexible and comprehensive enough to address each of these factors. One such treatment approach is Multisystemic Therapy…

Discovery of Antinuclear Antibodies in Pigs Infected with Porcine Circovirus Type 2

USDA-ARS?s Scientific Manuscript database

Introduction. Porcine circovirus type 2 (PCV2) causes post-weaning-multisystemic-wasting-syndrome (PMWS), a swine disease first observed in Canada in 1991 (1). It is characterized by general wasting, respiratory disease, jaundice and pallor in young pigs resulting in production losses and variable...

Renal failure as a suspected adverse reaction to benoxaprofen

PubMed Central

Fine, Wilfred; Tallis, R. C.; Osman, K. M.

1982-01-01

A 77-year-old woman suffering from osteoarthritis was treated with benoxaprofen. She developed diarrhoea, skin rash and renal failure. Renal failure has not been reported before as an adverse reaction to benoxaprofen. The case is discussed in the context of multisystem and immunological response to benoxaprofen. PMID:6213949

Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.

PubMed

Mao, Mao; Alavi, Marcel V; Labelle-Dumais, Cassandre; Gould, Douglas B

2015-01-01

Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry.

PubMed

Tilson, Hugh; Primatesta, Paola; Kim, Dennis; Rauer, Barbara; Hawkins, Philip N; Hoffman, Hal M; Kuemmerle-Deschner, Jasmin; van der Poll, Tom; Walker, Ulrich A

2013-09-10

The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare hereditary autoinflammatory diseases and encompass Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody directed against IL-1 beta and approved for CAPS patients but requires post-approval monitoring due to low and short exposures during the licensing process. Creative approaches to observational methodology are needed, harnessing novel registry strategies to ensure Health Care Provider reporting and patient monitoring. A web-based registry was set up to collect information on long-term safety and effectiveness of canakinumab for CAPS. Starting in November 2009, this registry enrolled 241 patients in 43 centers and 13 countries by December 31, 2012. One-third of the enrolled population was aged < 18; the overall population is evenly divided by gender. Enrolment is ongoing for children. Innovative therapies in orphan diseases require post-approval structures to enable in depth understanding of safety and natural history of disease. The rarity and distribution of such diseases and unpredictability of treatment require innovative methods for enrolment and follow-up. Broad international practice-based recruitment and web-based data collection are practical.

Evolving landscape in the management of transthyretin amyloidosis

PubMed Central

Hawkins, Philip N.; Ando, Yukio; Dispenzeri, Angela; Gonzalez-Duarte, Alejandra; Adams, David; Suhr, Ole B.

2015-01-01

Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease. PMID:26611723

Premature Ovarian Insufficiency - an update on recent advances in understanding and management

PubMed Central

Torrealday, Saioa; Kodaman, Pinar; Pal, Lubna

2017-01-01

Premature ovarian insufficiency is a complex and relatively poorly understood entity with a myriad of etiologies and multisystem sequelae that stem from premature deprivation of ovarian sex hormones. Timely diagnosis with a clear understanding of the various comorbidities that can arise from estrogen deficiency is vital to appropriately counsel and treat these patients. Prompt initiation of hormone therapy is critical to control the unsolicited menopausal symptoms that many women experience and to prevent long-term health complications. Despite ongoing efforts at improving our understanding of the mechanisms involved, any advancement in the field in recent decades has been modest at best and researchers remain thwarted by the complexity and heterogeneity of the underpinnings of this entity. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Ongoing research is clearly needed to allow pre-emptive identification of the at-risk population and to identify mechanisms that if addressed in a timely manner, can prolong ovarian function and physiology. PMID:29225794

Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal †

PubMed Central

Peres, Gonçalo Miguel; Mariana, Melissa

2018-01-01

Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy, considered major causes of maternal and perinatal death worldwide. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury. Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and classification of the disease are essential, since the therapies for the mild and severe forms of pre-eclampsia are different. Thus, this review aims to describe the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia applied in Portugal and based on several national and international available guidelines. Slow-release nifedipine is the most recommended drug for mild pre-eclampsia, and labetalol is the drug of choice for the severe form of the disease. Magnesium sulfate is used to prevent seizures caused by eclampsia. Corticosteroids are used for fetal lung maturation. Overall, the pharmacological prevention of these diseases is limited to low-dose aspirin, so it is important to establish the safest and most effective available treatment. PMID:29367581

Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap)

PubMed Central

Church, Leigh D; Savic, Sinisa; McDermott, Michael F

2008-01-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of inherited inflammatory disorders consisting of familial cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome). These rare disorders are associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NALP3 or cryopyrin, and inflammation driven by excessive production of the cytokine interleukin-1β (IL-1β). Amyloidosis is a serious complication with 25% of MWS patients developing amyloidosis, with occasional fatal consequences, whilst up to 20% of CINCA/NOMID patients die from various complications, before reaching the early adulthood. In some CINCA/NOMID adult survivors amyloidosis can also occur. Prior to the discovery of the CIAS1 gene mutations and the advent of IL-1 targeted therapy, treatment was aimed at suppressing inflammation, with limited success. The selective blockade of IL-1β, with anakinra (IL-1 receptor antagonist), not only provided supportive evidence for the role of IL-1β in CAPS, but also demonstrated the efficacy of targeting IL-1β for treatment of these conditions. In February, 2008, ‘Orphan Drug’ approval from the Food and Drug Administration (FDA) for rilonacept (IL-1 Trap/Arcalyst™, Regeneron Pharmaceuticals, Inc) was given for the treatment of two CAPS disorders, FCAS and MWS in adults and children 12 years and older, making rilonacept the first therapy approved for the treatment of CAPS. PMID:19707454

Understanding Teachers' Perceptions of Student Support Systems in Relation to Teachers' Stress

ERIC Educational Resources Information Center

Ball, Annahita; Anderson-Butcher, Dawn

2014-01-01

Expanded school mental health (ESMH) programs are critical for addressing children's social and emotional development in schools. As broad, multisystem approaches, ESMH programs rely on teachers for effective and sustainable primary, secondary, and tertiary school mental health service delivery. In light of the increasing mental health needs…

Ordinary Families, Special Children: A Systems Approach to Childhood Disability. Third Edition

ERIC Educational Resources Information Center

Seligman, Milton; Darling, Rosalyn Benjamin

2007-01-01

Now in a revised and expanded third edition, this popular clinical reference and text provides a multisystems perspective on childhood disability and its effects on family life. The volume examines how child, family, ecological, and sociocultural variables intertwine to shape the ways families respond to disability, and how professionals can…

Disseminated yeast (Order Saccharomycetales) infection in a Muscovy duckling (Cairina moschata)

PubMed Central

Ravi, Madhu; Hill, Janet E.; Fernando, Champika; Wobeser, Gary

2016-01-01

A Muscovy duckling was presented for necropsy due to ongoing mortalities on a farm. Microscopic examination revealed multisystemic inflammatory lesions with intralesional and intracytoplasmic yeast-like organisms. We identified these agents as yeast belonging to the Order Saccharomycetales based on sequence data obtained from the ribosomal RNA operon. PMID:27807382

Annual Research Review: What is Resilience within the Social Ecology of Human Development?

ERIC Educational Resources Information Center

Ungar, Michael; Ghazinour, Mehdi; Richter, Jorg

2013-01-01

Background: The development of Bronfenbrenner's bio-social-ecological systems model of human development parallels advances made to the theory of resilience that progressively moved from a more individual (micro) focus on traits to a multisystemic understanding of person-environment reciprocal processes. Methods: This review uses…

Microglossia in three littermate puppies.

PubMed

Wiggs, R B; Lobprise, H B; de Lahunta, A

1994-12-01

Three of five two-day-old Miniature Schnauzer puppies were diagnosed as having 'bird-tongue,' a microglossia that prevents normal nursing. With intensive nursing care, the puppies survived to seven weeks of age, then deteriorated and were euthanized. From clinical and pathological examinations, a multi-system defect is suspected, though no primary neuromuscular abnormality could be determined.

Adolescent Sexual Behavior in Two Ethnic Minority Groups: A Multisystem Perspective.

ERIC Educational Resources Information Center

Miller, Kim S.; Forehand, Rex; Kotchick, Beth A.

2000-01-01

Black and Hispanic adolescents (N=907) and their mothers were interviewed concerning the adolescents' experiences with penile-vaginal intercourse. Factors from three systems (self, family, and extrafamilial) that are influential in the lives of adolescents were evaluated using four outcome measures. Factors from most or all systems emerged as…

From mTOR to Cognition: Molecular and Cellular Mechanisms of Cognitive Impairments in Tuberous Sclerosis

ERIC Educational Resources Information Center

Ehninger, D.; de Vries, P. J.; Silva, A. J.

2009-01-01

Background: Tuberous sclerosis (TSC) is a multi-system disorder caused by heterozygous mutations in the "TSC1" or "TSC2" gene and is often associated with neuropsychiatric symptoms, including intellectual disability, specific neuropsychological deficits, autism, other behavioural disorders and epilepsy. Method: Here, we review evidence from animal…

A Diagnosis to Consider in an Adult Patient with Facial Features and Intellectual Disability: Williams Syndrome.

PubMed

Doğan, Özlem Akgün; Şimşek Kiper, Pelin Özlem; Utine, Gülen Eda; Alikaşifoğlu, Mehmet; Boduroğlu, Koray

2017-03-01

Williams syndrome (OMIM #194050) is a rare, well-recognized, multisystemic genetic condition affecting approximately 1/7,500 individuals. There are no marked regional differences in the incidence of Williams syndrome. The syndrome is caused by a hemizygous deletion of approximately 28 genes, including ELN on chromosome 7q11.2. Prenatal-onset growth retardation, distinct facial appearance, cardiovascular abnormalities, and unique hypersocial behavior are among the most common clinical features. Here, we report the case of a patient referred to us with distinct facial features and intellectual disability, who was diagnosed with Williams syndrome at the age of 37 years. Our aim is to increase awareness regarding the diagnostic features and complications of this recognizable syndrome among adult health care providers. Williams syndrome is usually diagnosed during infancy or childhood, but in the absence of classical findings, such as cardiovascular anomalies, hypercalcemia, and cognitive impairment, the diagnosis could be delayed. Due to the multisystemic and progressive nature of the syndrome, accurate diagnosis is critical for appropriate care and screening for the associated morbidities that may affect the patient's health and well-being.

A multisystemic Acanthamoeba infection in a dog in Tenerife, Canary Islands, Spain.

PubMed

Valladares, María; Reyes-Batlle, María; Mora-Peces, Inmaculada; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Dorta-Gorrín, Alexis; Comyn-Afonso, Estefanía; Martínez-Carretero, Enrique; Maciver, Sutherland K; Piñero, José E; Valladares, Basilio; Lorenzo-Morales, Jacob

2014-10-15

A 22-month-old male Spanish water dog was hospitalized after its physical examination revealed fever and movement difficulty. After 24h, the dog was found to have a high fever (39.5 °C) and was treated empirically with doxycycline/ciprofloxacin. At 48 h, after submission the fever rose to 41 °C and the animal presented with a stiff neck and dehydration. Peripheral blood and cerebrospinal fluid (CSF) were sampled and trophozoites with an Acanthamoeba-like morphology were observed in the CSF. PCR specific for Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris were performed and the CSF sample found positive for Acanthamoeba. Lungs, kidney, liver and spleen samples were collected post mortem. All collected organ samples were positive for Acanthamoeba by PCR, thus confirming a multisystemic infection. Water samples taken at a suspected site of infection yielded an almost identical PCR fragment to those of the clinical samples, indicating that this was probably where the infection originated. This is the first report of a fatal case of Acanthamoeba disseminated infection in a dog in Spain. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative, competitive PCR analysis of porcine circovirus DNA in serum from pigs with postweaning multisystemic wasting syndrome.

PubMed

Liu, Q; Wang, L; Willson, P; Babiuk, L A

2000-09-01

A competitive PCR (cPCR) assay was developed for monitoring porcine circovirus (PCV) DNA in serum samples from piglets. The cPCR was based on competitive coamplification of a 502- or 506-bp region of the PCV type 1 (PCV1) or PCV2 ORF2, respectively, with a known concentration of competitor DNA, which produced a 761- or 765-bp fragment, respectively. The cPCR was validated by quantification of a known amount of PCV wild-type plasmids. We also used this technique to determine PCV genome copy numbers in infected cells. Furthermore, we measured PCV DNA loads in clinical samples. More than 50% of clinically healthy piglets could harbor both types of PCV. While PCV1 was detected in only 3 of 16 pigs with postweaning multisystemic wasting syndrome (PMWS), all the sick piglets contained PCV2. A comparison of the PCV2 DNA loads of healthy and sick animals revealed a significant difference, indicating that the development of PMWS may require a certain amount of PCV2.

Recapitulating muscle disease phenotypes with myotonic dystrophy 1 iPS cells: a tool for disease modeling and drug discovery.

PubMed

Mondragon-Gonzalez, Ricardo; Perlingeiro, Rita C R

2018-06-13

Myotonic Dystrophy 1 (DM1) is a multi-system disorder primarily affecting the central nervous system, heart and skeletal muscle. It is caused by an expansion of the CTG trinucleotide repeats in the 3' untranslated region of the DMPK gene. Although patient myoblasts have been used for studying the disease in vitro , the invasiveness as well as the low accessibility to muscle biopsies motivate the development of alternative reliable myogenic models. Here, we established two DM1 iPS cell lines from patient-derived fibroblasts, and using the PAX7 conditional expression system, differentiated these into myogenic progenitors, and subsequently, terminally differentiated myotubes. Both DM1 myogenic progenitors and myotubes were found to express the intranuclear RNA foci exhibiting sequestration of MBNL1. Moreover, we found the DM1-related mis-splicing, namely BIN1 exon 11 in DM1 myotubes. We use this model to test a specific therapy, antisense oligonucleotide treatment, and find that this efficiently abolished RNA foci and rescued BIN1 mis-splicing in DM1 iPS cell-derived myotubes. Together, our results demonstrate that myotubes derived from DM1 iPS cells recapitulate the critical molecular features of DM1 and are sensitive to ASO treatment, confirming that these cells can be used for in vitro disease modeling and candidate drug testing or screening. © 2018. Published by The Company of Biologists Ltd.

Management of hypertension in pregnancy.

PubMed

Chung, N A; Beevers, D G; Lip, G Y

2001-01-01

Hypertension is an important cause of both maternal and fetal morbidity and mortality in pregnant women. There are still no definitive guidelines as to when and how patients should be treated, but it is important that appropriate treatment is initiated early in patients at highest risk and they are closely monitored. Hypertension in pregnancy can be a difficult condition to diagnose and treat because of the numerous and differing classification systems that have been used in the past. One classification system, which accounts for the multisystem involvement which can occur in pre-eclampsia and eclampsia, divides hypertension in pregnancy into 3 main groups: pre-eclampsia, gestational hypertension and chronic hypertension. Little benefit to the fetus has been shown from treating gestational and chronic hypertension, but studies in this area have been small and would not have had the power to show a difference in outcome between treated and untreated groups. However, the reduction in morbidity and mortality in the treatment of pre-eclampsia is significant. Therefore, all pregnancies complicated by hypertension require monitoring to detect the possible onset of superimposed pre-eclampsia/eclampsia. Institutions should have a management strategy for those mothers with severe hypertension including a multidisciplinary approach, where the patient is to be monitored and which antihypertensive agents are to be used. It should not be forgotten that the definitive treatment for severe hypertension is delivery of the fetus despite risks to fetal morbidity and mortality. This will reduce blood pressure, but hypertension per se may still persist post partum requiring short term therapy.

Sarcoid-like reactions in patients receiving modern melanoma treatment.

PubMed

Dimitriou, Florentia; Frauchiger, Anna L; Urosevic-Maiwald, Mirjana; Naegeli, Mirjam C; Goldinger, Simone M; Barysch, Marjam; Franzen, Daniel; Kamarachev, Jivko; Braun, Ralph; Dummer, Reinhard; Mangana, Joanna

2018-06-01

The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today's standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features. We carried out a single-center observational study in patients with stage IIB-IV melanoma treated with BRAF/MEK inhibitors and immune checkpoint inhibitors. A description of the sarcoidosis-related manifestations was provided from patients' records. We observated eight cases of SLRs in a cohort of 200 patients. The clinical courses were characterized by a variety of symptoms, accompanied by cutaneous signs and extracutaneous manifestations such as bilateral, hilar lymphadenopathy. We identified a histologically granulomatous inflammation involving the skin, the lungs, and the lymph nodes. Two patients presented with cutaneous lesions only, and three patients had lung involvement only. Three patients achieved complete and partial response of the melanoma disease, and three patients had stable disease. Disease progression was documented in two patients. The reported immune-related adverse events were mild to severe and in most of the cases were continued without any treatment cessation. SLRs appear during treatment with both kinase and immune checkpoint inhibitors. Awareness of these can avoid misdiagnosis of disease progression and unnecessary treatment changes.

Biomarker Discovery by Modeling Behçet's Disease with Patient-Specific Human Induced Pluripotent Stem Cells.

PubMed

Son, Mi-Young; Kim, Young-Dae; Seol, Binna; Lee, Mi-Ok; Na, Hee-Jun; Yoo, Bin; Chang, Jae-Suk; Cho, Yee Sook

2017-01-15

Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. In this study, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells. Based on comparative transcriptome analysis using our BD model cells, we identified eight novel BD-specific genes, AGTR2, CA9, CD44, CXCL1, HTN3, IL-2, PTGER4, and TSLP, which were differentially expressed in BD patients compared with healthy controls or patients with other immune diseases. The use of CXCL1 as a BD biomarker was further validated at the protein level using both a BD iPSC-HPC-based assay system and BD patient serum samples. Furthermore, we show that our BD iPSC-HPC-based drug screening system is highly effective for testing CXCL1 BD biomarkers, as determined by monitoring the efficacy of existing anti-inflammatory drugs. Our results shed new light on the usefulness of patient-specific iPSC technology in the development of a benchmarking platform for disease-specific biomarkers, phenotype- or target-driven drug discovery, and patient-tailored therapies.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

PubMed

Kim, Bo Eun; Koh, Kyung-Nam; Suh, Jin Kyung; Im, Ho Joon; Song, Joon Sup; Lee, Ji Won; Kang, Hyoung Jin; Park, Kyung Duck; Shin, Hee Young; Choi, Hyoung Soo; Lee, Soo Hyun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Jung, Hye Lim; Chung, Nak-Gyun; Cho, Bin; Kim, Hack Ki; Lyu, Chuhl Joo; Baek, Hee Jo; Kook, Hoon; Park, Jun Eun; Park, Hyeon Jin; Park, Byung-Kiu; Yoo, Eun Sun; Ryu, Kyung Ha; Lee, Kun Soo; Kim, Heung Sik; Lee, Jae Min; Park, Eun Sil; Yoon, Hoi Soo; Lee, Kwang Chul; Lee, Mee Jeong; Lim, Young Tak; Kim, Hwang Min; Park, Sang Kyu; Park, Jeong-A; Kim, Soon Ki; Park, Meerim; Lim, Yeon-Jung; Lee, Young Ho; Seo, Jong Jin

2014-03-01

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

The Obesity Prevention Initiative: A Statewide Effort to Improve Child Health in Wisconsin.

PubMed

Adams, Alexandra K; Christens, Brian; Meinen, Amy; Korth, Amy; Remington, Patrick L; Lindberg, Sara; Schoeller, Dale

2016-11-01

Obesity rates have increased dramatically, especially among children and disadvantaged populations. Obesity is a complex issue, creating a compelling need for prevention efforts in communities to move from single isolated programs to comprehensive multisystem interventions. To address these issues, we have established a childhood Obesity Prevention Initiative (Initiative) for Wisconsin. This Initiative seeks to test community change frameworks that can support multisystem interventions and provide data for local action as a means for influencing policies, systems, and environments that support individuals’ healthy eating and physical activity. The Initiative is comprised of three components: (1) infrastructure to support a statewide obesity prevention and health promotion network with state- and local-level public messaging and dissemination of evidence-based solutions (healthTIDE); (2) piloting a local, multisetting community-led intervention study in 2 Wisconsin counties; and (3) developing a geocoded statewide childhood obesity and fitness surveillance system. This Initiative is using a new model that involves both coalition action and community organizing to align resources to achieve health improvement at local and state levels. We expect that it will help lead to the implementation of cohesive and sustainable policy, system, and environment health promotion and obesity prevention strategies in communities statewide, and it has the potential to help Wisconsin become a national model for multisetting community interventions to address obesity. Addressing individual-level health through population-level changes ultimately will result in reductions in the prevalence of childhood obesity, current and future health care costs, and chronic disease mortality.

The Obesity Prevention Initiative: A Statewide Effort to Improve Child Health in Wisconsin.

PubMed

Adams, Alexandra K; Christens, Brian; Meinen, Amy; Korth, Amy; Remington, Patrick L; Lindberg, Sara; Schoeller, Dale

2016-11-01

Obesity rates have increased dramatically, especially among children and disadvantaged populations. Obesity is a complex issue, creating a compelling need for prevention efforts in communities to move from single isolated programs to comprehensive multisystem interventions. To address these issues, we have established a childhood Obesity Prevention Initiative (Initiative) for Wisconsin. This Initiative seeks to test community change frameworks that can support multisystem interventions and provide data for local action as a means for influencing policies, systems, and environments that support individuals' healthy eating and physical activity. The Initiative is comprised of three components: (1) infrastructure to support a statewide obesity prevention and health promotion network with state- and local-level public messaging and dissemination of evidence-based solutions (healthTIDE); (2) piloting a local, multisetting community-led intervention study in 2 Wisconsin counties; and (3) developing a geocoded statewide childhood obesity and fitness surveillance system. This Initiative is using a new model that involves both coalition action and community organizing to align resources to achieve health improvement at local and state levels. We expect that it will help lead to the implementation of cohesive and sustainable policy, system, and environment health promotion and obesity prevention strategies in communities statewide, and it has the potential to help Wisconsin become a national model for multisetting community interventions to address obesity. Addressing individual-level health through population-level changes ultimately will result in reductions in the prevalence of childhood obesity, current and future health care costs, and chronic disease mortality.

Gorlin-Goltz Syndrome: Case report and literature review

PubMed Central

Ramesh, Maya; Krishnan, Ramesh; Chalakkal, Paul; Paul, George

2015-01-01

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, with complete penetrance and variable expressivity, though sporadic cases have been described. This article includes a case report and an extensive review of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumor and treatment modalities. PMID:26604511

Gorlin-Goltz Syndrome: Case report and literature review.

PubMed

Ramesh, Maya; Krishnan, Ramesh; Chalakkal, Paul; Paul, George

2015-01-01

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, with complete penetrance and variable expressivity, though sporadic cases have been described. This article includes a case report and an extensive review of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumor and treatment modalities.

Central Nervous System Brucellosis Granuloma and White Matter Disease in Immunocompromised Patient.

PubMed

Alqwaifly, Mohammed; Al-Ajlan, Fahad S; Al-Hindi, Hindi; Al Semari, Abdulaziz

2017-06-01

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen.

76 FR 31951 - Energy Conservation Program for Certain Commercial and Industrial Equipment: Decision and Order...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... specific to the Carrier Super Modular Multi-System (SMMSi) variable refrigerant flow (VRF) multi-split... in this notice to test and rate its SMMSi VRF multi-split commercial heat pumps. DATES: This Decision... its SMMSi VRF multi-split products. Carrier must use the alternate test procedure provided in this...

Multisystem involvement of alveolar echinococcosis in a child.

PubMed

Kantarci, Mecit; Bayraktutan, Ummugulsum; Pirimoglu, Berhan; Ogul, Hayri; Oral, Akgun; Eren, Suat; Gundogdu, Betul

2014-11-13

Alveolar echinococcosis (AE) is a chronic progressive infestation inducing a slowly progressing, life-threatening tumor-like growth in the liver. It may spread to other organs by regional extension or hematogenous or lymphatic metastasis. Herein, we report a fifteen-year-old patient diagnosed with AE of the liver and simultaneous lung and brain metastasis with a literature review.

Cognitive, Emotional, Physical and Social Effects of Growth Hormone Treatment in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Hoybye, C; Thoren, M.; Bohm, B.

2005-01-01

Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of…

New Insights in the Clinical Understanding of Behçet's Disease

PubMed Central

Cho, Sung Bin; Cho, Suhyun

2012-01-01

Behçet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behçet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behçet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness. PMID:22187230

Genomics of Systemic Lupus Erythematosus: Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus.

PubMed

Hiraki, Linda T; Silverman, Earl D

2017-08-01

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

[Educational and Professional Qualifications of Adults With Myotonic Dystrophies - A Misleading Perception by the Myopathic Face?].

PubMed

Stahl, K; Wenninger, S; Schüller, A; Montagnese, F; Schoser, B

2016-04-01

Myotonic dystrophies types 1 and 2 (DM1 / DM2) are the most frequent inherited progressive, segmental progeroid, multisystemic neuromuscular diseases in adulthood. The executive impairment is one of the key disease features. The myopathic face triggers the general perception of DM1 patients being associated with a low educational level. We used a standardized questionnaire to evaluate educational levels in adults with genetically confirmed DM1 and DM2 in comparison to data of the general population. Investigated topics included the level of education, e. g. the highest university degree aquired. Out of a total cohort of 546 DM patients, 125 DM1 and 156 DM2 patients (51 %) participated in this study. There was no statistically significant difference between the two collectives as far as high school levels are concerned. 50.4 % of DM1 and 48.3 % of DM2 patients obtained the higher education entrance qualification compared to 29.6 % of the normal German population. However, there were significant differences between the two collectives in "spelling problems" (DM1 cohort: p = 0.039), "difficulty in mental arithmetic" (p = 0.043), and classification of patients "with learning difficulties" (p = 0.012). Misled by a myopathic face, many physicians associate myotonic dystrophy with cognitive deficiency. Based on our study, the minimal deviation between DM1 and DM2 and the normal German population indicates that the multisystemic disease does not significantly influence the maximum attainable level of education in adults with DM1. In summary, physicians should be aware that the general educational levels are rather normal in patients with myotonic dystrophy type 1 and rethink their perception of DM1 patients. © Georg Thieme Verlag KG Stuttgart · New York.

Sleep and Physiological Dysregulation: A Closer Look at Sleep Intraindividual Variability.

PubMed

Bei, Bei; Seeman, Teresa E; Carroll, Judith E; Wiley, Joshua F

2017-09-01

Variable daily sleep (ie, higher intraindividual variability; IIV) is associated with negative health consequences, but potential physiological mechanisms are poorly understood. This study examined how the IIV of sleep timing, duration, and quality is associated with physiological dysregulation, with diurnal cortisol trajectories as a proximal outcome and allostatic load (AL) as a multisystem distal outcome. Participants are 436 adults (Mage ± standard deviation = 54.1 ± 11.7, 60.3% women) from the Midlife in the United States study. Sleep was objectively assessed using 7-day actigraphy. Diurnal cortisol was measured via saliva samples (four/day for 4 consecutive days). AL was measured using 23 biomarkers from seven systems (inflammatory, hypothalamic-pituitary-adrenal axis, metabolic glucose and lipid, cardiovascular, parasympathetic, sympathetic) using a validated bifactor model. Linear and quadratic effects of sleep IIV were estimated using a validated Bayesian model. Controlling for covariates, more variable sleep timing (p = .04 for risetime, p = .097 for bedtime) and total sleep time (TST; p = .02), but not mean sleep variables, were associated with flatter cortisol diurnal slope. More variable sleep onset latency and wake after sleep onset, later average bedtime, and shorter TST were associated with higher AL adjusting for age and sex (p-values < .05); after controlling for all covariates, however, only later mean bedtime remained significantly associated with higher AL (p = .04). In a community sample of adults, more variable sleep patterns were associated with blunted diurnal cortisol trajectories but not with higher multisystem physiological dysregulation. The associations between sleep IIV and overall health are likely complex, including multiple biopsychosocial determinants and require further investigation. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Preliminary Results

NASA Technical Reports Server (NTRS)

Warren, L. E.; Paloski, William H.; Young, L. R.

2006-01-01

Artificial gravity paradigms may offer effective, efficient, multi-system protection from the untoward effects of adaptation to the microgravity of space or the hypogravity of planetary surfaces. Intermittent artificial gravity (AG) produced by a horizontal short-radius centrifuge (SRC) has recently been utilized on human test subjects deconditioned by bed rest. This presentation will review preliminary results of a 41 day study conducted at the University of Texas Medical Branch, Galveston, TX bed rest facility. During the first eleven days of the protocol, subjects were ambulatory, but confined to the facility. They began a carefully controlled diet, and participated in multiple baseline tests of bone, muscle, cardiovascular, sensory-motor, immunological, and psychological function. On the twelfth day, subjects entered the bed rest phase of the study, during which they were confined to strict 6deg head down tilt bed rest for 21 days. Beginning 24 hrs into this period, treatment subjects received one hour daily exposures to artificial gravity which was produced by spinning the subjects on a 3.0 m radius SRC. They were oriented radially in the supine position so that the centrifugal force was aligned with their long body axis, and while spinning, they "stood" on a force plate, supporting the centrifugal loading (2.5 g at the feet, 1.0 g at the heart). The subject station allowed free translation over approximately 10 cm to ensure full loading of the lower extremities and to allow for anti-orthostatic muscle contractions. Control subjects were positioned on the centrifuge but did not spin. Following the bed rest phase, subjects were allowed to ambulate again, but remained within the facility for an additional 9 days and participated in multiple follow-up tests of physiological function.

The Cardio-oncology Program: A Multidisciplinary Approach to the Care of Cancer Patients With Cardiovascular Disease.

PubMed

Parent, Sarah; Pituskin, Edith; Paterson, D Ian

2016-07-01

Improved cancer survivorship has resulted in a growing number of Canadians affected by cancer and cardiovascular disease. As a consequence, cardio-oncology programs are rapidly emerging to treat cancer patients with de novo and preexisting cardiovascular disease. The primary goal of a cardio-oncology program is to preserve cardiovascular health to allow the timely delivery of cancer therapy and achieve disease-free remission. Multidisciplinary programs in oncology and cardiology have been associated with enhanced patient well-being and improved clinical outcomes. Because of the complex needs of these multisystem patients, a similar model of care is gaining acceptance. The optimal composition of the cardio-oncology team will typically involve support from cardiology, oncology, and nursing. Depending on the clinical scenario, additional consultation from dietetics, pharmacy, and social services might be required. Timely access to consultation and testing is another prerequisite for cardio-oncology programs because delays in treating cardiac complications and nonadherence to prescribed cancer therapy are each associated with poor outcomes. Recommended reasons for referral to cardio-oncology programs include primary prevention for those at high risk for cardiotoxicity and the secondary treatment of new or worsening cardiovascular disease in cancer patients and survivors. Management is multifaceted and can involve lifestyle education, pharmacotherapy, enhanced cardiovascular surveillance, and support services, such as exercise training. The lack of evidence to guide clinical decisions and recommendations in cardio-oncology is a major challenge and opportunity for health care professionals. Large multicentre prospective registries are needed to adequately power risk model calculations and generate hypotheses for novel interventions. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS)

PubMed Central

Haverkamp, M H; van de Vosse, E; Goldbach-Mansky, R; Holland, S M

2014-01-01

Cryopyrin-associated periodic syndrome (CAPS) is characterized by dysregulated inflammation with excessive interleukin (IL)-1β activation and secretion. Neonatal-onset multi-system inflammatory disease (NOMID) is the most severe form. We explored cytokine responses in 32 CAPS patients before and after IL-1β blocking therapy. We measured cytokines produced by activated peripheral blood monuclear cells (PBMCs) from treated and untreated CAPS patients after stimulation for 48 h with phytohaemagglutinin (PHA), PHA plus IL-12, lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ. We measured IL-1β, IL-6, IL-10, tumour necrosis factor (TNF), IL-12p70 and IFN-γ in the supernatants. PBMCs from three untreated CAPS patients were cultured in the presence of the IL-1β blocker Anakinra. Fifty healthy individuals served as controls. CAPS patients had high spontaneous production of IL-1β, IL-6, TNF and IFN-γ by unstimulated cells. However, stimulation indexes (SIs, ratio of stimulated to unstimulated production) of these cytokines to PHA and LPS were low in NOMID patients compared to controls. Unstimulated IL-10 and IL-12p70 production was normal, but up-regulation after PHA and LPS was also low. LPS plus IFN-γ inadequately up-regulated the production of IL-1β, IL-6, TNF and IL-10 in CAPS patients. In-vitro but not in-vivo treatment with Anakinra improved SIs by lowering spontaneous cytokine production. However, in-vitro treatment did not improve the low stimulated cytokine levels. Activating mutations in NLRP3 in CAPS are correlated with poor SIs to PHA, LPS and IFN-γ. The impairment in stimulated cytokine responses in spite of IL-1β blocking therapy suggests a broader intrinsic defect in CAPS patients, which is not corrected by targeting IL-1β. PMID:24773462

Cryopyrin-associated periodic syndrome in Australian children and adults: Epidemiological, clinical and treatment characteristics.

PubMed

Mehr, Sam; Allen, Roger; Boros, Christina; Adib, Navid; Kakakios, Alyson; Turner, Paul J; Rogers, Maureen; Zurynski, Yvonne; Singh-Grewal, Davinder

2016-09-01

Cryopyrin-associated periodic syndromes (CAPS) encapsulate three auto-inflammatory conditions, ranging in severity from mild (familial cold auto-inflammatory syndrome: FCAS), moderate (Muckle-Wells syndrome: MWS) and severe (neonatal onset multi-inflammatory disorder: NOMID). We aimed to describe the epidemiology, clinical features and outcomes of Australian children and adults with CAPS. Patients were identified and clinical data collected through a questionnaire sent during 2012-2013 to clinicians reporting to the Australian Paediatric Surveillance Unit and subscribing to the Australasian Societies for Allergy/Immunology, Rheumatology and Dermatology. Eighteen cases of CAPS were identified (8 NOMID; 8 MWS, 2 FCAS); 12 in children <18 years of age. The estimated population prevalence of CAPS was 1 per million persons. Diagnostic delay was frequent, particularly in those with milder phenotypes (median diagnostic delay in MWS/FCAS 20.6 years compared with NOMID 2.1 years; P = 0.04). Common presenting features included urticaria (100%), periodic fever (78%), arthralgia (72%) and sensorineural hearing loss (61%). Almost all (90%) MWS patients had a family member similarly affected compared with none in the NOMID group (P = 0.004). A significant proportion of patients on anti-interleukin (IL)-1 therapy (n = 13) no longer had systemic inflammation. Only 50% with sensorineural hearing loss had hearing restored on anti-IL-1 therapy. Although CAPS are rare, patients often endured prolonged periods of systemic inflammation. This is despite almost all MWS patients having family members with similar symptoms and children with NOMID presenting with chronic infantile urticaria associated with multi-system inflammation. Hearing loss in NOMID/MWS was frequent, and reversible in only 50% of cases. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Development of a Multisystemic Parent Management Training Intervention for Incarcerated Parents, Their Children and Families

ERIC Educational Resources Information Center

Eddy, J. Mark; Martinez, Charles R.; Schiffmann, Tracy; Newton, Rex; Olin, Laura; Leve, Leslie; Foney, Dana M.; Shortt, Joann Wu

2008-01-01

The majority of men and women prison inmates are parents. Many lived with children prior to incarceration, and most have at least some contact with their children and families while serving their sentences. Because prison populations have increased in the United States, there has been a renewed interest in finding ways not only to reduce…

Gorlin syndrome.

PubMed

Devi, Basanti; Behera, Binodini; Patro, Sibasish; Pattnaik, Subhransu S; Puhan, Manas R

2013-05-01

Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.

What the Literature Tells Us: Relationships between Family Violence, School Behavior Problems, Juvenile Delinquency, and Adult Crime.

ERIC Educational Resources Information Center

Rudo, Zena H.

This paper constructs a multi-systemic picture of the impact of family violence on children, families, and society through a review of the empirical literature in these areas and their inter-relationships. Findings from the review include: (1) the experience of physical abuse has been associated with aggression toward others, children who have…

Central Nervous System Brucellosis Granuloma and White Matter Disease in Immunocompromised Patient

PubMed Central

Al-Ajlan, Fahad S.; Al-Hindi, Hindi; Al Semari, Abdulaziz

2017-01-01

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen. PMID:28518039

Exercise Attenuates the Major Hallmarks of Aging

PubMed Central

Garatachea, Nuria; Pareja-Galeano, Helios; Santos-Lozano, Alejandro; Fiuza-Luces, Carmen; Morán, María; Emanuele, Enzo; Joyner, Michael J.; Lucia, Alejandro

2015-01-01

Abstract Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people. PMID:25431878

Loeys–Dietz syndrome: a primer for diagnosis and management

PubMed Central

MacCarrick, Gretchen; Black, James H.; Bowdin, Sarah; El-Hamamsy, Ismail; Frischmeyer-Guerrerio, Pamela A.; Guerrerio, Anthony L.; Sponseller, Paul D.; Loeys, Bart; Dietz, Harry C.

2014-01-01

Loeys–Dietz syndrome is a connective tissue disorder predisposing individuals to aortic and arterial aneurysms. Presenting with a wide spectrum of multisystem involvement, medical management for some individuals is complex. This review of literature and expert opinion aims to provide medical guidelines for care of individuals with Loeys–Dietz syndrome. Genet Med 16 8, 576–587. PMID:24577266

Multimodality Imaging in Cardiac Sarcoidosis: Is There a Winner?

PubMed Central

Perez, Irving E.; Garcia, Mario J.; Taub, Cynthia C.

2016-01-01

Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect the heart. Cardiac sarcoidosis may be present in as many as 25% of patients with systemic sarcoidosis, and it is frequently underdiagnosed. The early and accurate diagnosis of myocardial involvement is challenging. Advanced imaging techniques play important roles in the diagnosis and management of patients with cardiac sarcoidosis. PMID:25784137

The Resilience of Kepler Multi-systems to Stellar Obliquity

NASA Astrophysics Data System (ADS)

Spalding, Christopher; Marx, Noah W.; Batygin, Konstantin

2018-04-01

The Kepler mission and its successor K2 have brought forth a cascade of transiting planets. Many of these planetary systems exhibit multiple transiting members. However, a large fraction possesses only a single transiting planet. This high abundance of singles, dubbed the "Kepler Dichotomy," has been hypothesized to arise from significant mutual inclinations between orbits in multi-planet systems. Alternatively, the single-transiting population truly possesses no other planets in the system, but the true origin of the overabundance of single systems remains unresolved. In this work, we propose that planetary systems typically form with a coplanar, multiple-planetary architecture, but that quadrupolar gravitational perturbations from their rapidly-rotating host star subsequently disrupt this primordial coplanarity. We demonstrate that, given sufficient stellar obliquity, even systems beginning with 2 planetary constituents are susceptible to dynamical instability soon after planet formation, as a result of the stellar quadrupole moment. This mechanism stands as a widespread, yet poorly explored pathway toward planetary system instability. Moreover, by requiring that observed multi-systems remain coplanar on Gyr timescales, we are able to place upper limits on the stellar obliquity in systems such as K2-38 (obliquity < 20 degrees), where other methods of measuring spin-orbit misalignment are not currently available.

Kcne2 Deletion Creates a Multisystem Syndrome Predisposing to Sudden Cardiac Death

PubMed Central

Hu, Zhaoyang; Kant, Ritu; Anand, Marie; King, Elizabeth C.; Krogh-Madsen, Trine; Christini, David J.; Abbott, Geoffrey W.

2014-01-01

Background Sudden cardiac death (SCD) is the leading global cause of mortality, exhibiting increased incidence in diabetics. Ion channel gene perturbations provide a well-established ventricular arrhythmogenic substrate for SCD. However, most arrhythmia susceptibility genes - including the KCNE2 K+ channel β subunit - are expressed in multiple tissues, suggesting potential multiplex SCD substrates. Methods and Results Using “whole transcript” transcriptomics, we uncovered cardiac angiotensinogen upregulation and remodeling of cardiac angiotensinogen interaction networks in P21 Kcne2−/− mouse pups, and adrenal remodeling consistent with metabolic syndrome in adult Kcne2−/− mice. This led to the discovery that Kcne2 disruption causes multiple acknowledged SCD substrates of extracardiac origin: diabetes, hypercholesterolemia, hyperkalemia, anemia and elevated angiotensin II. Kcne2 deletion was also prerequisite for aging-dependent QT prolongation, ventricular fibrillation and SCD immediately following transient ischemia, and fasting-dependent hypoglycemia, myocardial ischemia and atrioventricular block. Conclusions Disruption of a single, widely expressed arrhythmia susceptibility gene can generate a multisystem syndrome comprising manifold electrical and systemic substrates and triggers of SCD. This paradigm is expected to apply to other arrhythmia susceptibility genes, the majority of which encode ubiquitously expressed ion channel subunits or regulatory proteins. PMID:24403551

Ehlers–Danlos Syndrome—Hypermobility Type: A Much Neglected Multisystemic Disorder

PubMed Central

Gazit, Yael; Jacob, Giris; Grahame, Rodney

2016-01-01

Ehlers–Danlos syndrome (EDS)—hypermobility type (HT) is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems. PMID:27824552

[Streptococcal toxic shock syndrome].

PubMed

Gvozdenović, Ljiljana; Pasternak, Janko; Milovanović, Stanislav; Ivanov, Dejan; Milić, Sasa

2010-01-01

Streptococcal toxic shock syndrome is now recognized as a toxin-mediated, multisystem illness. It is characterized by an early onset of shock with multiorgan failure and continues to be associated with high morbidity and mortality, caused by group A Streptococcus pyogenes. The symptoms for staphylococcal and streptococcal toxic shock syndrome are similar. Streptococcal toxic shock syndrome was not well described until 1993, when children who had suffered from varicella presented roughly 2-4 weeks later with a clinical syndrome highly suggestive of toxic shock syndrome. It is characterized by a sudden onset of fever, chills, vomiting, diarrhea, muscle aches and rash. It can rapidly progress to severe and intractable hypotension and multisystem dysfunction. Almost every organ system can he involved. Complications of streptococcal toxic shock syndrome may include kidney failure, liver failure (and even death. Crystalloids and inotropic agents are used to treat the hypovolemic shock aggressively, with close monitoring of the patient's mean arterial pressure and central venous pressure. An immediate and aggressive management of hypovolemic shock is essential in streptococcal toxic shock syndrome. Targeted antibiotics are indicated: penicillin or a beta-lactam antibiotic is used for treating group A streptococci, and clindamycin has emerged as a key portion of the standard treatment.

The Therapeutic Potential of Anti-Inflammatory Exerkines in the Treatment of Atherosclerosis

PubMed Central

Yu, Megan; Tsai, Sheng-Feng; Kuo, Yu-Min

2017-01-01

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed “exerkines”) are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed. PMID:28608819

Judging sound rotation when listeners and sounds rotate: Sound source localization is a multisystem process.

PubMed

Yost, William A; Zhong, Xuan; Najam, Anbar

2015-11-01

In four experiments listeners were rotated or were stationary. Sounds came from a stationary loudspeaker or rotated from loudspeaker to loudspeaker around an azimuth array. When either sounds or listeners rotate the auditory cues used for sound source localization change, but in the everyday world listeners perceive sound rotation only when sounds rotate not when listeners rotate. In the everyday world sound source locations are referenced to positions in the environment (a world-centric reference system). The auditory cues for sound source location indicate locations relative to the head (a head-centric reference system), not locations relative to the world. This paper deals with a general hypothesis that the world-centric location of sound sources requires the auditory system to have information about auditory cues used for sound source location and cues about head position. The use of visual and vestibular information in determining rotating head position in sound rotation perception was investigated. The experiments show that sound rotation perception when sources and listeners rotate was based on acoustic, visual, and, perhaps, vestibular information. The findings are consistent with the general hypotheses and suggest that sound source localization is not based just on acoustics. It is a multisystem process.

[An approach to the patients with cryopyrin-associated periodic syndrome (CAPS) : a new biologic response modifier, canakinumab].

PubMed

Yokota, Shumpei; Kikuchi, Masako; Nozawa, Tomo; Kizawa, Toshiatsu; Kanetaka, Taichi; Miyamae, Takako; Mori, Masa-aki; Nishikomori, Ryohta; Takata, Hidetoshi; Heike, Toshio; Hara, Toshiro; Imagawa, Tomoyuki

2012-01-01

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of rare, but severe, autoinflammatory syndrome, and includes 3 distinct conditions, familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (MONID). These syndromes are characterized by urticarial-like rash, periodic fever, central nervous system inflammation, an arthropathy, and the risk of amyloidosis. About 20% die by age 20 years in the most severe cases. The disease is associated with mutations in the NLRP3 gene that encodes for the protein cryopyrin, a component of the inflammasome complex that regulates the production and secretion of IL-1β. Canakinumab is a human IgG monoclonal antibody targeting IL-1β. The clinical trials of canakinumab for patients with CAPS in both western countries and Japan were well-tolerated in most patients, and provided significant advantages over existing competitive therapies. Although no serious adverse effects have been reported, the frequencies of common infectious diseases including nasopharyngitis, upper respiratory tract infections, and gastroenteritis were reported presumably due to the blockade of proinflammatory cytokine, IL-1β. For us pediatrician, it will be important to be more careful for infectious diseases to provide the maximum safety of canakinumab for these patients.

Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry

PubMed Central

2013-01-01

Background The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare hereditary autoinflammatory diseases and encompass Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody directed against IL-1 beta and approved for CAPS patients but requires post-approval monitoring due to low and short exposures during the licensing process. Creative approaches to observational methodology are needed, harnessing novel registry strategies to ensure Health Care Provider reporting and patient monitoring. Methods A web-based registry was set up to collect information on long-term safety and effectiveness of canakinumab for CAPS. Results Starting in November 2009, this registry enrolled 241 patients in 43 centers and 13 countries by December 31, 2012. One-third of the enrolled population was aged < 18; the overall population is evenly divided by gender. Enrolment is ongoing for children. Conclusions Innovative therapies in orphan diseases require post-approval structures to enable in depth understanding of safety and natural history of disease. The rarity and distribution of such diseases and unpredictability of treatment require innovative methods for enrolment and follow-up. Broad international practice-based recruitment and web-based data collection are practical. PMID:24016338

Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presenting as acute meningoencephalitis: a case report.

PubMed

Hsu, Yu-Chuan; Yang, Fu-Chi; Perng, Cherng-Lih; Tso, An-Chen; Wong, Lee-Jun C; Hsu, Chang-Hung

2012-09-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Epileptic seizures are common features of both MELAS and meningoencephalitis and are typically treated with anticonvulsants. To provide the reader with a better understanding of MELAS and the adverse effects of valproic acid. A 47-year-old man with a history of diabetes, hearing loss, sinusitis, and otitis media was brought to our emergency department due to acute onset of fever, headache, generalized seizure, and agitation. Because acute meningoencephalitis was suspected, the patient was treated with antibiotics on an empirical basis. The seizure activity was aggravated by valproic acid and abated after its discontinuation. MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. Detailed history-taking and systematic review help emergency physicians differentiate MELAS from meningoencephalitis in patients with the common presentation of epileptic seizures. Use of valproic acid to treat epilepsy in patients suspected of having mitochondrial disease should be avoided. Underlying mitochondrial disease should be suspected if seizure activity worsens with valproic acid therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Growth hormone deficiency in a patient with mitochondrial disease.

PubMed

Rocha, Vera; Rocha, Dalila; Santos, Helena; Sales Marques, Jorge

2015-09-01

Mitochondrial respiratory chain (MRC) disorders, defined as primary diseases of the oxidative phosphorylation system, are a protean group of metabolic disorders, difficult to diagnose and classify. The diagnosis is complex and requires the integration of information obtained by clinical, laboratory testing, imaging and muscle biopsy. They may be associated with endocrine disorders, including hypothyroidism, diabetes mellitus, hyperinsulinemia and growth hormone (GH) deficiency. We describe a case of five years old male with polymalformative syndrome with a systemic involvement. At 6 months of age, he was sent to metabolic consultation because of facial dysmorphy and short stature. During the investigation it was diagnosed at the boy a growth hormone deficiency and because of his multisystemic involvement, muscle biopsy was carried out and showed reduced activity of complex II (38%) of the mitochondrial respiratory chain. Currently, the boy is under GH therapy with growth in the 5th percentile and coenzime Q10. Mitochondrial biology is one of the fastest growing areas in genetics and medicine. Disturbances in mitochondrial metabolism are now known to play a role not only in rare childhood diseases, but also in many common diseases of aging. In mitochondrial disorders, short stature is a common symptom, but its underlying lesion, growth hormone deficiency, is rarely investigated.

[POEMS syndrome with plasmocytoma lytic bone lesion].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Sibai, M; Rafai, M; El Moutawakkil, B; Bourezgui, M; Trafeh, M; Slassi, I

2008-01-01

Crow-Fukase or Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes syndrome (POEMS) is a rare multisystemic affection with incompletely elucidated etiopathogenesis. We report a case of POEMS syndrome in a 48-year-old adult revealed four months before admission by areflexic flask tetraparesis prevalent on the lower limbs in connection with demyelinating and axonal CIDP "like" sensoriomotor neuropathy of the four limbs electroneuromyographically. The patient presented elevated protein level in the CSF with monoclonal standard IgG gammapathy associated with a narrow band lambda, suggesting POEMS syndrome. Further explorations revealed skin lesions with glomeruloid angiomas, edematous vasomotor disorders as well as erythrocyanose, hypogonadism, papillar edema and a lytic bone lesion of the left scapula. Radiotherapy was associated with corticosteroids and plasma exchanges. Outcome was good with resolution of the symptoms and stabilization of the neuropathy. POEMS syndrome is rare; the diagnosis is based on necessary criteria, the presence of a demyelinating and axonal polyneuropathy associated with an IgA or IgG monoclonal gammapathy, the light chain being almost entirely lambda, associated to other characteristic elements, in particular glomeruloid angiomas, endocrinopathy, sclerosing plasmocytoma which must be carefully required. Treatment is based on surgical cure or radiotherapy for bone lesion and non specific treatments such as corticosteroid therapy, plasma exchanges and IVIG.

A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I.

PubMed

Mendez, Daniel C; Stover, Alexander E; Rangel, Anthony D; Brick, David J; Nethercott, Hubert E; Torres, Marissa A; Khalid, Omar; Wong, Andrew Ms; Cooper, Jonathan D; Jester, James V; Monuki, Edwin S; McGuire, Cian; Le, Steven Q; Kan, Shih-Hsin; Dickson, Patricia I; Schwartz, Philip H

2015-01-01

Mucopolysaccharidosis type I (MPS I) is an inherited α-L-iduronidase (IDUA, I) deficiency in which glycosaminoglycan (GAG) accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS) background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG) background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI) mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches.

Treatment with antioxidants ameliorates oxidative damage in a mouse model of propionic acidemia.

PubMed

Rivera-Barahona, Ana; Alonso-Barroso, Esmeralda; Pérez, Belén; Murphy, Michael P; Richard, Eva; Desviat, Lourdes R

2017-09-01

Oxidative stress contributes to the pathogenesis of propionic acidemia (PA), a life threatening disease caused by the deficiency of propionyl CoA-carboxylase, in the catabolic pathway of branched-chain amino acids, odd-number chain fatty acids and cholesterol. Patients develop multisystemic complications including seizures, extrapyramidal symptoms, basal ganglia deterioration, pancreatitis and cardiomyopathy. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species and oxidative damage, all of which have been documented in patients' samples and in a hypomorphic mouse model. Here we set out to investigate whether treatment with a mitochondria-targeted antioxidant, MitoQ, or with the natural polyphenol resveratrol, which is reported to have antioxidant and mitochondrial activation properties, could ameliorate the altered redox status and its functional consequences in the PA mouse model. The results show that oral treatment with MitoQ or resveratrol decreases lipid peroxidation and the expression levels of DNA repair enzyme OGG1 in PA mouse liver, as well as inducing tissue-specific changes in the expression of antioxidant enzymes. Notably, treatment decreased the cardiac hypertrophy marker BNP that is found upregulated in the PA mouse heart. Overall, the results provide in vivo evidence to justify more in depth investigations of antioxidants as adjuvant therapy in PA. Copyright © 2017 Elsevier Inc. All rights reserved.

How does the Canadian juvenile justice system respond to detained youth with substance use associated problems? Gaps, challenges, and emerging issues.

PubMed

Erickson, Patricia G; Butters, Jennifer E

2005-01-01

Despite a juvenile justice system that, since its inception in 1908, has been predicated on meeting the rehabilitative needs of youth, Canada has few specialized programs for substance misusing young offenders, preferring more holistic approaches. This is in keeping with an addictions treatment system that has evolved recently in the direction of more integrated services within the general health care and social services delivery systems. In addition, Canada has tended to emphasize community-based over institutional treatment programs. Nevertheless, for youth in conflict with the law, "substance abuse" is recognized as a significant risk factor for recidivism. The approximately 9000 young persons held in custodial facilities on any given day across the country are exposed to a variety of programs aimed at reducing antisocial behavior and hence, re-offending. Some of these have a substance use component. Programs for Aboriginal youth offer some of the most innovative approaches for particular drug use problems. This article provides an overview of the Canadian response and elaborates features of some programs, particularly Multisystemic Therapy, mainly in the province of Ontario. Few programs have received adequate evaluation, however, and the need for systematic assessment is crucial for the development of future effective interventions for youth with multiple drug and other problems.

The AAA+ ATPase p97, a cellular multitool

PubMed Central

Stach, Lasse

2017-01-01

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. PMID:28819009

A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I

PubMed Central

Mendez, Daniel C; Stover, Alexander E; Rangel, Anthony D; Brick, David J; Nethercott, Hubert E; Torres, Marissa A; Khalid, Omar; Wong, Andrew MS; Cooper, Jonathan D; Jester, James V; Monuki, Edwin S; McGuire, Cian; Le, Steven Q; Kan, Shih-hsin; Dickson, Patricia I; Schwartz, Philip H

2015-01-01

Mucopolysaccharidosis type I (MPS I) is an inherited α-L-iduronidase (IDUA, I) deficiency in which glycosaminoglycan (GAG) accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS) background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG) background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI) mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches. PMID:26052536

Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

PubMed

Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

2013-09-01

Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement.

Chronic behavior disturbance and neurocognitive deficits in neuro-Behcet's disease: a case study.

PubMed

Fisher, Caroline A; Sewell, Katherine; Baker, Amy

2016-06-01

Behcet's disease is a vasculitis and multisystem inflammatory syndrome. Neurological abnormalities occur in a subset of patients. This report presents a case of neuro-Behcet's disease characterized by an initial onset of behavior changes prior to diagnosis, which evolved into a chronic behavioral syndrome. Neuroimaging investigations revealed progressive periventricular white matter and brainstem atrophy and lesions in the basal ganglia and deep white matter tracts, while neuropsychological investigations revealed reductions in information processing, executive functioning, and memory. The case indicates that behavior changes may be the first symptoms to emerge in Behcet's, before other defining features of the disease.

Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.

PubMed

Lopez, Adam M; Jones, Ryan Dale; Repa, Joyce J; Turley, Stephen D

2018-06-07

Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Mutations in either NPC1 or NPC2 lead to continuing entrapment of UC in all organs, resulting in multisystem disease which includes hepatic dysfunction and in some cases liver failure. These studies investigated primarily whether elimination of SOAT2 in NPC1-deficient mice impacted hepatic UC sequestration, inflammation, and transaminase activities. Measurements were made in 7 wk-old mice fed a low-cholesterol chow diet or one enriched with cholesterol starting 2 wk before study. In the chow-fed mice, NPC1:SOAT2 double knockouts, compared to their littermates lacking only NPC1, had 20% less liver mass, 28% lower hepatic UC concentrations, and plasma ALT and AST activities that were decreased by 48% and 36%, respectively. mRNA expression levels for several markers of inflammation were all significantly lower in the NPC1 mutants lacking SOAT2. The existence of a new class of potent and selective SOAT2 inhibitors provides an opportunity for exploring if suppression of this enzyme could potentially become an adjunctive therapy for liver disease in NPC1 deficiency.

[Role of cardiac magnetic resonance in cardiac involvement of Fabry disease].

PubMed

Serra, Viviana M; Barba, Miguel Angel; Torrá, Roser; Pérez De Isla, Leopoldo; López, Mónica; Calli, Andrea; Feltes, Gisela; Torras, Joan; Valverde, Victor; Zamorano, José L

2010-09-04

Fabry disease is a hereditary disorder. Clinical manifestations are multisystemic. The majority of the patients remain undiagnosed until late in life, when alterations could be irreversible. Early detection of cardiac symptoms is of major interest in Fabry's disease (FD) in order to gain access to enzyme replacement therapy. Echo-Doppler tissular imaging (TDI) has been used as a cardiologic early marker in FD. This study is intended to determine whether the cardiac magnetic resonance is as useful tool as TDI for the early detection of cardiac affectation in FD. Echocardiography, tissue Doppler and Cardio magnetic resonance was performed in 20 patients with confirmed Fabry Disease. Left ventricular hypertrophy was defined as septum and left ventricular posterior wall thickness ≥12 mm. An abnormal TDI velocity was defined as (Sa), (Ea) and/or (Aa) velocities <8 cm/s at either the septal or lateral corner. Late phase gadolinium-enhanced images sequences were obtained using magnetic resonance. Twenty patients included in the study were divided into three groups: 1. Those without left ventricular hypertrophy nor tissue Doppler impairment 2. Those without left ventricular hypertrophy and tissue Doppler impairment 3. Those with left ventricular hypertrophy and Tissue Doppler impairment. Late gadolinium enhancement was found in only one patient, who has already altered DTI and LVH. Tissue Doppler imaging (TDI) is the only diagnostic tool able to provide early detection of cardiac affectation in patients with FD. Magnetic resonance provides information of the disease severity in patients with LVH, but can not be used as an early marker of cardiac disease in patients with FD. However MRI could be of great value for diagnostic stratification. Copyright © 2009 Elsevier España, S.L. All rights reserved.

ALS-Plus Syndrome: Non-Pyramidal Features in a Large ALS Cohort

PubMed Central

McCluskey, Leo; Vandriel, Shannon; Elman, Lauren; Van Deerlin, Vivianna M.; Powers, John; Boller, Ashley; Wood, Elisabeth McCarty; Woo, John; McMillan, Corey T.; Rascovsky, Katya; Grossman, Murray

2014-01-01

Objective Autopsy studies show widespread pathology in amyotrophic lateral sclerosis (ALS), but clinical surveys of multisystem disease in ALS are rare. We investigated ALS-Plus syndrome, an understudied group of patients with clinical features extending beyond pyramidal and neuromuscular systems with or without cognitive/behavioral deficits. Methods In a large, consecutively-ascertained cohort of 550 patients with ALS, we documented atypical clinical manifestations. Genetic screening for C9orf72 hexanucleotide expansions was performed in 343 patients, and SOD1, TARDBP, and VCP were tested in the subgroup of patients with a family history of ALS. Gray matter and white matter imaging was available in a subgroup of 30 patients. Results Seventy-five (13.6%) patients were identified with ALS-Plus syndrome. We found disorders of ocular motility, cerebellar, extrapyramidal and autonomic functioning. Relative to those without ALS-Plus, cognitive impairment (8.0% vs 2.9%, p=0.029), bulbar-onset (49.3% vs 23.2%, p<0.001), and pathogenic mutations (20.0% vs 8.4%, p=0.015) were more than twice as common in ALS-Plus. Survival was significantly shorter in ALS-Plus (29.66 months vs 42.50 months, p=0.02), regardless of bulbar-onset or mutation status. Imaging revealed significantly greater cerebellar and cerebral disease in ALS-Plus compared to those without ALS-Plus. Conclusions ALS-Plus syndrome is not uncommon, and the presence of these atypical features is consistent with neuropathological observations that ALS is a multisystem disorder. ALS-Plus syndrome is associated with increased risk for poor survival and the presence of a pathogenic mutation. PMID:25086858

Genetic mutations in Gorlin-Goltz syndrome

PubMed Central

Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

2013-01-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management. PMID:24339558

Genetic mutations in Gorlin-Goltz syndrome.

PubMed

Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

2013-07-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management.

Elephantiasis nostras verrucosa on the legs and abdomen with morbid obesity in an Indian lady.

PubMed

Sarma, Podila S; Ghorpade, Ashok

2008-12-15

Elephantiasis nostras verrucosa (ENV) of the legs and abdomen in a morbidly obese woman with multiple medical problems is reported. The diagnosis was suggested by the classical clinical features and confirmed by histopathology. The patient succumbed due to her multisystem diseases. Elephantiasis nostras verrucosa involving the abdomen is uncommon and has been reported only five times in the past.

Acute liver failure.

PubMed

Slack, Andy; Wendon, Julia

2011-06-01

ALF is a multisystem disorder necessitating both predictive and reactive management strategies to support and protect organs from the initial and subsequent insults encountered. Early referral to a specialist liver centre with the option of liver transplantation is recommended. Furthermore, a good understanding of the poor prognostic variables is necessary to determine those most at risk of developing ALF in order to facilitate timely, safe transfer and listing for liver transplantation.

Churg-Strauss syndrome masquerading as an acute coronary syndrome.

PubMed

Triantafyllis, Andreas S; Sakadakis, Eleftherios A; Papafilippaki, Argyro; Katsimbri, Pelagia; Panou, Fotios; Anastasiou-Nana, Maria; Lekakis, Ioannis

2015-02-01

Churg-Strauss Syndrome (CSS) is a rare vasculitis with multiorgan involvement. Cardiac manifestations are common causing serious complications. We report a case of CSS masquerading as a non-ST elevation myocardial infarction with heart failure. CSS should be considered in the differential diagnosis of an acute coronary syndrome(ACS)with normal coronary arteries when history of asthma, peripheral eosinophilia and multisystemic involvement is present.

Systemic Sclerosis and the Gastrointestinal Tract-Clinical Approach.

PubMed

Braun-Moscovici, Yolanda; Brun, Rita; Braun, Marius

2016-10-31

Systemic sclerosis (SSc) is a multisystem disease characterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs, immune system activation, and autoimmunity. The gastrointestinal tract is involved in nearly all patients and is a source of significant morbidity and even mortality. The aim of this review is to summarize the pathogenesis and to provide a clinical approach to these patients.

Anti-Idiotype Probes for Toxin Detection

DTIC Science & Technology

1991-09-13

NMurine macrophage activation by staphylococcal exotoxins. Gordo,, Conference .)n Staphylococcal Diseases . Salve Regina Univ. Newport. RI. 16 I I...multisystem disease , toxic shock syndrome. The toxins are serologically distinct, single polypeptide chains, with sizes ranging from 22 kDa to approximately...pleotropic effects on the immune system and in the pathogenesis of disease (21,22,66). Glucocorticoids were reported to be potent inhibitors of the LPS

Beyond Reason: Emotion

NASA Astrophysics Data System (ADS)

Suárez Araujo, Carmen Paz; Barahona da Fonseca, Isabel; Barahona da Fonseca, José; Simões da Fonseca, J.

2004-08-01

A theoretical approach that aims to the identification of information processing that may be responsible for emotional dimensions of subjective experience is studied as an initial step in the construction of a neural net model of affective dimensions of psychological experiences. In this paper it is suggested that a way of orientated recombination of attributes can be present not only in the perceptive processing but also in cognitive ones. We will present an analysis of the most important emotion theories, we show their neural organization and we propose the neural computation approach as an appropriate framework for generating knowledge about the neural base of emotional experience. Finally, in this study we present a scheme corresponding to framework to design a computational neural multi-system for Emotion (CONEMSE).

Therapist perception of treatment outcome: Evaluating treatment outcomes among youth with antisocial behavior problems.

PubMed

Crandal, Brent R; Foster, Sharon L; Chapman, Jason E; Cunningham, Phillippe B; Brennan, Patricia A; Whitmore, Elizabeth A

2015-06-01

Effective evaluation of treatment requires the use of measurement tools producing reliable scores that can be used to make valid decisions about the outcomes of interest. Therapist-rated treatment outcome scores that are obtained within the context of empirically supported treatments (ESTs) could provide clinicians and researchers with data that are easily accessible and complimentary to existing instrumentation. We examined the psychometric properties of scores from the Therapist Perception of Treatment Outcome: Youth Antisocial Behavior (TPTO:YAB), an instrument developed to assess therapist judgments of treatment success among families participating in an EST, Multisystemic Therapy (MST), for youth with antisocial behavior problems. Data were drawn from a longitudinal study of MST. The initial 20-item TPTO:YAB was completed by therapists of 111 families at midtreatment and 163 families at treatment termination. Rasch model dimensionality analyses provided evidence for 2 dimensions reflecting youth- and caregiver-related aspects of treatment outcome, although a bifactor analyses suggested that these dimensions reflected a single more general construct. Rasch analyses were also used to assess item and rating scale characteristics and refine the number of items. These analyses suggested items performed similarly across time and that scores reflect treatment outcome in similar ways at mid and posttreatment. Multilevel and zero-order analyses provided evidence for the validity of TPTO:YAB scores. TPTO:YAB scores were moderately correlated with scores of youth and caregiver behaviors targeted in treatment, adding support to its use as a treatment outcome measurement instrument. (c) 2015 APA, all rights reserved).

Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision.

PubMed

Bansal, Aditya; Bhama, Jay K; Patel, Rajan; Desai, Sapna; Mandras, Stacy A; Patel, Hamang; Collins, Tyrone; Reilly, John P; Ventura, Hector O; Parrino, P Eugene

2016-01-01

Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Minimally invasive LVAD therapy using the Impella 5.0 via the RSA cutdown is an attractive option in acute on chronic decompensated heart failure. Improvement in end organ function allows for transition to recovery or to advanced surgical therapies such as permanent LVAD and heart transplantation. Significant advantages to this approach include improved left ventricular unloading, lower anticoagulation need, and the potential for ambulation and physical therapy.

Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision

PubMed Central

Bansal, Aditya; Bhama, Jay K.; Patel, Rajan; Desai, Sapna; Mandras, Stacy A.; Patel, Hamang; Collins, Tyrone; Reilly, John P.; Ventura, Hector O.; Parrino, P. Eugene

2016-01-01

Background: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. Methods: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. Results: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Conclusion: Minimally invasive LVAD therapy using the Impella 5.0 via the RSA cutdown is an attractive option in acute on chronic decompensated heart failure. Improvement in end organ function allows for transition to recovery or to advanced surgical therapies such as permanent LVAD and heart transplantation. Significant advantages to this approach include improved left ventricular unloading, lower anticoagulation need, and the potential for ambulation and physical therapy. PMID:27660567

Psychological interventions for parents of children and adolescents with chronic illness.

PubMed

Eccleston, Christopher; Fisher, Emma; Law, Emily; Bartlett, Jess; Palermo, Tonya M

2015-04-15

Psychological therapies have been developed for parents of children and adolescents with a chronic illness. Such therapies include interventions directed at the parent only or at parent and child/adolescent, and are designed to improve parent, child, and family outcomes. This is an updated version of the original Cochrane review published in Issue 8, 2012, (Psychological interventions for parents of children and adolescents with chronic illness). To evaluate the efficacy of psychological therapies that include parents of children and adolescents with chronic illnesses including painful conditions, cancer, diabetes mellitus, asthma, traumatic brain injury (TBI), inflammatory bowel diseases (IBD), skin diseases, or gynaecological disorders. We also aimed to evaluate the adverse events related to implementation of psychological therapies for this population. Secondly, we aimed to evaluate the risk of bias of included studies and the quality of outcomes using the GRADE assessment. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO for randomised controlled trials (RCTs) of psychological interventions that included parents of children and adolescents with a chronic illness. Databases were searched to July 2014. Included studies were RCTs of psychological interventions that delivered treatment to parents of children and adolescents with a chronic illness compared to an active control, waiting list, or treatment as usual control group. Study characteristics and outcomes were extracted from included studies. We analysed data using two categories. First, we analysed data by each individual medical condition collapsing across all treatment classes at two time points. Second, we analysed data by each individual treatment class; cognitive behavioural therapy (CBT), family therapy (FT), problem solving therapy (PST) and multisystemic therapy (MST) collapsing across all medical conditions. For both sets of analyses we looked immediately post-treatment and at the first available follow-up. We assessed treatment effectiveness for two primary outcomes: parent behaviour and parent mental health. Five secondary outcomes were extracted; child behaviour/disability, child mental health, child symptoms, family functioning, and adverse events. Risk of bias and quality of evidence were assessed. Thirteen studies were added in this update, giving a total of 47 RCTs. The total number of participants included in the data analyses was 2985, 804 of whom were added to the analyses in the update. The mean age of the children was 14.6 years. Of the 47 RCTs, the studies focused on the following paediatric conditions: n = 14 painful conditions, n = 13 diabetes, n =10 cancer, n = 5 asthma, n = 4 TBI, and n = 1 atopic eczema. We did not identify any studies treating parents of children with gynaecological disorders or IBD. Risk of bias assessments of included studies were predominantly unclear. Evidence quality, assessed using the GRADE criteria, was judged to be of low or very low quality.Analyses of separate medical conditions, across all treatment types, revealed two beneficial effects of psychological therapies for our primary outcomes. First, psychological therapies led to improved adaptive parenting behaviour in parents of children with cancer post-treatment (standardised mean difference (SMD) -0.20, 95% confidence interval (CI) -0.36 to -0.04, Z = 2.44, p = 0.01). In addition, therapies also improved parent mental health at follow-up in this group (SMD = -0.18, 95% CI -0.32 to -0.04, Z = 2.58, p = 0.01). We did not find any effect of therapies for parent behaviour for parents of children with a painful condition post-treatment or at follow-up, or for parent mental health for parents of children with cancer, diabetes, asthma, or TBI post-treatment. For all other primary outcomes, no analysis could be conducted due to lack of data.Across all medical conditions, three effects were found for the primary outcomes of psychological therapies. PST had a beneficial effect on parent adaptive behaviour (SMD = -0.25, 95% CI -0.39 to -0.11, Z = 3.59, p < 0.01) and parent mental health (SMD= -0.24, 95% CI -0.42 to -0.05, Z = 2.50, p = 0.01) immediately post-treatment and this effect was maintained at follow-up for parent mental health (SMD= -0.19, 95% CI -0.34 to -0.04, Z = 2.55, p = 0.01). The remaining analysis for PST on parent behaviour found no effect. No effects were found for CBT post-treatment or at follow-up for either parent outcome. For FT, only one analysis could be run on parent mental health and no effect was found. Due to lack of data, the remaining analyses of primary outcomes could not be run. For MST, no parent outcomes could be analysed due to lack of data.Secondary outcome analyses are presented in the Results section. Five studies reported that there were no adverse events during the trial. The remaining 42 studies did not report adverse events. This update includes 13 additional studies, although our conclusions have not changed from the original version. There is little evidence for the efficacy of psychological therapies that include parents on most outcome domains of functioning, for a large number of common chronic illnesses in children. However, psychological therapies are efficacious for some outcomes. CBT that includes parents is beneficial for reducing children's primary symptoms, and PST that includes parents improved parent adaptive behaviour and parent mental health. There is evidence that the beneficial effects can be maintained at follow-up for diabetes-related symptoms in children, and for the mental health of parents of children with cancer and parents who received PST.

A Prospective, Cross-Sectional Survey Study of the Natural History of Niemann-Pick B Disease

PubMed Central

McGovern, Margaret M.; Wasserstein, Melissa P.; Giugliani, Roberto; Bembi, Bruno; Vanier, Marie; Mengel, Eugen; Brodie, Scott E.; Mendelson, David; Skloot, Gwen; Desnick, Robert J.; Kuriyama, Noriko; Cox, Gerald F.

2009-01-01

Objective The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease Type B and to identify efficacy endpoints for future clinical trials of enzyme replacement therapy. Patients and Methods Fifty-nine patients who had Niemann-Pick disease Type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; and assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life were obtained during a 2 to 3 day period. Results Fifty-three percent of the patients were male, 92% white, and the median age was 17.6 years. The R508del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of LDL, VLDL, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function tests. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. Conclusions This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy endpoints were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate endpoint in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring treatment responses. PMID:18625664

Epidural therapy for the treatment of severe pre-eclampsia in non labouring women.

PubMed

Ray, Amita; Ray, Sujoy

2017-11-28

Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required. To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review. The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction. We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomesThe included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups. Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.

Treatment of pathological gambling - integrative systemic model.

PubMed

Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

2015-03-01

Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of the effectiveness of our model, at this time it exceeds 90%. Given the relatively short period of application, it is necessary to continue to monitor and evaluate the model after 5 years.

Childhood Sarcoidosis Presenting as Recurrent Facial Palsy.

PubMed

Passi, Gouri Rao; Arora, Kriti; Gokhale, Narendra

2018-04-15

Recurrent facial palsy in a patient merits investigation for underlying etiology. 8-year-old boy with erythematous itchy skin lesion and recurrent facial palsy. He had a past history of aseptic meningitis and nephrocalcinosis. Raised angiotensin converting enzyme levels, interstitial lung disease on CT chest, and non caseating granulomas on skin biopsy clinched the diagnosis of sarcoidosis. Multisystem involvement and recurrent lower motor facial nerve palsy is a clinical clue for sarcoidosis.

Langerhans Cell Histiocytosis Treatment (PDQ®)—Health Professional Version

Cancer.gov

Langerhans cell histiocytosis (LCH) treatment is based on whether high-risk (liver, spleen, hematopoietic system) or low-risk organs (skin, bone, lung, lymph nodes, GI tract, pituitary gland, thyroid, thymus or CNS) are involved and whether LCH presents as unifocal, multifocal, or multisystem disease. Get detailed information about LCH in adults and children, including etiology, molecular features, presentation, diagnosis, prognosis, and treatment in this summary for clinicians.

Brain Transcriptome Profiles in Mouse Model Simulating Features of Post-traumatic Stress Disorder

DTIC Science & Technology

2015-02-28

comorbid-related signaling pathways indicate the pervasive and multisystem effects of aggressor exposure in mice, potentially mirroring the pathologic...11,12]. Impaired extinction of fear- potentiated startle and en- hanced cue conditioning in these brain regions (of trau- matized patients and animal...lead to either a long-term synap- tic potentiation (LTP) increase in synaptic strength and in- crease in excitatory post-synaptic potential

Cryopyrin-associated periodic syndrome: an autoinflammatory disease manifested as neutrophilic urticarial dermatosis with additional perieccrine involvement.

PubMed

Kolivras, Athanassios; Theunis, Anne; Ferster, Aline; Lipsker, Dan; Sass, Ursula; Dussart, Anneliese; André, Josette

2011-02-01

A female newborn presented with a congenital urticarial rash that consisted of fluctuating well-demarcated pink or pale reddish macules or slightly raised papules and plaques. In addition, purulent cerebrospinal fluid was present in the absence of evidence of congenital infection. Skin biopsy revealed a sparse infiltrate throughout the entire dermis, including the eccrine adventitia. The infiltrate was composed mostly of neutrophils, but rarely lymphocytes and eosinophils could also be seen. No vasculitis was present. Because of the presenting attributes, a diagnosis of cryopyrin-associated periodic syndrome (CAPS) was considered and the neonatal-onset multisystem inflammatory disorder (NOMID) that represents the most severe expression of the CAPS clinical spectrum was favored. Diagnosis was confirmed by identification of a mutation in the cold-induced autoinflammatory syndrome-1 gene and by an observed response to treatment with the interleukin-1 receptor antagonist anakinra. Both the clinical and histopathological findings of the presented case may represent a distinct entity within the spectrum of aseptic neutrophilic dermatitis. We refer to this spectrum as neutrophilic urticarial dermatosis (NUD), which may serve as a cutaneous marker of autoinflammation. NUD with perieccrine involvement should prompt consideration of CAPS, especially NOMID, in the context of neonatal multisystem disease. Copyright © 2010 John Wiley & Sons A/S.

H syndrome: the first 79 patients.

PubMed

Molho-Pessach, Vered; Ramot, Yuval; Camille, Frances; Doviner, Victoria; Babay, Sofia; Luis, Siekavizza Juan; Broshtilova, Valentina; Zlotogorski, Abraham

2014-01-01

H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. We sought to investigate the clinical and molecular findings in 79 patients with this disorder. A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation. In the 31 patients described by others, data were collected from the medical literature. H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

PubMed Central

Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

2015-01-01

The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

Development of a Multisystemic Parent Management Training Intervention for Incarcerated Parents, Their Children and Families

PubMed Central

Eddy, J. Mark; Martinez, Charles R.; Schiffmann, Tracy; Newton, Rex; Olin, Laura; Leve, Leslie; Foney, Dana M.; Shortt, Joann Wu

2008-01-01

The majority of men and women prison inmates are parents. Many lived with children prior to incarceration, and most have at least some contact with their children and families while serving their sentences. As prison populations have increased in the United States, there has been a renewed interest in finding ways not only to reduce recidivism, but also to prevent incarceration in the first place, particularly amongst the children of incarcerated parents. Positive family interaction is related to both issues. The ongoing development of a multisystemic intervention designed to increase positive family interaction for parents and families involved in the criminal justice system is described. The intervention package currently includes a prison-based parent management training program called Parenting Inside Out (PIO); a prison-based therapeutic visitation program; and complimentary versions of PIO designed for jail and probation and parole settings. Work on other components designed for justice-involved parents, children and for caregivers during reunification from prison is ongoing. Program development has occurred within the context of strong support from the state department of corrections and other key governmental and non-profit sector groups, and support systems have been established to help maintain the interventions as well as to develop complimentary interventions, policies and procedures. PMID:19885365

Multi-system verification of registrations for image-guided radiotherapy in clinical trials.

PubMed

Cui, Yunfeng; Galvin, James M; Straube, William L; Bosch, Walter R; Purdy, James A; Li, X Allen; Xiao, Ying

2011-09-01

To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6±2.1 mm (mean±SD; range 0.1-8.6 mm, left-right [LR]), 1.7±1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8±1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1±1.0 mm (0.0-4.6 mm, LR), 2.1±1.7 mm (0.0-6.6 mm, SI), and 2.0±1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. The extent of differences was reported when different systems were used for image registration. Careful examination and quality assurance of the image registration process are crucial before considering margin reduction using IGRT in clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterization and evolution of dermal filaments from patients with Morgellons disease.

PubMed

Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process.

A case of scrotal swelling mimicking testicular torsion preceding Henoch-Schönlein vasculitis.

PubMed

Akgun, C

2012-01-01

Henoch-Schönlein purpura, is one of the most common types of multisystemic vasculitis seen in childhood. The major clinical manifestations are cutaneous purpura, arthritis, abdominal pain, gastrointestinal bleeding, and nephritis. Isolated central nervous system vasculitis, seizures, coma and hemorrhage, Guillan--Barré syndrome, ataxia and central and peripheral neuropathy, ocular involvement, orchitis, epididymitis or testicular torsion are medical or surgical complications. In this study, we report a 7-year-old boy with scrotal swelling mimicking testicular torsion with ultrasonographic and clinical findings that the typical clinical features of Henoch-Schönlein purpura including rashes and arthritis were developed after one week of surgery (Ref. 15).

Systemic lupus erythematosus associated with acute Epstein-Barr virus infection.

PubMed

Dror, Y; Blachar, Y; Cohen, P; Livni, N; Rosenmann, E; Ashkenazi, A

1998-11-01

Systemic lupus erythematosus (SLE) is a multisystem disease of unknown origin, characterized by a variety of autoimmune phenomena. Viruses have long been postulated to play a role in its pathogenesis. Several observations suggested a link between Epstein-Barr virus (EBV) and SLE. We describe a 14-year-old girl who presented with acute onset of SLE concurrently with clinical and laboratory findings consistent with EBV-induced infectious mononucleosis (IM). Evidence for acute EBV infection was confirmed by serological studies and detection of specific EBV antigens on kidney biopsy. This close association between EBV and SLE suggests a possible role of the virus in the pathogenesis of SLE in this patient.

[Neurologic disorders in Whipple's disease].

PubMed

Jović, N S; Jović, J Z

1996-01-01

The disease is named after George H. Whipple who, in 1907, was the first to describe an intestinal "lipodystrophy". Although Whipple's disease is generally recognized as a multisystem chronic granulomatous disease, primarily involving the digestive system, it can also appear as a primary neurological disorder in rare cases. Most often it is manifested with loss of weight, diarrhea, malabsorption, abdominal pain, lymphadenopathy, cardiopathy, hyperpigmentation and hypotension. The presence of periodic acid-Schiff (PAS)-positive macrophages in biopsy specimens (not only jejunal) and demonstration of "Whipple's bacilli" visible by electron microscopy, are diagnostic signs of active Whipple's disease. Whipple's disease confined to the CNS is rare. It is rarely found in the differential diagnosis of patients with progressive neurological deterioration. The most common neurological picture includes progressive dementia, external ophalmoplegia, myoclonus, seizures, ataxia, hypothalamic dysfunction (sleep disorders, hyperphagia, polydipsia) and meningitis. Oculofacial-skeletal myorhythmia as a movement disorder, associated with Whipple's disease, is reported. Fulminant course of cerebral Whipple's disease is unusual and unfavourable. The confusing and nonspecific clinical appearance is typical for primary CNS involvement. It has recently been suggested that CNS involvement occurs in all cases, although only 10-20% of patients may show it. The CNS is the most common site of disease relapse. The CT scans and MRI of the brain are often normal, but may show cortical/subcortical atrophy, hydrocephalus, focal or intracerebral mass lesions. The cerebrospinal fluid can sometimes contain PAS-positive macrophages. Brain biopsy is suggested as a diagnostic method in cases of high suspicion of CNS Whipple's disease. However, the lesions are frequently inaccessible and false negative. Without extended antibiotic therapy, the course of Whipple's disease is lethal. Now, the prognosis is good, although the optimal antimicrobial regimen is not clearly established. Initial parenteral therapy (tetracycline, penicilline, streptomycine, chloramphenicol, ampicilline) and peroral long-term treatment with trimetoprime-sulphametoxasole, are recommended. As CNS relapse of Whipple's disease may occur after several years, long-term treatment should include antibiotics that are able to cross the blood-brain barrier. The CNS relapse, in contrast to the systemic ones, is resistant to the treatment. Appropriate therapy instituted earlier in the course of the disease is associated with a better neurological outcome. Early recognition can be critical in Whipple's disease because of irreversible neurological sequelae seen later in the course of this potentially treatable condition. In cases with high clinical suspicion in which Whipple's disease cannot be diagnosed with procedures such as jejunal biopsy, antibiotic therapy is recommended. Recovery of an established neurological deficit may rarely occur. Longterm follow-up studies would help to identify the optimal antibiotic regimen and duration of treatment.

Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies

PubMed Central

Ilkovski, Biljana; Pagnamenta, Alistair T.; O'Grady, Gina L.; Kinoshita, Taroh; Howard, Malcolm F.; Lek, Monkol; Thomas, Brett; Turner, Anne; Christodoulou, John; Sillence, David; Knight, Samantha J.L.; Popitsch, Niko; Keays, David A.; Anzilotti, Consuelo; Goriely, Anne; Waddell, Leigh B.; Brilot, Fabienne; North, Kathryn N.; Kanzawa, Noriyuki; Macarthur, Daniel G.; Taylor, Jenny C.; Kini, Usha; Murakami, Yoshiko; Clarke, Nigel F.

2015-01-01

Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20–50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5′-UTR regions despite their typically low coverage in exome data. PMID:26293662

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.

PubMed

Mazor, Roei D; Manevich-Mazor, Mirra; Kesler, Anat; Aizenstein, Orna; Eshed, Iris; Jaffe, Ronald; Pessach, Yakov; Goldberg, Ilan; Sprecher, Eli; Yaish, Iris; Gural, Alexander; Ganzel, Chezi; Shoenfeld, Yehuda

2014-12-01

Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

PubMed

Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

2014-11-05

Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies.

PubMed

Ilkovski, Biljana; Pagnamenta, Alistair T; O'Grady, Gina L; Kinoshita, Taroh; Howard, Malcolm F; Lek, Monkol; Thomas, Brett; Turner, Anne; Christodoulou, John; Sillence, David; Knight, Samantha J L; Popitsch, Niko; Keays, David A; Anzilotti, Consuelo; Goriely, Anne; Waddell, Leigh B; Brilot, Fabienne; North, Kathryn N; Kanzawa, Noriyuki; Macarthur, Daniel G; Taylor, Jenny C; Kini, Usha; Murakami, Yoshiko; Clarke, Nigel F

2015-11-01

Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20-50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5'-UTR regions despite their typically low coverage in exome data. © The Author 2015. Published by Oxford University Press.

The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies.

PubMed

Moses, Shimon W; Parvari, Ruti

2002-03-01

Glycogen storage disease type IV (GSD-IV), also known as Andersen disease or amylopectinosis (MIM 23250), is a rare autosomal recessive disorder caused by a deficiency of glycogen branching enzyme (GBE) leading to the accumulation of amylopectin-like structures in affected tissues. The disease is extremely heterogeneous in terms of tissue involvement, age of onset and clinical manifestations. The human GBE cDNA is approximately 3-kb in length and encodes a 702-amino acid protein. The GBE amino acid sequence shows a high degree of conservation throughout species. The human GBE gene is located on chromosome 3p14 and consists of 16 exons spanning at least 118 kb of chromosomal DNA. Clinically the classic Andersen disease is a rapidly progressive disorder leading to terminal liver failure unless liver transplantation is performed. Several mutations have been reported in the GBE gene in patients with classic phenotype. Mutations in the GBE gene have also been identified in patients with the milder non-progressive hepatic form of the disease. Several other variants of GSD-IV have been reported: a variant with multi-system involvement including skeletal and cardiac muscle, nerve and liver; a juvenile polysaccharidosis with multi-system involvement but normal GBE activity; and the fatal neonatal neuromuscular form associated with a splice site mutation in the GBE gene. Other presentations include cardiomyopathy, arthrogryposis and even hydrops fetalis. Polyglucosan body disease, characterized by widespread upper and lower motor neuron lesions, can present with or without GBE deficiency indicating that different biochemical defects could result in an identical phenotype. It is evident that this disease exists in multiple forms with enzymatic and molecular heterogeneity unparalleled in the other types of glycogen storage diseases.

Rat MHC-linked peptide transporter alleles strongly influence peptide binding by HLA-B27 but not B27-associated inflammatory disease

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

Simmons, W.A.; Satumtira, Nimman; Taurog, J.D.

1996-02-15

Rats transgenic for the human MHC molecule HLA-B27 were used to study the effect of two alleles, cim{sup a} and cim{sup b}, which are associated with peptide transport by the MHC-encoded Tap2 transporter, on the function of HLA-B27 as a restriction element for CTL recognition of the male H-Y minor H Ag and on the multisystem inflammatory disease characteristic of B27 transgenic rats. Anti-H-Y CTL generated in cim{sup a} B27 transgenic rats lysed male B27 cim{sup b/b} targets significantly less well than cim{sup a/a} or cim{sup a/b} targets. Addition of exogenous H-Y peptides to male B27 cim{sup b/b} targets increasedmore » susceptibility to lysis to the level of cim{sup a/a} targets sensitized with exogenous H-Y peptides. {sup 3}H-labeled peptides eluted from B27 molecules of lymphoblasts from rats of two cim{sup b} and three cim{sup a} RT1 haplotypes showed that the cim{sup b} peptide pool favors comparatively longer and/or more hydrophobic peptides. These results indicate that RT1-linked Tap2 polymorphism in the rat strongly influences peptide loading of HLA-B27. Nonetheless, the prevalence and severity of multisystem inflammatory lesions were comparable in backcross rats bearing either cim{sup a/b} or cim{sup b/b}. It thus appears either that binding of specific peptides to B27 is unimportant in the pathogenesis of B27-associated disease or that the critical peptides, unlike H-Y and many others, are not influenced by Tap transporter polymorphism. 42 refs., 6 figs., 3 tabs.« less

Population-based study of ischemic stroke risk after trauma in children and young adults.

PubMed

Fox, Christine K; Hills, Nancy K; Vinson, David R; Numis, Adam L; Dicker, Rochelle A; Sidney, Stephen; Fullerton, Heather J

2017-12-05

To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort. We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression. From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation). Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected. © 2017 American Academy of Neurology.

Annual Research Review: What is resilience within the social ecology of human development?

PubMed

Ungar, Michael; Ghazinour, Mehdi; Richter, Jörg

2013-04-01

  The development of Bronfenbrenner's bio-social-ecological systems model of human development parallels advances made to the theory of resilience that progressively moved from a more individual (micro) focus on traits to a multisystemic understanding of person-environment reciprocal processes.   This review uses Bronfenbrenner's model and Ungar's social-ecological interpretation of four decades of research on resilience to discuss the results of a purposeful selection of studies of resilience that have been done in different contexts and cultures.   An ecological model of resilience can, and indeed has been shown to help researchers of resilience to conceptualize the child's social and physical ecologies, from caregivers to neighbourhoods, that account for both proximal and distal factors that predict successful development under adversity. Three principles emerged from this review that inform a bio-social-ecological interpretation of resilience: equifinality (there are many proximal processes that can lead to many different, but equally viable, expressions of human development associated with well-being); differential impact (the nature of the risks children face, their perceptions of the resources available to mitigate those risks and the quality of the resources that are accessible make proximal processes more or less influential to children's development); and contextual and cultural moderation (different contexts and cultures provide access to different processes associated with resilience as it is defined locally).   As this review shows, using this multisystemic social-ecological theory of resilience can inform a deeper understanding of the processes that contribute to positive development under stress. It can also offer practitioners and policy makers a broader perspective on principles for the design and implementation of effective interventions. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model

PubMed Central

Fan, Rachel Y. Y.; Zhang, Anna J. X.; Chan, Brandon C. C.; Lam, Carol S. F.; Yip, Cyril C. Y.; Chan, Kwok-Hung; Chen, Zhi-Wei; Yuen, Kwok-Yung

2016-01-01

While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses. PMID:27737017

Assessment and quantification of post-weaning multi-systemic wasting syndrome severity at farm level.

PubMed

Alarcon, Pablo; Velasova, Martina; Werling, Dirk; Stärk, Katharina D C; Chang, Yu-Mei; Nevel, Amanda; Pfeiffer, Dirk U; Wieland, Barbara

2011-01-01

Post-weaning multi-systemic wasting syndrome (PMWS) causes major economic losses for the English pig industry and severity of clinical signs and economic impact vary considerably between affected farms. We present here a novel approach to quantify severity of PMWS based on morbidity and mortality data and presence of porcine circovirus type 2 (PCV2). In 2008-2009, 147 pig farms across England, non-vaccinating for PCV2, were enrolled in a cross-sectional study. Factor analysis was used to generate variables representing biologically meaningful aspects of variation among qualitative and quantitative morbidity variables. Together with other known variables linked to PMWS, the resulting factors were included in a principal component analysis (PCA) to derive an algorithm for PMWS severity. Factor analysis resulted in two factors: Morbidity Factor 1 (MF1) representing mainly weaner and grower morbidity, and Morbidity Factor 2 (MF2) which mainly reflects variation in finisher morbidity. This indicates that farms either had high morbidity mainly in weaners/growers or mainly in finishers. Subsequent PCA resulted in the extraction of one component representing variation in MF1, post-weaning mortality and percentage of PCV2 PCR positive animals. Component scores were normalised to a value range from 0 to 10 and farms classified into: non or slightly affected farms with a score <4, moderately affected farms with scores 4-6.5 and highly affected farms with a score >6.5. The identified farm level PMWS severities will be used to identify risk factors related to these, to assess the efficacy of PCV2 vaccination and investigating the economic impact of potential control measures. Copyright © 2010 Elsevier B.V. All rights reserved.

A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull

PubMed Central

Capitan, Aurélien; Allais-Bonnet, Aurélie; Pinton, Alain; Marquant-Le Guienne, Brigitte; Le Bourhis, Daniel; Grohs, Cécile; Bouet, Stéphan; Clément, Laëtitia; Salas-Cortes, Laura; Venot, Eric; Chaffaux, Stéphane; Weiss, Bernard; Delpeuch, Arnaud; Noé, Guy; Rossignol, Marie-Noëlle; Barbey, Sarah; Dozias, Dominique; Cobo, Emilie; Barasc, Harmonie; Auguste, Aurélie; Pannetier, Maëlle; Deloche, Marie-Christine; Lhuilier, Emeline; Bouchez, Olivier; Esquerré, Diane; Salin, Gérald; Klopp, Christophe; Donnadieu, Cécile; Chantry-Darmon, Céline; Hayes, Hélène; Gallard, Yves; Ponsart, Claire; Boichard, Didier; Pailhoux, Eric

2012-01-01

Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation. PMID:23152852

Pearson Syndrome: A Retrospective Cohort Study from the Marrow Failure Study Group of A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica).

PubMed

Farruggia, Piero; Di Cataldo, Andrea; Pinto, Rita M; Palmisani, Elena; Macaluso, Alessandra; Valvo, Laura Lo; Cantarini, Maria E; Tornesello, Assunta; Corti, Paola; Fioredda, Francesca; Varotto, Stefania; Martire, Baldo; Moroni, Isabella; Puccio, Giuseppe; Russo, Giovanna; Dufour, Carlo; Pillon, Marta

2016-01-01

Pearson syndrome (PS) is a very rare and often fatal multisystemic mitochondrial disorder involving the liver, kidney, pancreas, and hematopoietic and central nervous system. It is characterized principally by a transfusion-dependent anemia that usually improves over time, a tendency to develop severe infections, and a high mortality rate. We describe a group of 11 PS patients diagnosed in Italy in the period 1993-2014. The analysis of this reasonably sized cohort of patients contributes to the clinical profile of the disease and highlights a rough incidence of 1 case/million newborns. Furthermore, it seems that some biochemical parameters like increased serum alanine and urinary fumaric acid can help to address an early diagnosis.

Basal cell nevus syndrome or Gorlin syndrome.

PubMed

Thalakoti, Srikanth; Geller, Thomas

2015-01-01

Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial. © 2015 Elsevier B.V. All rights reserved.

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

PubMed

Salido-Vallejo, R; Ruano, J; Garnacho-Saucedo, G; Godoy-Gijón, E; Llorca, D; Gómez-Fernández, C; Moreno-Giménez, J C

2014-12-01

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients. © 2014 British Association of Dermatologists.

Are evoked potentials in patients with adult-onset pompe disease indicative of clinically relevant central nervous system involvement?

PubMed

Wirsching, Andreas; Müller-Felber, Wolfgang; Schoser, Benedikt

2014-08-01

Pompe disease is a multisystem autosomal recessive glycogen storage disease. Autoptic findings in patients with classic infantile and late-onset Pompe disease have proven that accumulation of glycogen can also be found in the peripheral and central nervous system. To assess the functional role of these pathologic findings, multimodal sensory evoked potentials were analyzed. Serial recordings for brainstem auditory, visual, and somatosensory evoked potentials of 11 late-onset Pompe patients were reviewed. Data at the onset of the enzyme replacement therapy with alglucosidase alfa were compared with follow-up recordings at 12 and 24 months. Brainstem auditory evoked potentials showed a delayed peak I in 1/10 patients and an increased I-III and I-V interpeak latency in 1/10 patients, respectively. The III-V interpeak latencies were in the normal range. Visual evoked potentials were completely normal. Median somatosensory evoked potentials showed an extended interpeak latency in 3/9 patients. Wilcoxon tests comparing age-matched subgroups found significant differences in brainstem auditory evoked potentials and visual evoked potentials. We found that the majority of recordings for evoked potentials were within the ranges for standard values, therefore reflecting the lack of clinically relevant central nervous system involvement. Regular surveillance by means of evoked potentials does not seem to be appropriate in late-onset Pompe patients.

Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis.

PubMed

Rudenko, N; Golovchenko, M; Vancova, M; Clark, K; Grubhoffer, L; Oliver, J H

2016-03-01

Lyme borreliosis is a multisystem disorder with a diverse spectrum of clinical manifestations, caused by spirochaetes of the Borrelia burgdorferi sensu lato complex. It is an infectious disease that can be successfully cured by antibiotic therapy in the early stages; however, the possibility of the appearance of persistent signs and symptoms of disease following antibiotic treatment is recognized. It is known that Lyme borreliosis mimics multiple diseases that were never proven to have a spirochaete aetiology. Using complete modified Kelly-Pettenkofer medium we succeeded in cultivating live B. burgdorferi sensu lato spirochaetes from samples taken from people who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but who had undergone antibiotic treatment due to a suspicion of having Lyme disease even though they were seronegative. We report the first recovery of live B. burgdorferi sensu stricto from residents of southeastern USA and the first successful cultivation of live Borrelia bissettii-like strain from residents of North America. Our results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Adapting CBT for traumatized refugees and ethnic minority patients: examples from culturally adapted CBT (CA-CBT).

PubMed

Hinton, Devon E; Rivera, Edwin I; Hofmann, Stefan G; Barlow, David H; Otto, Michael W

2012-04-01

In this article, we illustrate how cognitive behavioral therapy (CBT) can be adapted for the treatment of PTSD among traumatized refugees and ethnic minority populations, providing examples from our treatment, culturally adapted CBT, or CA-CBT. CA-CBT has a unique approach to exposure (typical exposure is poorly tolerated in these groups), emphasizes the treatment of somatic sensations (a particularly salient part of the presentation of PTSD in these groups), and addresses comorbid anxiety disorders and anger. To accomplish these treatment goals, CA-CBT emphasizes emotion exposure and emotion regulation techniques such as meditation and aims to promote emotional and psychological flexibility. We describe 12 key aspects of adapting CA-CBT that make it a culturally sensitive treatment of traumatized refugee and ethnic minority populations. We discuss three models that guide our treatment and that can be used to design culturally sensitive treatments: (a) the panic attack-PTSD model to illustrate the many processes that generate PTSD in these populations, highlighting the role of arousal and somatic symptoms; (b) the arousal triad to demonstrate how somatic symptoms are produced and the importance of targeting comorbid anxiety conditions and psychopathological processes; and (c) the multisystem network (MSN) model of emotional state to reveal how some of our therapeutic techniques (e.g., body-focused techniques: bodily stretching paired with self-statements) bring about psychological flexibility and improvement.

Mid-aortic syndrome with renovascular hypertension and multisystem involvement in a girl with familiar neurofibromatosis von Recklinghausen type 1.

PubMed

Petrak, Borivoj; Bendova, Sarka; Seeman, Tomas; Klein, Tibor; Lisy, Jiri; Zatrapa, Tomas; Marikova, Tana

2007-12-01

Neurofibromatosis von Recklinghausen type 1 (NF1) is an autosomal dominant neurocutaneous disorder affecting one in 3 000-4 000 individuals. Mid-aortic syndrome (MAS) is a rare condition characterized by segmental narrowing of abdominal aorta and stenosis of its major branches - mainly renal arteries, including manifestation of renovascular hypertension. MAS can be caused by different diseases, including NF1. A 9 years old girl with primary diagnosis of NF1 combined with renovascular hypertension due to MAS, suffered of bilateral optic and chiasm glioma, pubertas praecox, speech disorder, light mental retardation and scoliosis. We have found a mutation in exone 34 of the NF1 gene (17q11.2). Her father has been also diagnosed with NF1 and hypertension developed at early age. He has the same mutation in exone 34 of NF1 gene. The girl is currently treated with conservative antihypertensive medication with positive effect. Bilateral optic and chiasm glioma are asymptomatic at the time and they had been without progress over period of time. Any vascular surgery, neurosurgical and oncological therapy are not indicated at the present time. This article is a summary of clinical findings in patient with NF1 due to NF1 gene mutation in exone 34. It confirms the importance of complex multidisciplinar approach to examination and taking care of NF1 patients and their families.

Mechanisms and Clinical Application of Tetramethylpyrazine (an Interesting Natural Compound Isolated from Ligusticum Wallichii): Current Status and Perspective.

PubMed

Zhao, Yingke; Liu, Yue; Chen, Keji

Tetramethylpyrazine, a natural compound from Ligusticum wallichii ( Chuan Xiong ), has been extensively used in China for cardiovascular and cerebrovascular diseases for about 40 years. Because of its effectiveness in multisystems, especially in cardiovascular, its pharmacological action, clinical application, and the structural modification have attracted broad attention. In this paper its mechanisms of action, the clinical status, and synthetic derivatives will be reviewed briefly.

American College of Sports Medicine Roundtable on Exertional Heat Stroke - Return to Duty/Return to Play: Conference Proceedings

DTIC Science & Technology

2010-01-01

individuals with EHS experience long-term complica- tions that may include multisystem organ (liver, kidney, muscle ) and neurologic damage, as well as... reduced exercise capacity and heat intolerance (12,52,57,69). Animal and human research suggest late or untreated EHS may result in organ damage that...collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and

Noonan syndrome

PubMed Central

Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

2014-01-01

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

Diesel exhaust exposure, its multi-system effects, and the effect of new technology diesel exhaust.

PubMed

Reis, Haley; Reis, Cesar; Sharip, Akbar; Reis, Wenes; Zhao, Yong; Sinclair, Ryan; Beeson, Lawrence

2018-05-01

Exposure to diesel exhaust (DE) from vehicles and industry is hazardous and affects proper function of organ systems. DE can interfere with normal physiology after acute and chronic exposure to particulate matter (PM). Exposure leads to potential systemic disease processes in the central nervous, visual, hematopoietic, respiratory, cardiovascular, and renal systems. In this review, we give an overview of the epidemiological evidence supporting the harmful effects of diesel exhaust, and the numerous animal studies conducted to investigate the specific pathophysiological mechanisms behind DE exposure. Additionally, this review includes a summary of studies that used biomarkers as an indication of biological plausibility, and also studies evaluating new technology diesel exhaust (NTDE) and its systemic effects. Lastly, this review includes new approaches to improving DE emissions, and emphasizes the importance of ongoing study in this field of environmental health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measuring allostatic load in the workforce: a systematic review

PubMed Central

MAUSS, Daniel; LI, Jian; SCHMIDT, Burkhard; ANGERER, Peter; JARCZOK, Marc N.

2014-01-01

The Allostatic Load Index (ALI) has been used to establish associations between stress and health-related outcomes. This review summarizes the measurement and methodological challenges of allostatic load in occupational settings. Databases of Medline, PubPsych, and Cochrane were searched to systematically explore studies measuring ALI in working adults following the PRISMA statement. Study characteristics, biomarkers and methods were tabulated. Methodological quality was evaluated using a standardized checklist. Sixteen articles (2003–2013) met the inclusion criteria, with a total of 39 (range 6–17) different variables used to calculate ALI. Substantial heterogeneity was observed in the number and type of biomarkers used, the analytic techniques applied and study quality. Particularly, primary mediators were not regularly included in ALI calculation. Consensus on methods to measure ALI in working populations is limited. Research should include longitudinal studies using multi-systemic variables to measure employees at risk for biological wear and tear. PMID:25224337

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

PubMed Central

Divatia, Mukul; Kim, Sun A

2012-01-01

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives.

PubMed

Sen, Ayan; Callisen, Hannelisa E; Alwardt, Cory M; Larson, Joel S; Lowell, Amelia A; Libricz, Stacy L; Tarwade, Pritee; Patel, Bhavesh M; Ramakrishna, Harish

2016-01-01

Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure was proposed more than 40 years ago. Despite the publication of the ARDSNet study and adoption of lung protective ventilation, the mortality for acute respiratory failure due to acute respiratory distress syndrome has continued to remain high. This technology has evolved over the past couple of decades and has been noted to be safe and successful, especially during the worldwide H1N1 influenza pandemic with good survival rates. The primary indications for ECMO in acute respiratory failure include severe refractory hypoxemic and hypercarbic respiratory failure in spite of maximum lung protective ventilatory support. Various triage criteria have been described and published. Contraindications exist when application of ECMO may be futile or technically impossible. Knowledge and appreciation of the circuit, cannulae, and the physiology of gas exchange with ECMO are necessary to ensure lung rest, efficiency of oxygenation, and ventilation as well as troubleshooting problems. Anticoagulation is a major concern with ECMO, and the evidence is evolving with respect to diagnostic testing and use of anticoagulants. Clinical management of the patient includes comprehensive critical care addressing sedation and neurologic issues, ensuring lung recruitment, diuresis, early enteral nutrition, treatment and surveillance of infections, and multisystem organ support. Newer technology that delinks oxygenation and ventilation by extracorporeal carbon dioxide removal may lead to ultra-lung protective ventilation, avoidance of endotracheal intubation in some situations, and ambulatory therapies as a bridge to lung transplantation. Risks, complications, and long-term outcomes and resources need to be considered and weighed in before widespread application. Ethical challenges are a reality and a multidisciplinary approach that should be adopted for every case in consideration.

Akt Links Insulin Signaling to Albumin Endocytosis in Proximal Tubule Epithelial Cells

PubMed Central

Coffey, Sam; Costacou, Tina; Orchard, Trevor; Erkan, Elif

2015-01-01

Diabetes mellitus (DM) has become an epidemic, causing a significant decline in quality of life of individuals due to its multisystem involvement. Kidney is an important target organ in DM accounting for the majority of patients requiring renal replacement therapy at dialysis units. Microalbuminuria (MA) has been a valuable tool to predict end-organ damage in DM but its low sensitivity has driven research efforts to seek other alternatives. Albumin is taken up by albumin receptors, megalin and cubilin in the proximal tubule epithelial cells. We demonstrated that insulin at physiological concentrations induce albumin endocytosis through activation of protein kinase B (Akt) in proximal tubule epithelial cells. Inhibition of Akt by a phosphorylation deficient construct abrogated insulin induced albumin endocytosis suggesting a role for Akt in insulin-induced albumin endocytosis. Furthermore we demonstrated a novel interaction between Akt substrate 160kDa (AS160) and cytoplasmic tail of megalin. Mice with type 1 DM (T1D) displayed decreased Akt, megalin, cubilin and AS160 expression in their kidneys in association with urinary cubilin shedding preceding significant MA. Patients with T1D who have developed MA in the EDC (The Pittsburgh Epidemiology of Diabetes Complications) study demonstrated urinary cubilin shedding prior to development of MA. We hypothesize that perturbed insulin-Akt cascade in DM leads to alterations in trafficking of megalin and cubilin, which results in urinary cubilin shedding as a prelude to MA in early diabetic nephropathy. We propose that utilization of urinary cubilin shedding, as a urinary biomarker, will allow us to detect and intervene in diabetic nephropathy (DN) at an earlier stage. PMID:26465605

Dengue fever with diffuse cerebral hemorrhages, subdural hematoma and cranial diabetes insipidus.

PubMed

Jayasinghe, Nayomi Shermila; Thalagala, Eranga; Wattegama, Milanka; Thirumavalavan, Kanapathipillai

2016-05-10

Neurological manifestations in dengue fever occur in <1 % of the patients and known to be due to multisystem dysfunction secondary to vascular leakage. Occurrence of wide spread cerebral haemorrhages with subdural hematoma during the leakage phase without profound thrombocytopenia and occurrence of cranial diabetes insipidus are extremely rare and had not been reported in published literature earlier, thus we report the first case. A 24 year old previously healthy lady was admitted on third day of fever with thrombocytopenia. Critical phase started on fifth day with evidence of pleural effusion and moderate ascites. Thirty one hours into critical phase she developed headache, altered level of consciousness, limb rigidity and respiratory depression without definite seizures. Non-contrast CT brain done at tertiary care level revealed diffuse intracranial haemorrhages and sub arachnoid haemorrhages in right frontal, parietal, occipital lobes and brainstem, cerebral oedema with an acute subdural hematoma in right temporo- parietal region. Her platelet count was 40,000 at this time with signs of vascular leakage. She was intubated and ventilated with supportive care. Later on she developed features of cranial diabetes insipidus and it responded to intranasal desmopressin therapy. In spite of above measures signs of brainstem herniation developed and she succumbed to the illness on day 8. Dengue was confirmed serologically. Exact pathophysiological mechanism of diffuse cerebral haemorrhages without profound thrombocytopenia is not well understood. Increased awareness and high degree of clinical suspicion is needed among clinicians for timely diagnosis of this extremely rare complication of dengue fever. We postulate that immunological mechanisms may play a role in pathogenesis. However further comprehensive research and studies are needed to understand the pathophysiological mechanisms leading to this complication.

Scrub typhus in Uttarakhand & adjoining Uttar Pradesh: Seasonality, clinical presentations & predictors of mortality.

PubMed

Bhargava, Anurag; Kaushik, Reshma; Kaushik, Rajeev Mohan; Sharma, Anita; Ahmad, Sohaib; Dhar, Minakshi; Mittal, Garima; Khanduri, Sushant; Pant, Priyannk; Kakkar, Rajesh

2016-12-01

Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India. Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA. A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death. The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.

PubMed

Ouyang, Jingfeng; Huang, Wei; Yu, Wanwan; Xiong, Wei; Mula, Ramanjaneya V R; Zou, Hongbin; Yu, Yongping

2014-02-05

Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3β (HNF 3β) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis

PubMed Central

Manetti, Mirko; Guiducci, Serena; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

2010-01-01

Abstract Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem connective tissue disorder affecting the skin and various internal organs. Although the disease is characterized by a triad of widespread microangiopathy, fibrosis and autoimmunity, increasing evidence indicates that vascular damage is a primary event in the pathogenesis of SSc. The progressive vascular injury includes persistent endothelial cell activation/damage and apoptosis, intimal thickening, delamination, vessel narrowing and obliteration. These profound vascular changes lead to vascular tone dysfunction and reduced capillary blood flow, with consequent tissue ischemia and severe clinical manifestations, such as digital ulceration or amputation, pulmonary arterial hypertension and scleroderma renal crisis. The resulting tissue hypoxia induces complex cellular and molecular mechanisms in the attempt to recover endothelial cell function and tissue perfusion. Nevertheless, in SSc patients there is no evidence of significant angiogenesis and the disease evolves towards chronic tissue ischemia, with progressive and irreversible structural changes in multiple vascular beds culminating in the loss of capillaries. A severe imbalance between pro-angiogenic and angiostatic factors may also lead to impaired angiogenic response during SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers and functional defects of bone marrow-derived endothelial progenitor cells may contribute to the vascular pathogenesis of SSc. The purpose of this article is to review the contribution of recent studies to the understanding of the complex mechanisms of impaired vascular repair in SSc. Indeed, understanding the pathophysiology of SSc-associated vascular disease may be the key in dissecting the disease pathogenesis and developing novel therapies. Either angiogenic or vasculogenic mechanisms may potentially become in the future the target of therapeutic strategies to promote capillary regeneration in SSc. PMID:20132409

Psychological interventions for parents of children and adolescents with chronic illness

PubMed Central

Eccleston, Christopher; Fisher, Emma; Law, Emily; Bartlett, Jess; Palermo, Tonya M

2016-01-01

Background Psychological therapies have been developed for parents of children and adolescents with a chronic illness. Such therapies include interventions directed at the parent only or at parent and child/adolescent, and are designed to improve parent, child, and family outcomes. This is an updated version of the original Cochrane review published in Issue 8, 2012, (Psychological interventions for parents of children and adolescents with chronic illness). Objectives To evaluate the efficacy of psychological therapies that include parents of children and adolescents with chronic illnesses including painful conditions, cancer, diabetes mellitus, asthma, traumatic brain injury (TBI), inflammatory bowel diseases (IBD), skin diseases, or gynaecological disorders. We also aimed to evaluate the adverse events related to implementation of psychological therapies for this population. Secondly, we aimed to evaluate the risk of bias of included studies and the quality of outcomes using the GRADE assessment. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO for randomised controlled trials (RCTs) of psychological interventions that included parents of children and adolescents with a chronic illness. Databases were searched to July 2014. Selection criteria Included studies were RCTs of psychological interventions that delivered treatment to parents of children and adolescents with a chronic illness compared to an active control, waiting list, or treatment as usual control group. Data collection and analysis Study characteristics and outcomes were extracted from included studies. We analysed data using two categories. First, we analysed data by each individual medical condition collapsing across all treatment classes at two time points. Second, we analysed data by each individual treatment class; cognitive behavioural therapy (CBT), family therapy (FT), problem solving therapy (PST) and multisystemic therapy (MST) collapsing across all medical conditions. For both sets of analyses we looked immediately post-treatment and at the first available follow-up. We assessed treatment effectiveness for two primary outcomes: parent behaviour and parent mental health. Five secondary outcomes were extracted; child behaviour/disability, child mental health, child symptoms, family functioning, and adverse events. Risk of bias and quality of evidence were assessed. Main results Thirteen studies were added in this update, giving a total of 47 RCTs. The total number of participants included in the data analyses was 2985, 804 of whom were added to the analyses in the update. The mean age of the children was 14.6 years. Of the 47 RCTs, the studies focused on the following paediatric conditions: n = 14 painful conditions, n = 13 diabetes, n =10 cancer, n = 5 asthma, n = 4 TBI, and n = 1 atopic eczema. We did not identify any studies treating parents of children with gynaecological disorders or IBD. Risk of bias assessments of included studies were predominantly unclear. Evidence quality, assessed using the GRADE criteria, was judged to be of low or very low quality. Analyses of separate medical conditions, across all treatment types, revealed two beneficial effects of psychological therapies for our primary outcomes. First, psychological therapies led to improved adaptive parenting behaviour in parents of children with cancer post-treatment (standardised mean difference (SMD) −0.20, 95% confidence interval (CI) −0.36 to −0.04, Z = 2.44, p = 0.01). In addition, therapies also improved parent mental health at follow-up in this group (SMD = −0.18, 95% CI −0.32 to −0.04, Z = 2.58, p = 0.01). We did not find any effect of therapies for parent behaviour for parents of children with a painful condition post-treatment or at followup, or for parent mental health for parents of children with cancer, diabetes, asthma, or TBI post-treatment. For all other primary outcomes, no analysis could be conducted due to lack of data. Across all medical conditions, three effects were found for the primary outcomes of psychological therapies. PST had a beneficial effect on parent adaptive behaviour (SMD = −0.25, 95% CI −0.39 to −0.11, Z = 3.59, p < 0.01) and parent mental health (SMD= −0.24, 95% CI −0.42 to −0.05, Z = 2.50, p = 0.01) immediately post-treatment and this effect was maintained at follow-up for parent mental health (SMD= −0.19, 95% CI −0.34 to −0.04, Z = 2.55, p = 0.01). The remaining analysis for PST on parent behaviour found no effect. No effects were found for CBT post-treatment or at follow-up for either parent outcome. For FT, only one analysis could be run on parent mental health and no effect was found. Due to lack of data, the remaining analyses of primary outcomes could not be run. For MST, no parent outcomes could be analysed due to lack of data. Secondary outcome analyses are presented in the Results section. Five studies reported that there were no adverse events during the trial. The remaining 42 studies did not report adverse events. Authors’ conclusions This update includes 13 additional studies, although our conclusions have not changed from the original version. There is little evidence for the efficacy of psychological therapies that include parents on most outcome domains of functioning, for a large number of common chronic illnesses in children. However, psychological therapies are efficacious for some outcomes. CBT that includes parents is beneficial for reducing children’s primary symptoms, and PST that includes parents improved parent adaptive behaviour and parent mental health. There is evidence that the beneficial effects can be maintained at follow-up for diabetes-related symptoms in children, and for the mental health of parents of children with cancer and parents who received PST. PMID:25874881

Colloid cyst and multiple meningiomata in Gorlin syndrome.

PubMed

Li, Yan-Lin; Kwok, Stephen Kai-Yan; Shiu, Kenneth Chun-Kit

2018-01-01

A middle-aged man presented with syncope and confusion. Neuroimaging revealed a third ventricular mass with obstructive hydrocephalus and bilateral convexity meningiomata. The masses were excised and pathology showed a colloid cyst and WHO grade 1 meningiomata respectively. Multisystem workup confirmed Gorlin syndrome. To our knowledge, this is the fourth reported case of Gorlin syndrome associated with colloid cyst, and the first case where multiple meningiomata are also present. Copyright © 2017 Elsevier Ltd. All rights reserved.

Von Hippel-Lindau Disease: A Rare Familiar Multi-System Disorder and the Impact of the Clinical Nurse Specialist

DTIC Science & Technology

1993-01-01

would undergo removal of both adrenal glands, the renal cell carcinomas, a cholecystectomy and a choledochoduodenostomy for biliary drainage . The...bleeding, renal failure, and pancreatitis. After recovery, a craniotomy would be done to remove the hemangioblastoma that had been bleeding. The...analgesia. After a three month convalescence, the patient had a craniotomy and was home within a week. The patient’s siblings have all had negative eye

Severe panuveitis in neuro-Behçet's disease in Malaysia: a case series.

PubMed

Othman, Khairuddin; Liza-Sharmini, Ahmad Tajudin; Ibrahim, Mohtar; Tharakan, John; Yanai, Ryoji; Zunaina, Embong

2017-01-01

Behçet's disease (BD) is a multisystemic disease that is very rare in Malaysia. About 5% of patients develop central nervous system involvement, termed neuro-Behçet's. Neuro-Behçet's is one of the most serious causes of long-term morbidity and mortality. We report two cases of neuro-Behçet's associated with uveitis (ocular BD) highlighting the clinical presentation, diagnostic measurement, and therapeutic management of these cases.

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

DTIC Science & Technology

2009-10-01

Specified (PDD-NOS), Asperger disorder, Childhood Disintegrative Disorder (CDD) and Rett syndrome . According to the Centers for Disease Control (CDC), 1 in...induced epilepsy (Fernandes et al., 1996; Reime et al., 2007), and in Crush syndrome (Desai and Desai, 2007). In chronic fatigue syndrome , the...the gene encoding the L-type voltage-gated Ca2+channel CaV1.2 (CACNA1C) cause Timothy syndrome , a multisystem disorder that includes cardiac

Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease.

PubMed

Chonat, Satheesh; Quinn, Charles T

2017-01-01

Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on current standards of clinical management and recent research findings. The importance of a comprehensive, multidisciplinary and lifelong system of care is also emphasized.

Coexistence of Ankylosing Spondylitis and Neurofibromatosis Type 1.

PubMed

Gundogdu, Baris; Yolbas, Servet; Yildirim, Ahmet; Gonen, Murat; Koca, Suleyman Serdar

2016-01-01

Ankylosing spondylitis (AS) is a systemic disease primarily characterized by the inflammation of sacroiliac joints and axial skeleton. Neurofibromatosis type 1 (NF1) is a multisystem genetic disease which is characterized by cutaneous findings, most importantly café-au-lait spots and axillary freckling, by skeletal dysplasia, and by the growth of both benign and malignant nervous system neoplasms, most notably benign neurofibromas. In this case report, we present a 43-year-old male with AS and NF1.

Stem cells in psoriasis.

PubMed

Hou, Ruixia; Li, Junqin; Niu, Xuping; Liu, Ruifeng; Chang, Wenjuan; Zhao, Xincheng; Wang, Qiang; Li, Xinhua; Yin, Guohua; Zhang, Kaiming

2017-06-01

Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system. Many cell types have been confirmed to participate in the pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to psoriasis that have been investigated recently. Copyright © 2016. Published by Elsevier B.V.

Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency☆

PubMed Central

Simon, Mariella T.; Ng, Bobby G.; Friederich, Marisa W.; Wang, Raymond Y.; Boyer, Monica; Kircher, Martin; Collard, Renata; Buckingham, Kati J.; Chang, Richard; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Van Hove, Johan L.K.; Freeze, Hudson H.; Abdenur, Jose E.

2017-01-01

We report the clinical, biochemical, and molecular findings in two brothers with encephalopathy and multi-systemic disease. Abnormal transferrin glycoforms were suggestive of a type I congenital disorder of glycosylation (CDG). While exome sequencing was negative for CDG related candidate genes, the testing revealed compound heterozygous mutations in the mitochondrial elongation factor G gene (GFM1). One of the mutations had been reported previously while the second, novel variant was found deep in intron 6, activating a cryptic splice site. Functional studies demonstrated decreased GFM1 protein levels, suggested disrupted assembly of mitochondrial complexes III and V and decreased activities of mitochondrial complexes I and IV, all indicating combined OXPHOS deficiency. PMID:28216230

Characterization and evolution of dermal filaments from patients with Morgellons disease

PubMed Central

Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process. PMID:23326202

A Novel Mitochondrial DNA Deletion in Patient with Pearson Syndrome.

PubMed

Khasawneh, Rame; Alsokhni, Hala; Alzghoul, Bayan; Momani, Asim; Abualsheikh, Nazih; Kamal, Nazmi; Qatawneh, Mousa

2018-04-01

Arteriovenous Pearson syndrome is a very rare multisystemic mitochondrial disease characterized by sideroblastic anemia and exocrine pancreatic insufficiency. It is usually fatal in infancy. We reported a four-month-old infant presented with fever and pancytopenia. Bone marrow examination showed hypoplastic changes and sideroblastic features. Molecular Study showed a novel hetroplasmic mitochondrial deletions (m. 10760 -m. 15889+) in multiple genes (ND4,ND5,ND6, CYTB). In our patient the pathogenic mutation was 5.1 kb heteroplasmic deletions in multiple genes that are important and crucial for intact oxidative phosphorylation pathway and ATP production in the mitochondrial DNA. This mutation was not reported in literature including the mitomap.org website (which was last edited on Nov 30, 2017 and accessed on Jan 13, 2018).

Disseminated Multi-system Sarcoidosis Mimicking Metastases on 18F-FDG PET/CT.

PubMed

Makis, William; Palayew, Mark; Rush, Christopher; Probst, Stephan

2018-06-07

A 60-year-old female with no significant medical history presented with hematuria. A computed tomography (CT) scan revealed extensive lymphadenopathy with hypodensities in the liver and spleen, and she was referred for an 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/CT (PET/CT) study to assess for malignancy of unknown primary. PET/CT revealed extensive 18 F-FDG avid lymphadenopathy as well as innumerable intensely 18 F-FDG avid lung, liver and splenic nodules, highly concerning for malignancy. A PET-guided bone marrow biopsy of the posterior superior iliac spine revealed several non-necrotizing, well-formed granulomas, consistent with sarcoidosis. The patient was managed conservatively and remained clinically well over the subsequent 9 years of follow-up.

Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome.

PubMed

Baertling, Fabian; Sánchez-Caballero, Laura; Timal, Sharita; van den Brand, Mariël Am; Ngu, Lock Hock; Distelmaier, Felix; Rodenburg, Richard Jt; Nijtmans, Leo Gj

2017-03-01

NDUFAF3 is an assembly factor of mitochondrial respiratory chain complex I. Variants in NDUFAF3 have been identified as a cause of severe multisystem mitochondrial disease. In a patient presenting with Leigh syndrome, which has hitherto not been described as a clinical feature of NDUFAF3 deficiency, we identified a novel homozygous variant and confirmed its pathogenicity in patient fibroblasts studies. Furthermore, we present an analysis of complex I assembly routes representative of each functional module and, thereby, link NDUFAF3 to a specific step in complex I assembly. Therefore, our report expands the phenotype of NDUFAF3 deficiency and further characterizes the role of NDUFAF3 in complex I biogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

The Santa Monica crash: an urban multicasualty event.

PubMed

McGory, Marcia; Cryer, H Gill; Chandler, Charles; Cohen, Marilyn; Hiatt, Jonathan R

2004-10-01

Mass casualty events provide dramatic challenges for trauma centers and trauma systems. We analyzed the management of victims and assessed the response of the UCLA Healthcare System to the Santa Monica multicasualty event of July 16, 2003, when an elderly man drove his car through a crowded outdoor market and injured 73 people, 10 of whom died (eight at the scene). Of the victims, 26 were treated at UCLA (n = 15) and Santa Monica (n = 11) Medical Centers. Fourteen patients (54%) were female; average age was 41.9 years (range 7 months to 88 years). Fifteen patients were treated in the ER only, and 11 patients required admission. Of the latter, 10 (91%) had multisystem injuries, most commonly musculoskeletal, which occurred in nine patients (82%). Seven patients required immediate operations (orthopedic in six and a pericardial window in one). Three patients required delayed operations (orthopedic and plastic surgery). Most surgical and medical specialties were needed in consultation. Average LOH was 11.8 (range 2-23) days. Mean ISS was 21.2 (range 1-75). There were six complications (three early and three late) and one death from head injury. Seven patients (64%) required rehabilitation. We conclude that mass casualty victims have multisystem injuries of variable severity, which underscores the importance of trauma centers and trauma systems. The large trauma scene and particular need for orthopedic services were notable features of this event.

Assessing interactions among multiple physiological systems during walking outside a laboratory: An Android based gait monitor

PubMed Central

Sejdić, E.; Millecamps, A.; Teoli, J.; Rothfuss, M. A.; Franconi, N. G.; Perera, S.; Jones, A. K.; Brach, J. S.; Mickle, M. H.

2015-01-01

Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18 to 35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardivascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults. PMID:26390946

Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS).

PubMed

Haverkamp, M H; van de Vosse, E; Goldbach-Mansky, R; Holland, S M

2014-09-01

Cryopyrin-associated periodic syndrome (CAPS) is characterized by dysregulated inflammation with excessive interleukin (IL)-1β activation and secretion. Neonatal-onset multi-system inflammatory disease (NOMID) is the most severe form. We explored cytokine responses in 32 CAPS patients before and after IL-1β blocking therapy. We measured cytokines produced by activated peripheral blood monuclear cells (PBMCs) from treated and untreated CAPS patients after stimulation for 48 h with phytohaemagglutinin (PHA), PHA plus IL-12, lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ. We measured IL-1β, IL-6, IL-10, tumour necrosis factor (TNF), IL-12p70 and IFN-γ in the supernatants. PBMCs from three untreated CAPS patients were cultured in the presence of the IL-1β blocker Anakinra. Fifty healthy individuals served as controls. CAPS patients had high spontaneous production of IL-1β, IL-6, TNF and IFN-γ by unstimulated cells. However, stimulation indexes (SIs, ratio of stimulated to unstimulated production) of these cytokines to PHA and LPS were low in NOMID patients compared to controls. Unstimulated IL-10 and IL-12p70 production was normal, but up-regulation after PHA and LPS was also low. LPS plus IFN-γ inadequately up-regulated the production of IL-1β, IL-6, TNF and IL-10 in CAPS patients. In-vitro but not in-vivo treatment with Anakinra improved SIs by lowering spontaneous cytokine production. However, in-vitro treatment did not improve the low stimulated cytokine levels. Activating mutations in NLRP3 in CAPS are correlated with poor SIs to PHA, LPS and IFN-γ. The impairment in stimulated cytokine responses in spite of IL-1β blocking therapy suggests a broader intrinsic defect in CAPS patients, which is not corrected by targeting IL-1β. © 2014 British Society for Immunology.

Multi-system Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

PubMed Central

Fears, Scott C.; Service, Susan K.; Kremeyer, Barbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Franco, Juliana; Lopez, Maria C.; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier; Glahn, David C.; Ospina-Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

2014-01-01

IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), yet its pathogenesis remains poorly understood. A focus on measuring multi-system quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that impact on BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomic phenotypes that appear heritable and associated with severe bipolar disorder (BP-I), and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN Multi-generational pedigree study in two closely related, genetically isolated populations: the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). PARTICIPANTS 738 individuals, all from CVCR and ANT pedigrees, of whom 181 are affected with BP-I. MAIN OUTCOME MEASURE Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) phenotypes. RESULTS Seventy-five percent (126) of the phenotypes investigated were significantly heritable, and 31% (53) were associated with BP-I. About 1/4 of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions, and volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE This is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I-association within families that is consistent with expectations from case-control studies. Together these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder. PMID:24522887

Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5 years of treatment.

PubMed

Hendriksz, Christian; Santra, Saikat; Jones, Simon A; Geberhiwot, Tarekegn; Jesaitis, Lynne; Long, Brian; Qi, Yulan; Hawley, Sara M; Decker, Celeste

2018-04-01

Elosulfase alfa is an enzyme replacement therapy for Morquio A syndrome (mucopolysaccharidosis IVA), a multisystemic progressive lysosomal storage disorder. This report includes the primary treatment outcomes and immunogenicity profile of elosulfase alfa in patients with Morquio A syndrome from 2 sequential studies, MOR-002 (ClinicalTrials.govNCT00884949) and MOR-100 (NCT01242111), representing >5 years of clinical study data. MOR-002 was an open-label, single-arm phase 1/2 study that evaluated the pharmacokinetics, safety, immunogenicity, and preliminary efficacy of 3 sequential doses of elosulfase alfa (0.1, 1.0, and 2.0 mg/kg/week) in patients with Morquio A syndrome (n = 20) over 36 weeks, followed by an optional 36- to 48-week treatment period using elosulfase alfa 1.0 mg/kg once weekly (qw). During the 0.1 mg/kg dosing phase, 1 patient discontinued due to a type I hypersensitivity adverse event (AE), and that patient's sibling voluntarily discontinued in the absence of AEs. An additional patient discontinued due to recurrent infusion reactions during the 1.0 mg/kg continuation phase. The remaining 17 patients completed MOR-002 and enrolled in MOR-100, an open-label, long-term extension study that further evaluated safety and clinical outcomes with elosulfase alfa administered at 2.0 mg/kg qw. During the course of MOR-100, patients were given the option of receiving elosulfase alfa infusions at home with nursing assistance. Over the course of both studies, all patients experienced ≥1 AE and most patients experienced a drug-related AE, generally of mild or moderate severity. Hypersensitivity reactions reported as related to study drug occurred in 25% of patients. Thirteen patients who chose to receive infusions at home had the same tolerability and safety profile, as well as comparable compliance rates, as patients who chose to receive on-site infusions. All patients developed antibodies to elosulfase alfa. Positivity for neutralizing antibodies was associated with increased drug half-life and decreased drug clearance. Despite formation of antidrug-binding (total antidrug antibodies, TAb) and in vitro neutralizing antibodies (NAb) in all patients, these types of immunogenicity to elosulfase alfa were not correlated with safety or clinical outcomes. In contrast with the reported natural history of Morquio A, no trends toward decreasing endurance, respiratory function, or ability to perform activities of daily living were observed in this cohort over the 5-year period. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Tuberculoid leprosy masquerading as systemic lupus erythematosus: an interesting observation.

PubMed

Zawar, Vijay; Kumavat, Shrikant; Pawar, Manoj; Desai, Dipti

2017-09-01

Leprosy is a chronic granulomatous infectious multisystem disease that may present with protean manifestations. It mimics many systemic and dermatological disorders. Here we report a case in which an elderly female presented with malar rash, intermittent fever, and arthralgia. Her diagnosis was significantly delayed due to a close clinical resemblance to systemic lupus erythematosus. It is important to be aware of such manifestations of leprosy and improve awareness of it in clinicians to avoid misdiagnosis and delay in treatment.

Why are kids with lupus at an increased risk of cardiovascular disease?

PubMed

Quinlan, Catherine; Marks, Stephen D; Tullus, Kjell

2016-06-01

Juvenile-onset systemic lupus erythematosus (SLE) is an aggressive multisystem autoimmune disease. Despite improvements in outcomes for adult patients, children with SLE continue to have a lower life expectancy than adults with SLE, with more aggressive disease, a higher incidence of lupus nephritis and there is an emerging awareness of their increased risk of cardiovascular disease (CVD). In this review, we discuss the evidence for an increased risk of CVD in SLE, its pathogenesis, and the clinical approach to its management.

Hemophagocytic Lymphohistiocytosis in a Young Child.

PubMed

Saikia, Uma Nahar; Gupta, Anju; Vignesh, Pandiarajan; Suri, Deepti; Singh, Mini P

2016-06-08

Hemophagocytic lymphohistiocytosis (HLH) is a multisystem disorder mediated by cytokine storm and is characterized by fever, pancytopenia and organomegaly coupled with laboratory features like hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia and transaminitis. Etiology can be genetic or acquired such as infections, malignancy and autoimmune disorders. Diagnosis, identification of underlying etiology and management of HLH remain tough clinical puzzles to sort out for the managing physician. We report a clinico-pathological conference of a three-year-old boy who had such a presentation and succumbed during the hospital stay.

Obstetric nephrology: preeclampsia--the nephrologist's perspective.

PubMed

Umans, Jason G

2012-12-01

Preeclampsia, a common and potentially devastating multisystem disorder unique to human pregnancy, represents a novel form of secondary hypertension with complex renal and systemic effects. Recent translational and clinical research reveals key pathophysiologic contributions due to dysregulation of angiogenic factors and of angiotensin signaling. Despite these insights, there are still difficulties in the clinical definition of preeclampsia and in the diagnosis of women with this disorder. Although recent research suggests the potential for new preventive and treatment strategies, most have not yet been shown ready for clinical use.

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-

PubMed Central

Park, Jin Suk; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-01-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome. PMID:20508802

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-.

PubMed

Park, Jin Suk; Baek, Chong Wha; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-04-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome.

Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

PubMed

McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

2013-12-17

Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

A case report for fatal Churg-Strauss syndrome complications: first reported death due to rapid progression of prominently huge hepatic capsular hematoma and multi-system organ hemorrhage

PubMed Central

Qian, Jiejing; Tong, Hongyan; Chen, Feifei; Mai, Wenyuan; Lou, Yinjun; Jin, Jie

2014-01-01

Churg-Strauss syndrome (CSS) is a rare disease that has an extremely low incidence rate. CSS prognosis is good, in general; and there are no reports of multiple-organ hemorrhage in CSS. We report a unique case of CSS, wherein, an elderly man experienced multiple organ hemorrhage -- a particularly huge hematoma under the capsule of the liver and poor prognosis. PMID:25419420

Familial Churg-Strauss Syndrome in a Sister and Brother.

PubMed

Alyasin, Soheyla; Khoshkhui, Maryam; Amin, Reza

2015-06-01

Churg-Strauss syndrome (CSS) is a granulomatous small vessel vasculitis. It is characterized by asthma, allergic granulomatosis and vasculitis. This syndrome is rare in children. A 5 years old boy was admitted with cough, fever and dyspnea for 2 weeks. On the basis of laboratory data (peripheral eosinophilia), associated with skin biopsy, and history of CSS in his sister, this disease was eventually diagnosed. The patient had good response to corticosteroid. In every asthmatic patient with prolonged fever, eosinophilia and multisystemic involvment, CSS should be considered.

Acute anterior uveitis as the initial presentation of alkaptonuria.

PubMed

John, S S; Padhan, P; Mathews, J V; David, S

2009-01-01

Alkaptonuria is a rare autosomal recessive metabolic disorder that may present with multi-system involvement such as ochronotic arthropathy, renal, urethral and prostatic calculi, cardiac valvular lesions and pigmentation of the skin, sclera, cartilage and other connective tissues. An association of the disease with uveitis has never been reported. We report the first case of alkaptonuria with ochronotic arthropathy presenting with recurrent acute anterior uveitis as the initial manifestation. The possible common link with the HLA-B27 gene is discussed.

Mitral valve prolapse and Marfan syndrome.

PubMed

Thacoor, Amitabh

2017-07-01

Marfan syndrome is a multisystemic genetic condition affecting connective tissue. It carries a reduced life expectancy, largely dependent on cardiovascular complications. More common cardiac manifestations such as aortic dissection and aortic valve incompetence have been widely documented in the literature. Mitral valve prolapse (MVP), however, has remained poorly documented. This article aims at exploring the existing literature on the pathophysiology and diagnosis of MVP in patients with Marfan syndrome, defining its current management and outlining the future developments surrounding it. © 2017 Wiley Periodicals, Inc.

JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.

PubMed

Baris, S; Karakoc-Aydiner, E; Ozen, A; Delil, K; Kiykim, A; Ogulur, I; Baris, I; Barlan, I B

2015-05-01

Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement.

Cushing's syndrome presenting as treatment-resistant bipolar affective disorder: A step in understanding endocrine etiology of mood disorders

PubMed Central

Ummar, I. Syed; Rajaraman, Venkateswaran; Loganathan, N.

2015-01-01

Cushing's syndrome (CS) is the multisystem disorder which is due to cortisol excess. It is very difficult to diagnose in early stages, especially when psychiatric manifestations are the predominant complaints. It could result in significant morbidity and mortality. We report a case of resistant bipolar affective disorder secondary to CS. Early diagnosis and treatment will lead to better functional outcome and prevention of neurocognitive side-effects of excessive cortisol. PMID:26124528

Synchronous bilateral carcinoma of the breasts occurring in a young woman with a history of Langerhans' cell histiocytosis in infancy.

PubMed

Churn, M; Davies, C; Slater, A

1999-01-01

We report the case history of a 28-year-old woman who developed synchronous bilateral carcinoma of the breasts, having been diagnosed with multisystem Langerhans' cell histiocytosis in infancy. She had been treated with vinblastine and corticosteroids for 3 years and made a full recovery without late sequelae. We review the association of Langerhans' cell histiocytosis and its treatment with subsequent malignancy, with particular reference to carcinoma of the breast, and discuss the possible causes.