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Sample records for immunoglobulin substitution therapy

  1. [Subcutaneous immunoglobulin substitution and therapy].

    PubMed

    Gulácsy, Vera; Maródi, László

    2011-01-09

    Patients with combined primary immunodeficiency or B-cell deficiency with low serum concentration of immunoglobulin G can be efficiently treated with immunoglobulin G concentrates. From the 1950s IgG was used intramuscularly, and from the 1980s intravenous immunoglobulin (IVIG) replacement has become widely available for replacement therapy. Among the potential side effects of IVIG (including anaphylaxis), further disadvantages of IVIG are hospitalization during treatment and varying concentrations of IgG. Over the past ten years, subcutaneous IgG (SCIG) preparations have become reasonable alternatives to IVIG. SCIG given weekly assures a more balanced serum IgG level, side affects are mostly local and temporary; systemic, severe adverse events have not been observed. In addition, SCIG can be used for home treatment of patients which improves their quality of life remarkably.

  2. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    PubMed

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

    PubMed

    del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime

    2014-11-01

    Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.

  4. 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.

  5. Immunoglobulin therapy in idiopathic hypothalamic dysfunction.

    PubMed

    Huppke, Peter; Heise, Alexander; Rostasy, Kevin; Huppke, Brenda; Gärtner, Jutta

    2009-09-01

    Idiopathic hypothalamic dysfunction is a rare disorder presenting at age 3-7 years. Severe hypothalamic and brainstem dysfunction leads to death in 25% of patients. The disease is presumed to be autoimmune, or in some cases paraneoplastic. No successful treatment has been reported. Patient V. developed hyperphagia, hypersomnia, and extreme aggression at age 7 years, accompanied by episodes of hyperthermia, hypothermia, sinus bradycardia, hypernatremia, hyponatremia, persistent hyperprolactinemia, hypothyroidism, and growth-hormone deficiency. At age 9 years, a diagnosis of idiopathic hypothalamic dysfunction was rendered, and immunoglobulin therapy was commenced. Nine courses of immunoglobulins, at a dose of 2 g/kg every 4 weeks, were administered. Reproducible improvements in behavior and no further episodes of hyponatremia or hypernatremia and sinus bradycardia were evident. The endocrinologic abnormalities and poor thermoregulation remained. Administration of immunoglobulins during late stages of idiopathic hypothalamic dysfunction led to improvement in some but not all signs. Assuming an autoimmune basis for this disorder, treatment during early stages of disease should be more effective. To facilitate such early treatment, increased awareness of this disorder is necessary, to allow for early diagnosis.

  6. Intravenous and subcutaneous immunoglobulin G replacement therapy.

    PubMed

    Bonilla, Francisco A

    2016-11-01

    Human polyclonal immunoglobulin G (IgG) for therapeutic use has been available for decades. This drug was developed for treatment of antibody deficiency (replacement therapy), although its use has expanded into many anti-inflammatory and immunomodulatory applications in recent years. This review focuses on IgG prescribing for replacement therapy. IgG for replacement is most often administered via the intravenous IgG (IVIG) or subcutaneous IgG (SCIG) routes. IVIG is usually administered every 34 weeks, and SCIG is usually administered weekly, although variations may be considered in all cases. Recently, a new product became available that uses hyaluronidase to facilitate absorption of large doses of SCIG less frequently (every 34 weeks, as with IVIG). There are important differences between the pharmacokinetics of these three routes of administration. IVIG therapy leads to high peaks and low troughs between infusions. IgG concentration fluctuates much less over time with SCIG. Hyaluronidase-facilitated SCIG is intermediate. SCIG may have lower bioavailability in comparison with IVIG and may require higher doses over time; this is not true for hyaluronidase SCIG. However, there are large variations in IgG half-life among individuals and with different products. Therefore, individualization of therapy is essential. Mild systemic flu-like adverse effects may affect up to 2025% of patients who receive IVIG, smaller fractions may experience more-severe symptoms, whereas anaphylaxis is exceedingly rare. General flu-like systemic adverse effects are minimal with SCIG (intermediate with hyaluronidase SCIG), but transient (24 hours), mild, local inflammatory symptoms at infusion sites are relatively common with both forms. Additional rare but important complications of IgG therapy include thrombotic events and hemolysis that can be seen at high doses with any route of administration. Renal adverse effects may occur with IVIG as well. The variety of IgG products and routes of

  7. [Replacement therapy with subcutaneous immunoglobulin in primary immunodeficiency in children].

    PubMed

    Pac, Małgorzata

    2011-06-01

    Primary antibody deficiency (PAD) is the most common form of primary immunodeficiency (PID), and presents up to 60-70% of PID. The hallmark of PAD are low antibody level and recurrent infections. Patients require life-long immunoglobulin replacement therapy. Now they can be treated either with intravenous (IVIG) or subcutaneous (SCIG) immunoglobulin. The last one is indicated in patients with unacceptable adverse reactions to the intravenous immunoglobulin preparations, with poor vein access or willing to improve the quality of their life. Several data and clinical trials proved that SCIG therapy is at least as safe and efficacious as IVIG to prevent infections in patients with PAD.

  8. Intravenous immunoglobulin therapy for antibody deficiency.

    PubMed Central

    Nolte, M T; Pirofsky, B; Gerritz, G A; Golding, B

    1979-01-01

    Twenty patients with antibody deficiency were treated at random with either intramuscular immune serum globulin (ISG) or intravenous modified immune serum globulin (M-ISG). Fourteen patients received of 259 M-ISG infusions during 242 months of treatment. Catastrophic vasomotor reactions were not observed. A single dose of 150 mg/kilo M-ISG increased serum IgG values a mean 248 mg%. Intravenous M-ISG therapy was effective in reducing the incidence of acute infections. Subjects receiving M-ISG developed 0.103 acute infections per month of treatment. Patients injected with ISG had 0.295 acute infections per month of treatment. Seven subjects had separate courses of both intravenous M-ISG and intramuscular ISG. Acute infections per month of treatment for M-ISG and ISG were 0.104 and 0.406, respectively. PMID:477026

  9. Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis.

    PubMed

    Hansen-Schmidt, S; Silomon, J; Keller, F

    1996-09-01

    Acute renal failure has been described as a complication of immunoglobulin therapy. It is not clear whether the immunoglobulin per se or the sucrose that is used as a stabilizer is the cause. We describe a patient with immunoglobulin A nephropathy who was treated with sucrose-containing immunoglobulin. He developed acute renal failure with osmotic nephrosis found on kidney biopsy. When using a glycine-containing immunoglobulin no acute renal impairment was observed in this patient.

  10. [Substitution therapy tested against amphetamine dependence].

    PubMed

    Bloniecki Kallio, Victor; Guterstam, Joar; Franck, Johan

    2016-01-06

    Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options are limited but recently substitution therapy with psychostimulant medication has been evaluated in several clinical trials. Such treatment is controversial in Sweden, perhaps due to the failure of experimental prescription of psychostimulants in the 1960s. Recent clinical trials however indicate that structured treatment programs with psychostimulants might have positive effects, although the results are inconsistent and the evidence base is still limited. Future research is needed in order to determine the potential role of substitution therapy for amphetamine dependence in clinical practice.

  11. Managing patients with side effects and adverse events to immunoglobulin therapy.

    PubMed

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hossein; Shaghaghi, Shiva; Negahdari, Babak; Mohammadi, Javad; Rezaei, Nima; Aghamohammadi, Asghar

    2016-01-01

    Immunoglobulin therapy has not only served as a lifesaving approach for the prevention and treatment of infections in primary and secondary immunodeficiency diseases, but has also been used as an immunomodulatory agent for autoimmune and inflammatory disorders and to provide passive immunity for some infectious diseases. Most of the adverse effects associated with immunoglobulin therapy are mild, transient and self-limiting. However, serious side effects also occur. Therefore, to minimize the adverse events of immunoglobulin therapy, specialist review of patient clinical status and immunoglobulin products, in addition to selection of appropriate treatment strategy for the management of patients with associated side effects and adverse events, are crucial.

  12. Facilitated subcutaneous immunoglobulin (fSCIg) therapy--practical considerations.

    PubMed

    Ponsford, M; Carne, E; Kingdon, C; Joyce, C; Price, C; Williams, C; El-Shanawany, T; Williams, P; Jolles, S

    2015-12-01

    There is an increasing range of therapeutic options for primary antibody-deficient patients who require replacement immunoglobulin. These include intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg). Advantages of fSCIg include fewer needle punctures, longer infusion intervals and an improved adverse effect profile relative to IVIg. Limited real-life experience exists concerning the practical aspects of switching or starting patients on fSCIg. We describe the first 14 patients who have been treated with fSCIg at the Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years of experience. The regimen was well tolerated, with high levels of satisfaction and no increase in training requirement, including for a treatment-naive patient. Two patients discontinued fSCIg due to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality.

  13. Structural analysis of substitution patterns in alleles of human immunoglobulin VH genes.

    PubMed

    Romo-González, Tania; Vargas-Madrazo, Enrique

    2005-05-01

    The diversity in repertoires of antibodies (Abs) needed in response to the antigen challenge is produced by evolutionary and somatic processes. The mechanisms operating at a somatic level have been studied in great detail. In contrast, neither the mechanisms nor the strategies of diversification at an evolutionary level have yet been understood in similar detail. Particularly, the substitution patterns in alleles of immunoglobulin genes (Igs) have not been systematically studied. Furthermore, there is a scarcity of studies which link the analysis at a genetic level of the diversification of repertoires with the structural consequences at the protein level of the changes in DNA information. For the purpose of systematically characterizing the strategies of evolutionary diversification through sequence variation at alleles, in this work, we built a database for all the alleles of the IGHV locus in humans reported until now. Based on these data, we performed diverse analyses of substitution patterns and linked these results with studies at the protein level. We found that the sequence diversification in different alleles does not operate with equal intensity for all V genes. Our studies, both of the number of substitutions and of the type of amino acid change per sub-segment of the V-REGION evidenced differences in the selective pressure to which these regions are exposed. The implications of these results for understanding the evolutionary diversification strategies, as well as for the somatic generation of antibody repertoires are discussed.

  14. Use of intravenous immunoglobulin therapy in autoimmune blistering diseases.

    PubMed

    Ahmed, A Razzaque

    2006-04-01

    Autoimmune mucocutaneous blistering diseases (AMBD) are an interesting group of rare diseases that affect the mucous membranes and the skin and are frequently or potentially fatal. The clinical presentation is significantly variable, as is the course and prognosis. The immunopathology is well characterized and the target antigens to which the autoantibodies are directed have been studied by various investigators. A significant majority of the patients respond to conventional therapy, which consists of high-dose long-term systemic corticosteroids and immunosuppressive agents. This treatment program has significantly improved the prognosis in many patients. In such patients, significant side effects of the drugs may appear and produce a very poor quality of life. In patients with progressive diseases, especially those with mucous membrane pemphigoid, the significant sequela; such as blindness, aphonia, and stenosis of the anal and vaginal canals can occur. In several patients treated with conventional immunosuppressive therapy, death occurs as a consequence of prolonged immune suppression leading to opportunistic infections. In this manuscript, the published data on the use of immunoglobulins intravenous (IGIV) in patients with AMBD is presented. The most important features of IGIV in patients with AMBD are: 1) the ability to clinically control the disease; 2) the ability to induce and maintain a long-term clinical remission; 3) a lower incidence of side effects; and 4) a higher quality of life. The important characteristic of the IGIV therapy in the AMBD is two-fold. First, the therapy, when given according to a published protocol, produces a lasting and long-term clinical remission, rather than a temporary arrest of the disease. Second, the therapy, as described in the protocol, has a very definitive endpoint. Consequently, once the patients are treated and go into long-term remission, the therapy is no longer required. The significant positive results obtained

  15. Treatment of autoimmune mucocutaneous blistering diseases with intravenous immunoglobulin therapy.

    PubMed

    Ahmed, A Razzaque

    2004-08-01

    Autoimmune mucocutaneous blistering diseases (AMBDs) are a group of rare diseases that affect the skin and mucous membranes and are potentially fatal. They have variable clinical presentation, course and prognosis. Their immunopathology is well-characterised and target antigens have been studied. Many patients respond to conventional therapy, which consists of high-dose long-term systemic corticosteroids with an immunosuppressive agent, but side effects develop that can produce a poor quality of life. Many patients develop significant sequelae, such as blindness, loss of voice, vaginal and anal stenosis. In most patients cause of death is opportunistic infections secondary to immune suppression. To date, intravenous immunoglobulin (IVIg) has been reported to have benefited 156 patients with AMBDs. Its most important features include the ability to reduce or eliminate conventional therapy, the enabling of clinical control, the ability to induce and maintain long-term clinical remission, the capacity for usage based on a defined protocol with a described end point and a resulting increase in quality of life. IVIg produces the best clinical outcome when combined with aggressive topical therapy, sublesional injections of triamcinolone and rapid detection, and early treatment of cutaneous and mucosal infection. Successful therapy requires a physician to spend significant time with each patient. This manuscript provides the opinion of the author on the current use of IVIg to treat AMBDs.

  16. Differential protein analysis of serum exosomes post-intravenous immunoglobulin therapy in patients with Kawasaki disease.

    PubMed

    Zhang, Li; Song, Qi-Fang; Jin, Jing-Jie; Huang, Ping; Wang, Zhou-Ping; Xie, Xiao-Fei; Gu, Xiao-Qiong; Gao, Xue-Juan; Jia, Hong-Ling

    2017-08-14

    Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin. Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy. Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function. Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.

  17. Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

    PubMed Central

    Park, Hyo Min; Hyun, Myung Chul; Lee, Sang Bum

    2013-01-01

    Purpose It has been reported that 10% to 20% of children with Kawasaki disease (KD) will not respond to intravenous immunoglobulin (IVIG) treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. Methods We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. Results Among the 309 children, 30 (9.7%) did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT), total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIG-nonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. Conclusion Two independent predictors (ALT≥84 IU/L, total bilirubin≥0.9 mg/dL) for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD. PMID:23482814

  18. Targeted therapy in severe asthma today: focus on immunoglobulin E.

    PubMed

    Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

    2017-01-01

    Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard "one size fits all" approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma.

  19. Immunoglobulin therapy in the treatment of multifocal motor neuropathy.

    PubMed

    Kumar, Aditya; Patwa, Huned S; Nowak, Richard J

    2017-04-15

    Multifocal motor neuropathy (MMN) is a chronic immune-mediated disorder leading to slowly progressive muscle weakness and wasting. Current treatments are aimed at modulating the immune system in order to avoid further decline and to maintain functional status. Intravenous immunoglobulin (IVIg) is widely used in the treatment of immune-mediated disorders and is the only treatment approved for MMN. While patients do remain stable with maintenance IVIg treatment, most patients will slowly deteriorate over many years. The use of subcutaneous immunoglobulin (ScIg) is also gaining acceptance in this disease. The amount of axonal loss and the number of years without immunoglobulin (Ig) treatment appear to be associated with the permanence of weakness. We summarize the key literature to date that supports Ig use in the treatment of MMN.

  20. Intravenous immunoglobulin therapy for hypocomplementemic urticarial vasculitis associated with systemic lupus erythematosus in a child.

    PubMed

    Yamazaki-Nakashimada, Marco A; Duran-McKinster, Carola; Ramírez-Vargas, Nadia; Hernandez-Bautista, Victor

    2009-01-01

    Hypocomplementemic urticarial vasculitis is a type of urticarial vasculitis with multisystemic involvement and poor prognosis, sometimes associated with systemic lupus erythematosus. Several therapies have been attempted with no consensus on an effective therapeutic regimen. Intravenous immunoglobulin has been used in severe manifestations of systemic lupus erythematosus and recently in hypocomplementemic urticarial vasculitis. We present a 7-year-old girl with hypocomplementemic urticarial vasculitis associated with systemic lupus erythematosus and pneumonia who responded favorably to intravenous immunoglobulin.

  1. Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer

    SciTech Connect

    Ettinger, D.S.; Order, S.E.; Wharam, M.D.; Parker, M.K.; Klein, J.L.; Leichner, P.K.

    1982-02-01

    A phase I-II study of isotopic immunoglobulin therapy was performed in 18 patients with primary liver cancer; 14 were evaluable for toxicity. The patients received a dose of 37-157 millicuries of 131I-labeled antibody. The dose-limiting factor appears to be hematologic toxicity, especially thrombocytopenia. An objective antitumor effect was seen in six of nine patients who were evaluable for response. Present results suggest that further clinical studies with isotopic immunoglobulin are indicated.

  2. Subcutaneous immunoglobulin therapy in a patient with myopathic dropped head syndrome and common variable immunodeficiency.

    PubMed

    Rosato, E; Molinaro, I; Pisarri, S; Salsano, F

    2011-01-01

    Prominent neck extension weakness is an uncommon clinical entity, also termed dropped-head syndrome, that may be part of a generalized neuromuscular disorder. We report here the case of a woman with dropped-head syndrome and pulmonary arterial hypertension secondary to systemic sclerosis. Subsequently, she developed common variable immunodeficiency and subcutaneous immunoglobulin therapy was started. After two months from the start of therapy we did not observe any improvement in the degree of flexion of the head, although the clinical examination shows an improvement in neck extensor muscle strength. Subcutaneous immunoglobulin therapy could be a possible therapeutic option for the treatment of myopathic neck extensor weakness.

  3. Immunoglobulin Replacement Therapy: When You Need It -- and When You Don't

    MedlinePlus

    ... Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when you don’t DOWNLOAD PDF Some ... the treatment even though they don’t need it. That’s not a good idea. Here’s why. The ...

  4. Endogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies.

    PubMed

    Bermejo-Martin, Jesús F; Giamarellos-Bourboulis, Evangelos J

    2015-12-01

    The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. The first is that circulating IgM is a phenomenon associated with progression from severe sepsis to septic shock. Deficient kinetics of circulating IgM during the first 7 days following the start of vasopressors is linked with unfavourable outcome. The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach.

  5. Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective

    PubMed Central

    2012-01-01

    Sepsis represents a dysregulated host response to infection, the extent of which determines the severity of organ dysfunction and subsequent outcome. All trialled immunomodulatory strategies to date have resulted in either outright failure or inconsistent degrees of success. Intravenous immunoglobulin (IVIg) therapy falls into the latter category with opinion still divided as to its utility. This article provides a narrative review of the biological rationale for using IVIg in sepsis. A literature search was conducted using the PubMed database (1966 to February 2011). The strategy included the following text terms and combinations of these: IVIg, intravenous immune globulin, intravenous immunoglobulin, immunoglobulin, immunoglobulin therapy, pentaglobin, sepsis, inflammation, immune modulation, apoptosis. Preclinical and extrapolated clinical data of IVIg therapy in sepsis suggests improved bacterial clearance, inhibitory effects upon upstream mediators of the host response (for example, the nuclear factor kappa B (NF-κB) transcription factor), scavenging of downstream inflammatory mediators (for example, cytokines), direct anti-inflammatory effects mediated via Fcγ receptors, and a potential ability to attenuate lymphocyte apoptosis and thus sepsis-related immunosuppression. Characterizing the trajectory of change in immunoglobulin levels during sepsis, understanding mechanisms contributing to these changes, and undertaking IVIg dose-finding studies should be performed prior to further large-scale interventional trials to enhance the likelihood of a successful outcome. PMID:22424150

  6. Cerebral infarction complicating intravenous immunoglobulin therapy in a patient with Miller Fisher syndrome

    PubMed Central

    Turner, B.; Wills, A.

    2000-01-01

    Intravenous immunoglobulin (IVIg) therapy is being increasingly used in a wide range of neurological conditions. However, treatment is expensive and side effects may be severe. A patient with Miller Fisher syndrome who developed cortical blindness as a consequence of occipital infarction precipitated by IVIg is reported on.

 PMID:10811710

  7. Subcutaneous immunoglobulin therapy for inflammatory neuropathy: current evidence base and future prospects.

    PubMed

    Rajabally, Yusuf A

    2014-06-01

    Intravenous immunoglobulin therapy is of proven effect in chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In more recent years, there have been a number of anecdotal case reports and small series, followed by a few trials of variable design, of subcutaneous immunoglobulin therapy in these neuropathies. To date, limited evidence suggests that the subcutaneous route may be a more clinically effective, better-tolerated, at least cost-equivalent and a more patient-friendly option than the still more used intravenous alternative. Long-term efficacy is not as yet established in neuropathic indications by randomised controlled clinical trial evidence, and it is likely that the subcutaneous route may not be suitable in all cases with some hints to this effect appearing from the limited data available to date. Further studies are ongoing, including those of dose comparison, and more are likely to be planned in future. The literature on the use of subcutaneous immunoglobulin therapy in chronic inflammatory neuropathy is reviewed here. The current use in clinical practice, day-to-day benefits, including quality of life measures and health economics as published thus far, are evaluated. The limitations of this form of treatment in CIDP and MMN are also analysed in the light of current literature and taking into account the remaining unknowns. Future prospects and research with this mode of immunoglobulin therapy administration are discussed.

  8. Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders.

    PubMed

    Sanford, Mark

    2014-08-01

    Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.

  9. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases.

    PubMed

    Casadevall, Arturo; Pirofski, Liise-Anne

    2012-05-17

    Only two decades ago antibodies to fungi were thought to have little or no role in protection against fungal diseases. However, subsequent research has provided convincing evidence that certain antibodies can modify the course of fungal infection to the benefit or detriment of the host. Hybridoma technology was the breakthrough that enabled the characterization of antibodies to fungi, illuminating some of the requirements for antibody efficacy. As discussed in this review, fungal-specific antibodies mediate protection through direct actions on fungal cells and through classical mechanisms such as phagocytosis and complement activation. Although mechanisms of antibody-mediated protection are often species-specific, numerous fungal antigens can be targeted to generate vaccines and therapeutic immunoglobulins. Furthermore, the study of antibody function against medically important fungi has provided fresh immunological insights into the complexity of humoral immunity that are likely to apply to other pathogens.

  10. IMMUNOGLOBULINS IN DEFENSE, PATHOGENESIS AND THERAPY OF FUNGAL DISEASES

    PubMed Central

    Casadevall, Arturo; Pirofski, Liise-anne

    2012-01-01

    Summary Only two decades ago antibodies to fungi were thought to have little or no role in protection against fungal diseases. However, subsequent research has provided convincing evidence that certain antibodies can modify the course of fungal infection to the benefit or detriment of the host. Hybridoma technology was the breakthrough that enabled the characterization of antibodies to fungi, illuminating some of the requirements for antibody efficacy. As discussed in this review, fungal specific antibodies mediate protection through direct actions on fungal cells and through classical mechanisms such as phagocytosis and complement activation. Although mechanisms of antibody-mediated protection are often species-specific, numerous fungal antigens can be targeted to generate vaccines and therapeutic immunoglobulins. Furthermore, the study of antibody function against medically important fungi has provided fresh immunological insights into the complexity of humoral immunity that are likely to apply to other pathogens. PMID:22607798

  11. High-dose immunoglobulin infusion for thrombotic thrombocytopenic purpura refractory to plasma exchange and steroid therapy.

    PubMed

    Park, Seh Jong; Kim, Seok Jin; Seo, Hee Yun; Jang, Moon Ju; Oh, Doyeun; Kim, Byung Soo; Kim, Jun Suk

    2008-09-01

    The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

  12. Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy

    PubMed Central

    Miura, Masaru; Tamame, Takuya; Naganuma, Takashi; Chinen, Shino; Matsuoka, Megumi; Ohki, Hirotaka

    2011-01-01

    BACKGROUND: The optimal management of Kawasaki disease (KD) unresponsive to intravenous immunoglobulin (IVIG) therapy remains unclear. OBJECTIVE: To prospectively evaluate the efficacy and safety of intravenous methylprednisolone pulse (IVMP) therapy in KD cases unresponsive to additional IVIG. METHODS: KD patients who initially received IVIG (2 g/kg/24 h) and acetylsalicylic acid within nine days after disease onset were studied. Patients who did not respond received additional IVIG (2 g/kg/24 h), and those who still did not respond were given IVMP (30 mg/kg/day) for three days, followed by oral prednisolone. The response to treatment, echocardiographic findings and adverse effects were evaluated. RESULTS: Among 412 KD cases, 74 (18.0%) were treated with additional IVIG; 21 (28.4%) of the latter cases subsequently received IVMP followed by prednisolone. All cases became afebrile soon after IVMP infusion and did not have a high-grade fever during treatment with prednisolone for two to six weeks. Four weeks after disease onset, coronary artery lesions (CAL) were diagnosed according to the Japanese Ministry of Health and Welfare or the American Heart Association criteria in two of the 21 cases treated with IVMP plus prednisolone; among all 412 cases, three (0.7%) and eight (1.9%) had CAL according to each criteria, respectively. All CAL regressed completely one year after disease onset. Adverse effects of IVMP, such as hypothermia and sinus bradycardia, resolved spontaneously. CONCLUSIONS: In KD patients unresponsive to additional IVIG, IVMP promptly induced defervescence, and subsequent oral prednisolone suppressed recurrence of fever. IVMP followed by prednisolone therapy may prevent CAL, without severe adverse effects. PMID:23024586

  13. Substitution with Alternative Anti-TNFα Therapy (SAVANT)-Outcomes of a Crohn's Disease Cohort Undergoing Substitution Therapy with Certolizumab.

    PubMed

    Boktor, Moheb; Motlis, Andrew; Aravantagi, Avinash; Sheth, Ankur; Jordan, Paul; Morris, James; Manas, Kenneth; Hussain, Nazneen; Cvek, Urska; Trutschl, Marjan; Becker, Felix; Alexander, J Steven

    2016-06-01

    Biological therapy targeting tumor necrosis factor-alfa has revolutionized the treatment of Crohn's disease (CD). Our study retrospectively reviewed clinical outcomes of 60 patients administratively substituted from Infliximab or Adalimumab to Certolizumab. Maintenance of disease and failure rates after substitution of anti-tumor necrosis factor-alfa agents in CD patients were monitored over 1 year, and this is the first outcomes study of patients maintained on Infliximab or Adalimumab substituted to Certolizumab. A hospital pharmacy directive required all patients on biological therapy to be administratively substituted to Certolizumab therapy. This single-center retrospective analysis initially included 68 CD patients presenting at Louisiana State University Health Sciences Center-Shreveport. Clinical, endoscopic, and serologic data were compared at baseline and at 4 intervals over 1 year. Of 60 enrolled CD patients, 45 (75%) successfully transitioned to Certolizumab and had stable disease at 1 year. Of the 15 (25%) patients who "failed" substitution at 1 year, 5 were returned to Adalimumab and 7 to Infliximab; 3 were maintained on steroids awaiting subsequent therapy. Importantly, when patients were segregated on the basis of initial disease control, it was found that 3 (12.5%) previously well-controlled patients failed therapy, whereas 12 (33.3%) who initially had active disease failed Certolizumab substitution. Our study found that 25% of CD patients substituted to Cimzia failed substitution, whereas 75% still exhibited a good clinical response with stable disease at 1 year. Our findings indicate that disease status and behavior at the time of biological substitution may predict therapeutic responsiveness.

  14. Effects of intravenous immunoglobulin therapy on behavior deficits and functions in sepsis model.

    PubMed

    Ozcan, Perihan Ergin; Senturk, Evren; Orhun, Gunseli; Gumru, Salih; Arican, Nadir; Orhan, Nurcan; Yılmaz, Canan Ugur; Kaya, Mehmet; Aricioglu, Feyza; Esen, Figen

    2015-12-01

    We aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with IgA and IgM (IgGAM). We divided 48 Wistar albino rats into five groups: control group, sham-operated group (only antibiotic treatment), cecal ligation and puncture (CLP) group (CLP plus antibiotic treatment), IgG group (250 mg/kg IV IgG) and IgGAM group (250 mg/kg IV IgGAM). Intravenous immunoglobulins were given 5 min after the CLP procedure. Experimental animals put into three behavioral tasks 10, 30 and 60 days after the surgery; to evaluate the locomotor activity, an open field test was performed, elevated plus maze test was used to measure anxiety levels, and depressive state was assessed by forced swimming test. The effects of therapy which were acquired from the results of these tests were used to estimate the behavioral changes after CLP. The mortality rate of 50% in the septic rats decreased to 30 and 20% with the administration of IgG and IgGAM, respectively. Significant changes on locomotor activity and depressive-like behavior were reported in the sepsis group; on the other hand, the treatment with immunoglobulins reduced the symptoms. Treatment with immunoglobulins attenuated the sepsis-related anxiogenic-like responses. Behavioral alterations returned to normal on day 60 in all groups. Sepsis caused deterioration on behavioral parameters. Immunoglobulin treatments alleviated the symptoms of functional disturbances and caused early reversal of behavioral deficits in septic animals.

  15. [A case of primary erythromelalgia successfully treated with high-dose intravenous immunoglobulin therapy].

    PubMed

    Kuroda, Takeshi; Sugimoto, Azusa; Ishigaki, Seiichirou; Murakami, Hidetomo; Kawamura, Mitsuru

    2014-02-01

    Erythromelalgia is a rare condition characterized by constant or paroxysmal burning pain, erythema, and the elevation of skin temperature in the extremities. Recently, the impairment of C-fiber function due to autoimmune system involvement is considered as the primary cause of erythromelalgia. However, a successful treatment has yet not been established. We report a case of a 39-year-old woman with primary erythromelalgia accompanied by high cerebrospinal fluid protein concentration and axonal neuropathy. She received various antiepileptic and anti-inflammatory drugs, but failed to improve. She finally underwent high-dose intravenous immunoglobulin therapy, which dramatically improved her symptoms and normalized cerebrospinal fluid protein concentration. This result demonstrates the effectiveness of high-dose intravenous immunoglobulin therapy for the treatment of primary erythromelalgia and the possibility of autoimmune system involvement.

  16. Improving current immunoglobulin therapy for patients with primary immunodeficiency: quality of life and views on treatment.

    PubMed

    Espanol, Teresa; Prevot, Johan; Drabwell, Jose; Sondhi, Seema; Olding, Laurence

    2014-01-01

    Subcutaneous or intravenous immunoglobulin replacement is the mainstay of treatment for most patients with primary immunodeficiency disease (PID). The purpose of this study was to gain an understanding of how existing PID therapies affect patient lives and to identify desired improvements to immunoglobulin treatments. An online questionnaire was made available through the International Patient Organisation for Primary Immunodeficiencies to patients with PID and their caregivers regarding current treatment satisfaction, living with PID, and patient preferences using a conjoint approach. Health-related quality of life was canvassed via questionnaires using the Short Form 12 Health Survey and EuroQoL 5 Dimensions. A total of 300 responded to the survey (72% patients with PID and 28% caregivers) from across 21 countries, mostly the UK, Sweden, Canada, France, Germany, and Spain. Fifty-three percent and 45% of patients received intravenous and subcutaneous therapy, respectively. Most respondents (76%) were satisfied with their current treatment, reflecting the benefits that immunoglobulin therapy provides for patient health and well-being. However, patients remained below the physical and mental well-being norms for health-related quality of life as determined by the questionnaire. All respondents expressed a desire for 4-weekly infusions, the ability to administer these at home, self-administration, shorter duration of administration, and fewer needle sticks. The results of this survey highlight the importance of providing access to different treatment options and modes of administration to ensure individual patient needs are best met.

  17. Improving current immunoglobulin therapy for patients with primary immunodeficiency: quality of life and views on treatment

    PubMed Central

    Espanol, Teresa; Prevot, Johan; Drabwell, Jose; Sondhi, Seema; Olding, Laurence

    2014-01-01

    Background Subcutaneous or intravenous immunoglobulin replacement is the mainstay of treatment for most patients with primary immunodeficiency disease (PID). The purpose of this study was to gain an understanding of how existing PID therapies affect patient lives and to identify desired improvements to immunoglobulin treatments. Methods An online questionnaire was made available through the International Patient Organisation for Primary Immunodeficiencies to patients with PID and their caregivers regarding current treatment satisfaction, living with PID, and patient preferences using a conjoint approach. Health-related quality of life was canvassed via questionnaires using the Short Form 12 Health Survey and EuroQoL 5 Dimensions. Results A total of 300 responded to the survey (72% patients with PID and 28% caregivers) from across 21 countries, mostly the UK, Sweden, Canada, France, Germany, and Spain. Fifty-three percent and 45% of patients received intravenous and subcutaneous therapy, respectively. Most respondents (76%) were satisfied with their current treatment, reflecting the benefits that immunoglobulin therapy provides for patient health and well-being. However, patients remained below the physical and mental well-being norms for health-related quality of life as determined by the questionnaire. All respondents expressed a desire for 4-weekly infusions, the ability to administer these at home, self-administration, shorter duration of administration, and fewer needle sticks. Conclusion The results of this survey highlight the importance of providing access to different treatment options and modes of administration to ensure individual patient needs are best met. PMID:24833896

  18. Autologous Immunoglobulin Therapy in Patients With Severe Recalcitrant Atopic Dermatitis: A Preliminary Report

    PubMed Central

    Cho, Su-Mi; Kim, Myoung-Eun; Kim, Yeo-Jin; Jeon, Sook-Yeong

    2014-01-01

    The management of severe recalcitrant atopic dermatitis (AD) is a challenging issue for clinicians and patients. We hypothesized that repeated intramuscular injections of autologous immunoglobulin (autologous immunoglobulin therapy: AIGT) might induce clinical improvements in patients with AD by stimulation of the active immune response to antigen-binding-site of pathogenic antibodies. We tried AIGT in 3 adult patients with severe recalcitrant AD whose clinical conditions could not be effectively controlled by medical treatments (including oral cyclosporine) for more than 2 years. Autologous immunoglobulin was purified from the autologous plasma by affinity chromatography using Protein A. The patients were treated by an intramuscular injection of 50 mg of autologous immunoglobulin twice a week for 4 weeks. A clinical severity score of AD (SCORAD value) showed a decrease greater than 30% at 8 weeks after the initiation of AIGT compared with the baseline before the initiation of AIGT in all 3 patients with severe recalcitrant AD. No significant side effects from treatment were observed. Further studies with larger numbers of patients are required to evaluate the clinical usefulness of AIGT for AD. PMID:24404399

  19. Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins.

    PubMed

    Pituch-Noworolska, Anna; Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2015-01-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose.

  20. [Autoimmune hemolytic anemia refractory to corticosteroids and high dosage immunoglobulin therapy].

    PubMed

    Hasanbegović, Edo

    2008-01-01

    We report about very rare case of autoimune hemolytic anemia (AIHA) with "warm" antibodies in eight months old boy. Diagnosis was set up according blood picture results, distinct anaemia in blood picture, positive Coombs test (IgG) for "warm" antibodies. Therapy with high doses of corticosteroids, with immunoglobulins, with two exchange transfusions and with frequent transfusions of deplasmatic erythrocytes (DPE) was without good result. Introducing of Rituximab (Mathera) therapy in dose of 375 mg/m2, four times had good effect. For last six months boy has still been in complete clinical and hematologic remission. His his blood picture is normal and his Coombs test is within normal range.

  1. Hypogammaglobulinemia after heart transplantation: use of intravenous immunoglobulin replacement therapy in relapsing CMV disease.

    PubMed

    Sarmiento, E; Fernàndez-Yáñez, J; Muñoz, P; Palomo, J; Rodríguez-Molina, J J; Bermejo, J; Catalan, P; Bouza, E; Fernández-Cruz, E; Carbone, J

    2005-01-01

    Secondary hypogammaglobulinemia after heart transplantation may follow immunosuppressive therapy with the resultant increased risk of infections, including cytomegalovirus (CMV) disease. There is limited information on the use of intravenous immunoglobulin replacement therapy (IVIG) in heart-transplanted patients with hypogammaglobulinemia and CMV disease. We present data on five consecutive heart-transplanted patients with relapsing CMV disease, four of whom developed gastrointestinal disease. The immunosuppressive regimen included prednisone, cyclosporine A, azathioprine, mycophenolate mofetil, tacrolimus and antithymocyte globulin (ATG). Evaluation revealed CMV antigenemia. All the patients had been treated with intravenous ganciclovir. In addition, hyperimmune CMV immunoglobulin was administered in three patients. Significantly reduced levels of immunoglobulin G (IgG) were observed in the patients as compared with 15 heart-transplanted individuals without CMV disease [mean IgG levels: 323+/-18 and 639+/-63 mg/dl, respectively (p=0.003)]. IVIG [FLEBOGAMMA], 200-400 mg/kg every 21 days with the goal of maintaining normal serum IgG levels, was added for the treatment of CMV disease. Selected batches with the highest anti-CMV titers were set apart for the treatment of the patients. IVIG treatment, in combination with antiviral therapy, proved able to control CMV disease. There was a favorable clinical response and the patients became free of gastrointestinal symptoms. Detection of CMV antigens was negative after treatment. During IVIG therapy no immediate or delayed adverse effects were observed. Even if our survey was limited to five cases, the results suggest that addition of IVIG to antiviral chemotherapy might improve outcome in heart-transplanted patients with hypogammaglobulinemia and CMV disease.

  2. Remarkable alkaline stability of an engineered protein A as immunoglobulin affinity ligand: C domain having only one amino acid substitution

    PubMed Central

    Minakuchi, Kazunobu; Murata, Dai; Okubo, Yuji; Nakano, Yoshiyuki; Yoshida, Shinichi

    2013-01-01

    Protein A affinity chromatography is the standard purification process for the capture of therapeutic antibodies. The individual IgG-binding domains of protein A (E, D, A, B, C) have highly homologous amino acid sequences. From a previous report, it has been assumed that the C domain has superior resistance to alkaline conditions compared to the other domains. We investigated several properties of the C domain as an IgG-Fc capture ligand. Based on cleavage site analysis of a recombinant protein A using a protein sequencer, the C domain was found to be the only domain to have neither of the potential alkaline cleavage sites. Circular dichroism (CD) analysis also indicated that the C domain has good physicochemical stability. Additionally, we evaluated the amino acid substitutions at the Gly-29 position of the C domain, as the Z domain (an artificial B domain) acquired alkaline resistance through a G29A mutation. The G29A mutation proved to increase the alkaline resistance of the C domain, based on BIACORE analysis, although the improvement was significantly smaller than that observed for the B domain. Interestingly, a number of other amino acid mutations at the same position increased alkaline resistance more than did the G29A mutation. This result supports the notion that even a single mutation on the originally alkali-stable C domain would improve its alkaline stability. An engineered protein A based on this C domain is expected to show remarkable performance as an affinity ligand for immunoglobulin. PMID:23868198

  3. Subcutaneous Immunoglobulin Therapy in the Chronic Management of Myasthenia Gravis: A Retrospective Cohort Study

    PubMed Central

    Bourque, P. R.; Pringle, C. E.; Cameron, W.; Cowan, J.; Chardon, J. Warman

    2016-01-01

    Background Immunoglobulin therapy has become a major treatment option in several autoimmune neuromuscular disorders. For patients with Myasthenia Gravis (MG), intravenous immunoglobulin (IVIg) has been used for both crisis and chronic management. Subcutaneous Immunoglobulins (SCIg), which offer the advantage of home administration, may be a practical and effective option in chronic management of MG. We analyzed clinical outcomes and patient satisfaction in nine cases of chronic disabling MG who were either transitioned to, or started de novo on SCIg. Methods and Findings This was a retrospective cohort study for the period of 2015–2016, with a mean follow-up period of 6.8 months after initiation of SCIg. All patients with MG treated with SCIg at the Ottawa Hospital, a large Canadian tertiary hospital with subspecialty expertise in neuromuscular disorders were included, regardless of MG severity, clinical subtype and antibody status. The primary outcome was MG disease activity after SCIg initiation. This outcome was measured by 1) the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and 2) subjective scales of disease activity including the Myasthenia Gravis activities of daily living profile (MG-ADL), Myasthenia Gravis Quality-of-life (MG-QOL 15), Visual Analog (VA) satisfaction scale. We also assessed any requirement for emergency department visits or hospitalizations. Safety outcomes included any SCIg related complication. All patients were stable or improved for MGFA class after SCIg initiation. Statistically significant improvements were documented in the MG-ADL, MG-QOL and VAS scales. There were no exacerbations after switching therapy and no severe SCIg related complications. Conclusions SCIg may be a beneficial therapy in the chronic management of MG, with favorable clinical outcome and patient satisfaction results. PMID:27490101

  4. Subcutaneous Immunoglobulin Therapy in the Chronic Management of Myasthenia Gravis: A Retrospective Cohort Study.

    PubMed

    Bourque, P R; Pringle, C E; Cameron, W; Cowan, J; Chardon, J Warman

    2016-01-01

    Immunoglobulin therapy has become a major treatment option in several autoimmune neuromuscular disorders. For patients with Myasthenia Gravis (MG), intravenous immunoglobulin (IVIg) has been used for both crisis and chronic management. Subcutaneous Immunoglobulins (SCIg), which offer the advantage of home administration, may be a practical and effective option in chronic management of MG. We analyzed clinical outcomes and patient satisfaction in nine cases of chronic disabling MG who were either transitioned to, or started de novo on SCIg. This was a retrospective cohort study for the period of 2015-2016, with a mean follow-up period of 6.8 months after initiation of SCIg. All patients with MG treated with SCIg at the Ottawa Hospital, a large Canadian tertiary hospital with subspecialty expertise in neuromuscular disorders were included, regardless of MG severity, clinical subtype and antibody status. The primary outcome was MG disease activity after SCIg initiation. This outcome was measured by 1) the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and 2) subjective scales of disease activity including the Myasthenia Gravis activities of daily living profile (MG-ADL), Myasthenia Gravis Quality-of-life (MG-QOL 15), Visual Analog (VA) satisfaction scale. We also assessed any requirement for emergency department visits or hospitalizations. Safety outcomes included any SCIg related complication. All patients were stable or improved for MGFA class after SCIg initiation. Statistically significant improvements were documented in the MG-ADL, MG-QOL and VAS scales. There were no exacerbations after switching therapy and no severe SCIg related complications. SCIg may be a beneficial therapy in the chronic management of MG, with favorable clinical outcome and patient satisfaction results.

  5. Immunoglobulin therapy for plasma cell-rich rejection in the renal allograft.

    PubMed

    Adrogue, Horacio E; Soltero, Liliana; Land, Geoffrey A; Ramanathan, Venkataraman; Truong, Luan D; Suki, Wadi N

    2006-08-27

    Plasma cell-rich acute rejection (PCAR) is associated with poor allograft outcome in renal transplantation. Previous studies report a graft half-life of six months after a single PCAR episode. However, the management of this condition is unclear. Intravenous immunoglobulin (IVIG) therapy, by virtue of its immunomodulating properties, and its influence on B-cell maturation into plasma cells, may be a good candidate for reversing this type of rejection. We report four episodes of PCAR in two patients who responded well to IVIG with improvement in renal function.

  6. Stereotype threat and social function in opioid substitution therapy patients.

    PubMed

    von Hippel, Courtney; Henry, Julie D; Terrett, Gill; Mercuri, Kimberly; McAlear, Karen; Rendell, Peter G

    2017-06-01

    People with a history of substance abuse are subject to widespread stigmatization. It seems likely that this societal disapproval will result in feelings of stereotype threat, or the belief that one is the target of demeaning stereotypes. If so, stereotype threat has the potential to contribute to functional difficulties including poor social outcomes. Eighty drug users on opioid substitution therapy and 84 demographically matched controls completed measures of mental health and social function. The opioid substitution therapy group were additionally asked to complete a measure that focused on their feelings of stereotype threat in relation to their drug use history. Bivariate correlations and hierarchical regression analyses were conducted to establish the magnitude and specificity of the relationship between stereotype threat and social functioning. Relative to controls, the opioid substitution therapy group reported higher levels of negative affect and schizotypy, and poorer social functioning, with all three of these indices significantly correlated with their feelings of stereotype threat. The results also showed that stereotype threat contributed significant unique variance to social functioning in the opioid substitution therapy group, even after taking into account other background, clinical, and mental health variables. Social functioning is an important aspect of recovery, yet these data indicate that people with a history of drug abuse who believe they are the target of stereotypical attitudes have poorer social functioning. This relationship holds after controlling for the impact of other variables on social functioning, including mental health. The theoretical and practical implications of these findings are discussed. Concerns about being stereotyped can shape the social experiences of opioid substitution therapy patients. Opioid substitution therapy patients who feel negatively stereotyped experience greater social function deficits, and this

  7. High-dose immunoglobulin therapy in renal transplant recipients with hemophagocytic histiocytic syndrome.

    PubMed

    Asci, Gulay; Toz, Huseyin; Ozkahya, Mehmet; Cagirgan, Seckin; Duman, Soner; Sezis, Meltem; Ok, Ercan

    2006-01-01

    Hemophagocytic histiocytic syndrome (HHS) generally occurs in immunocompromised patients and often has a rapidly fatal course. HHS may be cured by treatment of the underlying disorder, especially when it is triggered by an infection. If no cause has been found, no therapy is known and outcome is poor. The aim of this study was to investigate the clinical course and response to intravenous immunoglobulin treatment in renal transplant patients diagnosed with HHS. Thirteen patients who were diagnosed with HHS between 1995 and 2003 were retrospectively assessed. The mean age of HHS patients was 38.6 +/- 10 years (5 women, 8 men). Median time to onset of symptoms after renal transplantation was 15.1 +/- 12.1 months (range 0.5-30 months). The first 2 patients in whom no etiologic factor was found were seen before 1998 and died due to multiorgan failure. HHS was related to an infectious etiology in 6 of 13 patients: tuberculosis (n=3), cytomegalovirus (CMV) infection (n=2), Escherichia coli (E. coli)-associated septicemia (n=1), but HHS was cured by antimicrobial therapy in only 2 of them (1 with tuberculosis, the other with E. coli-associated septicemia). After June 1998, high-dose immunoglobulin (IVIg) therapy was used in 6 patients. HHS was related to an infectious etiology in 2 patients unresponsive to antimicrobial treatment, and of unknown etiology in 4 patients. All of them completely recovered. Before 1998, 2 patients unresponsive to antimicrobial therapy (1 with tuberculosis, the other with CMV) died. They were not given IVIg. We concluded that when HHS does not respond to treatment of the underlying infection, or is of unknown etiology in immunocompromised patients, high-dose IVIg therapy should be administered.

  8. Uzbekistan: government discontinues pilot opiate substitution therapy program.

    PubMed

    Khachatrian, Avet

    2009-12-01

    In this decade, with support from the international community, most countries of the former Soviet Union introduced opiate substitution therapy (OST) programs, using methadone or buprenorphine, in order to curb the spread of HIV and to introduce more efficient drug dependence treatment options. However, the development is uneven:While some countries have expanded their pilot projects, others have not gone beyond the pilot stage. One Central Asian country--Uzbekistan--has recently closed its pilot OST project.

  9. Does Intravenous Immunoglobulin Therapy Prolong Immunodeficiency in Transient Hypogammaglobulinemia of Infancy?

    PubMed Central

    Memmedova, Lale; Azarsiz, Elif; Edeer Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil

    2013-01-01

    Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin levels. Typically, THI patients recover spontaneously, mostly within 30-40 months of age, but sometimes recovery may be delayed until 5-6 years of age. The use of intravenous immunoglobulin (IVIg) as an alternative to antibiotic prophylaxis remains contraversial also in symptomatic THI patients. In fact, some authors believe that IVIg therapy may cause a delay in the maturation of the humoral immune system because of the interference from passively transfered antibodies. The aim of this study was to investigate the effect of IVIg replacement on recovery from immunodeficiency in THI patients and determine new parameters in order to include these patients in IVIg therapy groups. In this retrospective study, 43 patients (65%) received IVIg replacement therapy while 23 patients (34.8%) showed spontaneous normalization without IVIg. The percentages of patients who had more than six times the number of febrile infections in a year decreased from 91% to 21% in the group receiving IVIg treatment. At admission, before being recruited to IVIg therapy, serum immunoglobulin G (IgG) levels and anti-hemophilus B (Hib) antibody titers were found to be significantly low in cases who were selected for IVIg replacement. The percentages of patients who did not have protective levels of anti-Hib, anti-rubella or anti-rubeola-IgG were also significantly high in IVIg cases. There was no statistically significant difference in the age at which IgG levels normalized between the IVIg and the non-IVIg group. Patients in the IVIg group and non-IVIg group reached normal IgG levels at the age of 42.9±22.0 and 40.7±19.8 months, respectively. In conclusion, IVIg infusions do not cause a delay in the maturation of the immune system in THI patients. Besides the well-established criteria, very low and non-protective specific antibody responses against previously

  10. [Clinical and pharmacological aspects of pancreatic enzyme substitution therapy].

    PubMed

    Löser, C; Fölsch, U R

    1991-03-01

    The adequate therapy of pancreatic enzyme replacement in patients with exocrine pancreatic insufficiency is still a difficult clinical problem especially in patients following pancreatectomys, with chronic alcoholic pancreatitis or cystic fibrosis. The substitution of lipase to eliminate steatorrhoea is the most important aim but due to its acid lability even the most serious problem in pancreatic enzyme replacement therapy. Various different medications are meanwhile available: conventional preparations from porcine pancreatin or fungal enzymes as rizolipase, enteric-coated tablets or even enteric-coated microspheres or adjunctive therapy with H2-receptor antagonists. While dosage requirements vary widely and therefore have to be tried out individually, the choice of the adequate preparation should be influenced by the realization of the physiological and pathophysiological characteristics of the individual patient and the pharmaceutical characteristics of the different supplements. The advantages and disadvantages of the various medications for enzyme replacement therapy in patients with exocrine pancreatic insufficiency are reviewed in this article.

  11. Efficacy and safety of home-based subcutaneous immunoglobulin replacement therapy in paediatric patients with primary immunodeficiencies.

    PubMed

    Borte, M; Bernatowska, E; Ochs, H D; Roifman, C M

    2011-06-01

    Subcutaneous immunoglobulin infusions are effective, safe and well tolerated in the treatment of primary immunodeficiencies, but only limited data on the treatment of children are available. We investigated the efficacy, safety and pharmacokinetics of home therapy with a 16% liquid human immunoglobulin G preparation (Vivaglobin®) when administered subcutaneously in children with primary immunodeficiencies. Data were analysed from 22 children (2-<12 years) who participated in two prospective, open-label studies (one in Europe/Brazil, one in North America). All children had previously received intravenous immunoglobulins. They started weekly subcutaneous immunoglobulin infusions with an approximately 3-month wash-in/wash-out period, followed by a 6-month (Europe/Brazil) or 12-month (North America) efficacy evaluation period. In Europe/Brazil, subcutaneous doses generally equalled the previous weekly equivalent intravenous doses. In North America, subcutaneous doses during the efficacy evaluation period were 126% (median) of the previous weekly equivalent intravenous doses. Efficacy end-points in both studies included the occurrence of serious bacterial infections and any infections, and serum immunoglobulin G trough levels. Median serum immunoglobulin G trough levels exceeded those during previous intravenous therapy by 13% (North America) and 16% (Europe/Brazil). During the efficacy evaluation period of both studies, none of the children had a serious bacterial infection; the mean overall infection rate/patient year was 4·7 in Europe/Brazil and 5·6 in North America, concurring with previous reports in adults. The adverse event profile was comparable to previous reports in adults. Both studies confirmed the efficacy and safety of subcutaneous immunoglobulin therapy with Vivaglobin in children with primary immunodeficiencies. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  12. Efficacy and safety of home-based subcutaneous immunoglobulin replacement therapy in paediatric patients with primary immunodeficiencies

    PubMed Central

    Borte, M; Bernatowska, E; Ochs, H D; Roifman, C M

    2011-01-01

    Subcutaneous immunoglobulin infusions are effective, safe and well tolerated in the treatment of primary immunodeficiencies, but only limited data on the treatment of children are available. We investigated the efficacy, safety and pharmacokinetics of home therapy with a 16% liquid human immunoglobulin G preparation (Vivaglobin®) when administered subcutaneously in children with primary immunodeficiencies. Data were analysed from 22 children (2–<12 years) who participated in two prospective, open-label studies (one in Europe/Brazil, one in North America). All children had previously received intravenous immunoglobulins. They started weekly subcutaneous immunoglobulin infusions with an approximately 3-month wash-in/wash-out period, followed by a 6-month (Europe/Brazil) or 12-month (North America) efficacy evaluation period. In Europe/Brazil, subcutaneous doses generally equalled the previous weekly equivalent intravenous doses. In North America, subcutaneous doses during the efficacy evaluation period were 126% (median) of the previous weekly equivalent intravenous doses. Efficacy end-points in both studies included the occurrence of serious bacterial infections and any infections, and serum immunoglobulin G trough levels. Median serum immunoglobulin G trough levels exceeded those during previous intravenous therapy by 13% (North America) and 16% (Europe/Brazil). During the efficacy evaluation period of both studies, none of the children had a serious bacterial infection; the mean overall infection rate/patient year was 4·7 in Europe/Brazil and 5·6 in North America, concurring with previous reports in adults. The adverse event profile was comparable to previous reports in adults. Both studies confirmed the efficacy and safety of subcutaneous immunoglobulin therapy with Vivaglobin in children with primary immunodeficiencies. PMID:21413943

  13. Facilitated subcutaneous immunoglobulin (fSCIg) therapy – practical considerations

    PubMed Central

    Ponsford, M; Carne, E; Kingdon, C; Joyce, C; Price, C; Williams, C; El-Shanawany, T; Williams, P; Jolles, S

    2015-01-01

    There is an increasing range of therapeutic options for primary antibody-deficient patients who require replacement immunoglobulin. These include intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg). Advantages of fSCIg include fewer needle punctures, longer infusion intervals and an improved adverse effect profile relative to IVIg. Limited real-life experience exists concerning the practical aspects of switching or starting patients on fSCIg. We describe the first 14 patients who have been treated with fSCIg at the Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years of experience. The regimen was well tolerated, with high levels of satisfaction and no increase in training requirement, including for a treatment-naive patient. Two patients discontinued fSCIg due to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality. PMID:26288095

  14. Does the proper intravenous immunoglobulin substitution in primary immunodeficiency protect against HBV infections?: a description of a case series.

    PubMed

    Joanna, Glück; Slawomir, Zeglen; Barbara, Rymarczyk; Barbara, Rogala

    2008-09-01

    There are no recommendations concerning preoperative management of primary immunodeficiency patients in cases of emergency or planned surgery in relation to risk of hepatitis type B virus infection. To assess if immunodeficient patients regularly supplemented with immunoglobulins are protected against hepatitis B. IgG, IgM and IgA total levels and anti-HBs level were estimated in adult patients with primary humoral immunodeficiency before and after immunoglobulins supplementation according to a standardized schedule. Serum IgG and anti-HBs level significantly increased after immunoglobulin supplementation. Anti-HBs titer increased in all cases over 100 IU/L regardless of initial total IgG serum value, reaching a highly protective level. There was no correlation between increase in concentration of IgG (DeltaIgG) versus Deltaanti-HBs in the studied patients. Patients with primary hypogammaglobulinemia supplemented with immunoglobulin are protected against hepatitis type B.

  15. Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A retrospective study.

    PubMed

    Yu, Dan-Qing; Wang, Ying; Ma, Gui-Zhou; Xu, Rong-He; Cai, Zhi-Xiong; Ni, Chu-Min; Chen, Ping; Zhu, Zhi-Dan

    2014-01-01

    Acute fulminant myocarditis (AFM) is a serious heart disease with limited treatment. This observational retrospective study aimed to investigate whether intravenous immunoglobulin (IVIG) was able to improve left ventricular function and reduce the episodes of arrhythmia in adult patients with AFM. The medical records of all patients with AFM who were admitted to the Critical Care Unit of Guangdong General Hospital (Guangzhou, China) between January 2001 and December 2010 were reviewed. A cohort of 58 patients was included in the study. Of these 58, 32 patients were treated with IVIG (400 mg/kg per day) for five days, while the remaining patients did not receive IVIG therapy. The patients who received IVIG therapy had a higher left ventricular ejection fraction (LVEF) and a reduced left ventricular end-diastolic diameter (LVDD) compared with the non-IVIG therapy patients four weeks subsequent to the treatment (PLVEF=0.011 and PLVDD=0.048). The post-treatment incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) and atrioventricular block (AVB) was reduced in the patients who received IVIG therapy compared with the baseline values (PVT/VF=0.025, PAVB=0.003); however, no significant differences were observed in the non-IVIG therapy patients (PVT/VF=0.564, PAVB=0.083) following treatment. There were two mortalities in the IVIG therapy group and seven in the non-IVIG therapy group (P=0.072). This retrospective study suggested that the use of IVIG for the treatment of AFM may be associated with improved left ventricular function and reduced episodes of fulminant arrhythmias.

  16. Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A retrospective study

    PubMed Central

    YU, DAN-QING; WANG, YING; MA, GUI-ZHOU; XU, RONG-HE; CAI, ZHI-XIONG; NI, CHU-MIN; CHEN, PING; ZHU, ZHI-DAN

    2014-01-01

    Acute fulminant myocarditis (AFM) is a serious heart disease with limited treatment. This observational retrospective study aimed to investigate whether intravenous immunoglobulin (IVIG) was able to improve left ventricular function and reduce the episodes of arrhythmia in adult patients with AFM. The medical records of all patients with AFM who were admitted to the Critical Care Unit of Guangdong General Hospital (Guangzhou, China) between January 2001 and December 2010 were reviewed. A cohort of 58 patients was included in the study. Of these 58, 32 patients were treated with IVIG (400 mg/kg per day) for five days, while the remaining patients did not receive IVIG therapy. The patients who received IVIG therapy had a higher left ventricular ejection fraction (LVEF) and a reduced left ventricular end-diastolic diameter (LVDD) compared with the non-IVIG therapy patients four weeks subsequent to the treatment (PLVEF=0.011 and PLVDD=0.048). The post-treatment incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) and atrioventricular block (AVB) was reduced in the patients who received IVIG therapy compared with the baseline values (PVT/VF=0.025, PAVB=0.003); however, no significant differences were observed in the non-IVIG therapy patients (PVT/VF=0.564, PAVB=0.083) following treatment. There were two mortalities in the IVIG therapy group and seven in the non-IVIG therapy group (P=0.072). This retrospective study suggested that the use of IVIG for the treatment of AFM may be associated with improved left ventricular function and reduced episodes of fulminant arrhythmias. PMID:24348772

  17. Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

    PubMed

    Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y

    2000-01-01

    The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

  18. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis.

    PubMed

    Suzuki, Yuzo; Hayakawa, Hiroshi; Miwa, Seiichi; Shirai, Masahiro; Fujii, Masato; Gemma, Hitoshi; Suda, Takafumi; Chida, Kingo

    2009-01-01

    Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.

  19. N3-substituted thymidine bioconjugates for cancer therapy and imaging

    PubMed Central

    Khalil, Ahmed; Ishita, Keisuke; Ali, Tehane; Tjarks, Werner

    2013-01-01

    The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors. This review presents an overview on the design, synthesis, and biological evaluation of first- and second-generation 3CTAs. Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described. In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed. PMID:23617430

  20. Effects of IgM-enriched immunoglobulin therapy in septic-shock-induced multiple organ failure: pilot study.

    PubMed

    Toth, Ildiko; Mikor, Andras; Leiner, Tamas; Molnar, Zsolt; Bogar, Lajos; Szakmany, Tamas

    2013-08-01

    Mortality due to septic-shock-induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.

  1. On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

    PubMed Central

    Späth, Peter J.; Granata, Guido; La Marra, Fabiola; Kuijpers, Taco W.; Quinti, Isabella

    2015-01-01

    Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates. PMID:25699039

  2. Effect of meropenem with or without immunoglobulin as second-line therapy for pediatric febrile neutropenia.

    PubMed

    Kobayashi, Ryoji; Suzuki, Daisuke; Sano, Hirozumi; Kishimoto, Kenji; Yasuda, Kazue; Kobayashi, Kunihiko

    2014-08-01

    Meropenem (MEPM) is widely used for treatment of febrile neutropenia. There have been many reports on MEPM for pediatric febrile neutropenia showing success rates of approximately 50-75%. Although i.v. immunoglobulin (IVIG) is widely used for treatment of infection with antibiotics, there has been no report on the efficacy of IVIG for pediatric febrile neutropenia. This prospective randomized study was therefore carried out to clarify the usefulness of MEPM with or without IVIG as second line-therapy for pediatric febrile neutropenia. A total of 61 pediatric patients with 146 episodes were judged to have failure of first-line therapy (August 2008-April 2010: cefozopran vs cefepime; April 2010-April 2012: cefepime vs piperacillin/tazobactam) for febrile neutropenia, and were randomized to MEPM and MEPM + IVIG groups. MEPM with or without IVIG as second-line therapy was effective in 68.1% of a total of 144 episodes. Success rates in the MEPM and MEPM + IVIG groups were 66.3% and 70.5%, respectively. Furthermore, success rates for patients with IgG <500 mg/dL were 62.5% in the MEPM group and 81.3% in the MEPM + IVIG group. This result, however, was not statistically significant, possibly because of the small sample size. MEPM is effective and safe for second-line treatment of febrile episodes in neutropenic pediatric patients. Moreover, IVIG is effective for patients with low serum IgG. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  3. Parameters to Guide Retreatment After Initial Intravenous Immunoglobulin Therapy in Kawasaki Disease

    PubMed Central

    Kim, Hyun Kwon; Oh, Jungeun; Hong, Young Mi

    2011-01-01

    Background and Objectives We sought to determine parameters to guide the decision of retreatment in patients with Kawasaki disease (KD) who remained febrile after initial intravenous immunoglobulin (IVIG). Subjects and Methods A total of 129 children with KD were studied prospectively. Patients were treated with IVIG 2 to 9 days after the onset of disease. Laboratory measures, such as white blood cell (WBC), percentage of neutrophils, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP), were determined before and 48 to 72 hours after IVIG treatment. Patients were classified into IVIG-responsive and IVIG-resistant groups, based on the response to IVIG. Results Of a total of 129 patients, 107 patients (83%) completely responded to a single IVIG therapy and only 22 patients (17%) required retreatment: 14 had persistent fever and 8 had recrudescent fever. There was no significant difference between the groups in age, gender distribution, and duration of fever to IVIG initiation, but coronary artery lesions developed significantly more often in the resistant group than in the responsive group (31.8% vs. 2.8%, p=0.000). Compared with pre-IVIG data, post-IVIG levels of WBC, percentage of neutrophils, CRP, and NT-proBNP decreased to within the normal range in the responsive group, whereas they remained high in the resistant group. Multivariate logistic regression indicated that neutrophil counts, CRP, and NT-proBNP were independent parameters of retreatment. Conclusion Additional therapy at an early stage of the disease should be administered for febrile patients who have high values of CRP, NT-proBNP, and/or neutrophil counts after IVIG therapy. PMID:21860639

  4. Salvage therapy with high dose Intravenous Immunoglobulins in acquired Von Willebrand Syndrome and unresponsive severe intestinal bleeding

    PubMed Central

    2014-01-01

    A 91-year-old woman affected with acquired Von Willebrand (VW) syndrome and intestinal angiodysplasias presented with severe gastrointestinal bleeding (hemoglobin 5 g/dl). Despite replacement therapy with VW factor/factor VIII concentrate qid, bleeding did not stop (eleven packed red blood cell units were transfused over three days). High circulating levels of anti-VW factor immunoglobulin M were documented immunoenzimatically. Heart ultrasound showed abnormalities of the mitral and aortic valves with severe flow alterations. When intravenous immunoglobulins were added to therapy, prompt clinical and laboratory responses occurred: complete cessation of bleeding, raise in hemoglobin, VW factor antigen, VW ristocetin cofactor and factor VIII levels as well as progressive reduction of the anti-VWF autoantibody levels. PMID:24926417

  5. Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

    PubMed Central

    Lecendreux, Michel; Berthier, Johanna; Corny, Jennifer; Bourdon, Olivier; Dossier, Claire; Delclaux, Christophe

    2017-01-01

    -treated patients achieved remission more rapidly than control patients. Commentary: A commentary on this article appears in this issue on page 363. Citation: Lecendreux M, Berthier J, Corny J, Bourdon O, Dossier C, Delclaux C. Intravenous immunoglobulin therapy in pediatric narcolepsy: a nonrandomized, open-label, controlled, longitudinal observational study. J Clin Sleep Med. 2017;13(3):441–453. PMID:28095967

  6. Review of five consecutive studies of radiolabeled immunoglobulin therapy in Hodgkin's disease.

    PubMed

    Vriesendorp, H M; Morton, J D; Quadri, S M

    1995-12-01

    Recurrent Hodgkin's Disease (HD) provides unique opportunities to improve radiolabeled immunoglobulin therapy (RIT). Normal tissue toxicity after RIT is limited to bone marrow damage and is well documented and quantified in HD patients. Anti-antibody formation is rare in patients with HD, allowing for multiple RIT cycles. Overall, 134 patients with recurrent HD were treated on five different studies with i.v. antiferritin, labeled with 131I or with 111In for diagnostic purposes and 90Y for therapeutic purposes. Patients with recurrent, end-stage HD obtain a 60% response rate following 90Y-labeled antiferritin. One-half of the therapy responses are complete. Responses are more common in patients with longer disease histories (> 3 years) and smaller tumor volumes (< 30 cm3) and in patients receiving at least 0.4 mCi 90Y-labeled antiferritin/kg body weight. Complete responders survive significantly longer than partial responders (2 years versus 1 year). Partial responders survive longer than patients with progressive disease (1 year versus 4 months). HD in one-third of the patients recurs in new areas. A low protein dose (2-5 mg) and a moderate specific activity (10 mCi/mg) are recommended. Results obtained with 90Y-labeled antiferritin are significantly better than results with 131I-labeled antiferritin. Further translational research in vitro in the radio pharmacy and in vivo with experimental animals is ongoing to improve the therapeutic results of RIT in HD. Obviously, many permutations of RIT cannot be explored in HD patients for ethical, financial, or logistic reasons, and predictive preclinical research is required to achieve further progress. Currently, RIT is a low-toxicity, low-cost outpatient procedure for recurrent HD with a high response rate in a patient population with an unfavorable prognosis.

  7. Epidemiology of hepatitis C virus infection among people receiving opioid substitution therapy (ECHO): study protocol.

    PubMed

    Strada, Lisa; Schulte, Bernd; Schmidt, Christiane Sybille; Verthein, Uwe; Cremer-Schaeffer, Peter; Krückeberg, Sabine; Reimer, Jens

    2015-12-10

    Hepatitis C virus infection is highly prevalent among people who inject drugs. Opioid substitution therapy, the standard treatment for opioid dependence, provides an excellent opportunity for the treatment of hepatitis C virus infection due to the close and regular contact between patients and clinicians. However, there is little research on the impact of opioid substitution therapy on the prevalence of the hepatitis C virus at a national level. This paper describes the protocol for the Epidemiology of Hepatitis C Virus Infection among People Receiving Opioid Substitution Therapy (ECHO) study. The aim of this study is to estimate the national prevalence and incidence of hepatitis C virus infection among people receiving opioid substitution therapy in Germany and to describe factors associated with hepatitis C treatment uptake and seroconversion. An observational, longitudinal, multicentre study is being conducted between 2014 and 2016 in a representative sample of approximately 2500 people receiving opioid substitution therapy from about 100 clinicians providing opioid substitution therapy in Germany. Data will be collected during routine patient care and by means of patient and clinician questionnaires at baseline and 12-month follow-up. Stratified sampling will be performed to obtain a representative sample of clinicians providing opioid substitution therapy. The strata will be constructed based on the distribution of the total sample of clinicians providing opioid substitution therapy in Germany according to German Federal State and the number of patients per clinician. Opioid substitution therapy may be an important strategy to prevent the spread of hepatitis C virus in opioid dependent populations, but its effectiveness may be diminished by our limited understanding of factors associated with treatment uptake and seroconversion. The present study will provide important information for developing strategies to address hepatitis C virus-related disease burden in

  8. Proteomic Analysis of Sera from Common Variable Immunodeficiency Patients Undergoing Replacement Intravenous Immunoglobulin Therapy

    PubMed Central

    Spadaro, Giuseppe; D'Orio, Concetta; Genovese, Arturo; Galeotafiore, Antonella; D'Ambrosio, Chiara; Di Giovanni, Stefano; Vitale, Monica; Capasso, Mario; Lamberti, Vincenzo; Scaloni, Andrea; Marone, Gianni; Zambrano, Nicola

    2011-01-01

    Common variable immunodeficiency is the most common form of symptomatic primary antibody failure in adults and children. Replacement immunoglobulin is the standard treatment of these patients. By using a differential proteomic approach based on 2D-DIGE, we examined serum samples from normal donors and from matched, naive, and immunoglobulin-treated patients. The results highlighted regulated expression of serum proteins in naive patients. Among the identified proteins, clusterin/ApoJ serum levels were lower in naive patients, compared to normal subjects. This finding was validated in a wider collection of samples from newly enrolled patients. The establishment of a cellular system, based on a human hepatocyte cell line HuH7, allowed to ascertain a potential role in the regulation of CLU gene expression by immunoglobulins. PMID:21960740

  9. Opioid substitution therapy in Tajikistan: Another perpetual pilot?

    PubMed

    Latypov, Alisher

    2010-09-01

    Opioid substitution therapy (OST) continues to face strong resistance in the former Soviet Central Asian republics. OST was discontinued by the Uzbek government in 2009. In Kyrgyzstan, with about 950 people currently receiving OST, the programme was about to be suspended in 2009. In Kazakhstan, a small pilot project serves 50 clients. Turkmenistan may introduce OST in 2010, while the Tajik Ministry of Health approved the introduction of an OST pilot in summer 2009. This paper draws upon the analysis of interests of the OST-affected groups in Tajikistan as a case study to understand the roots of resistance to OST. In Tajikistan, OST may be contrary to the interests of some narcologists, law enforcement officers and drug dealers. People who use drugs do not play any role in national drug-policy making. The HIV prevention community within the Tajik executive bodies receives major financial support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) to respond to an IDU driven epidemic, and yet it is the only group which has nothing to gain from the absence of OST. The Tajik government agreed to introduce OST in order not to jeopardize its future funding from GFATM. If the interests of the OST-affected groups are ignored, there is a high chance that OST in Tajikistan may remain a perpetual pilot project even despite all the necessary resources would come from GFATM and other donors. Putting "narcology on pilot" may prove helpful in both tackling the OST "perpetual pilots" and shifting the focus of public attention towards major inadequacies of the existing state-funded drug treatment systems in the region. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy.

    PubMed

    Kuzyniak, Weronika; Ermilov, Eugeny A; Atilla, Devrim; Gürek, Ayşe Gül; Nitzsche, Bianca; Derkow, Katja; Hoffmann, Björn; Steinemann, Gustav; Ahsen, Vefa; Höpfner, Michael

    2016-03-01

    Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT. ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1-10 μM) cancer cells was achieved by illumination with a broad band white light source (400-700 nm) at a power density of 10 J/cm(2). Photoactivation of ZnPc-loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT.

  11. Clearance of BK Virus Nephropathy by Combination Antiviral Therapy With Intravenous Immunoglobulin

    PubMed Central

    Kable, Kathy; Davies, Carmen D.; O'connell, Philip J.; Chapman, Jeremy R.; Nankivell, Brian John

    2017-01-01

    Background Reactivation of BK polyoma virus causes a destructive virus allograft nephropathy (BKVAN) with graft loss in 46%. Treatment options are limited to reduced immunosuppression and largely ineffective antiviral agents. Some studies suggest benefit from intravenous immunoglobulin (IVIG). Methods We evaluated effectiveness of adjuvant IVIG to eliminate virus from blood and tissue, in a retrospective, single-center cohort study, against standard-of-care controls. Both groups underwent reduced immunosuppression; conversion of tacrolimus to cyclosporine; and mycophenolate to leflunomide, oral ciprofloxacin, and intravenous cidofovir. Results Biopsy-proven BKVAN occurred in 50 kidneys at 7 (median interquartile range, 3-12) months after transplantation, predominantly as histological stage B (92%), diagnosed following by dysfunction in 46%, screening viremia in 20%, and protocol biopsy in 34%. After treatment, mean viral loads fell from 1581 ± 4220 × 103 copies at diagnosis to 1434 ± 70 639 midtreatment, and 0.138 ± 0.331 after 3 months (P < 0.001). IVIG at 1.01 ± 0.18 g/kg was given to 22 (44%) patients. The IVIG group more effectively cleared viremia (hazard ratio, 3.68; 95% confidence interval, 1.56-8.68; P = 0.003) and BK immunohistochemistry from repeated tissue sampling (hazard ratio, 2.24; 95% confidence interval, 1.09-4.58; P = 0.028), and resulted in faster (11.3 ± 10.4 months vs 29.1 ± 31.8 months, P = 0.015) and more complete resolution of viremia (33.3% vs 77.3%, P = 0.044). Numerically, fewer graft losses occurred with IVIG (27.3% vs 53.6% for control, P = 0.06), although graft and patient survivals were not statistically different. Acute renal dysfunction requiring pulse corticosteroid was common (59.1% vs 78.6%, P = 0.09), respectively, after immunosuppression reduction. Conclusions Combination treatment incorporating adjuvant IVIG was more effective eliminating virus from BKVAN, compared with conventional therapy. Validation by multicenter

  12. Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

    PubMed

    Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

    2012-05-01

    A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

  13. Clinical use of immunoglobulins.

    PubMed

    McClelland, D B; Yap, P L

    1984-02-01

    The use of immunoglobulins for prophylaxis and therapy are reviewed. Normal and hyperimmune immunoglobulins have well established clinical applications. These are summarized in Table 14. This form of therapy has now entered a period of rapid change due to the availability of human immunoglobulins which are safe for intravenous use, permitting large doses to be given rapidly. This will permit reappraisal of many conventional applications and exploration of new possibilities for the use of these products. The approaching wide availability of monoclonal antibodies for clinical use will open up a further wide range of new therapeutic applications, providing that concerns over the products' safety are allayed .

  14. Intravenous immunoglobulin therapy for small fiber neuropathy: study protocol for a randomized controlled trial.

    PubMed

    de Greef, Bianca T A; Geerts, Margot; Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J

    2016-07-20

    Small fiber neuropathy is the most common cause of neuropathic pain in peripheral neuropathies, with a minimum prevalence of 53/100,000. Patients experience excruciating pain, and currently available anti-neuropathic and other pain drugs do not relieve the pain substantially. Several open-label studies have suggested an immunological basis in small fiber neuropathy and have reported efficacy of treatment with intravenous immunoglobulin. Therefore, immunological mechanisms conceivably may play a role in small fiber neuropathy. To date, no randomized controlled study with intravenous immunoglobulin in patients with small fiber neuropathy has been performed. This study is a randomized, double-blind, placebo-controlled, clinical trial in patients with idiopathic small fiber neuropathy. The primary objective is to investigate the efficacy of intravenous immunoglobulin versus placebo on pain alleviation. A 1-point change in the PI-NRS compared to baseline is considered the minimum clinically important difference. In the IVIg-treated group, we assume a response rate of approximately 60 % based on the criteria composed by the IMMPACT group for measurement of pain. Based on this, a sample size of 60 patients is needed. Eligible patients fulfilling the inclusion/exclusion criteria will be randomized to receive either intravenous immunoglobulin or placebo (0.9 % saline). The treatment regimen will start with a loading dose of 2 g/kg body weight over 2-4 consecutive days, followed by a maintenance dose of 1 g/kg body weight over 1-2 consecutive days given three times at a 3-week interval. The primary endpoint is the comparison of the percentage of responder subjects between the two treatment groups from the first randomization during the 12 weeks of treatment. A responder is defined as ≥ 1-point Pain Intensity Numerical Rating Scale improvement on the mean weekly peak pain relative to baseline. The secondary outcomes are pain intensity, pain qualities, other small

  15. Observation of Classroom Performance Using Therapy Balls as a Substitute for Chairs in Elementary School Children

    ERIC Educational Resources Information Center

    Burgoyne, Molly E.; Ketcham, Caroline J.

    2015-01-01

    Many classrooms are beginning to substitute standard chairs with therapy balls, which help to improve students' focus and classroom performance, according to teacher and student reports. Researchers conducted an observational study in a classroom at a local elementary school that implemented therapy balls. For each hour-long observation, three…

  16. A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia

    PubMed Central

    Lachance, S.; Christofides, A.L.; Lee, J.K.; Sehn, L.H.; Ritchie, B.C.; Shustik, C.; Stewart, D.A.; Toze, C.L.; Haddad, E.; Vinh, D.C.

    2016-01-01

    Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (cll), who typically have increased susceptibility because of hypogammaglobulinemia (hgg) related to their disease and its treatment. Immunoglobulin replacement therapy (igrt) has been shown to reduce the frequency of bacterial infections and associated hospitalizations in patients with hgg or a history of infection, or both. However, use of igrt in cll is contentious. Studies examining such treatment were conducted largely before the use of newer chemoimmunotherapies, which can extend lifespan, but do not correct the hgg inherent to the disease. Thus, the utility of igrt has to be re-evaluated in the current setting. Here, we discuss the evidence for the use of igrt in cll and provide a practical approach to its use in the prevention and management of infections. PMID:26966403

  17. Acute tubulointerstitial nephritis following intravenous immunoglobulin therapy in a male infant with minimal-change nephrotic syndrome.

    PubMed

    Tanaka, H; Waga, S; Tateyama, T; Sugimoto, K; Kakizaki, Y; Yokoyama, M

    1999-10-01

    A boy aged 4 years with nephrotic syndrome (NS) was referred to our hospital because of the third relapse of NS. Hypogammaglobulinemia associated with massive proteinuria was observed at the presentation. Residual urinary tract infection required intravenous piperacillin and immunoglobulin therapy (IVIG). Soon after IVIG, he complained of high fever with chills, bilateral knee joint pain, dry cough and chest discomfort. Although he did not develop renal insufficiency, a transient increase in the urinary beta2-microglobulin and decrease in the serum complement hemolytic activity were observed. These clinical manifestations spontaneously ceased. A percutaneous renal biopsy for his NS performed 19 days after the episode of allergic reaction revealed tubulointerstitial nephritis (TIN) with marked eosinophil infiltrates. Glomeruli showed minor glomerular abnormalities. Renal complications associated with IVIG treatment have been reported to date, however, acute TIN has rarely been seen.

  18. Immunoglobulin G(κ) [IgG(κ)] and IgG(λ) Paraproteinemia in a Child with AIDS and Response to Highly Active Antiretroviral Therapy

    PubMed Central

    Seeborg, Filiz Odabasi; Gay, Hannah; Schmiege, Lorenz M.; Bernard, David; Shearer, William T.

    2005-01-01

    We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G (IgG) concentration and IgG kappa [IgG(κ)] and IgG lambda [IgG(λ)] paraproteinemia. This paraproteinemia partially responded to highly active antiretroviral therapy. This case emphasizes the importance of controlling B-cell activation. PMID:16275950

  19. Flebogamma® 5% DIF development: rationale for a new option in intravenous immunoglobulin therapy

    PubMed Central

    Jorquera, J I

    2009-01-01

    Flebogamma® 5% dual inactivation and filtration (DIF), a new 5% liquid intravenous immunoglobulin with a stability of 2 years when stored at temperatures between 2 and 30°C, has been developed. This new product is the result of the accumulated experience provided by Flebogamma®, with more than 30 million grams administered since 1992 in Europe and the United States, and the implementation of the latest technology to improve Flebogamma® even more by increasing its viral safety margin further. In addition to the specific inactivation stage for Flebogamma® 5% (pasteurization), the new process includes a solvent–detergent treatment and nanofiltration through a Planova filter down to 20 nm. The preparation presents a mean purity of 99·6 ± 0·2% with a correct chromatographic profile. Percentage values of immunoglobulin (Ig)G subclasses are equivalent to the physiological values of normal serum. The content in IgA as well as other possible impurities is very low, and the product presents a mean result of 109 ± 5% in the Fc fragment functionality assay, demonstrating the integrity of the IgG molecule. The functionality is also reflected in neutralization tests carried out against poliomyelitis, diphtheria, measles and vaccinia which, apart from the antibody titres determined by enzyme-linked immunosorbent assay, guarantees that antibodies are capable of reacting against these pathogens. Regarding safety, the combination of multiple methods with capacity to inactivate or remove biological agents which include chemical inactivation, heat inactivation, nanofiltration and precipitations, with very different mechanisms of action, provides Flebogamma® 5% DIF very wide margins of safety regarding to potential pathogens. PMID:19630865

  20. Effects of hospital generic drug substitution on diabetes therapy

    PubMed Central

    Chen, Hui-Yin; Chang, Hui-Ru; Lang, Hui-Chu

    2014-01-01

    Objectives To evaluate the effects on physicians’ prescribing behavior and on the therapeutic outcome of non-insulin-dependent diabetes patients of substituting different generic brands of metformin. Methods We adopt a retrospective cohort study involving 280 type-2 diabetes patients who regularly used the outpatient services of one medical center and who had changed metformin brands five times between 2003 and 2008. The aim was to examine the effects of switching brands. The generalized estimating equation was used to determine whether drug brand switching affected patient glycated hemoglobin A1c (HbA1c) levels, their prescribed daily dose, or their adherence to medication with metformin. Results HbA1c levels increased from 7.91 to 8.34 throughout the study period, although it was found that brand switching did not adversely affect HbA1c levels after controlling for patient characteristics and the time course of the study. Furthermore, the prescribed daily dose of metformin was stable throughout the study period, and was approximately 0.8 of the defined daily dose. Finally, although adherence was significantly higher with the original metformin than with the four generic brands, patients still maintained high levels of adherence of >0.8. Conclusion Although switching between different brands of metformin slightly affected the prescribing behavior of the physicians, there was no unfavorable effect on patient HbA1c levels. Thus, the policy of substituting between different generic brands of metformin is a good cost-effective approach that does not adversely affect the quality of diabetes patient care. PMID:24511228

  1. The INIS Study. International Neonatal Immunotherapy Study: non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: an international, placebo controlled, multicentre randomised trial

    PubMed Central

    2008-01-01

    Background Sepsis is an important cause of neonatal death and perinatal brain damage, particularly in preterm infants. While effective antibiotic treatment is essential treatment for sepsis, resistance to antibiotics is increasing. Adjuvant therapies, such as intravenous immunoglobulin, therefore offer an important additional strategy. Three Cochrane systematic reviews of randomised controlled trials in nearly 6,000 patients suggest that non-specific, polyclonal intravenous immunoglobulin is safe and reduces sepsis by about 15% when used as prophylaxis but does not reduce mortality in this situation. When intravenous immunoglobulin is used in the acute treatment of neonatal sepsis, however, there is a suggestion that it may reduce mortality by 45%. However, the existing trials of treatment were small and lacked long-term follow-up data. This study will assess reliably whether treatment of neonatal sepsis with intravenous immunoglobulin reduces mortality and adverse neuro-developmental outcome. Methods and design A randomised, placebo controlled, double blind trial. Babies with suspected or proven neonatal sepsis will be randomised to receive intravenous immunoglobulin therapy or placebo. Eligibility criteria Babies must be receiving antibiotics and have proven or suspected serious infection AND have at least one of the following: birthweight less than 1500 g OR evidence of infection in blood culture, cerebrospinal fluid or usually sterile body fluid OR be receiving respiratory support via an endotracheal tube AND there is substantial uncertainty that intravenous immunoglobulin is indicated. Exclusion criteria Babies are excluded if intravenous immunoglobulin has already been given OR intravenous immunoglobulin is thought to be needed OR contra-indicated. Trial treatment Babies will be given either 10 ml/kg of intravenous immunoglobulin or identical placebo solution over 4–6 hours, repeated 48 hours later. Primary outcome Mortality or major disability at two years

  2. Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study

    PubMed Central

    2014-01-01

    Background Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. Methods We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Results Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. Conclusions The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine

  3. Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study.

    PubMed

    Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; Simão, Raquel Maria; de Moraes Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares

    2014-06-21

    Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist

  4. Long-term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy.

    PubMed

    Kawasaki, Yukihiko; Maeda, Ryo; Kanno, Shuto; Suzuki, Yuichi; Ohara, Shinichiro; Suyama, Kazuhide; Hosoya, Mitsuaki

    2017-01-01

    The aim of this study was to clarify the long-term efficacy of tonsillectomy plus methylprednisolone pulse therapy (tonsillectomy pulse therapy [TMP]) for pediatric immunoglobulin A nephropathy (IgAN). The clinical and laboratory findings as well as the prognosis for IgAN treated with TMP at long-term follow up were evaluated. We collected data on 33 IgAN children treated with TMP. The children were retrospectively divided into two groups. Group 1 consisted of 18 children treated with TMP as the initial therapy, and group 2 consisted of 15 children treated with TMP as rescue therapy for IgAN relapse. The clinical features, and laboratory and pathological findings, including those at first and second renal biopsy as well as at the latest follow up, were analyzed for both groups. Mean urinary protein excretion, incidence of hematuria, and serum creatinine in groups 1 and 2 were all decreased significantly after TMP compared with beforehand. The percentage of glomeruli showing crescents after TMP in groups 1 and 2 was significantly lower than before TMP. At the most recent follow up, 94% of patients in group 1 and 87% in group 2 had normal urine, 6% in group 1 and 13% in group 2 had minor urinary abnormalities, and no patients in either group had active renal disease or renal insufficiency. TMP is effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN both as an initial and as a rescue treatment. © 2016 Japan Pediatric Society.

  5. [A case of sensory ataxic axonal polyneuropathy with IgGλ monoclonal gammopathy successfully treated with intravenous immunoglobulin therapy].

    PubMed

    Kanatsuka, Yoichi; Hasegawa, Osamu; Imazeki, Ryoko; Yamamoto, Masahiro

    2015-01-01

    We report the case of an 84-year-old man with sensory ataxic polyneuropathy and IgGλ monoclonal gammopathy of undetermined significance (MGUS), which was successfully treated with intravenous immunoglobulin (IVIG) therapy. He had developed progressive ataxic gait over the span of 2 years before he was admitted to our hospital. On admission, he was unable to walk without assistance because of severe sensory ataxia. He performed poorly on the finger-nose-finger and heel-knee tests, and his vibration and position sense in the feet was remarkably diminished. However, motor involvement was not remarkable. Serum immunoelectrophoresis revealed IgGλ monoclonal gammopathy, and MGUS was diagnosed. Nerve conduction studies revealed sensory-dominant axonal polyneuropathy. The patient was successfully treated with IVIG (400 mg/kg/day, for 5 days). He regained his capacity to walk independently after treatment, but his nerve conduction results remained unchanged. This sensory ataxia might be partially due to underlying cervical spondylotic myelopathy. To our knowledge, this is the first report in our country of the successful use of IVIG therapy to treat a patient with IgGλ monoclonal gammopathy and related sensory ataxic axonal polyneuropathy.

  6. Spatial disorientation in Parkinson's disease: no effect of levodopa substitution therapy.

    PubMed

    Hovestadt, A; De Jong, G J; Meerwaldt, J D

    1988-11-01

    In 22 patients with idiopathic Parkinson's disease, we tested spatial orientation with the rod orientation test, before and after levodopa substitution therapy was started. In both situations an impairment of spatial orientation could be demonstrated: levodopa did not improve this impairment.

  7. Cost analysis of substitutive renal therapies in children.

    PubMed

    Camargo, Maria Fernanda Carvalho de; Barbosa, Klenio de Souza; Fetter, Seiji Kumon; Bastos, Ana; Feltran, Luciana de Santis; Koch-Nogueira, Paulo Cesar

    2017-07-24

    End-stage renal disease is a health problem that consumes public and private resources. This study aimed to identify the cost of hemodialysis (either daily or conventional hemodialysis) and transplantation in children and adolescents. This was a retrospective cohort of pediatric patients with End-stage renal disease who underwent hemodialysis followed by kidney transplant. All costs incurred in the treatment were collected and the monthly total cost was calculated per patient and for each renal therapy. Subsequently, a dynamic panel data model was estimated. The study included 30 children who underwent hemodialysis (16 conventional/14 daily hemodialysis) followed by renal transplantation. The mean monthly outlay for hemodialysis was USD 3500 and USD 1900 for transplant. Hemodialysis costs added up to over USD 87,000 in 40 months for conventional dialysis patients and USD 131,000 in 50 months for daily dialysis patients. In turn, transplant costs in 50 months reached USD 48,000 and USD 70,000, for conventional and daily dialysis patients, respectively. For conventional dialysis patients, transplant is less costly when therapy exceeds 16 months, whereas for daily dialysis patients, the threshold is around 13 months. Transplantation is less expensive than dialysis in children, and the estimated thresholds indicate that renal transplant should be the preferred treatment for pediatric patients. Copyright © 2017. Published by Elsevier Editora Ltda.

  8. Fiscal strain and access to opiate substitution therapy at Department of Veterans Affairs Medical Centers.

    PubMed

    Rosenheck, Robert; Leslie, Douglas; Woody, George

    2003-01-01

    This study examines the relationship between institutional fiscal strain and the availability of opiate substitution therapy (eg, methadone maintenance), an effective but relatively expensive treatment for heroin addiction. An observational design was used to examine the association of changes in funding and changes in provision for treating opiate addiction at 29 VA Medical Centers (VAMCs). We hypothesized that VAMCs experiencing greater fiscal strain would show reduced availability of opiate substitution treatment. Administrative records from each of 29 VAMCs that provided opiate substitution therapy in both Fiscal Year (FY) 1995 and FY 1999 were used to measure changes in the availability of this service, ie, the percent change in total patients treated, annual visits per patient, and total services delivered. Institutional fiscal strain was measured by the percent decline in per capita funding at four levels at each VAMC: the entire medical center, all mental health programs, all substance abuse programs (inpatient and outpatient), and outpatient substance abuse programs alone. The total number of patients receiving opiate substitution increased from 5,549 in FY 1995 to 6,884 in FY 1999 (24%), annual visits per patient decreased by 16%, and the total number of units of services increased by 4%. There were no significant relationships between changes in the delivery of opiate substitution services and changes in per capita funding at any of the four institutional levels. No new programs were started during these years. Although no new programs were started, the availability of opiate substitution therapy at VA facilities with existing programs was maintained over a five-year period regardless of local funding changes, although at somewhat reduced intensity.

  9. Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta-Analysis

    PubMed Central

    Low, Andrea J.; Mburu, Gitau; Welton, Nicky J.; May, Margaret T.; Davies, Charlotte F.; French, Clare; Turner, Katy M.; Looker, Katharine J.; Christensen, Hannah; McLean, Susie; Rhodes, Tim; Platt, Lucy; Hickman, Matthew; Guise, Andy; Vickerman, Peter

    2016-01-01

    Background. Human immunodeficiency virus (HIV)–infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. Methods. We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I2 statistic. Results. We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32–2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17–2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41–3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63–.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21–1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65–1.25). Conclusions. These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID. PMID:27343545

  10. Breastfeeding and Opiate Substitution Therapy: Starting to Understand Infant Feeding Choices

    PubMed Central

    Graves, Lisa E.; Turner, Suzanne; Nader, Maya; Sinha, Sucheta

    2016-01-01

    INTRODUCTION Despite research demonstrating the safety and benefit of breastfeeding in opioid substitution therapy, few women in treatment breastfeed. Understanding the factors contributing to the choices women on opioid substitution therapy make about infant feeding is important. OBJECTIVES The aim of this study was to better understand and support infant feeding choices and breastfeeding experiences in women on opioid substitution therapy. METHODS A systematic review was conducted on five databases: (1) Ovid MEDLINE(R) without revisions, (2) Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, (3) EMBASE, (4) CINAHL, and (5) FRANCIS. From 1081 articles, 46 articles were reviewed. RESULTS The literature supports breastfeeding as an appropriate and safe option for women on opioid substitution treatment. Breastfeeding and rooming-in reduce neonatal abstinence. Women face barriers to breastfeeding due to societal stigma and the lack of patient and health-care provider education. CONCLUSIONS Efforts are needed to increase the knowledge that women and health-care professionals have about the safety and benefits of breastfeeding. PMID:27429549

  11. Uncertainties in endocrine substitution therapy for central hypocortisolism.

    PubMed

    Swords, Francesca M

    2014-01-01

    Central hypocortisolism is common, and has multiple potential causes. However, the treatment aims remain the same whatever the cause: to maximize quality of life, while minimizing treatment-related adverse effects. The majority of patients with central hypocortisolism now receive hydrocortisone in two to three divided doses with a total daily dose of 10-20mg, or a weight-based regimen of 8.1mg/m(2)/day. However, various areas of controversy remain: how to assess the patient with suspected hypocortisolism, which is the optimal agent to use, what is the optimal total daily dose, how to administer divided daily doses, how to monitor therapy and individually tailor doses, whether to replace other adrenal androgens, how to approach the patient with adrenal suppression, and how to best educate patients with hypocortisolism and treat them in emergency situations. This chapter will discuss the evidence behind each of these controversial areas in turn. The evidence for newer agents such as prolonged- and delayed-release preparations of hydrocortisone will also be explored, with a discussion on their potential role in the future management of this major clinical problem. © 2014 Elsevier B.V. All rights reserved.

  12. Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

    PubMed

    Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

    2015-05-01

    Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events.

  13. Intravenous immunoglobulin therapy influences T cell adhesion to extracellular matrix in women with a history of recurrent spontaneous abortions.

    PubMed

    Jerzak, M; Rechberger, T; Górski, A

    2000-12-01

    To determine activated T cell adhesion level to extracellular matrix (ECM) in non-pregnant women with a history of recurrent spontaneous abortions (RSA). In addition, to evaluate a small-dose intravenous immunoglobulin (IVIG) therapy influences on T cell adhesion to ECM. Phytohemaglutinin (PHA) or phorbol myristate acetate (PMA) activated T cell adhesion to the following extracellular matrix proteins: collagen IV, fibronectin and elastin were studied in women with the history of RSA. In addition, IVIG immunotherapy influence on T cell adhesion was studied. Normal T cells adhesion values were established in non-pregnant healthy women with the previous successful pregnancy outcome and in normal healthy pregnant women. PHA activated T cell adhesion to collagen IV (P = 0.04), fibronectin (P = 0.0003) nad elastin (P = 0.02) were significantly higher in women with the history of RSA when compared to non-pregnant healthy women wit the previous successful pregancy outcome. IVIG immunotherapy normalized the T cell adhesion level and favored a successful pregnancy. Increased T cell adhesion to collagen IV, fibronectin and elastin characterize women with the history of RSA. Decreased T cell adhesion to the main extracellular matrix components of human placenta may underlie possible effect of IVIG action.

  14. Intravenous immunoglobulin therapy for resistant ocular Behçet's disease

    PubMed Central

    Seider, N.; Beiran, I.; Scharf, J.; Miller, B.

    2001-01-01

    AIMS—The present report was aimed at finding out whether gammaglobulin could have a role in treating ocular Behçet's disease (BD) refractory to accepted medical therapy.
METHODS—Six eyes of four patients with ocular BD refractory to steroids and cyclosporin A were treated with a course of intravenous gammaglobulin and followed up for their response to treatment.
RESULTS—All six eyes of all four patients showed good response to gammaglobulin therapy.
CONCLUSION—Gamma globulin may have a role in treating refractory ocular BD. A wide range of controlled studies with longer follow up is needed to substantiate this impression.

 PMID:11673289

  15. A pilot survey of attitudes and knowledge about opioid substitution therapy for HIV-infected prisoners.

    PubMed

    Springer, Sandra A; Bruce, Robert D

    2008-01-01

    A majority of inmates in the state of Connecticut Department of Corrections use opioids or are opioid dependent before incarceration. None of the state's prisons offer opioid substitution therapy other than for detoxification or maintenance therapy for women during pregnancy. On release to the community, most prisoners relapse to drug use and this has been associated with higher recidivism rates, and less adherence to antiretroviral medications for HIV-infected persons. Nationally and internationally, methadone (METH) and buprenorphine (BUP) have been found to decrease relapse to drug use, decrease recidivism rates, improve adherence to antiretroviral medications, decrease HIV-risk taking behaviors, and improve mortality. However, the general knowledge about opioid substitution therapy among correctionalfacility staff has been reported as substandard. This pilot study compiled results of answers to anonymous surveys from 27 individuals who work directly with inmates in a patient-care capacity for the Connecticut Department of Corrections (CT DOC) and CT DOC case-management referral program (Project TLC) in the year 2006. The surveys included questions regarding current attitudes and knowledge about opioid substitution therapy for prisoners. A minority of respondents refer released prisoners with a history of opioid dependency to METH or BUP treatment. The majority of correctional workers and case-management referral workers did not have knowledge about BUP or METH's ability to improve health and decrease HIV risk taking behaviors. This study found that more education of individuals treating and caring for HIV-infected opioid dependent prisoners is needed.

  16. Safety of anti-immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection

    PubMed Central

    Cruz, A A; Lima, F; Sarinho, E; Ayre, G; Martin, C; Fox, H; Cooper, P J

    2007-01-01

    Background Although the role of immunoglobulin E (IgE) in immunity against helminth parasites is unclear, there is concern that therapeutic antibodies that neutralize IgE (anti-IgE) may be unsafe in subjects at risk of helminth infection. Objective We conducted an exploratory study to investigate the safety of omalizumab (anti-IgE) in subjects with allergic asthma and/or perennial allergic rhinitis at high risk of intestinal helminth infection. The primary safety outcome was risk of infections with intestinal helminths during anti-IgE therapy. Methods A randomized, double-blind, placebo-controlled trial was conducted in 137 subjects (12–30 years) at high risk of geohelminth infection. All subjects received pre-study anthelmintic treatment, followed by 52 weeks' treatment with omalizumab or placebo. Results Of the omalizumab subjects 50% (34/68) experienced at least one intestinal geohelminth infection compared with 41% (28/69) of placebo subjects [odds ratio (OR) 1.47, 95% confidence interval (CI) 0.74–2.95, one-sided P = 0.14; OR (adjusted for study visit, baseline infection status, gender and age) 2.2 (0.94–5.15); one-sided P = 0.035], providing some evidence for a potential increased incidence of geohelminth infection in subjects receiving omalizumab. Omalizumab therapy was well tolerated, and did not appear to be associated with increased morbidity attributable to intestinal helminths as assessed by clinical and laboratory adverse events, maximal helminth infection intensities and additional anthelmintic requirements. Time to first infection (OR 1.30, 95% CI 0.79–2.15, one-sided P = 0.15) was similar between treatment groups. Infection severity and response to anthelmintics appeared to be unaffected by omalizumab therapy. Conclusions In this exploratory study of allergic subjects at high risk of helminth infections, omalizumab therapy appeared to be safe and well tolerated, but may be associated with a modest increase in the incidence of geohelminth

  17. Gene Expression Profiling in Peripheral Blood Mononuclear Cells of Patients with Common Variable Immunodeficiency: Modulation of Adaptive Immune Response following Intravenous Immunoglobulin Therapy

    PubMed Central

    Barbieri, Alessandro; Tinazzi, Elisa; Rizzi, Monica; Beri, Ruggero; Argentino, Giuseppe; Ottria, Andrea; Lunardi, Claudio; Puccetti, Antonio

    2014-01-01

    Background Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. Methods We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. Results A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23−CD27−IgM−IgG− B cells (centrocytes). Conclusions Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency. PMID:24831519

  18. Advances in treating skin defects of the hand: skin substitutes and negative-pressure wound therapy.

    PubMed

    Watt, Andrew J; Friedrich, Jeffrey B; Huang, Jerry I

    2012-11-01

    Surgeons and scientists have been developing alternative methods of hand reconstruction that may play an adjunctive role to, or completely supplant, more traditional reconstructive modalities. This article provides an overview of these emerging techniques, with an emphasis on skin substitutes and negative-pressure wound therapy as they apply to the treatment of soft tissue defects of the hand. The indications, contraindications, and relative advantages and disadvantages of these techniques are discussed in detail. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The effect of substitution therapy on symptoms in patients with hypothyroidism following treatment for laryngeal and hypopharyngeal carcinomas.

    PubMed

    Lo Galbo, A M; Verdonck-De Leeuw, I M; Lips, P; Kuik, D J; Leemans, C R; De Bree, R

    2013-08-01

    Hypothyroidism is a well-known complication following treatment of laryngeal or hypopharyngeal carcinomas, and may cause various psychological and physical problems that negatively affect quality of life. The aim of this study was to evaluate the effect of substitution therapy on symptoms in patients with hypothyroidism. A study-specific questionnaire on physical and psychological problems (before and after substitution therapy) was sent to 70 patients who had been treated between 1977 and 2008 with clinical or subclinical hypothyroidism. Ninety-four percent returned the questionnaire. Symptoms on energy levels were reported most often (67% always tired and 70% lack of energy). Moodiness and emotional and physical symptoms were reported more often in substituted (sub)clinical hypothyroidism. Substitution therapy resulted in an improvement of energy (P = 0.013), sense of general interest and enjoyment (P = 0.022) and a reduction of puffy face (P = 0.041). Most symptoms in patients with thyroid dysfunction do not improve after substitution therapy. Nevertheless, due to its impact on health-related quality of life and the low burden of substitution therapy, screening for hypothyroidism and subsequent substitution therapy remains important.

  20. Effective intravenous immunoglobulin therapy for Churg-Strauss syndrome (allergic granulomatous angiitis) complicated by neuropathy of the eighth cranial nerve: a case report.

    PubMed

    Ozaki, Yoshio; Tanaka, Akihiro; Shimamoto, Keiko; Amuro, Hideki; Son, Yonsu; Ito, Tomoki; Nomura, Shosaku

    2012-09-18

    We report the case of a patient with Churg-Strauss syndrome with eighth cranial nerve palsy. Vestibulocochlear nerve palsy is extremely rare in Churg-Strauss syndrome. To the best of our knowledge, only one case of complicated neuropathy of the eighth cranial nerve has been described in a previous report presenting an aggregate calculation, but no differentiation between polyarteritis nodosa and Churg-Strauss syndrome was made. High-dose immunoglobulin was administered to our patient, and her neuropathy of the eighth cranial nerve showed improvement. At the age of 46, a Japanese woman developed Churg-Strauss syndrome that later became stable with low-dose prednisolone treatment. At the age of 52, she developed sudden difficulty of hearing in her left ear, persistent severe rotary vertigo, and mononeuritis multiplex. At admission, bilateral perceptive deafness of about 80dB and eosinophilia of 4123/μL in peripheral blood were found. A diagnosis of cranial neuropathy of the eighth cranial nerve associated with exacerbated Churg-Strauss syndrome was made. Although high doses of steroid therapy alleviated the inflammatory symptoms and markers, the vertigo and bilateral hearing loss remained. Addition of a high-dose immunoglobulin finally resulted in marked alleviation of the symptoms associated with neuropathy of the eighth cranial nerve. A high dose of immunoglobulin therapy shows favorable effects in neuropathy of the eighth cranial nerve, but no reports regarding its efficacy in cranial neuropathy have been published.

  1. The efficacy of immunoglobulin replacement therapy in the long-term follow-up of the B-cell deficiencies (XLA, HIM, CVID).

    PubMed

    Bayrakci, Benan; Ersoy, Fügen; Sanal, Ozden; Kiliç, Sebnem; Metin, Ayşe; Tezcan, Ilhan

    2005-01-01

    Immunoglobulin replacement therapy is the essential treatment of B-cell deficiencies. Because of the high expense of therapy, optimal dose, infusion intervals and serum IgG levels should be well defined. Data of 19 X-linked agammaglobulinemia (XLA), 7 hyper-IgM syndrome (HIM) and 20 common variable immunodeficiency (CVID) patients were analyzed. Infection frequencies and hospitalization requirements were correlated with the immunoglobulin doses used and serum IgG levels achieved. The characteristics before diagnosis and after treatment were compared among the XLA, HIM and CVID groups. By using a median dose of 370 mg/kg/month immunoglobulin, which maintained serum IgG levels at a median concentration of 440 mg/dl, the annual incidence of infections dropped from 12.4 to 3.2 and annual hospitalization requirements decreased from 1.6 to 0.16 per patient. Serum IgG levels of 300-500 mg/dl were found to be satisfactory, except in the CVID group. Increasing the level over 500 mg/dl neither prevented pneumonia further nor decreased the need for hospitalization. Monthly replacement was found to be adequate, except for XLA patients. Serum IgG levels between 300-500 mg/dl are sufficient for effective treatment of hypogammaglobulinemias. These concentrations can be maintained with 300-400 mg/kg/month doses. Higher doses and IgG levels are not needed.

  2. Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies.

    PubMed

    Canessa, Clementina; Iacopelli, Jessica; Pecoraro, Antonio; Spadaro, Giuseppe; Matucci, Andrea; Milito, Cinzia; Vultaggio, Alessandra; Agostini, Carlo; Cinetto, Francesco; Danieli, Maria Giovanna; Gambini, Simona; Marasco, Carolina; Trizzino, Antonino; Vacca, Angelo; De Mattia, Domenico; Martire, Baldassarre; Plebani, Alessandro; Di Gioacchino, Mario; Gatta, Alessia; Finocchi, Andrea; Licciardi, Francesco; Martino, Silvana; De Carli, Marco; Moschese, Viviana; Azzari, Chiara

    2017-03-01

    In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra(®)) has been developed and has replaced Vivaglobin(®) (SCIG 16%). An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra(®) would affect frequency of infusions, number of infusion sites, patients' satisfaction, and tolerability in patients previously treated with Vivaglobin(®) or intravenous immunoglobulins (IVIG). Any variations of dosage, frequency and duration of the infusions, and of number of infusion sites induced by Hizentra(®) with respect to the former treatment were recorded. Practical advantages and disadvantages of Hizentra(®), with respect to the medicinal product formerly used, and the variations in patients' therapy-related satisfaction were monitored by means of the TSQM (Treatment Satisfaction Questionnaire for Medication); number, frequency, and duration of infectious events and adverse effects were recorded. Eighty-two patients switched to Hizentra(®): 19 (23.2%) from IVIG and 63 (76.8%) from Vivaglobin(®). The mean interval between infusions was not affected by the shift (7.0 ± 2.0 days with previous treatment versus 7.1 ± 1.2 during Hizentra(®)). A decrease in the number of infusion sites with Hizentra(®) was recorded in 12 out of 56 patients for whom these data were available. At 6 months, 89.7% of patients were satisfied with Hizentra(®); no difference in terms of effectiveness, side effects, convenience, and global satisfaction was observed. No difference in the incidence of adverse events was reported.

  3. Acute and late coronary outcomes in 1073 patients with Kawasaki disease with and without intravenous γ-immunoglobulin therapy.

    PubMed

    Lin, Ming-Tai; Sun, Li-Chuan; Wu, En-Ting; Wang, Jou-Kou; Lue, Hung-Chi; Wu, Mei-Hwan

    2015-06-01

    To explore acute and late coronary outcomes and their risk/modifiers in patients with Kawasaki disease (KD). Retrospective study. 1073 patients with KD identified from a tertiary care medical centre (1980-2012; 8677 patient-years). The acute coronary severities and late outcomes (survival free of coronary aneurysm persistence and ischaemia) were assessed. Coronary arterial lesions occurred in 40.6% of cases at their acute febrile stages, and persisted beyond 1 month in 196 (18.3%, M/F=138/58) patients: 125 (11.6%) had small aneurysms, 44 (4.1%) had medium aneurysms, and 27 (2.5%) had giant aneurysms. At follow-up (1-46 years), coronary aneurysms persisted in all with giant aneurysms, in 55% of those with medium aneurysms (18% with stenosis), and in 9% of those with small aneurysms. Ischaemia events occurred in 14 patients (M/F=13/1) and caused four deaths. Among the patients with KD with coronary aneurysms, 10-year ischaemia event-free and aneurysm persistence probability was 87.5% and 20.6%, respectively. The only independent risk for aneurysm persistence was the aneurysm severity 1 month after KD onset (χ(2)=80.73, p<10(-3)). Male patients and intravenous γ-immunoglobulin (IVIG) therapy were independent risk factors of initial coronary severity but were not associated with the late coronary outcomes, even in severity stratified subgroups. The coronary severity 1 month after KD onset is most crucial to the late coronary outcomes. Although IVIG use improves the initial severity of coronary lesions, it does not further modify the long-term fate of coronary aneurysms. 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.

  4. Clinical outcome in patients with chronic antibody-mediated rejection treated with and without rituximab and intravenous immunoglobulin combination therapy.

    PubMed

    Chung, Byung Ha; Kim, Yaeni; Jeong, Hyeong Seok; Hong, Yu Ah; Choi, Bum Soon; Park, Cheol Whee; Choi, Yeong Jin; Kim, Yong-Soo; Yang, Chul Woo

    2014-09-01

    We previously reported that rituximab (RTX) and intravenous immunoglobulin (IVIg) combination therapy (RIT) is effective in treating patients with chronic active antibody-mediated rejection (CAMR), and the proteinuria level can determine the response to RIT. However, the results were not compared to those of patients who did not receive RIT. Fifty-nine patients with CAMR were divided into 2 groups: an RIT treated group (n = 25) and a historic control (HC) group who had not received RIT (n = 29). The RIT group was treated with RTX (375 mg/m(2)) and IVIg (0.4 g/kg) for 4 days. We compared the decline in glomerular filtration rate/month (ΔeGFR), RIT-related complications, and allograft survival rate in both groups. We also compared the allograft survival rate between patients with high proteinuria (spot urine protein/creatinine [PC] ratio > 3.5 g/g) and low proteinuria (PC ratio < 3.5 g/g). ΔeGFR was significantly decreased in the RIT group compared with the HC group after 6 months (P < 0.05). No serious complications were associated with RIT, and only one case of herpes zoster infection developed. The overall allograft survival rate in the RIT group was significantly higher than in the HC group. In both groups, patients with low proteinuria survived better than patients with heavy proteinuria (P < 0.05). The allograft survival rate was greater in the high proteinuria RIT group than that in the HC group. RIT treatment is recommended for delaying the progression of CAMR without serious complications, and is not limited by the presence of heavy proteinuria.

  5. Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis

    PubMed Central

    Kumar, Shaji K.; Dispenzieri, Angela; Lacy, Martha Q.; Hayman, Suzanne R.; Buadi, Francis K.; Zeldenrust, Steven R.; Tan, Tow; Sinha, Shirshendu; Leung, Nelson; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2013-01-01

    Current response criteria for light-chain amyloidosis (AL) relegate FLC response to a subsidiary status relative to serum M-protein response. Given that light chains form the substrate for amyloid fibril formation, we hypothesized that changes in FLC might better predict outcome compared to changes in intact immunoglobulin levels. Two patient cohorts were studied, 347 patients who underwent an autologous stem-cell transplant (SCT) and 96 patients treated with melphalan/dexamethasone. We identified the lowest value following therapy for intact serum M-protein and the difference between involved and uninvolved FLC (FLC-diff). We first examined the relative contribution of M-protein and FLC-diff on the overall survival (OS), and found that FLC reduction, rather than M-protein reduction, significantly impacted OS. The median OS was not reached among those with a 50% decrease in FLC-diff compared to 20 months for the remainder. On regression analysis, a 90% reduction in FLC-diff following SCT best predicted being alive at 3 or 5 years. The median OS among those with a 90% decrease was not reached compared to 37.4 months for the rest P < 0.001. The current study supports the notion that FLC response is a more useful measure of hematological response than M-protein response. It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of patients with light-chain AL. Am. J. Hematol. 86:251–255, 2011. PMID:21328431

  6. A 2-month-old boy with hemolytic anemia and reticulocytopenia following intravenous immunoglobulin therapy for Kawasaki disease: a case report and literature review

    PubMed Central

    Kim, Na Yeon; Kim, Joon Hwan; Park, Jin Suk; Kim, Soo Hyun; Cho, Yeon Kyung; Cha, Dong Hyun; Kim, Ki Eun; Kang, Myung Suh; Lim, Kyung Ah

    2016-01-01

    Herein, we report a rare case of hemolytic anemia with reticulocytopenia following intravenous immunoglobulin therapy in a young infant treated for Kawasaki disease. A 2-month-old boy presented with fever lasting 3 days, conjunctival injection, strawberry tongue, erythematous edema of the hands, and macular rash, symptoms and signs suggestive of incomplete Kawasaki disease. His fever resolved 8 days after treatment with aspirin and high dose infusion of intravenous immunoglobulin. The hemoglobin and hematocrit decreased from 9.7 g/dL and 27.1% to 7.4 g/dL and 21.3%, respectively. The patient had normocytic hypochromic anemia with anisocytosis, poikilocytosis, immature neutrophils, and nucleated red blood cells. The direct antiglobulin test result was positive, and the reticulocyte count was 1.39%. The patient had an uneventful recovery. However, reticulocytopenia persisted 1 month after discharge. PMID:28018448

  7. Fish Immunoglobulins

    PubMed Central

    Mashoof, Sara; Criscitiello, Michael F.

    2016-01-01

    The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies an exception. PMID:27879632

  8. Intravenous Immunoglobulin as Salvage Therapy in Refractory Pyoderma Gangrenosum: Report of a Case and Review of the Literature

    PubMed Central

    Cafardi, John; Sami, Naveed

    2014-01-01

    Pyoderma gangrenosum is a neutrophilic dermatosis that occurs both as a primary disorder as well as secondary to an underlying disease. Due to its low prevalence there are limited data on therapeutics, particularly in refractory cases. Here, we discuss a case successfully managed with intravenous immunoglobulin and review the supporting literature. PMID:25493078

  9. The influence of IgM-enriched immunoglobulin therapy on neonatal mortality and hematological variables in newborn infants with blood culture-proven sepsis.

    PubMed

    Abbasoğlu, Aslıhan; Ecevit, Ayşe; Tuğcu, Ali Ulaş; Yapakçı, Ece; Tekindal, Mustafa Agah; Tarcan, Aylin; Ecevit, Zafer

    2014-01-01

    The aim of this study was to determine the effects of adjuvant immunoglobulin M (IgM)-enriched intravenous immunoglobulin (IVIG) therapy on mortality rate, hematological variables and length of hospital stay in newborn infants with blood culture-proven sepsis. Demographic and clinical features and outcome measures of 63 newborn infants with blood culture-proven sepsis were documented retrospectively from the medical records. The patients were divided into two groups according to their treatment history. The patients in Group 1 received antibiotic therapy only and the patients in Group 2 received both antibiotic and adjuvant IgMenriched IVIG. The study revealed that mortality rates were 28.1% and 12.9% in Group 1 and Group 2, respectively. The mortality rate was lower in Group 2, but the difference between the two groups was not statistically significant (p=0.21). Coagulase-negative Staphylococcus was the most common type of bacteria isolated from the blood culture in both groups. When changing laboratory results were compared between the two groups, hemoglobin, leukocyte count and C-reactive protein levels were different during the first three days of antibiotic treatment. Our study revealed that if diagnosed at an early stage and treated aggressively with appropriate and effective antibiotics, adjuvant IgM-enriched IVIG treatment has no additional benefits in neonatal sepsis.

  10. Injection drug users' perceptions of drug treatment services and attitudes toward substitution therapy: a qualitative study in three Russian cities.

    PubMed

    Bobrova, Natalia; Alcorn, Ron; Rhodes, Tim; Rughnikov, Iurii; Neifeld, Elena; Power, Robert

    2007-12-01

    This study explored injection drug users' (IDUs) perceptions of drug abuse treatment and treatment providers in three Russian cities as well as their attitudes toward opiate substitution therapy, which is currently not available in Russia. Data were collected from 121 qualitative interviews with IDUs conducted in 2003-2004. Negative perceptions of available treatments were related to poor treatment outcomes, judgmental service providers, lack of psychologic services, and short lengths of stay in treatment. Positive perceptions were associated with receiving psychosocial care and nonjudgmental attitudes from providers. Most participants had heard about opiate substitution therapy, and some had treated themselves using methadone from the black market. Although respondents had doubts that opiate substitution therapy could work effectively in Russia, most agreed that this type of treatment would help IDUs function better in the society.

  11. [Hematological disturbances in subclinical hypothyroidism and their dynamics during substitution therapy].

    PubMed

    Nekrasova, T A; Strongin, L G; Ledentsova, O V

    2013-01-01

    The aim of the study was to estimate dynamics of hematological disturbances in autoimmune thyroiditis and subclinical hypothyroidism (SH) during substitution therapy and without it and to elucidate factors promoting successful correction. The control group included 36 women, 60 others had SH. They were matched for age, BMI, free T3 level but differed in TSH (1.8 +/- 0.81 vs 7.0 +/- 3.41 mcunits/ml, p < 0.001) and T4 (p < 0.001) levels. 53 women with SH were followed up for 1 year; 18 of them were not treated (subgroup A) while 35 were given levothyroxin (subgroup B). The following red blood parameters were measured hemoglobin (Hb), ferritin, mean erythrocyte volume, erythrocyte Hb content and concentration, blood iron (Fe) level. SH was characterized by decreased (compared with control) Hb levels (125.8 +/- 13.75 and 133.2 +/- 9.12 g/l, p = 0.005), erythrocyte volume (p = 0.022), Hb content per erythrocyte (p = 0.001), ferritin (24.6 +/- 20.56 vs 36.6 +/- 30.66 mcg/l, p = 0.02), and Fe (p = 0.001). The frequency of anemia (28.3 vs 11.1%, p = 0.039) especially microcytic anemia (p = 0.035) increased A year later women of subgroup A showed further decrease in ferritin level (p = 0.011) and increase in anemia frequency (p = 0.016): microcytic (p = 0.23) and normocytic (p = 0.015). In subgroup B, the frequency of anemia decreased (p = 0.001) while ferritin, Fe and Hb levels slightly increased (p > 0.05). The best effect of therapy and highest rise in ferritin level were documented in younger patients (p = 0.06), in the absence of obesity (p = 0.003) and at the low initial ferritin level (p < 0.001). In regression analysis, ferritin level (094 [0.89; 0.99], p = 0.035) proved the most significant predictor of therapeutic effectiveness. SH was characterized by Fe deficiency, tendency to microcytosis and anemia that progressed in the absence of therapy. Substitution therapy promotes normalization of hematological problems especially in young and non-obese patients

  12. Improved IgG3 levels and reduced infection rate in a woman with CVID switched from intravenous to subcutaneous immunoglobulin therapy.

    PubMed

    Shapiro, Ralph S

    2012-12-01

    To report the interesting case of a patient with common variable immune deficiency disease who demonstrated varied responses to intravenous (IV) and subcutaneous (SC) immunoglobulin (Ig) therapy with regard to both infection frequencies and IgG3 subclass determinations. As part of routine medical care, the author monitored total and IgG subclass levels, along with infection frequencies in a 35-year-old woman, with recurrent sinopulmonary infections diagnosed with common variable immune deficiency disease. During treatment with IVIg, the patient's annual rate of infections decreased, although she experienced severe headaches. After being switched to daily SCIg therapy, the headaches stopped, and her annual infection rate declined further. Her IgG3 levels, which were undetectable during IVIg therapy, increased substantially during SCIg treatment. The reason for the observed correlation between IgG3 level restoration and a decline in infection rate after being switched to SCIg therapy is not entirely clear. At the minimum, it may suggest that IgG3 levels may be a simple and useful surrogate marker to monitor Ig replacement sufficiency in certain patients.

  13. Integrated opioid substitution therapy and HIV care: a qualitative systematic review and synthesis of client and provider experiences.

    PubMed

    Guise, Andy; Seguin, Maureen; Mburu, Gitau; McLean, Susie; Grenfell, Pippa; Islam, Zahed; Filippovych, Sergii; Assan, Happy; Low, Andrea; Vickerman, Peter; Rhodes, Tim

    2017-09-01

    People who use drugs in many contexts have limited access to opioid substitution therapy and HIV care. Service integration is one strategy identified to support increased access. We reviewed and synthesized literature exploring client and provider experiences of integrated opioid substitution therapy and HIV care to identify acceptable approaches to care delivery. We systematically reviewed qualitative literature. We searched nine bibliographic databases, supplemented by manual searches of reference lists of articles from the database search, relevant journals, conferences, key organizations and consultation with experts. Thematic synthesis was used to develop descriptive themes in client and provider experiences. The search yielded 11 articles for inclusion, along with 8 expert and policy reports. We identify five descriptive themes: the convenience and comprehensive nature of co-located care, contrasting care philosophies and their role in shaping integration, the limits to disclosure and communication between clients and providers, opioid substitution therapy enabling HIV care access and engagement, and health system challenges to delivering integrated services. The discussion explores how integrated opioid substitution therapy and HIV care needs to adapt to specific social conditions, rather than following universal approaches. We identify priorities for future research. Acceptable integrated opioid substitution therapy and HIV care for people who use drugs and providers is most likely through co-located care and relies upon attention to stigma, supportive relationships and client centred cultures of delivery. Further research is needed to understand experiences of integrated care, particularly delivery in low and middle income settings and models of care focused on community and non-clinic based delivery.

  14. Improved antimicrobial therapy with cationic tetra- and octa-substituted phthalocyanines

    NASA Astrophysics Data System (ADS)

    Angelov, I.; Mantareva, V.; Kussovski, V.; Woehrle, D.; Borisova, E.; Avramov, L.

    2008-12-01

    Photodynamic therapy (PDT) today is an innovative and not yet widespread light-drug initiated treatment that is based on the photoactive compound irradiated with proper light to produce oxygen species that are toxic to the pathogenic biological objects- bacteria, viruses, tumor cells. The obstacles that limited the efficacy of PDT concern to the selectivity and multi-drug resistance prolong time for cellular release and side effects of skin photosensitivity for commercial porphyrin originated photosensitizers (PS). Now there are very intensive investigations for introducing in practice a new, with a least side effects PSs for PDT. The usefulness of the more extended macromolecules structured with proper substituents refers not only to the improved optical properties like far-red and with intensive absorption and emission capacity, but mainly to the ability for selective delivery and adhesion to the target cells, such as bacteria or other pathogens. The present study focuses on the charge effect of photodynamic agent on the uptake capacity toward gram-negative bacteria cells and their further photoinactivation. The multi-drug resistant microorganism Aeromanas hydrophilla, which is causing diseases to fishes and humans, is treated. The new octa-cationic phthalocyanines are designed to compare PDT efficacy to the efficacy of tetra-substituted derivatives with the same functional peripheral substituents. The higher cellular accumulation to the bacteria cells as a result of the high number of positive charges of photosensitizer, leading to the better adhesion to the cellular membranes and improved photoinactivation of bacteria causing superficial and intraorgan infections. These results set a base of a rationale design of covalently octa-substituted phthalocyanines with positive charge for a successful treatment of microorganisms.

  15. Transcranial magnetic stimulation maintenance as a substitute for maintenance electroconvulsive therapy: a case series.

    PubMed

    Cristancho, Mario A; Helmer, Amanda; Connolly, Ryan; Cristancho, Pilar; O'Reardon, John P

    2013-06-01

    Transcranial magnetic stimulation (TMS) is an efficacious, well-tolerated, noninvasive brain stimulation treatment for major depressive disorder. Electroconvulsive therapy (ECT) is an effective maintenance treatment for depression but is not tolerated by some patients and declined by others. We evaluated the effectiveness of TMS as a substitution strategy for successful maintenance ECT. A consecutive clinical case series (n = 6) of maintenance ECT patients were transitioned to maintenance TMS because of adverse effects from ECT or because of specific patient request and preference. Patients were in either full remission or had clinical response to ECT at the time of transition. Primary outcome was the change in the Beck Depression Inventory (BDI) score from initiation of TMS maintenance sessions to the last observation time point. Relapse of depressive symptoms was also documented. Mean age of patients was 64 years, and most were female (n = 5). The majority (5 of 6) were diagnosed with major depressive disorder. Reasons for transition from ECT to TMS were, in order of frequency, cognitive adverse effects, fear of general anesthesia, time burden, lack of remission with ECT, and stigma associated with ECT. The mean frequency of TMS sessions was 1 every 3.5 weeks. Based on BDI scores, all patients maintained or improved their clinical status achieved with ECT at 3 and 6 months of TMS treatment. At last observation (range, 7-23 months), 4 patients maintained or improved their clinical status (total BDI score remained constant or decreased by 1-8 points). Two patients had a relapse after 8 and 9 months. Stimulation was well tolerated with adverse effects limited to headache and scalp discomfort. In this case series, TMS was effective and safe when used as a substitution strategy for successful maintenance ECT.

  16. Feline immunoglobulins.

    PubMed

    Schultz, R D; Scott, F W; Duncan, J R; Gillespie, J H

    1974-02-01

    Immunoglobulins (Ig) in feline sera and secretions were identified by immuno-electrophoresis and immunodiffusion with rabbit antisera prepared to feline IgG, IgA, IgM, and whole serum. Adult cat sera, colostral whey, postcolostral sera, tears, and nasal secretions contained IgG, IgA, and IgM. IgG was the only Ig identified in precolostral sera and cerebrospinal fluid. Milk, intestinal contents, pooled allantoic and amniotic fluids, and saliva from adult cats and urine from suckling kittens contained IgG and IgA. Ig were not detected in urine from adult cats. Bile was unique in that IgA and IgM were the predominant Ig.

  17. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial.

    PubMed

    Miyasaka, Nobuyuki; Hara, Masako; Koike, Takao; Saito, Eizo; Yamada, Masahito; Tanaka, Yoshiya

    2012-06-01

    High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo-controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy.

  18. Opioid substitution therapy as a strategy to reduce deaths in prison: retrospective cohort study

    PubMed Central

    Larney, Sarah; Gisev, Natasa; Farrell, Michael; Dobbins, Timothy; Burns, Lucinda; Gibson, Amy; Kimber, Jo; Degenhardt, Louisa

    2014-01-01

    Objectives To describe deaths in prison among opioid-dependent people, and examine associations between receipt of opioid substitution therapy (OST) and risk of death in prison. Design Retrospective cohort study. Setting Adult prisons in New South Wales (NSW), Australia. Participants 16 715 opioid-dependent people who were received to prison between 2000 and 2012. Interventions Opioid substitution therapy. Primary outcome measures Natural and unnatural (suicide, drug-induced, violent and other injury) deaths in prison. Results Cohort members were in prison for 30 998 person-years (PY), during which time there were 51 deaths. The all-cause crude mortality rate (CMR) in prison was 1.6/1000 PY (95% CI 1.2 to 2.2/1000 PY), and the unnatural death CMR was 1.1/1000 PY (95% CI 0.8 to 1.6/1000 PY). Compared to time out of OST, the hazard of all-cause death was 74% lower while in OST (adjusted HR (AHR): 0.26; 95% CI 0.13 to 0.50), and the hazard of unnatural death was 87% lower while in OST (AHR: 0.13; 95% CI 0.05 to 0.35). The all-cause and unnatural death CMRs during the first 4 weeks of incarceration were 6.6/1000 PY (95% CI 3.8 to 10.6/1000 PY) and 5.5/1000 PY (95% CI 2.9 to 9.4/1000 PY), respectively. Compared to periods not in OST, the hazard of all-cause death during the first 4 weeks of incarceration was 94% lower while in OST (AHR: 0.06; 95% CI 0.01 to 0.48), and the hazard of unnatural death was 93% lower while in OST (AHR: 0.07; 95% CI 0.01 to 0.53). Conclusions Mortality of opioid-dependent prisoners was significantly lower while in receipt of OST. PMID:24694626

  19. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology.

    PubMed

    Yong, Pierre L; Boyle, John; Ballow, Mark; Boyle, Marcia; Berger, Melvin; Bleesing, Jack; Bonilla, Franciso A; Chinen, Javier; Cunninghamm-Rundles, Charlotte; Fuleihan, Ramsay; Nelson, Lois; Wasserman, Richard L; Williams, Kathleen C; Orange, Jordan S

    2010-05-01

    There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.

  20. Pharmacoeconomics of immunoglobulins in primary immunodeficiency.

    PubMed

    Simoens, Steven

    2009-08-01

    Primary immunodeficiency disorders are associated with increased patient susceptibility to recurrent infections. Since the 1950s, intramuscular, intravenous and subcutaneous immunoglobulin products have been used to replace functionally deficient or absent immunoglobulins, reduce the incidence of infections and prevent organ damage caused by infections. This article aims to review the use of immunoglobulin therapy in primary immunodeficiency by focusing on costs, effectiveness, cost-effectiveness, supply and off-label use. To date, the economic burden of primary immunodeficiency is unknown. Past studies have supported minimal differences in effectiveness between intravenous and subcutaneous immunoglobulins. Subcutaneous therapy may be considered for patients who prefer treatment at home. The small number of economic evaluations and their methodological limitations precludes the recommendation of a specific product for use in primary immunodeficiency on pharmacoeconomic grounds. Demand for immunoglobulins has increased over time, leading to periodic shortages and emphasizing the importance of its appropriate use.

  1. Opioid substitution therapy--a study of GP participation in prescribing.

    PubMed

    Scarborough, Jane; Eliott, Jaklin; Braunack-Mayer, Annette

    2011-04-01

    Opioid substitution therapy (OST) is the most commonly provided treatment for heroin dependence in Australia and has been shown to be effective. Access to OST outside of specialised public clinics and prisons relies on the participation of general practitioners. In Australia there is a shortage of GPs available to prescribe OST, which results in an unmet need for OST services. Studies have reported barriers to GP involvement in drug and alcohol work and there is little research looking at the perceptions and experiences of GPs involved in prescribing OST. Semistructured qualitative interviews were conducted with eight experienced prescribers of OST in general practice settings in South Australia. All participants described similar positive and negative aspects associated with prescribing OST. Some participants commenced prescribing in such a manner as to limit the scope of their involvement. Ceasing OST prescribing was not necessarily linked to negative experiences. Exprescribers indicated that they were unlikely to recommence prescribing. This study has limited generalisability due to the small sample size but it does highlight some insights that can be gained from talking to experienced OST prescribers.

  2. A Retrospective Evaluation of Inpatient Transfer from High-Dose Methadone to Buprenorphine Substitution Therapy.

    PubMed

    Oretti, Rossana

    2015-10-01

    The product license of buprenorphine/naloxone for opioid substitution therapy indicates reducing methadone concentrations to 30 mg or less per day for a minimum of 1 week before transferring patients to buprenorphine and no sooner than 24 hours after the last methadone dose, because of the risk of precipitated withdrawal and a corresponding high risk of relapse to opioid use. There are few studies describing high-dose methadone transfers. This retrospective case review assessed the feasibility of transferring patients on methadone doses above 30 mg/day to buprenorphine or buprenorphine/naloxone in the inpatient setting. Six of seven patients on 60-120 mg/day of methadone successfully completed the transfer, and four cases tested negative for opiates at long-term follow-up (6-15 months). This suggests that methadone transfer to buprenorphine can be performed rapidly without the need to taper methadone doses in patients indicated for a therapeutic switch. This small study is hypothesis-generating; larger, well-designed trials are needed to define a protocol that can be used routinely to improve and widen transfers to buprenorphine when indicated.

  3. Advocating for opioid substitution therapy in Central Asia: much still to be done.

    PubMed

    Parsons, Danielle; Burrows, Dave; Bolotbaeva, Aisuluu

    2014-11-01

    Opioid substitution therapy (OST) was first introduced in the formerly-Soviet Central Asian Republics as an HIV prevention intervention for people who inject drugs (PWID) in 2002. Presently, pilot programs function in Kazakhstan and Tajikistan, and Kyrgyzstan has scaled-up from the pilot phase to the operation of over 20 OST sites nation-wide. All three countries have taken steps towards lower-threshold programs, allowing clients to enroll regardless of HIV status, and, in some cases, without documentation of failure to complete other drug treatment programs. However, OST programs remain exclusively funded by international donors, and political and societal opposition to these programs threaten their stability. In order to counter negative campaigns and political attacks on OST, organized advocacy efforts are needed. This commentary explores efforts undertaken by international donor partners supporting advocacy efforts to scale-up OST and assure a sustainable future for programming. It examines both proactive and reactive efforts, and the variety of target audiences that need to be reached to conduct effective advocacy. Ultimately we find that, while a range of tools are available for OST advocacy in the hostile environments of the former Soviet Union, the strengthening of advocacy groups is needed to assure an optimized platform exists for using the evidence and developing relevant materials in the appropriate languages (including, but not limited to, Russian) for both proactive and reactive efforts; and that more robust monitoring is desirable to bring sharper focus to replicable methods. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. For lack of wanting: Discourses of desire in Ukrainian opiate substitution therapy programs.

    PubMed

    Carroll, Jennifer J

    2016-04-01

    Available treatments for addiction and substance abuse in Ukraine have been shaped by the economic, political, and social shifts that have followed the country's independence. The introduction of methadone-based opiate substitution therapy (OST) for opiate addicts is especially representative of this. Biomedical paradigms of addiction, its etiology, and its treatment, promoted and paid for by international donors and elite global health entities, are being met by Ukrainian notions of personhood and psychology in both public discourse and clinical settings. Ukrainian physicians who work in OST programs frequently reference desire (желание) as the most significant factor in determining the success or failure of treatment. They refer to a desire to be treated, desire to get better, desire to live. The moralized imperative to possess this desire to get better is, in many ways, a reflection of how addiction and the addicted psyche is constructed and understood in the Ukrainian context. By exploring discourses of desire in narratives of addiction and treatment, I examine how notions of psychology, will, and self-control intersect, shaping the subjectivity, agency, and daily experiences of this vulnerable population.

  5. Reluctant to train, reluctant to prescribe: barriers to general practitioner prescribing of opioid substitution therapy.

    PubMed

    Longman, Christine; Temple-Smith, Meredith; Gilchrist, Gail; Lintzeris, Nicholas

    2012-01-01

    Opioid substitution therapy (OST) is a well-recognised, evidence-based treatment for opioid dependence. Since the early 1990s, Australia has used a community-based general practitioner (GP) model ofprescribing, particularly within the state of Victoria, where over 85% of OST prescribing is undertaken by GPs in community settings. Yet the majority of GPs invited to complete the required OST training decline the offer, while of those who complete training, the majority prescribe to few or no patients. This study aimed to determine the reasons for this. Twenty-two in-depth interviews were conducted with Victorian GPs exploring the reasons why the majority declined training, and for trained GPs, why they prescribed to few or no patients in the first 12 months after training. General practitioners who declined to train were predominantly influenced by negative experiences with drug-seeking patients, although other secondary reasons also affected their decision. Some GPs who completed the training were prevented from prescribing by several structural and operational barriers, many of which could be addressed. Fear of deskilling with time became a further impediment. General practitioners who became regular prescribers were highly committed with lengthy general practice experience. Concerns exist about the recruitment process for OST prescriber training, where nearly all GPs decline the offer of training, and the barriers that prevent GPs prescribing after training. Action is needed to address barriers to GP OST training and prescribing, and further research is necessary to ascertain measures required to facilitate long-term prescribing.

  6. 7th International Immunoglobulin Conference: Poster presentations.

    PubMed

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    The pan-European survey provides useful information on the accessibility and trends of intravenous and subcutaneous immunoglobulin (IVIg/SCIg) therapy, which is used to treat primary immunodeficiency disorders (PIDs). Although immunoglobulin (Ig) therapy is the first-line treatment for PIDs, the mechanisms of action of Ig therapy may differ according to the condition it is used to treat. Moreover, intriguing presentations suggest that further investigation is required to understand more clearly both the haematological and immunoregulatory effects of therapeutic immunoglobulin. This can ultimately provide more information on optimizing Ig therapy efficacy, and establish whether individualized dosing regimens for patients will be conducive to better clinical outcomes. In addition to treating autoimmune and inflammatory conditions, there is evidence to suggest that immunoglobulins can potentially play a role in transplantation, which warrants further investigation for future use.

  7. Nucleoside analogue therapy following one-year course of hepatitis B immunoglobulin in preventing hepatitis B virus reactivation after living donor liver transplantation.

    PubMed

    Kawagishi, Naoki; Takeda, Ikuo; Miyagi, Shigehito; Satoh, Kazushige; Akamatsu, Yorihiro; Sekiguchi, Satoshi; Satomi, Susumu

    2010-12-01

    The combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside analogue is well tolerated for the hepatitis B recipients after liver transplantation, but its cost is an important problem in these days. Here we report the efficacy of nucleoside analogue therapy following one-year course of HBIG plus nucleoside analogue after living donor liver transplantation (LDLT). Out of 103 LDLTs, we selected 14 recipients who received the post-transplant therapy against reactivation of hepatitis B virus for more than 30 months. Those were eight patients with chronic hepatitis B, three with fulminant hepatitis, and three whose donors were positive for antibody to HB core antigen (HBc). During two days after the operation, HBIG (40,000 units) was administered, and the serum level of antibody to HB surface antigen (HBs) was maintained at around 150 IU/L for one year by monthly administration of HBIG. After one year, HBIG was withdrawn. A nucleoside analogue was administered daily from just after LDLT, and it was continued up to the present. Among the 14 patients, two recipients had recurrence of hepatitis B. Three patients, including one patient with recurrence of hepatitis B, died due to hepatocellular carcinoma or its associated cirrhosis; namely, their deaths are unrelated to hepatitis B-related diseases. The remaining 11 patients are leading normal lives. In conclusion, nucleoside analogue therapy after one-year course of HBIG plus nucleoside analogue is feasible and cost-effective in preventing HBV reactivation. But the patients are still at risk of breakthrough and some patients may need continued prophylaxis with HBIG.

  8. Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis.

    PubMed

    Akyildiz, Murat; Karasu, Zeki; Zeytunlu, Murat; Aydin, Unal; Ozacar, Tijen; Kilic, Murat

    2007-12-01

    Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.

  9. Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.

    PubMed

    Park, G-C; Hwang, S; Ahn, C-S; Kim, K-H; Moon, D-B; Ha, T-Y; Song, G-W; Jung, D-H; Shin, Y W; Kim, S-H; Chang, K-H; Namgoong, J-M; Park, C-S; Park, H-W; Park, Y-H; Kang, S-H; Jung, B-H; Lee, S-G

    2013-10-01

    A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation or Treated with Immunomodulatory Agents.

    PubMed Central

    Khalafallah, Alhossain; Maiwald, Matthias; Cox, Amanda; Burns, Denise; Bates, Gerald; Hannan, Terry; Seaton, David; Fernandopulle, Bernadene; Meagher, Damien; Brain, Terry

    2010-01-01

    Multiple myeloma (MM) is associated with a significant risk of infection due to immune dysfunction. Infections are a major cause of morbidity and mortality in MM patients. There are few data available regarding the prevalence of infection in MM patients, especially in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide) or post autologous stem cell transplantation (ASCT). Intravenous immunoglobulin (IVIG) has been used successfully to reduce infection rates in the stable phase of MM, with limited data in other stages. We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequent to thalidomide, because of disease progression, and 22 patients underwent ASCT. The median age was 64 years (range 37–86), with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe bacterial infections, including the ASCT group. Fifteen patients suffered from different degrees of viral infections. All patients except 3 received IVIG therapy with a significant decline of the rate of infection thereafter (p<001). Our analysis shows that patients with MM treated with the new immunomodulatory drugs in conjunction with steroids are at significant increased risk of infection. Employing IVIG therapy appears to be an effective strategy to prevent infection in this cohort of patients. Further studies to confirm these findings are warranted. PMID:21415947

  11. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves.

    PubMed

    Altman, R; Rouvier, J; Gurfinkel, E; D'Ortencio, O; Manzanel, R; de La Fuente, L; Favaloro, R G

    1991-03-01

    After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.

  12. Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy--factors associated with advanced fibrosis.

    PubMed

    Jerkeman, Anna; Westin, Johan; Lagging, Martin; Norkrans, Gunnar; Lidman, Christer; Frimand, Jan; Simonsberg, Christian; Kakko, Johan; Widell, Anders; Björkman, Per

    2014-05-01

    Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs.

  13. The journey of opioid substitution therapy in India: Achievements and challenges

    PubMed Central

    Rao, Ravindra

    2017-01-01

    Opioids are one of the most problematic illegal substances globally. Opioid abuse is associated with complications in various spheres of the user's life, his/her family, and the society. Injecting drug use (IDU) is also linked to public health problems such as HIV infection and viral hepatitis. Medications form an important cornerstone in the treatment of opioid dependence. Treatment strategies such as “detoxification” alone or long-term treatment with opioid antagonist have limited acceptability and retention rates. Opioid substitution therapy (OST) has demonstrated better retention rates than other existing treatment strategies and helps improve the individual's functioning as well as his/her quality of life. The use of OST in India spans three decades, with initial use of low-dose buprenorphine followed by higher strength buprenorphine and buprenorphine-naloxone. Other medications such as slow-release oral morphine, and recently, methadone have also been introduced. Indian research also confirms the findings from Western literature on the effectiveness as well as acceptability of this treatment modality. OST received its biggest thrust when it became a part of the National AIDS Control Programme. In recent years, the number of OST centers in India has increased manifold. Practice guidelines, standard operating procedures, and capacity-building mechanisms have been put in place for effective OST implementation. Despite such widespread use, many challenges exist for OST implementation. The targets for ensuring adequate coverage of the population with this treatment are still far away. There is concern of OST being branded as a “harm reduction” intervention reserved only for injecting drug users. Despite three decades of advancements, certain sections of policymakers and practitioners still have reservations with this treatment modality. There is a need to overcome these barriers for OST to become easily accessible to those who need it. PMID:28529359

  14. Waiting room ambience and provision of opioid substitution therapy in general practice.

    PubMed

    Holliday, Simon M; Magin, Parker J; Dunbabin, Janet S; Ewald, Ben D; Henry, Julie-Marie; Goode, Susan M; Baker, Fran A; Dunlop, Adrian J

    2012-04-02

    To assess whether patients receiving opioid substitution therapy (OST) in general practice cause other patients sufficient distress to change practices--a perceived barrier that prevents general practitioners from prescribing OST. A cross-sectional questionnaire-based survey of consecutive adult patients in the waiting rooms of a network of research general practices in New South Wales during August-December 2009. Prevalence of disturbing waiting room experiences where drug intoxication was considered a factor, discomfort about sharing the waiting room with patients being treated for drug addiction, and likelihood of changing practices if the practice provided specialised care for patients with opiate addiction. From 15 practices (eight OST-prescribing), 1138 of 1449 invited patients completed questionnaires (response rate, 78.5%). A disturbing experience in any waiting room at any time was reported by 18.0% of respondents (203/1130), with only 3.1% (35/1128) reporting that drug intoxication was a contributing factor. However, 39.3% of respondents (424/1080) would feel uncomfortable sharing the waiting room with someone being treated for drug addiction. Respondents were largely unaware of the OST-prescribing status of the practice (12.1% of patients attending OST-prescribing practices [70/579] correctly reported this). Only 15.9% of respondents (165/1037) reported being likely to change practices if theirs provided specialised care for opiate-addicted patients. In contrast, 28.7% (302/1053) were likely to change practices if consistently kept waiting more than 30 minutes, and 26.6% (275/1033) would likely do so if consultation fees increased by $10. Despite the frequency of stigmatising attitudes towards patients requiring treatment for drug addiction, GPs' concerns that prescribing OST in their practices would have a negative impact on other patients' waiting room experiences or on retention of patients seem to be unfounded.

  15. Refractory Toxic Shock-Like Syndrome from Streptococcus dysgalactiae ssp. equisimilis and Intravenous Immunoglobulin as Salvage Therapy: A Case Series

    PubMed Central

    Karter, Dennis; Altshuler, Jerry; Altshuler, Diana; Schwartz, David; Torregrossa, Gianluca

    2016-01-01

    Infections from Streptococcus dysgalactiae ssp. equisimilis (SDSE) can cause a wide variety of infections, ranging from mild cellulitis to invasive disease, such as endocarditis and streptococcal toxic shock-like syndrome (TSLS). Despite prompt and appropriate antibiotics, mortality rates associated with shock have remained exceedingly high, prompting the need for adjunctive therapy. IVIG has been proposed as a possible adjunct, given its ability to neutralize a wide variety of superantigens and modulate a dysregulated inflammatory response. We present the first reported cases of successful IVIG therapy for reversing shock in the treatment of SDSE TSLS. PMID:27597908

  16. The impact of dispensing fees on compliance with opioid substitution therapy: a mixed methods study

    PubMed Central

    2014-01-01

    Background Opioid substitution therapy (OST) programs involve the dispensing of OST medicines to patients to address their dependence on heroin and/or other opioid substances. OST medicines are subsidised by the Australian government but patients need to pay the dispensing fees. This study explored opinions from OST patients and stakeholders about the potential impact of dispensing fees on compliance and OST program retention. Current and past experiences and the potential impact of OST dispensing fees were evaluated. Methods Mixed methodology was used to obtain data from OST patients and stakeholders. This involved 1) interviews with OST stakeholders, 2) a focus group of OST patients and 3) surveys of OST patients in Perth, Australia, between June and August 2013. Results The majority of the eight stakeholders declared cost as the factor mostly impacting on OST compliance. Almost all of the stakeholders commented that there was a positive correlation between time on the OST program and success in terms of relapse. Most stakeholders advocated for OST fees to contribute towards the Pharmaceutical Benefits Scheme Safety Net, and for fee subsidy. Focus group themes supported stakeholder interview findings. A total of 138 surveys were completed. Survey analysis illustrated a strong correlation between patient debt and impacted lifestyle: 82.4% (p < 0.001, Chi-square test) of the 138 survey participants stated that dispensing fees impacted significantly on patients’ finances and lifestyle, specifically those patients with major debt. The cost of dispensing fees was identified by 46.3% (64/138) of survey participants as the biggest impacting factor on patient success. Logistic regression models showed that the cost of dispensing fees was also found to significantly influence both the occurrence of debt (57.7%, p < 0.0001) and lifestyle difficulties (80.0%, p = 0.0004). Conclusion Findings provided insight into OST patients’ financial difficulties with

  17. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus b19 infection: a retrospective study of 10 patients and review of the literature.

    PubMed

    Crabol, Yoann; Terrier, Benjamin; Rozenberg, Flore; Pestre, Vincent; Legendre, Christophe; Hermine, Olivier; Montagnier-Petrissans, Catherine; Guillevin, Loïc; Mouthon, Luc

    2013-04-01

    We evaluated the efficacy of intravenous immunoglobulin (IVIG) therapy in patients with pure red cell aplasia (PRCA) related to human parvovirus B19 (HPV-B19) infection. We retrospectively reviewed all HPV-B19 PRCA cases treated with IVIG between January 2000 and December 2005 in the Assistance Publique-Hôpitaux de Paris hospitals and reviewed all cases of HPV-B19 PRCA cases treated with IVIG in the literature. Among our 36 patients, PRCA was confirmed in 22, including 10 with proven HPV-B19 infection. Nine patients were immunocompromised, including 4 who had undergone transplant. All patients had severe anemia (mean hemoglobin level, 5.0 ± 1.9 g/dL). Seven patients who underwent bone-marrow aspiration had positive HPV-B19 polymerase chain reaction (PCR) results at diagnosis. Patients received a mean of 2.7 ± 2.1 IVIG courses (1.3 ± 0.5 g/kg/course). Hemoglobin level was corrected in 9 of the 10 patients within a mean of 80 ± 54 days. The only nonresponsive patient had underlying myelodysplasia. Blood HPV-B19 PCR results were negative from 35 to 159 days after treatment. Four patients showed side effects of IVIG treatment: acute reversible renal failure (n = 2) and pulmonary edema (n = 2). Among 133 patients with HPV-B19 PRCA who received IVIG (our 10 patients and 123 from the literature), 63 had undergone solid-organ transplant and 39 had human immunodeficiency virus infection. Hemoglobin level was corrected after the first IVIG course in 124 patients (93%); disease relapsed in 42 (33.9%), at a mean of 4.3 months. IVIG therapy appears to be effective in the short term in immunocompromised patients with HPV-B19 PRCA.

  18. A combination therapy protocol of plasmapheresis, intravenous immunoglobulins and betamethasone to treat anti-Ro/La-related congenital atrioventricular block. A case series and review of the literature.

    PubMed

    Ruffatti, Amelia; Marson, Piero; Svaluto-Moreolo, Giorgio; Marozio, Luca; Tibaldi, Maria; Favaro, Maria; Calligaro, Antonia; Grava, Chiara; Hoxha, Ariela; Pengo, Vittorio; Punzi, Leonardo

    2013-05-01

    The aim of this report was to evaluate the efficacy and safety of a combined treatment protocol used to treat 2nd and 3rd degree anti-Ro/La-related congenital atrioventricular block (CAVB). Six consecutive women diagnosed with 2nd degree (three cases) or 3rd degree block (three cases) between 2009 and 2011 referred to our outpatient clinic underwent a combination therapy protocol composed of weekly plasmapheresis, fortnightly 1g/kg intravenous immunoglobulins (IVIG) and daily betamethasone (4mg/day) throughout pregnancy. IVIG (1g/kg) treatment in the neonates was begun at birth and administered every fifteen days until passive maternal antibodies became undetectable. The fetuses affected with 2nd degree block (cases 1, 2 and 3) reverted to a normal atrioventricular conduction after combined therapy, while those with a 3rd degree block remained stable (case 4), showed an increase in the ventricular rate (case 5) or an improvement in cardiac function (case 6). None of the fetuses with 3rd degree CAVB had other cardiac complications such as cardiomyopathy or fetal hydrops. The follow-up of the children affected with 2nd degree CAVB revealed a complete regression of the block in cases 1 and 3, and no signs of relevant worsening in case 2. The infants affected with 3rd degree block (cases 4, 5, and 6) remained stable and until now only one has required a pacemaker at the age of 10months. If these results are confirmed by large-scale studies, this protocol could lead to improved outcomes in the treatment of this devastating disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

    PubMed Central

    Absoud, M; Gadian, J; Hellier, J; Brex, P A; Ciccarelli, O; Giovannoni, G; Kelly, J; McCrone, P; Murphy, C; Palace, J; Pickles, A; Pike, M; Robertson, N; Jacob, A; Lim, M

    2015-01-01

    Introduction Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG. Methods and analysis 170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months’ recruitment futility analysis will be performed. Ethics and dissemination Research Ethics Committee Approval was obtained: 14/SC/1329. Current protocol: v3.0 (15/01/2015). Study findings will be published in peer-reviewed journals. Trial registration numbers This study is registered with EudraCT (REF: 2014

  20. [The effect of substitution therapy on the birth weight of the newborn, its postpartum adaptation, trophic and course of the neonatal abstinence syndrome].

    PubMed

    Vavrinková, B; Binder, T

    2007-08-01

    Evaluation of the effect of substitution therapy on the birth weight of the newborn, its postpartum adaptation and course of the neonatal abstinence syndrome. A three-year prospective study. The Department of Gynecology and Obstetrics of the Teaching Hospital and the 2nd Medical Faculty of the Charles University, Prague. This prospective study was carried out in the period of 2005-2007. Included in the study were heroin-addicted pregnant women and pregnant women who undergoing methadone and buprenorphine substitution therapy. During the 3 years we followed-up 47 heroin-addicted women and 60 women under substitution therapy for prenatal screening. Of this number, 36 pregnant women were methadone-substituted and 24 buprenorphine-substituted. Individual groups were compared using the Kruskal-Wallis ANOVA test. Correlation of dichotomic variables was evaluated by means of longlinear models. Calculations were done by means of NCSS 2002 statistical software (Number Cruncher Statistical Systems, Kaysville, UT, USA). Statistically birth weight of newborns was significantly lowest in the group of heroin-addicted women as compared to the group receiving substitution with buprenorphine p<0.01 and as compared to the group of methadone-substituted patients p<0.05. Having monitores changes in the placenta the statistically highest number of changes was exhibited by heroin users, both when compared to methadone users (p<0.01) and buprenorphine users (p<0.001). The highest statistically significant number of newborns with IUGR symptoms were born to heroin-addicted women. The lowest Apgar score was recorded in all three evaluations in the group of buprenorphine users and the highest in methadone-substituted women. Substitution therapy provides pregnant women with the possibility of social stabilization, adaptation, and adequate prenatal care. With regard to the fact that methadone substitution protracts the newborn's abstinence syndrome, attention has been recently focused on

  1. Immunoglobulin treatment in primary antibody deficiency.

    PubMed

    Maarschalk-Ellerbroek, L J; Hoepelman, I M; Ellerbroek, P M

    2011-05-01

    The primary antibody deficiency syndromes are characterised by recurrent respiratory tract infections and the inability to produce effective immunoglobulin (Ig) responses. The best-known primary antibody deficiencies are common variable immunodeficiency (CVID), X-linked agammaglobulinaemia (XLA), immunoglobulin G (IgG) subclass deficiency, and selective antibody deficiency with normal immunoglobulins (SADNI). Therapy in these patients consists of prophylactic antibiotics and/or Ig replacement therapy. Diagnostic delay remains common owing to limited awareness of the presenting features and may result in increased morbidity and mortality. Replacement therapy with immunoglobulins increases life expectancy and reduces the frequency and severity of infections, but the effect on end-organ damage is still unknown. Both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) treatment appear to be safe, with comparable efficacy. A starting dose of 300-400 mg/kg/month in IVIg and 100 mg/week for SCIg is recommended. IgG trough levels should be >5 g/L for patients with agammaglobulinaemia and 3 g/L greater than the initial IgG level for patients with CVID; however, the clinical response should be foremost in choosing the dose and trough level. Infusion-related adverse reactions are generally mild owing to improved manufacturing processes. In this paper, aspects of Ig replacement therapy in primary antibody-deficient patients will be addressed. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Adjuncts to preparing wounds for closure: hyperbaric oxygen, growth factors, skin substitutes, negative pressure wound therapy (vacuum-assisted closure).

    PubMed

    Hopf, H W; Humphrey, L M; Puzziferri, N; West, J M; Attinger, C E; Hunt, T K

    2001-12-01

    Achieving closure in a chronic wound requires provision of adequate oxygen delivery to the tissue, adequate protein and other nutritional factors, a moist environment, an appropriate inflammatory milieu, dèbridement, and correction of contributing medical diagnoses. In some patients, these conditions are achieved easily, whereas in others, greater effort is required. Adjunctive treatments, including HBO2, growth factors, skin substitutes, and negative-pressure wound therapy (e.g., V.A.C.) can provide the proper conditions for healing in appropriately selected patients.

  3. Efficacy of RhD monoclonal antibodies in clinical trials as replacement therapy for prophylactic anti-D immunoglobulin: more questions than answers.

    PubMed

    Kumpel, B M

    2007-08-01

    Prophylactic anti-D is a very safe and effective therapy for the suppression of D-immunization and prevention of haemolytic disease of the foetus and newborn. The primary mode of action of anti-D is rapid clearance of fetal D-positive red cells from the maternal circulation, mediated by interactions with immunoglobulin G Fc receptors on macrophages in the spleen. Many anti-D monoclonal antibodies (mAb) have been produced by a variety of methods. Twelve anti-D mAbs were tested in eight studies for their ability to mediate clearance of autologous red cells, and 13 antibodies studied in seven trials of the clearance of D-positive red cells injected into D-negative subjects. Antibodies produced by human B-cell lines, mouse-human heterohybridomas and Chinese hamster ovary cells varied in their activity with none being quite as effective as polyclonal anti-D. However, clearance mediated by recombinant anti-D produced by rat YB2/0 cells was extremely rapid, faster than polyclonal anti-D, but with haemolysis and some hepatic accumulation of red cells observed in one study. Two human anti-D mAbs prevented D-immunization. In contrast, anti-D mAbs from heterohybridomas increased the incidence and rapidity of anti-D responses. It is hypothesised that unnatural glycosylation of monoclonal anti-D produced by some cell lines may have caused these unexpected results. In some antibodies, unusual oligosaccharides on anti-D may have affected binding to Fc receptors resulting in reduced red cell clearance. For others, non-human glycoforms of anti-D might have bound to innate immune recognition molecules promoting pro-inflammatory reactions. These extensive data on the clinical activity of monoclonal anti-D produced by cell lines derived from four species will inform the future development of monoclonal anti-D for RhD prophylaxis.

  4. Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study.

    PubMed

    Ruffatti, Amelia; Favaro, Maria; Hoxha, Ariela; Zambon, Alessandra; Marson, Piero; Del Ross, Teresa; Calligaro, Antonia; Tonello, Marta; Nardelli, Giovanni B

    2016-06-01

    Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. The Effect of Combination Therapy with Rituximab and Intravenous Immunoglobulin on the Progression of Chronic Antibody Mediated Rejection in Renal Transplant Recipients

    PubMed Central

    Yun, Jintak; Khvan, Marina; Park, Cheol Whee; Choi, Yeong Jin; Kim, Yong-Soo; Yang, Chul Woo

    2014-01-01

    The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18), and overall ΔeGFR decreased significantly to 0.4 ± 1.7 mL·min−1 ·1.73 m−2 per month 6 months after RIT compared to that observed 6 months before RIT (1.8 ± 1.0, P < 0.05). Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5 ± 2.5 versus 7.0 ± 3.5 protein/creatinine (g/g), P < 0.001). The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT. PMID:24741626

  6. Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open-Label, Randomized Control Study.

    PubMed

    Nanishi, Etsuro; Nishio, Hisanori; Takada, Hidetoshi; Yamamura, Kenichiro; Fukazawa, Mitsuharu; Furuno, Kenji; Mizuno, Yumi; Saigo, Kenjiro; Kadoya, Ryo; Ohbuchi, Noriko; Onoe, Yasuhiro; Yamashita, Hironori; Nakayama, Hideki; Hara, Takuya; Ohno, Takuro; Takahashi, Yasuhiko; Hatae, Ken; Harada, Tatsuo; Shimose, Takayuki; Kishimoto, Junji; Ohga, Shouichi; Hara, Toshiro

    2017-07-06

    We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. We conducted an open-label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty-one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [P=0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P=0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P=0.049). Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Bence Jones proteins and light chains of immunoglobulins. XI. A transient Bence Jones-related protein associated with corticosteroid therapy.

    PubMed Central

    Solomon, A; McLaughlin, C L; Capra, J D

    1975-01-01

    Urine specimens from patients with multiple myeloma and Bence Jones proteinuria frequently contain low molecular weight proteins which correspond either to the amino-terminal, variant half (VL) or to the carboxyl-terminal, constant half (CL) of the Bence Jones protein. Analyses of urine specimens from such patients who had received high doses of corticosteroids as part of their treatment regimen revealed that concomitantly with a decrease in Bence Jones protein excretion was the appearance of a low molecular weight protein related to the Bence Jones protein but not identical to the VL or to the CL. Analyses of daily urine specimens obtained from one such patient over an extended time period revealed that a reproducible chain of events occurred during a treatment regimen which included oral administration of 75 mg of prednisone daily for 7 consecutive days. The amount of Bence Jones protein excreted decreased progressively, and by the 5th day was usually less than 10% of the pretreatment value. The urine specimen obtained on the 6th day of treatment was virtually devoid of Bence Jones protein but contained a newly appearing protein whose electrophoretic mobility was distinct from that of the Bence Jones protein or its VL or CL. Cessation of corticosteroid therapy resulted in a prompt disappearance of the new protein and in a progressive increase in the amount of Bence Jones protein excreted. The new protein was isolated from the urine of this patient and was purified for comparative studies with Bence Jones protein and with the VL and CL prepared by specific enzymatic cleavage of the Bence Jones protein. These studies revealed that the new protein was most related antigenically to the CL, but could be distinguished immunochemically from the CL. This new protein, a component found in vivo related to the constant half of the light polypeptide chain, was designated CL, and was structurally 25 amino acid residues longer than the CL, that is, the amino-terminus of the

  8. Polyclonal immunoglobulins and hyperimmune globulins in prevention and management of infectious diseases.

    PubMed

    Hsu, Jennifer L; Safdar, Nasia

    2011-12-01

    Immunoglobulin therapy has a rich history of use in preventing and treating infectious diseases; however, clinical data on the efficacy of immunoglobulin is lacking for many infectious diseases. Immunoglobulin therapy is routinely used in postexposure prophylaxis for bacterial infections, including tetanus, botulism, and diphtheria, and viral infections, including hepatitis A and B and varicella. Immunoglobulin therapy has also been used in many severe and life-threatening infections where treatments are limited, including toxic shock syndrome, respiratory syncytial virus infection, and cytomegalovirus infection. The authors review the evidence for the use of immunoglobulin therapy in common adult infectious diseases. Copyright © 2011. Published by Elsevier Inc.

  9. Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders

    PubMed Central

    Yoon, Min-Suk; Gold, Ralf

    2015-01-01

    Objective: Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes. Methods: This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years. Results: One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed. Conclusions: Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders. PMID:26136842

  10. An update on the use of immunoglobulin for the treatment of immunodeficiency disorders

    PubMed Central

    Albin, Stephanie; Cunningham-Rundles, Charlotte

    2015-01-01

    For patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement. PMID:25428649

  11. A multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin compared with standard therapy for the treatment of transverse myelitis in adults and children (STRIVE).

    PubMed

    Absoud, Michael; Brex, Peter; Ciccarelli, Olga; Diribe, Onyinye; Giovannoni, Gavin; Hellier, Jennifer; Howe, Rosemary; Holland, Rachel; Kelly, Joanna; McCrone, Paul; Murphy, Caroline; Palace, Jackie; Pickles, Andrew; Pike, Michael; Robertson, Neil; Jacob, Anu; Lim, Ming

    2017-05-01

    Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. Primary outcome measure - American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures - ASIA motor and sensory scales, Expanded Disability Status Scale

  12. Quantitative immunoglobulins in adulthood.

    PubMed

    Crisp, Howard C; Quinn, James M

    2009-01-01

    Although age-related changes in serum immunoglobulins are well described in childhood, alterations in immunoglobulins in the elderly are less well described and published. This study was designed to better define expected immunoglobulin ranges and differences in adults of differing decades of life. Sera from 404 patients, aged 20-89 years old were analyzed for quantitative immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA). The patients with diagnoses or medications known to affect immunoglobulin levels were identified while blinded to their immunoglobulin levels. A two-factor ANOVA was performed using decade of life and gender on both the entire sample population as well as the subset without any disease or medication expected to alter immunoglobulin levels. A literature review was also performed on all English language articles evaluating quantitative immunoglobulin levels in adults >60 years old. For the entire population, IgM was found to be higher in women when compared with men (p < 0.001) and lower in the oldest sample population compared with the youngest population (p < 0.001). For the population without diseases known to affect immunoglobulin levels, the differences in IgM with gender and age were maintained (p < or = 0.001) and IgA levels were generally higher in the older population when compared with the younger population (p = 0.009). Elderly patients without disease known to affect immunoglobulin levels have higher serum IgA levels and lower serum IgM levels. Women have higher IgM levels than men throughout life. IgG levels are not significantly altered in an older population.

  13. Immunoglobulin E in histoplasmosis.

    PubMed Central

    Cox, R A; Arnold, D R

    1980-01-01

    Immunoglobulin M, G, A, and E serum levels were quantitated in 20 patients with active histoplasmosis (group I), 24 healthy subjects who were skin test positive to histoplasmin (group II), and 47 healthy persons who were skin test negative to histoplasmin (group III). The results established that patients with this disease have increased immunoglobulin G (P less than 0.05), immunoglobulin A (P less than 0.001), and immunoglobulin E (P less than 0.01) serum levels when compared with the 71 healthy subjects in groups II and III. PMID:7399706

  14. 7th International Immunoglobulin Conference: Immunoglobulin in clinical practice.

    PubMed

    Shapiro, R S; Borte, M

    2014-12-01

    Intravenous and subcutaneous immunoglobulins (IVIg and SCIg, respectively) are increasingly used in clinical practice, not only as replacement therapy but also for immunomodulation. Physicians have learned that primary immunodeficiency (PID) patients are susceptible to recurrent respiratory tract infections even when appropriately treated with immunoglobulin (Ig) therapy. Further investigation will establish whether a combined therapeutic approach including Ig dose optimization will prevent progressive lung disease in PID. The wear-off effects observed with IVIg can be minimized by adjusting the dosing regimen. It is also possible to avoid the cyclic wear-off following transition to SCIg administration. Consideration of benefit versus risk with Ig therapy includes evaluating the potential occurrence of thromboembolic and haemolytic events, which may be more frequent when Ig is administered in high doses and in the presence of pre-existing risk factors. The ability to select an administration method from IVIg, SCIg or hyaluronidase-facilitated SCIg infusions provides patient choice and alternatives if one or other administration route is not suitable for a patient. The evolution in indications, applications, and understanding of Ig therapy described here has reinforced the need for robust methods to prioritize Ig use.

  15. [Using the preparation "human immunoglobulin against herpes simplex virus type 1 for intramuscular injections" in the complex therapy of nervous system diseases].

    PubMed

    Rudenko, A O; Diachenko, N S; Nesterova, N V; Kurishchuk, K V; Berestova, T H; Zahorodnia, S D; Riads'ka, L S; Muravs'ka, L V; Andrieieva, O H; Baranova, H V

    2004-01-01

    The technology of obtaining of specific immunoglobulin for serotherapy of neuroinfection caused by virus herpes simplex 1 type was developed. The patients presented with the following diseases: arachnoencephalitis, encephalopolyradiculoneuritis, encephalomyelitis, encephalitis, arachnoiditis, polyneuropathy, encephalomyelopolyradiculoneuritis, meningoencephalitis. The study showed good tolerance and safety of the medicine, no adverse effects registered during the study. The assessed median score of the efficacy was 2.8 from 3. The obtained results suggest using the liquid form preparation for intramuscular injection "Immunoglobulin for treatment of neuroinfection caused by virus herpes simplex type 1". The Close corporation "Biofarma" located in Kyiv produces this medicine.

  16. Rapidly Progressive Interstitial Lung Disease Associated with Dermatomyositis Treated with Combination of Immunosuppressive Therapy, Direct Hemoperfusion with a Polymyxin B Immobilized Fiber Column and Intravenous Immunoglobulin.

    PubMed

    Takai, Motohisa; Katsurada, Naoko; Nakashita, Tamao; Misawa, Masafumi; Mochizuki, Takahiro; Kaneko, Norihiro; Motojima, Shinji; Aoshima, Masahiro

    2015-01-01

    Rapidly progressive interstitial lung disease (ILD) is associated with dermatomyositis (DM) and has a high mortality rate even with immunosuppressive agents. For such cases, there is no evidence on the combined effect of direct hemoperfusion with a Polymyxin B immobilized fiber column and intravenous immunoglobulin. We herein report a case of 61-year-old woman who presented with respiratory failure. She showed ILD associated with DM which did not improve with immunosuppressive agents, but was improved with the addition of both direct hemoperfusion with a Polymyxin B immobilized fiber column and intravenous immunoglobulin.

  17. Highly substituted phthalocyanine derivatives as potential photosensitizers for photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

    Cook, Michael J.; Fabris, Clara; Ometto, Cristina; Mayes, Denise A.; Jori, Giulio; McMurdo, Jim; Milanesi, Carla; Russell, David A.

    1994-03-01

    An octakis-decyl-substituted Zn(II)-phthalocyanine (ZnODPc) was prepared by chemical synthesis and was shown to possess favorable photophysical properties to act as a photodynamic agent. Intravenous injection of ZnODPc incorporated into Cremophor emulsions (1.2 or 2.4 mg/kg) to Balb/c mice bearing a MS-2 fibrosarcoma resulted in an efficient and selective accumulation of the phthalocyanine in the tumor. Illumination of the ZnODPc-loaded neoplastic lesion at 24 h after injection caused tumor regression as a result of both intracellular and intravascular damage.

  18. YMDD Motif Mutation Profile Among Patients Receiving Liver Transplant Due to Hepatitis B Virus Infection With Long Term Lamivudine/Immunoglobulin Therapy

    PubMed Central

    Rahimi, Rahim; Hosseini, Seyed Younes; Fattahi, Mohammad Reza; Sepehrimanesh, Masood; Safarpour, Alireza; Malekhosseini, Seyed Ali; Nejabat, Maryam; Khodadad, Mahboobeh; Ardebili, Maryam

    2015-01-01

    Background: Recurrence of Hepatitis B Virus infection in patients undergoing liver transplanted (LT) is a serious and often fatal problem. Lamivudine (LAM) and Hepatitis B Immunoglobulin (HBIG) are widely used to manage hepatitis B recurrence after liver transplantation. However, the outcomes in patients are less elucidated. Objectives: The current study aimed to evaluate the YMDD motif mutations profile among the patients undergoing LT infected with HBV and treated with LAM/HBIG at least for one year. Patients and Methods: Thirty patients with liver transplantation due to HBV were enrolled, while DNA level remained under detection limit of 50 IU/mL before transplantation and abnormal higher levels of liver enzymes after LT. The HBV genome detection was performed by two different Polymerase Chain Reaction methods following viral quantification by commercial Real-Time PCR. HbsAg detection, besides liver function tests were conducted as complementary assays. To assess nucleotide analogue mutations, the major part of polymerase gene (aa 80 - 240) was amplified by Nested-PCR, introduced to sequencing and subjected to phylogenetic analysis. Results: Totally, according to the laboratory criteria there were 13 cases with detectable HBV genome, while the mean liver enzyme levels were higher in recurrent patients and HBsAg was detected only in four out of the 13 cases. Phylogenetic analysis demonstrated that all isolated genomes belonged to genotype D. Critical M204I mutation, as a proof for resistance to LAM, was detected among 46% of the subjects and natural entecavir resistance (S202I) was also distinguished in one subject. Viral quantification showed higher titer in LAM resistant group in comparison to the group with undetectable drug resistance mutant (P > 0.05). Conclusions: Although the patients carrying M204I mutation were more likely to show lack of responses to LAM therapy, LAM replacing by other nucleoside/tide analogs plus HBIG maybe still effective in

  19. Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy--a case-control study of the outcome in children.

    PubMed

    Nigro, Giovanni; Adler, Stuart P; Parruti, Giustino; Anceschi, Maurizio M; Coclite, Eleonora; Pezone, Ilaria; Di Renzo, Gian Carlo

    2012-01-15

    Primary cytomegalovirus (CMV) infection early in gestation causes severe disease. Case patients were 32 congenitally infected children aged 1-5 years who had either hearing deficit and/or psychomotor retardation and whose mothers had a confirmed or probable primary CMV infection at ≤ 20 weeks' gestation. Control subjects were 32 congenitally infected normal children whose mothers had a confirmed primary infection at ≤ 20 weeks' gestation. Case patients and control subjects were matched by the weeks of maternal gestation (± 1 week) at the mother's infection and by the child's age (± 1 year) at evaluation. For the case patients and control subjects, the mean age was 3.0 years. The mean number of weeks of gestation at maternal infection was 11 weeks. The only risk factor for an affected child was the mother not receiving immunoglobulin (P = .001). Of the 32 case patients, only 4 mothers received CMV immunoglobulin, compared with 27 of the 32 mothers of control infants (adjusted odds ratio, 14 [95% confidence interval, 1.7-110]). The rate of both psychomotor retardation and hearing deficit decreased with immunoglobulin. These results support the efficacy of immunoglobulins for decreasing the severity of disabilities caused by fetal CMV infection after a primary maternal infection during pregnancy.

  20. The Influence of Drug Testing and Benefit-Based Distribution of Opioid Substitution Therapy on Drug Abstinence.

    PubMed

    Gabrovec, Branko

    2015-01-01

    The objective of our research was to discover whether the new approach to urine drug testing has a positive effect on users' abstinence, users' treatment, and their cooperation, while remaining user-friendly, and whether this approach is more cost-effective. The centers are focused on providing high-quality treatment within a cost-efficient program. In this study, we focus on the influence of drug testing and benefit-based distribution of opioid substitution therapy (BBDOST) on drug abstinence. The purpose of this study was to find any possible positive effect of modified distribution of the therapy and illicit drug testing on the number of users who are abstinent from illicit drugs and users who are not abstinent from illicit drugs as well as the users' opinion on BBDOST and testing. We are also interested in a difference in abstinence rates between those on BBDOST and those not receiving BBDOST. In 2010, the method of drug testing at the center was changed (less frequent and random drug testing) to enable its users faster access to BBDOST (take-home therapy). It was found that the number of drug-abstinent program participants has increased from initial 44.5% (2010) to 54.1% (2014). According to the program participants, the new method allows them to achieve and maintain abstinence from drugs more easily. In addition, they are also satisfied with the modified way of drug testing. This opinion does not change with age, gender, and acquired benefits.

  1. Secondary hypogammaglobulinemia in Waldmann's disease treated with subcutaneous immunoglobulins.

    PubMed

    Patuzzo, G; Tinazzi, E; Micheletti, M; Puccetti, A; Lunardi, C

    2016-03-01

    Primary intestinal lymphangiectasia (PIL) is rare disorder characterized by congenital malformation or obstruction of intestinal lymphatic drainage; it is responsible for protein losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL management. The administration of intravenous immunoglobulins does not always lead to satisfactory plasma levels and therefore the replacement therapy with immunoglobulins is controversial. We describe here the case of a patient with PIL and severe hypogammaglobulinemia treated with immunoglobulins. The striking aspect of this case is the clinical and serological benefit obtained with the subcutaneous compared to the intravenous immunoglobulins administration.

  2. [Glucose or sugar substitutes in parenteral infusions? The choice of carbohydrates in postoperative infusion therapy].

    PubMed

    Leutenegger, A F

    1980-12-18

    The aim of parenteral nutrition should be to optimise fluid, energy and nitrogen balance. In the post-traumatic or post-operative phase a stress induced glucose intolerance may occur and it may become difficult to meet the patient's energy requirements with glucose alone. For these reasons the use of sugar substitutes (fructose, sorbitol and xylitol) in combination with glucose is recommended as an alternative. Patients receiving a mixed sugar solution of glucose, fructose and xylitol at a ratio of 1:2:1 require less exogenous insulin and yet maintain a lower blood glucose concentration. Used in limited quantities, we encountered no side effects either in patients undergoing elective surgery or requiring intensive care.

  3. Impact of opioid substitution therapy for Scotland's prisoners on drug‐related deaths soon after prisoner release

    PubMed Central

    Fischbacher, Colin M.; Graham, Lesley; Fraser, Andrew

    2015-01-01

    Abstract Aim To assess whether the introduction of a prison‐based opioid substitution therapy (OST) policy was associated with a reduction in drug‐related deaths (DRD) within 14 days after prison release. Design Linkage of Scotland's prisoner database with death registrations to compare periods before (1996–2002) and after (2003–07) prison‐based OST was introduced. Setting All Scottish prisons. Participants People released from prison between 1 January 1996 and 8 October 2007 following an imprisonment of at least 14 days and at least 14 weeks after the preceding qualifying release. Measurements Risk of DRD in the 12 weeks following release; percentage of these DRDs which occurred during the first 14 days. Findings Before prison‐based OST (1996–2002), 305 DRDs occurred in the 12 weeks after 80 200 qualifying releases, 3.8 per 1000 releases [95% confidence interval (CI) = 3.4–4.2]; of these, 175 (57%) occurred in the first 14 days. After the introduction of prison‐based OST (2003–07), 154 DRDs occurred in the 12 weeks after 70 317 qualifying releases, a significantly reduced rate of 2.2 per 1000 releases (95% CI = 1.8–2.5). However, there was no change in the proportion which occurred in the first 14 days, either for all DRDs (87: 56%) or for opioid‐related DRDs. Conclusions Following the introduction of a prison‐based opioid substitution therapy (OST) policy in Scotland, the rate of drug‐related deaths in the 12 weeks following release fell by two‐fifths. However, the proportion of deaths that occurred in the first 14 days did not change appreciably, suggesting that in‐prison OST does not reduce early deaths after release. PMID:25940815

  4. Two year follow-up of Crohn's patients substituted to certolizumab anti-TNFa therapy: SAVANT 2.

    PubMed

    Motlis, Andrew; Boktor, Moheb; Jordan, Paul; Cvek, Urska; Trutschl, Marjan; Alexander, J Steven

    2017-08-09

    The effectiveness of ant-TNF 'biologic' therapy in is well supported in the management of moderate to severe Crohn's Disease (CD). Our first 'SAVANT' study was to our knowledge the first study report one- year outcomes in patients (n=60) who switched from previous anti-TNFa treatment to Cimzia/Certolizumab. This current study (SAVANT 2) follows up on longer term outcomes and provides additional clinical and biochemical data that may contribute to therapeutic responses. This IRB approved study was a retrospective analysis of the initial patients included in SAVANT 1. Patients who were switched to TNF antagonist Certolizumab as an alternative biologic were followed an additional year. Retrospective consideration of immunomodulator use, smoking status and clinical data were also evaluated. Of 60 patients with moderate-severe CD who participated in the SAVANT 1 study, 15 patients were excluded due to inadequate follow up. 45 patients were studied for a total of two years following substitution with Certolizumab from prior anti TNF agent therapy. Clinical remission at 1 year was 75% (45/60) and 55% (25/45) at the second year. At the second year, 5 more patients had discontinued Certolizumab due to worse disease or adverse events, indicating a cumulative two-year failure rate of 33% (20/60). Smoking and concomitant use of immunomodulators were similar between 'success' and 'failure' groups. SAVANT 2, the first study to report long term outcomes of switching from Infliximab or Adalimumab to Certolizumab showed that at 2 years, 25 patient's maintained clinical remission. The discontinuation rates were 25 and 11% at years 1 & 2 respectively. The 5 patients who lost responsiveness after the first year were women, the majority of smoked. Additional prospective studies to assess the appropriateness and feasibility of biologic substitution are still needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The Long Winding Road of Opioid Substitution Therapy Implementation in South-East Asia: Challenges to Scale Up

    PubMed Central

    Reid, Gary; Sharma, Mukta; Higgs, Peter

    2014-01-01

    The South-East Asia Region contains an estimated 400,000-500,000 people who inject drugs (PWID). HIV prevalence among PWID is commonly 20% or higher in Indonesia, Thailand, Myanmar and some regions of India. Opioid substitution therapy (OST) is an important HIV prevention intervention in this part of the world. However, key challenges and barriers to scale up of OST exist, including: pervasive stigma and discrimination towards PWID; criminalisation of drug use overshadowing a public health response; lack of political will and national commitment; low financial investment; focus towards traditional treatment models of detoxification and rehabilitation; inadequate dosing of OST; and poor monitoring and evaluation of programmes. Our review of local evidence highlights that OST can be successful within the Asian context. Such evidence should be utilised more widely to advocate for policy change and increased political commitment to ensure OST reaches substantially more drug users. Significance for public health Several countries in the World Health Organization South-East Asia Region can be commended for introducing opioid substitution therapy (OST) to address the ongoing HIV epidemic among people who inject drugs (PWID). Local evidence shows OST is an effective drug treatment approach in the Asian context given sufficient technical and institutional support. However, despite much progress, the number of OST dispensing sites and recipients remains totally inadequate in terms of impact upon the current HIV epidemic among PWID. Ongoing advocacy is needed if countries are to achieve the WHO’s target of 40% of PWID being dosed with OST. Greater political commitment a strengthened policy environment, capacity building for OST clinics, lessening the criminalisation of drug use and promoting a public health response will give many more PWID access to OST and slow the advance of the HIV epidemic. PMID:25170509

  6. Transcranial Magnetic Stimulation (TMS) Maintenance as a Substitute for Maintenance Electroconvulsive Therapy (ECT) - A Case Series

    PubMed Central

    Cristancho, Mario A.; Helmer, Amanda; Connolly, Ryan; Cristancho, Pilar; O’Reardon, John P.

    2012-01-01

    Background TMS is an efficacious, well–tolerated, non-invasive brain stimulation treatment for major depressive disorder. ECT is an effective maintenance treatment for depression but is not tolerated by some patients and declined by others. Objective We evaluated the effectiveness of TMS as a substitution strategy for successful maintenance ECT. Methods A consecutive clinical case series (n=6) of maintenance ECT patients were transitioned to maintenance TMS due to side effects from ECT or because of specific patient request and preference. Patients were in either full remission or had clinical response to ECT at the time of transition. Primary outcome was the change in the Beck Depression Inventory (BDI) score from initiation of TMS maintenance sessions to the last observation time point. Relapse of depressive symptoms was also documented. Results Mean age of patient was 64 years and most were female (n=5). The majority (5 out of 6) were diagnosed with major depressive disorder (MDD). Reasons for transition from ECT to TMS were in order of frequency: cognitive side effects, fear of general anesthesia, time burden, lack of remission with ECT, and stigma associated with ECT. The mean frequency of TMS sessions was 1 every 3.5 weeks . Based on BDI scores, all patients maintained or improved their clinical status achieved with ECT at 3 and 6 months of TMS treatment. At last observation (Range: 7 to 23 months) 4 patients maintained or improved their clinical status (total BDI score remained constant or decreased by 1–8 points). Two patients relapsed after 8 and 9 months. Stimulation was well tolerated with side effects limited to headache and scalp discomfort. Discussion In this case series TMS was effective and safe when used as a substitution strategy for successful maintenance ECT. PMID:23519219

  7. Successful treatment of systemic lupus erythematosus with subcutaneous immunoglobulin.

    PubMed

    Brasileiro, A; Fonseca Oliveira, J; Pinheiro, S; Paiva-Lopes, M J

    2016-05-01

    The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients.

  8. [The use of human immunoglobulins--adverse reactions].

    PubMed

    Pituch-Noworolska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2010-09-01

    The primary immunodeficiency, mainly humoral immunity, secondary immunodeficiency and autoimmune diseases are the indications for immunoglobulins substitution. The prolonged substitution in primary immunodeficiency includes regular intravenous infusion of immunoglobulins in 0.4-0.6 g/kg of body weight every 21-28 days. The purpose of such substitution is decrease of frequency and diminishes the clinical course of infections. The high-dose use of immunoglobulins (1-2 g/kg body weight) is preferred in autoimmune diseases based on suppressive and anti-inflammatory activity of immunoglobulins. The subcutaneous administration of immunoglobulins is an alternative to intravenous way, but the singular dose (0.1 g/kg body weight) is too low for suppressive and anti-inflammatory activity of immunoglobulins, so this substitution is indicated in primary immunodeficiency only. The adverse events of immunoglobulins differentiate because of time of occurrence and clinical character. The rapid symptoms occurred just after beginning of infusion and often present the clinical features of anaphylactoid reaction. During the infusion the occurring adverse symptoms are mild and the life-threatening situations are very rare. The next periods of typical adverse reaction are 24-48 hrs after infusion, 72 hrs and later. The mechanisms leading to adverse reaction to immunoglobulins are based on presence of IgG dimmers, stimulating high production of pro-inflammatory cytokines by immunocompetent cells. High level of cytokines is associated with high fever, chills, flu-like symptoms, feeling malaise and sick. The reaction of anti-IgA antibodies present in patient serum with IgA in immunoglobulins preparation is responsible for moderate and severe adverse clinical symptoms. The late adverse events present the symptoms of aseptic meningo-encephalitis. In case of adverse events the stopping of infusion, additions saline/ glucose infusion, anti-histaminic drugs of I and II generation and steroids

  9. Hyperalgesia in Heroin Dependent Patients and the Effects of Opioid Substitution Therapy

    PubMed Central

    Compton, Peggy; Canamar, Catherine P.; Hillhouse, Maureen; Ling, Walter

    2012-01-01

    Evidence suggests that patients on opiate maintenance therapy for the treatment of addiction present with opioid-induced hyperalgesia (OIH). This study compared the experimental (cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent adults randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy, with matched drug free controls (n = 21). Heroin-dependent participants were evaluated at baseline (treatment entry), medication (METH or BUP) stabilization (4-8 weeks), and chronic administration (12-18 weeks), at trough (just prior to dosing) and peak (3 hours after dosing) plasma levels. Collection of the control group’s pain responses occurred twice during a single session, three hours apart. Baseline comparisons indicate that heroin-dependent individuals demonstrate significantly shorter latencies to threshold and tolerance for cold-pressor pain than the control group. Across pain stimuli and time points, little change in pain responses were found over time, the exception being cold pressor pain tolerance, for which hyperalgesia significantly increased at trough METH/BUP levels in both groups as they stabilized in treatment. We conclude that heroin-dependent individuals are hyperalgesic, and that once stabilized in treatment, are not different in pain responses regardless of treatment agent. The effects of non-pharmacologic therapy and previous heroin use may explain increased hyperalgesia found with treatment. Perspective To better understand the clinical phenomenon of OIH, this article describes experimental pain responses of heroin-dependent participants both prior to and over the course of maintenance therapy with methadone or buprenorphine. Hyperalgesia is present with illicit and treatment opioid use, and does not appear to appreciably improve over the course of treatment. PMID:22424799

  10. Experiments to optimize enzyme substitution therapy in pancreatic duct-ligated pigs.

    PubMed

    Kammlott, E; Karthoff, J; Stemme, K; Gregory, P; Kamphues, J

    2005-01-01

    Ligation of the pancreatic duct in pigs leads to severe maldigestion and malabsorption of crude nutrients. Supplementation with 24 capsules of Creon (Solvay Pharmaceuticals GmbH, Hannover, Germany) per meal led to an increased digestibility of crude nutrients. With regard to optimization of the treatment of EPI no essential improvements can be achieved by adding omeprazol or lecithin to the diet. In pancreatic duct-ligated pigs the isolated addition of omeprazol led to an increase of the pre-caecal digestibility of crude fat and organic matter. With additional enzyme substitution, the application of omeprazol did not result in an improved fat digestibility. Isolated addition of lecithin to the diet resulted in a reduced total digestibility of crude fat. Offering the diet twice a day and using a higher frequency of enzyme applications (four or six instead of only two applications) had no effects on the digestibilty of crude fat or organic matter. According to the observations in pancreatic duct-ligated pigs, the addition of missing enzymes to the diet led to the best treatment results in EPI. Administration of omeprazol or a higher feeding frequency as well as the application of enzymes in small proportion of the whole meal or dosages given consecutively over the day showed no advantages. Furthermore, the present study suggests that the addition of lecithin cannot be recommended in EPI, when given diets with butter as the predominant fat source as in human dietetics.

  11. A novel dermal matrix generated from burned skin as a promising substitute for deep-degree burns therapy.

    PubMed

    Yu, Guanying; Ye, Lan; Tan, Wei; Zhu, Xuguo; Li, Yaonan; Jiang, Duyin

    2016-03-01

    The extensive skin defects induced by severe burns are dangerous and can be fatal. Currently, the most common therapy is tangential excision to remove the necrotic or denatured areas of skin, followed by skin grafting. Xenogeneic dermal substitutes, such as porcine acellular dermal matrix (ADM), are typically used to cover the burn wounds, and may accelerate wound healing. It is assumed that burned skin that still maintains partial biological activity may be recycled to construct an autologous acellular dermal matrix, termed 'deep‑degree burned dermal matrix (DDBDM)'. In theory, DDBDM may avoid the histoincompatibility issues associated with foreign or xenogeneic dermal matrices, and reduce therapy costs by making full use of discarded skin. In the present study, the collagens within prepared DDBDM were thickened, disorganized and partially fractured, however, they still maintained their reticular structure and tensile strength (P<0.01). Through microarray analysis of the cytokines present in ADM and DDBDM, it was determined that the DDBDM did not produce excessive levels of harmful burn toxins. Following 4 weeks of subcutaneous implantation, ADM and DDBDM were incompletely degraded and maintained good integrity. No significant inflammatory reaction or rejection were observed, which indicated that ADM and DDBDM have good histocompatibility. Therefore, DDBDM may be a useful material for the treatment of deep‑degree burns.

  12. A novel dermal matrix generated from burned skin as a promising substitute for deep-degree burns therapy

    PubMed Central

    YU, GUANYING; YE, LAN; TAN, WEI; ZHU, XUGUO; LI, YAONAN; JIANG, DUYIN

    2016-01-01

    The extensive skin defects induced by severe burns are dangerous and can be fatal. Currently, the most common therapy is tangential excision to remove the necrotic or denatured areas of skin, followed by skin grafting. Xenogeneic dermal substitutes, such as porcine acellular dermal matrix (ADM), are typically used to cover the burn wounds, and may accelerate wound healing. It is assumed that burned skin that still maintains partial biological activity may be recycled to construct an autologous acellular dermal matrix, termed 'deep-degree burned dermal matrix (DDBDM)'. In theory, DDBDM may avoid the histoincompatibility issues associated with foreign or xenogeneic dermal matrices, and reduce therapy costs by making full use of discarded skin. In the present study, the collagens within prepared DDBDM were thickened, disorganized and partially fractured, however, they still maintained their reticular structure and tensile strength (P<0.01). Through microarray analysis of the cytokines present in ADM and DDBDM, it was determined that the DDBDM did not produce excessive levels of harmful burn toxins. Following 4 weeks of subcutaneous implantation, ADM and DDBDM were incompletely degraded and maintained good integrity. No significant inflammatory reaction or rejection were observed, which indicated that ADM and DDBDM have good histocompatibility. Therefore, DDBDM may be a useful material for the treatment of deep-degree burns. PMID:26846279

  13. A Urinalysis-based Comparative Study of Treatment Adherence on Buprenorphine and Buprenorphine/Naloxone Combination Used as Opioid Substitution Therapy

    PubMed Central

    Jain, Raka

    2012-01-01

    Objective: The objective of the current study was to explore the difference in treatment adherence to directly supervised buprenorphine and take-home buprenorphine/ naloxone combination for opioid substitution therapy. Urinalysis findings have been used to check treatment adherence on opioid substitution therapy agent. Additionally the study aimed to explore the misuse rate of buprenorphine/naloxone combination based on urinalysis findings. Design: Cross-sectional chart review Setting: Laboratory of a tertiary care drug dependence treatment center Participants: One-year laboratory urinalysis records of a tertiary care, drug-dependence treatment center in India were analyzed. All the urine samples of subjects on opioid substitution therapy with buprenorphine or buprenorphine/naloxone combination were included in the study. Measurements: Urinalysis using thin layer chromatography for buprenorphine and naloxone. In between group difference for treatment adherence on buprenorphine and buprenorphine/ naloxone combination was done using Mantel-Haenszel test. Results: A higher proportion of samples from subjects on buprenorphine/naloxone tested positive for buprenorphine as compared to subjects on buprenorphine. Twelve (7.6%) urine samples from patients on buprenorphine/naloxone tested positive for naloxone. Conclusions: The findings of the current study suggest that buprenorphine/naloxone combination has a higher adherence rate as compared to buprenorphine when used for opioid substitution therapy. PMID:22984649

  14. [Use of a new sugar substitute, erithritol, in the diet therapy of type 2 diabetes patients].

    PubMed

    Sharafetdinov, Kh Kh; Gapparov, M M; Plotnikova, O A; Meshcheriakova, V A

    2002-01-01

    It was investigated the influence of a diet supplemented with erithritol on dynamic of basal and postprandial glycemia, lipid levels, blood pressure, body weight in 30 patients with type 2 diabetes. The results indicated that supplementation of erithritol (30 g/day) in traditional hypocaloric diet did not decrease the efficacy of dietary therapy in patients with type 2 diabetes. After ingestion 30 g erithritol dissolved in 300 ml of water, blood glucose did not show a marked increase in compared with 30 g isomalt (control).

  15. Equine immunoglobulins and organization of immunoglobulin genes.

    PubMed

    Walther, Stefanie; Rusitzka, Tamara V; Diesterbeck, Ulrike S; Czerny, Claus-Peter

    2015-12-01

    Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes.

  16. A review of substitute CT generation for MRI-only radiation therapy.

    PubMed

    Edmund, Jens M; Nyholm, Tufve

    2017-01-26

    Radiotherapy based on magnetic resonance imaging as the sole modality (MRI-only RT) is an area of growing scientific interest due to the increasing use of MRI for both target and normal tissue delineation and the development of MR based delivery systems. One major issue in MRI-only RT is the assignment of electron densities (ED) to MRI scans for dose calculation and a similar need for attenuation correction can be found for hybrid PET/MR systems. The ED assigned MRI scan is here named a substitute CT (sCT). In this review, we report on a collection of typical performance values for a number of main approaches encountered in the literature for sCT generation as compared to CT. A literature search in the Scopus database resulted in 254 papers which were included in this investigation. A final number of 50 contributions which fulfilled all inclusion criteria were categorized according to applied method, MRI sequence/contrast involved, number of subjects included and anatomical site investigated. The latter included brain, torso, prostate and phantoms. The contributions geometric and/or dosimetric performance metrics were also noted. The majority of studies are carried out on the brain for 5-10 patients with PET/MR applications in mind using a voxel based method. T1 weighted images are most commonly applied. The overall dosimetric agreement is in the order of 0.3-2.5%. A strict gamma criterion of 1% and 1mm has a range of passing rates from 68 to 94% while less strict criteria show pass rates > 98%. The mean absolute error (MAE) is between 80 and 200 HU for the brain and around 40 HU for the prostate. The Dice score for bone is between 0.5 and 0.95. The specificity and sensitivity is reported in the upper 80s% for both quantities and correctly classified voxels average around 84%. The review shows that a variety of promising approaches exist that seem clinical acceptable even with standard clinical MRI sequences. A consistent reference frame for method benchmarking

  17. 6th International Immunoglobulin Symposium: poster presentations.

    PubMed

    Fernandez-Cruz, E; Kaveri, S V; Peter, H-H; Durandy, A; Cantoni, N; Quinti, I; Sorensen, R; Bussel, J B; Danieli, M G; Winkelmann, A; Bayry, J; Käsermann, F; Späth, P; Helbert, M; Salama, A; van Schaik, I N; Yuki, N

    2009-12-01

    The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunodeficiencies, autoimmunity and basic research. The immunodeficiency presentations dealt with novel, rare class-switch recombination (CSR) deficiencies, attenuation of adverse events following IVIg treatment, association of immunoglobulin (Ig)G trough levels and protection against acute infection in patients with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID), and the reduction of class-switched memory B cells in patients with specific antibody deficiency (SAD). The impact of intravenous immunoglobulin on fetal alloimmune thrombocytopenia, pregnancy and postpartum-related relapses in multiple sclerosis and refractory myositis, as well as experiences with subcutaneous immunoglobulin in patients with multi-focal motor neuropathy, were the topics presented in the autoimmunity session. The interaction of dendritic cell (DC)-SIGN and alpha2,6-sialylated IgG Fc and its impact on human DCs, the enrichment of sialylated IgG in plasma-derived IgG, as wells as prion surveillance and monitoring of anti-measles titres in immunoglobulin products, were covered in the basic science session. In summary, the presentations illustrated the breadth of immunoglobulin therapy usage and highlighted the progress that is being made in diverse areas of basic and clinical research, extending our understanding of the mechanisms of immunoglobulin action and contributing to improved patient care.

  18. Recovery from lipodystrophy in HIV-infected children after substitution of stavudine with zidovudine in a non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

    PubMed

    Aurpibul, Linda; Puthanakit, Thanyawee; Taejaroenkul, Sineenart; Sirisanthana, Thira; Sirisanthana, Virat

    2012-04-01

    Substitution of stavudine with zidovudine may lead to recovery from lipodystrophy (LD) in HIV-infected children. We prospectively followed HIV-infected children enrolled in an earlier LD study conducted between 2002 and 2004 at Chiang Mai University Hospital in northern Thailand. In 2006, stavudine was substituted with zidovudine. All children were evaluated by a clinical LD checklist modified from that of the European Pediatric LD study group together with waist/hip measurement at baseline and 24, 48, 72, and 96 weeks after substitution. The waist-to-hip ratios were converted to age- and sex-adjusted z scores based on normal ranges in healthy Thai children. Forty-five lipodystrophic children with 36 episodes of lipohypertrophy and 22 episodes of lipoatrophy were enrolled. By weeks 48 and 96 after substitution, 40% and 47% of lipohypertrophy resolved, whereas 59% and 73% of lipoatrophy resolved, respectively. The rate of resolution of lipoatrophy was higher than that of lipohypertrophy at 48 weeks after substitution and thereafter. Ninety-six weeks after changing to zidovudine therapy, 8 children still had LD (1 with both lipoatrophy and lipohypertrophy, 7 with lipohypertrophy). No clinically significant hematologic adverse event was observed. Substitution of stavudine with zidovudine resulted in decreased severity or resolution of LD among HIV-infected children and adolescents.

  19. Nutritional hepatic iron overload is not prevented by parenteral hepcidin substitution therapy in mice.

    PubMed

    Sillerova, Tereza; Zivny, Jan; Vyoral, Daniel; Petrak, Jiri

    2012-11-28

    The peptide hormone hepcidin functions as a negative regulator of intestinal Fe absorption and Fe recycling. Since its discovery as a systemic negative regulator of Fe metabolism, hepcidin has attracted enormous interest as a potential drug for the treatment and/or prevention of several forms of Fe overload. We therefore tested whether multiple doses of intraperitoneally administered synthetic renatured hepcidin can prevent hepatic Fe loading in mice concurrently fed an Fe-rich diet, and whether the same treatment affects hepatic Fe stores in mice fed a normal diet. Cohorts of male mice were fed either a normal defined diet (180 parts per million Fe) or an Fe-rich diet (the same diet supplemented with 2 % carbonyl iron for 2 weeks). Concurrently, half of the animals in each diet group received 100 μg of renatured hepcidin intraperitoneally every 12 h, for the same 2-week period. The second half of the animals received PBS only. The renatured synthetic hepcidin demonstrated biological activity by significantly decreasing transferrin saturation, which lasted for up to 24 h after a single hepcidin dose. However, the 14 d intraperitoneal hepcidin therapy did not prevent hepatic Fe overload in mice fed the Fe-rich diet, nor did it affect hepatic Fe stores in mice fed the normal diet. Both hepcidin agonists and antagonists are expected to have broad therapeutic potential. The absence of an effect of biologically active hepcidin on hepatic Fe loading shows the need for thorough future studies on the hepcidin regulation of Fe absorption and tissue distribution.

  20. "Bureaucracy & Beliefs": Assessing the Barriers to Accessing Opioid Substitution Therapy by People Who Inject Drugs in Ukraine.

    PubMed

    Bojko, Martha J; Mazhnaya, Alyona; Makarenko, Iuliia; Marcus, Ruthanne; Dvoriak, Sergii; Islam, Zahedul; Altice, Frederick L

    Opioid substitution therapy (OST) is an evidence-based HIV prevention strategy for people who inject drugs (PWIDs). Yet, only 2.7% of Ukraine's estimated 310,000 PWIDs receive it despite free treatment since 2004. The multi-level barriers to entering OST among opioid dependent PWIDs have not been examined in Ukraine. A multi-year mixed methods implementation science project included focus group discussions with 199 PWIDs in 5 major Ukrainian cities in 2013 covering drug treatment attitudes and beliefs and knowledge of and experiences with OST. Data were transcribed, translated into English and coded. Coded segments related to OST access, entry, knowledge, beliefs and attitudes were analyzed among 41 PWIDs who were eligible for but had never received OST. A number of programmatic and structural barriers were mentioned by participants as barriers to entry to OST, including compulsory drug user registration, waiting lists, and limited number of treatment slots. Participants also voiced strong negative attitudes and beliefs about OST, especially methadone. Their perceptions about methadone's side effects as well as the stigma of being a methadone client were expressed as obstacles to treatment. Despite expressed interest in treatment, Ukrainian OST-naïve PWIDs evade OST for reasons that can be addressed through changes in program-level and governmental policies and social-marketing campaigns. Voiced OST barriers can effectively inform public health and policy directives related to HIV prevention and treatment in Ukraine to improve evidence-based treatment access and availability.

  1. Challenges to Implementing Opioid Substitution Therapy in Ukrainian Prisons: Personnel Attitudes Toward Addiction, Treatment, and People With HIV/AIDS

    PubMed Central

    Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A.; Taxman, Faye S.; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L.

    2015-01-01

    Background Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine’s Criminal Justice System (CJS) have been thwarted. Methods To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results Results revealed that Ukrainian CJS workers’ attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. Conclusion In Ukraine, adoption of OST is more influenced by ideological biases and prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this assessment will help direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. PMID:25620732

  2. Challenges to implementing opioid substitution therapy in Ukrainian prisons: Personnel attitudes toward addiction, treatment, and people with HIV/AIDS.

    PubMed

    Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A; Taxman, Faye S; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L

    2015-03-01

    Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine's Criminal Justice System (CJS) have been thwarted. To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results revealed that Ukrainian CJS workers' attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. In Ukraine, adoption of OST is more influenced by myths, biases and ideological prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this study will help to direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. [Case of anti-TPO/gliadin antibody-positive cerebellar atrophy that responded to intravenous immunoglobulin therapy begun 16 years after onset].

    PubMed

    Tanaka, Nobuyuki; Otake, Hiroaki; Ito, Suguru; Niiyama, Kazuhide; Nanri, Kazunori

    2012-01-01

    We present a case of slowly progressive gait ataxia with a 16-year history in an 87-year-old woman. In 1994 she became aware of a slight unsteadiness while walking and cortical cerebellar atrophy was diagnosed. She had no familial history of neurological disorders. In 2007, idiopathic thrombocytopenic purpura (ITP) was diagnosed. The symptoms gradually worsened, and she was admitted in 2010 because she could not walk without support. MRI voxel-based morphometry (VBM) imaging showed atrophy of the entire cerebellum, and SPECT using eZIS showed reduced perfusion in the same regions. Her blood was positive for both anti-TPO antibody (42 IU/ml) and anti-gliadin antibody (20.2 EU). We therefore diagnosed autoimmune cerebellar atrophy. The patient showed a positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. Her posture and gait disturbance scores on the International Cooperative Ataxia Rating Scale had improved from 20 to 9. Even 16 years after onset, intravenous immunoglobulins were effective. In cases of prolonged disease, immunotherapy can be effective in autoimmune cerebellar atrophy and should not be excluded from the treatment choices.

  4. Rabbit anti-rabies immunoglobulins production and evaluation.

    PubMed

    Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

    2011-04-01

    Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

  5. IN VIVO PERFORMANCE OF THE EXPERIMENTAL CHITOSAN BASED BONE SUBSTITUTE--ADVANCED THERAPY MEDICINAL PRODUCT. A STUDY IN SHEEP.

    PubMed

    Bojar, Witold; Kucharska, Martyna; Ciach, Tomasz; Paśnik, Iwona; Korobowicz, Elzbieta; Patkowski, Krzysztof; Gruszecki, Tomasz; Szymanowski, Marek; Rzodkiewicz, Przemysław

    2016-01-01

    When evaluating a novel bone substitute material, advanced in vivo testing is an important step in development and safety affirmation. Sheep seems to be a valuable model for human bone turnover and remodeling activity. The experimental material composed with the stem cells is an advanced therapy medicinal product (acc. to EC Regulation 1394/2007). Our research focuses on histological differences in bone formation (guided bone regeneration--GBR) in sheep maxillas after implantation of the new chitosan/tricalcium phosphate/alginate (CH/TCP/Alg) biomaterial in comparison to the commercially available xenogenic bone graft and a/m enhanced with the stem cells isolated from the adipose tissue. Twelve adult female sheep of BCP synthetic line, weighing 60-70 kg were used for the study. The 11 mm diameter defects in maxilla bone were prepared with a trephine bur under general anesthesia and then filled with the bone substitute materials: CH/TCP/Alg, BioOss Collagen, Geistlich AG (BO), CH/TCP/Alg composed with the stem cells (CH/S) or left just with the blood clot (BC). Inbreeding cycle of the animals terminated at 4 months after surgery. Dissected specimens of the maxilla were evaluated histologically and preliminary under microtomography. Histological evaluation showed early new bone formation observed around the experimental biomaterial and commercially available BO. There were no features of purulent inflammation and necrosis, or granulomatous inflammation. Microscopic examination after 4 months following the surgery revealed trabecular bone formation around chitosan based bone graft and xenogenic material with no significant inflammatory response. Different results--no bone recreation were observed for the negative control (BC). In conclusion, the tested materials (CH/TCP/Alg and BO) showed a high degree of biocompatibility and some osteoconductivity in comparison with the control group. Although the handiness, granules size and setting time of CHffCP/Alg may be refined

  6. Therapy discontinuation or substitution in patients with cardiovascular disease, switching among different products of the same off-patent active substance: a 'real-world' retrospective cohort study.

    PubMed

    Degli Esposti, Luca; Sangiorgi, Diego; Buda, Stefano; Degli Esposti, Ezio; Scaglione, Francesco

    2016-11-02

    The present study investigated the effects of switching to different products of the same off-patent active substance (brand name or generic) on therapy discontinuation or substitution with another molecule of the same class, in patients with cardiovascular disease treated with statins and antihypertensives in a 'real-world' setting. A retrospective cohort study in a 'real-world' setting. Analysis of data performed by integrating administrative databases that included approximately two million individuals who are assisted by the National Health System from three Local Health Units located in three different regions of Italy. All patients aged ≥18 years with at least one prescription of simvastatin, ramipril or amlodipine in the period 1 January to 31 December 2010 were included and followed up for 2 years. Prescription refills occurring during follow-up were evaluated. Frequency of discontinuation of therapy or substitution with another molecule of the same class (eg, from simvastatin to a different statin) during follow-up was identified. During follow-up, therapy discontinuation or substitution was found to be more frequent in patients switching to a different product of the same active substance compared with non-switching patients (11.5% vs 10.8% and 22.2% vs 20.8% (p=0.002), respectively, in the simvastatin group; 4.0% vs 3.5% and 24.6% vs 22.7% (p<0.001), respectively, in the amlodipine group). In the ramipril group, 8% of patients undertook a therapy substitution to another molecule; no trend towards a lower percentage of substitution was observed in the non-switching group, while 18% of patients discontinued treatment, with a significant difference in favour of patients not switching. These findings were partially confirmed by multivariate analysis. Switches among products of the same active substance are quite common in patients with cardiovascular disease. Our study suggests that switching may expose patients to a higher risk of therapy

  7. Immunoglobulin in intestinal secretions.

    PubMed

    Cutropia de Guirao, C

    1977-12-01

    The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.

  8. Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect.

    PubMed

    Bleeker, W K; Teeling, J L; Hack, C E

    2001-11-15

    Recently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the current study, in vivo experiments were performed with mice in which autoantibody production was mimicked by continuous infusion of monoclonal antibodies. In this model, a single dose of IVIG reduced the plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal antibody (mAb) by approximately 40% after 3 days, whereas the concentration of an IgA mAb was not affected. To extrapolate these findings to humans, a computational model for IgG clearance was established that accurately predicted the time course and magnitude of the decrease in IgG plasma levels observed in mice. Adapted for humans, this model predicted a gradually occurring decrease in autoantibody levels after IVIG administration (2 g/kg), with a maximum reduction of approximately 25% after 3 to 4 weeks and a continued decrease of several months. In conclusion, a single high dose of IVIG induces a relatively small but long-lasting reduction of autoantibody levels by accelerated IgG clearance. This mechanism has clinical relevance in the sense that it can fully explain, as the sole mechanism, the gradual decrease in autoantibody levels observed in several patient studies. However, in some clinical studies, larger or more rapid effects have been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as down-regulation of antibody production or neutralization by anti-idiotypic antibodies.

  9. Adjustment of L-T4 substitutive therapy in pregnant women with subclinical, overt or post-ablative hypothyroidism.

    PubMed

    Verga, Uberta; Bergamaschi, Silvia; Cortelazzi, Donatella; Ronzoni, Stefania; Marconi, Anna Maria; Beck-Peccoz, Paolo

    2009-05-01

    Maternal hyperthyrotropinaemia is associated with an increased risk of adverse maternal and neonatal outcomes. Physiological changes during pregnancy require an increased production of thyroid hormones (or an increase in daily substitutive doses of L-T4 in hypothyroid patients) to meet the maternal and foetal needs. The aim of the study was to evaluate variations of substitutive L-T4 doses that are able to maintain serum TSH between 0.5 and 2.5 mU/l in pregnant women with subclinical- (SH), overt- (OH) and post-ablative (PH) hypothyroidism. This was a retrospective study on hypothyroid pregnant women referred to the out-patient department between January 2004 and December 2006. A total of 185 pregnant women were studied during gestation; 155 patients (76 SH, 52 OH, 27 PH) were already on L-T4 before conception and 30 (SH) started L-T4 therapy during gestation. Thyroid function and body weight were evaluated every 4-6 weeks. In the group of patients already treated before conception, 134 (86.5%) increased L-T4 doses during gestation one or more times, eight (6%) reached a definitive therapeutic dosage within the 12th week of pregnancy, 64 (47.8%) within the 20th week and 62 (46.2%) within the 31st week. This initial L-T4 increase at the first evaluation during pregnancy was 22.9 +/- 9.8 microg/day. The final L-T4 doses were significantly different depending on the aetiology, being 101.0 +/- 24.6 microg/day in SH, 136.8 +/- 30.4 microg/day in OH and 159.0 +/- 24.6 microg/day in PH. The per cent increase of L-T4, expressed as Delta% of absolute dose, was +70% in SH, +45% in OH and +49% in PH as compared to baseline dose. In SH patients diagnosed during gestation, the starting L-T4 dose was higher than L-T4 dose before pregnancy of SH patients already treated (75.4 +/- 14.5 and 63.2 +/- 20.1 microg/day, respectively), whereas the final doses were similar. L-T4 dose was increased one or more times in 24 patients (80%), 8 reached the definitive dosage within the second

  10. “Bureaucracy & Beliefs”: Assessing the Barriers to Accessing Opioid Substitution Therapy by People Who Inject Drugs in Ukraine

    PubMed Central

    Bojko, Martha J.; Mazhnaya, Alyona; Makarenko, Iuliia; Marcus, Ruthanne; Dvoriak, Sergii; Islam, Zahedul; Altice, Frederick L.

    2016-01-01

    Aims Opioid substitution therapy (OST) is an evidence-based HIV prevention strategy for people who inject drugs (PWIDs). Yet, only 2.7% of Ukraine’s estimated 310,000 PWIDs receive it despite free treatment since 2004. The multi-level barriers to entering OST among opioid dependent PWIDs have not been examined in Ukraine. Methods A multi-year mixed methods implementation science project included focus group discussions with 199 PWIDs in 5 major Ukrainian cities in 2013 covering drug treatment attitudes and beliefs and knowledge of and experiences with OST. Data were transcribed, translated into English and coded. Coded segments related to OST access, entry, knowledge, beliefs and attitudes were analyzed among 41 PWIDs who were eligible for but had never received OST. Findings A number of programmatic and structural barriers were mentioned by participants as barriers to entry to OST, including compulsory drug user registration, waiting lists, and limited number of treatment slots. Participants also voiced strong negative attitudes and beliefs about OST, especially methadone. Their perceptions about methadone’s side effects as well as the stigma of being a methadone client were expressed as obstacles to treatment. Conclusions Despite expressed interest in treatment, Ukrainian OST-naïve PWIDs evade OST for reasons that can be addressed through changes in program-level and governmental policies and social-marketing campaigns. Voiced OST barriers can effectively inform public health and policy directives related to HIV prevention and treatment in Ukraine to improve evidence-based treatment access and availability. PMID:27087758

  11. Determination of buprenorphine, norbuprenorphine and naloxone in fingernail clippings and urine of patients under opioid substitution therapy.

    PubMed

    Tzatzarakis, Manolis N; Vakonaki, Elena; Kovatsi, Leda; Belivanis, Stamatis; Mantsi, Mary; Alegakis, Athanasios; Liesivuori, Jyrki; Tsatsakis, Aristidis M

    2015-05-01

    The aim of this study was to develop and validate a method for the determination of buprenorphine (BUP), norbuprenorphine (NBUP) and naloxone (NAL) in fingernails and urine samples collected from former heroin users under suboxone substitution therapy. The analytes were extracted by solid-liquid or solid-phase extraction and were analyzed by liquid chromatography-mass spectrometry. The validation of the analytical methods developed included linearity, recovery, accuracy, precision, ion suppression, sensitivity of interfaces and limits of determination and quantification. The validated methods were applied to samples from 46 individuals. The majority of the urine samples were positive for all analytes (93.5% for BUP, 95.7% for NBUP and 84.8% for NAL). In nails, a higher detection rate was observed for NBUP and BUP (89.1%), compared with NAL (10.9%). The median values of the NBUP/BUP and the NAL/BUP ratio were 2.5 and 0.3 in urine and 0.8 and 0.3 in nails, respectively. A statistically significant correlation was found between the BUP, NBUP and total BUP (BUP and NBUP) concentrations in urine and those in nails. A weak correlation was observed between the daily dose (mg/day) and total BUP (P = 0.069), or NBUP (P = 0.072) concentrations in urine. In contrast, a strong correlation was found between the total amount of BUP administered during the last 12 months and total BUP (P = 0.038), or NBUP (P = 0.023) concentrations in urine. Moreover urine BUP, NBUP and total BUP concentrations correlated significantly. Our study demonstrated successfully the application of the developed method for the determination of the three analytes in urine and nails. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Linear immunoglobulin A bullous dermatosis.

    PubMed

    Fortuna, Giulio; Marinkovich, M Peter

    2012-01-01

    Linear immunoglobulin A (IgA) bullous dermatosis, also known as linear IgA disease, is an autoimmune mucocutaneous disorder characterized by subepithelial bullae, with IgA autoantibodies directed against several different antigens in the basement membrane zone. Its immunopathologic characteristic resides in the presence of a continuous linear IgA deposit along the basement membrane zone, which is clearly visible on direct immunofluorescence. This disorder shows different clinical features and distribution when adult-onset of linear IgA disease is compared with childhood-onset. Diagnosis is achieved via clinical, histopathologic, and immunopathologic examinations. Two common therapies are dapsone and sulfapyridine, which reduce the inflammatory response and achieve disease remission in a variable period of time.

  13. Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment.

    PubMed

    Patel, Shiven S; Fergeson, Jennifer E; Glaum, Mark C; Lockey, Richard F

    2016-01-01

    Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.

  14. Total remission of thymus carcinoma after treatment with intravenous immunoglobulin.

    PubMed

    Murie-Fernández, Manuel; Gurpide, Alfonso; de la Cruz, Susana; de Castro, Purificación

    2006-09-01

    We report the case of a 42 year-old woman with myasthenia gravis associated with a malignant thymoma. Despite surgery, chemotherapy and radiotherapy, the thymoma showed soft tissues, pleural and mediastinic progression. Unexpectedly, a complete remission of the thymoma was confirmed by FDG-PET after four cycles of immunoglobulins, administered as treatment for a myasthenic crisis. To our knowledge this is the first case report of complete remission of a malignant thymoma with immunoglobulin therapy.

  15. [Selective immunoglobulin A deficiency].

    PubMed

    Binek, Alicja; Jarosz-Chobot, Przemysława

    2012-01-01

    Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future.

  16. THE IMMUNOGLOBULINS OF MICE

    PubMed Central

    Fahey, John L.; Wunderlich, John; Mishell, Robert

    1964-01-01

    Two classes of 7S γ-globulins are identified in normal mouse serum and are designated 7S γ2-globulins and 7S γ1-globulins. These two immunoglobulin classes are similar in size. They differ in range of electrophoretic mobility, in specific antigenic determinants, and in genetically determined isoantigens. Four classes of immunoglobulins in mouse serum, i.e. 7S γ2-, 7S γ1-, γ1A (β2A), and γM-globulins, were shown to have antibody activity. Each class was characterized and shown to have distinctive immunochemical and physicochemical properties. The genetically determined isoantigens, Iga-1 and Iga-2, were shown to be present only on 7S γ2-globulin molecules. PMID:14208249

  17. [Avidity of polyreactive immunoglobulins].

    PubMed

    Bobrovnik, S A

    2014-01-01

    An analysis of the mechanism of interaction between polyreactive immunoglobulins (PRIG) and antigen was conducted and it was shown that most of the traditional methods of antibody affinity evaluation are not applicable for PRIG affinity. The comparative assessment of the mouse and human PRIG avidity against ovalbumin and horse myoglobin and the avidity of specific monoclonal antibodies against ovalbumin have shown that the avidity of PRIG not only is much less than the avidity of monoclonal antibodies but even exceeds it.

  18. Efficacy of induction therapy with ATG and intravenous immunoglobulins in patients with low-level donor-specific HLA-antibodies.

    PubMed

    Bächler, K; Amico, P; Hönger, G; Bielmann, D; Hopfer, H; Mihatsch, M J; Steiger, J; Schaub, S

    2010-05-01

    Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.

  19. Subcutaneous immunoglobulin (16 or 20%) therapy in obese patients with primary immunodeficiency: a retrospective analysis of administration by infusion pump or subcutaneous rapid push.

    PubMed

    Shapiro, R

    2013-08-01

    A retrospective chart review was conducted at a single centre, capturing data on 173 primary immunodeficiency disease (PIDD) patients, including 40 obese patients, using subcutaneous administration of immunoglobulin (Ig) (SCIG) (16 or 20%) delivered by infusion pump or subcutaneous (s.c.) rapid push. Patients previously using Ig administered as intravenous (i.v.) infusions (IVIG) were converted to SCIG dosing on a 1:1 basis. In both obese and non-obese patients, mean serum Ig levels were higher during SCIG administration (steady state) compared with IVIG administration (trough values). Similar SCIG dose : serum IgG level relationships were observed between obese and non-obese patients, suggesting the consistent bioavailability of SCIG regardless of body mass index (BMI). The mean SCIG volume per dosing site and the mean number of dosing days per week were greater with s.c. rapid push compared with infusion pump in this cohort, but the mean number of sites per infusion session was lower with s.c. rapid push. Both methods were well tolerated. The use of 20 versus 16% SCIG in obese patients improved dosing efficiency, resulting in smaller weekly volumes (54·7 versus 74·5 ml/week) and dosing on fewer days per week (2·3 versus 3·4 days). These data do not suggest a need for SCIG dosing adjustments in obese individuals relative to non-obese patients. The administration of SCIG using either infusion pump or s.c. rapid push is a practical and well-tolerated alternative to IVIG in obese patients. Offering various administration techniques provides a greater opportunity for treatment satisfaction and patient empowerment, which may support high levels of patient compliance.

  20. Immunoglobulin genes of the turtles.

    PubMed

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-03-01

    The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.

  1. Effects of substitution and high-dose thyroid hormone therapy on deiodination, sulfoconjugation, and tissue thyroid hormone levels in prolonged critically ill rabbits.

    PubMed

    Debaveye, Yves; Ellger, Björn; Mebis, Liese; Visser, Theo J; Darras, Veerle M; Van den Berghe, Greet

    2008-08-01

    To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3'-diiodothyronine (T(2)) and T(4)S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T(4) and T(3), either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T(3) (P=0.006), hepatic T(3) (P=0.02), and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T(4) (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T(3) and tissue T(3)/reverse T(3) ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T(2). Plasma T(4)S was increased only by T(4) in high dose. We conclude that in prolonged critically ill rabbits, low plasma T(3) levels were associated with low liver and kidney T(3) levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation.

  2. Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect.

    PubMed

    Sala, Pierguido; Colatutto, Antonio; Fabbro, Dora; Mariuzzi, Laura; Marzinotto, Stefania; Toffoletto, Barbara; Perosa, Anna R; Damante, Giuseppe

    2016-04-01

    Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens.

  3. Gene Augmentation Therapy for a Missense Substitution in the cGMP-Binding Domain of Ovine CNGA3 Gene Restores Vision in Day-Blind Sheep.

    PubMed

    Gootwine, Elisha; Abu-Siam, Mazen; Obolensky, Alexey; Rosov, Alex; Honig, Hen; Nitzan, Tali; Shirak, Andrey; Ezra-Elia, Raaya; Yamin, Esther; Banin, Eyal; Averbukh, Edward; Hauswirth, William W; Ofri, Ron; Seroussi, Eyal

    2017-03-01

    Applying CNGA3 gene augmentation therapy to cure a novel causative mutation underlying achromatopsia (ACHM) in sheep. Impaired vision that spontaneously appeared in newborn lambs was characterized by behavioral, electroretinographic (ERG), and histologic techniques. Deep-sequencing reads of an affected lamb and an unaffected lamb were compared within conserved genomic regions orthologous to human genes involved in similar visual impairment. Observed nonsynonymous amino acid substitutions were classified by their deleteriousness score. The putative causative mutation was assessed by producing compound CNGA3 heterozygotes and applying gene augmentation therapy using the orthologous human cDNA. Behavioral assessment revealed day blindness, and subsequent ERG examination showed attenuated photopic responses. Histologic and immunohistochemical examination of affected sheep eyes did not reveal degeneration, and cone photoreceptors expressing CNGA3 were present. Bioinformatics and sequencing analyses suggested a c.1618G>A, p.Gly540Ser substitution in the GMP-binding domain of CNGA3 as the causative mutation. This was confirmed by genetic concordance test and by genetic complementation experiment: All five compound CNGA3 heterozygotes, carrying both p.Arg236* and p.Gly540Ser mutations in CNGA3, were day-blind. Furthermore, subretinal delivery of the intact human CNGA3 gene using an adeno-associated viral vector (AAV) restored photopic vision in two affected p.Gly540Ser homozygous rams. The c.1618G>A, p.Gly540Ser substitution in CNGA3 was identified as the causative mutation for a novel form of ACHM in Awassi sheep. Gene augmentation therapy restored vision in the affected sheep. This novel mutation provides a large-animal model that is valid for most human CNGA3 ACHM patients; the majority of them carry missense rather than premature-termination mutations.

  4. Gene Augmentation Therapy for a Missense Substitution in the cGMP-Binding Domain of Ovine CNGA3 Gene Restores Vision in Day-Blind Sheep

    PubMed Central

    Gootwine, Elisha; Abu-Siam, Mazen; Obolensky, Alexey; Rosov, Alex; Honig, Hen; Nitzan, Tali; Shirak, Andrey; Ezra-Elia, Raaya; Yamin, Esther; Banin, Eyal; Averbukh, Edward; Hauswirth, William W.; Ofri, Ron; Seroussi, Eyal

    2017-01-01

    Purpose Applying CNGA3 gene augmentation therapy to cure a novel causative mutation underlying achromatopsia (ACHM) in sheep. Methods Impaired vision that spontaneously appeared in newborn lambs was characterized by behavioral, electroretinographic (ERG), and histologic techniques. Deep-sequencing reads of an affected lamb and an unaffected lamb were compared within conserved genomic regions orthologous to human genes involved in similar visual impairment. Observed nonsynonymous amino acid substitutions were classified by their deleteriousness score. The putative causative mutation was assessed by producing compound CNGA3 heterozygotes and applying gene augmentation therapy using the orthologous human cDNA. Results Behavioral assessment revealed day blindness, and subsequent ERG examination showed attenuated photopic responses. Histologic and immunohistochemical examination of affected sheep eyes did not reveal degeneration, and cone photoreceptors expressing CNGA3 were present. Bioinformatics and sequencing analyses suggested a c.1618G>A, p.Gly540Ser substitution in the GMP-binding domain of CNGA3 as the causative mutation. This was confirmed by genetic concordance test and by genetic complementation experiment: All five compound CNGA3 heterozygotes, carrying both p.Arg236* and p.Gly540Ser mutations in CNGA3, were day-blind. Furthermore, subretinal delivery of the intact human CNGA3 gene using an adeno-associated viral vector (AAV) restored photopic vision in two affected p.Gly540Ser homozygous rams. Conclusions The c.1618G>A, p.Gly540Ser substitution in CNGA3 was identified as the causative mutation for a novel form of ACHM in Awassi sheep. Gene augmentation therapy restored vision in the affected sheep. This novel mutation provides a large-animal model that is valid for most human CNGA3 ACHM patients; the majority of them carry missense rather than premature-termination mutations. PMID:28282490

  5. Use of intravenous immunoglobulin compared with standard therapy is associated with improved clinical outcomes in children with acute encephalitis syndrome complicated by myocarditis.

    PubMed

    Bhatt, Girish Chandra; Sankar, Jhuma; Kushwaha, K P

    2012-12-01

    Although an autoimmune mechanism has been postulated for acute encephalitis syndrome (AES) complicated by myocarditis, immunomodulatory treatment strategies are still under investigation. To study the role of intravenous immunoglobulin (IVIG) in AES complicated by myocarditis in children age 2-12 years. This nonrandomized study was conducted in a tertiary care teaching hospital from July 2008 to January 2010. A total of 83 consecutive children with AES complicated by myocarditis were enrolled. Diagnosis of myocarditis was based on clinical, electrocardiogram, and echocardiogram findings. Patients were allocated to the two groups based on the days of the week: Those presenting on Monday and Friday were allocated to IVIG treatment (group I), and those presenting on the other days of the week to standard care (group II). Group I (n = 26) patients received IVIG at a dose of 400 mg/kg/day for 5 days in addition to standard care. All baseline and outcome data were recorded prospectively in a prestructured performa. The primary outcomes were mortality and improvement of left-ventricular dysfunction. A total of 83 children were studied: 26 in group I and 57 in group II. The mean (SD) age of the enrolled children was 4.6 years (3.1). The baseline characteristics were comparable between the two groups. A viral etiology could be established in 14 children, with the 2 most common agents isolated being Coxackie virus and enterovirus. Mortality was lower in the IVIG group [n = 1 (3.8 %)] patients compared with the standard care group [n = 13 (22.8 %)] with a relative risk of 0.17 (95 % CI = 0.02, 1.22). The difference in mortality reached borderline significance (p = 0.05). At discharge, mean (SD) ejection fraction improved from 32.8 % (6.31 %) to 49.5 % (9.04 %) in group I patients, which was significantly greater than that of group II (p = 0.001). Use of IVIG seemed to have a beneficial effect in terms of improved clinical outcomes in children with AES complicated by

  6. The discovery of immunoglobulin E.

    PubMed

    Ribatti, Domenico

    2016-03-01

    The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE.

  7. The patient: Emerging clinical applications of intravenous immunoglobulin.

    PubMed

    Harvey, R Donald

    2005-11-01

    Intravenous immunoglobulin (IGIV) originally was used as prophylactic treatment of infections in patients with primary immunodeficiency disease. Today, administration of IGIV, due in large part to its immunomodulatory activity, has expanded to include a number of other disorders. Available data suggest that the accepted indications for IGIV will continue to expand. As the number of clinical applications for this therapy grows, so will market opportunities; current preparations will be modified and improved and new products introduced. Intravenous immunoglobulin therapy has improved the lives of many patients with immune-related disorders. Future applications will ideally advance this paradigm further.

  8. [Blood serum immunoglobulins in thyrotoxicosis].

    PubMed

    Epishin, A V

    1978-01-01

    Serum immunoglobulin content was determined in 85 patients with thyrotoxicosis and in 80 healthy persons by radial immunodiffusion in agar after Mancini by means of monospecific antisera (made at the N. F. Gamaleya Institute of Epidemiology immunoglobulins of classes G and M. The most pronounced increase was noted in patients with severe and moderate thyrotoxicosis.

  9. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut

    PubMed Central

    2013-01-01

    Background Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform. Results Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment. Conclusion This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture. Trial registration Clinical trial registration number: CinicalTrials.gov NCT01372943 PMID:24467987

  10. Free Immunoglobulin Light Chains as Criteria of Extracorporeal Hemocorrection in Patients with Monoclonal Gammopathies.

    PubMed

    Lyubimova, N V; Timofeeva, Yu S; Gromova, E G; Kuznetsova, L S; Votyakova, O M; Kushlinskii, N E

    2017-08-01

    Elimination of free immunoglobulin light chains with the use of EMic2 selective filters was carried out in 12 patients with monoclonal gammopathies and high production of free immunoglobulin light chains. We showed that extracorporeal detoxification for direct removal of excessive free immunoglobulin light chains from the circulation is advisable for these patients, irrespective of the presence and severity of renal insufficiency. Rapid reduction or elimination of free light chains of immunoglobulins in the course of selective extracorporeal elimination helps to prevent the development of irreversible renal failure and to perform adequate antitumor therapy.

  11. THE IMMUNOGLOBULINS OF MICE

    PubMed Central

    Fahey, John L.; Wunderlich, John; Mishell, Robert

    1964-01-01

    Two subclasses of mouse 7S γ2-globulins are identified, and are designated γ2a- and γ2b-globulins. They are distinguished from 7S γ1-globulins, γ1A (β2A)-globulins, and γ1M-globulins of mouse serum. Antibody activity was detected among the γ2a-globulins and γ2b-globulins of hyperimmune mouse serum. γ2a- and γ2b-myeloma proteins were identified. The genetically determined isoantigen, Iga-1, was present on γ2a-myeloma proteins, but not on γ2b-myeloma proteins. These findings indicate a complexity among the 7S γ2-globulins which must be taken into account in structural, functional, and genetic studies of immunoglobulins. PMID:14206439

  12. Secondary erythromelalgia successfully treated with intravenous immunoglobulin.

    PubMed

    Moody, Shadé; Pacheco, Susan; Butler, Ian J; Koenig, Mary Kay

    2012-07-01

    Erythromelalgia is a rare condition characterized by episodic painful erythema and warmth often affecting, but not limited to, the distal extremities. This condition is notoriously difficult to treat. We report a young female patient with seronegative polyarthritis who presented with a 6-year history of recurrent bouts of painful erythema and swelling often triggered by minor trauma. An extensive evaluation was unremarkable. Several medical therapies provided limited and inconsistent relief of her symptoms over many years. Treatment with intravenous immunoglobulin significantly decreased the frequency and severity of her symptoms.

  13. Milk immunoglobulins and complement factors.

    PubMed

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The importance of colostrum for the growth and health of newborn offspring is well known. In bovine colostrum, the antibody (immunoglobulin) complement system provides a major antimicrobial effect against a wide range of microbes and confers passive immunity until the calf's own immune system has matured. Bovine serum and lacteal secretions contain three major classes of immunoglobulins: IgG, IgM and IgA. The immunoglobulins are selectively transported from the serum into the mammary gland, as a result of which the first colostrum contains very high concentrations of immunoglobulins (40-200 mg/ml). IgG1 accounts for over 75 % of the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2. All these immunoglobulins decrease within a few days to a total immunoglobulin concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk throughout the lactation period. Together with the antibodies absorbed from colostrum after birth, the complement system plays a crucial role in the passive immunisation of the newborn calf. The occurrence of haemolytic or bactericidal complement activity in bovine colostrum and milk has been demonstrated in several studies. This review deals with the characteristics of bovine Igs and the complement system to be exploited as potential ingredients for health-promoting functional foods.

  14. 7(th) International Immunoglobulin Conference: Poster presentations.

    PubMed

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  15. 7th International Immunoglobulin Conference: Poster Presentations

    PubMed Central

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-01-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  16. Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study.

    PubMed

    Boada, M; Ramos-Fernández, E; Guivernau, B; Muñoz, F J; Costa, M; Ortiz, A M; Jorquera, J I; Núñez, L; Torres, M; Páez, A

    2016-09-01

    There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in the brain by sequestering plasma Aβ, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aβ and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD. Results from preliminary research suggest that Albutein(®) (therapeutic albumin, Grifols) contains no quantifiable levels of Aβ. Studies also show that Albutein(®) has Aβ binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aβ that can induce albumin modification, thus affecting its biological functions. Results from the phase ii study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(®) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aβ and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein(®) with intravenous immunoglobulin replacement (Flebogamma(®) DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed. the AMBAR study represents a new therapeutic perspective for AD. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma.

    PubMed

    Ayres, J G; Higgins, B; Chilvers, E R; Ayre, G; Blogg, M; Fox, H

    2004-07-01

    Patients with poorly controlled asthma have greater morbidity and mortality. This study evaluated the efficacy and tolerability of omalizumab in patients with poorly controlled, moderate-to-severe allergic asthma. This was a randomized, open-label, multicentre, parallel-group study. A total of 312 patients (12-73 years) receiving >/=400 microg/day (adolescent) or >/=800 microg/day (adult) inhaled beclomethasone dipropionate, or equivalent were included. Patients received best standard care (BSC) with or without omalizumab [at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks] for 12 months. The annualized mean number of asthma deterioration-related incidents was reduced from 9.76 with BSC alone (n = 106) to 4.92 per patient-year with omalizumab (n = 206) (P < 0.001). Mean clinically significant asthma exacerbation rates were 2.86 and 1.12 per patient-year, respectively (P < 0.001). Omalizumab-treated patients (41.4%) required rescue medication <1 day/week compared with 20.7% for BSC alone (P < 0.001). Omalizumab improved absolute forced expiratory volume in 1 s (FEV(1)) compared with BSC alone (2.48 and 2.28 l, respectively; P < 0.05) and reduced symptom scores relative to BSC alone (decrease of 6.5 and 0.7 respectively; P < 0.001). Omalizumab was well-tolerated. Omalizumab administered as add-on therapy to BSC benefits patients with poorly controlled, moderate-to-severe allergic asthma.

  18. HIV treatment access and scale-up for delivery of opiate substitution therapy with buprenorphine for IDUs in Ukraine--programme description and policy implications.

    PubMed

    Bruce, R Douglas; Dvoryak, Sergey; Sylla, Laurie; Altice, Frederick L

    2007-08-01

    Injection drug use (IDU) accounts for 70 percent of HIV cases in Ukraine. Until buprenorphine maintenance therapy (BMT) was introduced, few effective strategies aimed at achieving reduction in illicit drug use were available as a conduit to anti-retroviral therapy (ARV) among IDUs. In October 2005, BMT was scaled-up using Global Fund resources in six regions within Ukraine. Entry criteria included opioid dependence, HIV-1 seropositivity, age >or=18 years and reported interest in BMT. All sites included a multidisciplinary team. To date, 207 patients have been initiated on BMT. The existing infrastructure allows for further scale-up of and administration of BMT and the possibility of co-administration with ARV. The process for prescription and administration of buprenorphine and ARV is at times cumbersome and constrained by current regulations. More IDU need BMT to improve overall health outcomes. Central to expanding access will be legislative changes to existing drug policy. Moreover, the cost of buprenorphine is prohibitively expensive. Sustainable substitution therapy in Ukraine requires lower negotiated prices for buprenorphine, the addition of methadone, or both to the existing formulary for HIV+ drug users.

  19. HIV Treatment Access and Scale-Up for Delivery for IDU in Ukraine with Opiate Substitution Therapy with Buprenorphine - Programme Description and Policy Implications

    PubMed Central

    Bruce, R. Douglas; Dvoryak, Sergey; Sylla, Laurie; Altice, Frederick L.

    2007-01-01

    Background Injection drug use (IDU) accounts for 70% of HIV cases in Ukraine. Until buprenorphine maintenance therapy (BMT) was introduced, few effective strategies aimed at achieving reduction in illicit drug use were available as a conduit to antiretroviral therapy (ARV) among IDUs. Description In October 2005, BMT was scaled-up using Global Fund resources in six regions within Ukraine. Entry criteria included opioid-dependence, HIV-1 seropositivity, age ≥18 years and reported interest in BMT. All sites included a multidisciplinary team. To date, 207 patients have been initiated on BMT. Lessons Learned The existing infrastructure allows for further scale-up of and administration of BMT and the possibility of co-administration with ARV. The process for prescription and administration of buprenorphine and ARV is at times cumbersome and constrained by current regulations. Recommendations More IDU need BMT to improve overall health outcomes. Central to expanding access will be legislative changes to existing drug policy. Moreover, the cost of buprenorphine is prohibitively expensive. Sustainable substitution therapy in Ukraine requires lower negotiated prices for buprenorphine and/or the addition of methadone to the existing formulary for HIV+ drug users. PMID:17689382

  20. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Van Schaik, I N; Winer, J B; De Haan, R; Vermeulen, M

    2002-01-01

    placebo. One trial with 17 patients compared intravenous immunoglobulin with plasma exchange in a cross-over design and one trial compared intravenous immunoglobulin with prednisolone in 32 patients. A significantly higher proportion of patients improved in disability within one month after the onset of intravenous immunoglobulin treatment as compared with placebo (relative risk 3.17, 95% confidence interval 1.74 to 5.75). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used a different disability scale with a unique definition of a significant improvement. To overcome this problem an attempt was made to transform the various disability scales to the modified Rankin score. In three trials including 87 patients this transformation could be carried out. A significantly higher proportion of patients improved one point after intravenous immunoglobulin treatment compared to placebo (relative risk 2.47, 95% confidence interval 1.02 to 6.01). The effect size for change of mean disability score at six weeks comparing intravenous immunoglobulin with plasma exchange revealed no difference between the two therapies (effect size -0.07, 95% confidence interval -0.76 to 0.63.) The proportion of patients with a significant improvement did not differ significantly between prednisolone and intravenous immunoglobulin (relative risk of 0.91 (95% CI 0.50 to 1.68). Also, no difference in mean improvement on the disability scale was found at two weeks (effect size -0.12, 95% confidence interval -0.68 to 0.45) or six weeks (effect size -0.07, 95% confidence interval -0.63 to 0.50) between prednisolone and intravenous immunoglobulin. There were no statistically significant differences in frequencies of side effects between the three types of treatment. The evidence from randomised controlled trials shows that intravenous immunoglobulin improves disability for at least two to six weeks compared with placebo, with a number

  1. Chronic malabsorption due to cryptosporidiosis in a child with immunoglobulin deficiency

    PubMed Central

    Sloper, K S; Dourmashkin, R R; Bird, R B; Slavin, G; Webster, A D B

    1982-01-01

    A case of fatal cryptosporidiosis in a child with primary immunoglobulin deficiency is described. This is always a serious complication in immunodeficient patients because there is no known effective therapy. ImagesFigure PMID:7056501

  2. Can needle and syringe programmes and opiate substitution therapy achieve substantial reductions in hepatitis C virus prevalence? Model projections for different epidemic settings.

    PubMed

    Vickerman, Peter; Martin, Natasha; Turner, Katy; Hickman, Matthew

    2012-11-01

    To investigate the impact of scaling-up opiate substitution therapy (OST) and high coverage needle and syringe programmes (100%NSP-obtaining more sterile syringes than you inject) on HCV prevalence among injecting drug users (IDUs). Hepatitis C virus HCV transmission modelling using U.K. estimates for effect of OST and 100%NSP on individual risk of HCV infection. Range of chronic HCV prevalent (20/40/60%) settings with no OST/100%NSP, and U.K. setting with 50% coverage of both OST and 100%NSP. Injecting drug users. Decrease in HCV prevalence after 5-20 years due to scale-up of OST and 100%NSP to 20/40/60% coverage in no OST/100%NSP settings, or from 50% to 60/70/80% coverage in the U.K. setting. For 40% chronic HCV prevalence, scaling-up OST and 100%NSP from 0% to 20% coverage reduces HCV prevalence by 13% after 10 years. This increases to a 24/33% relative reduction at 40/60% coverage. Marginally less impact occurs in higher prevalence settings over 10 years, but this becomes more pronounced over time. In the United Kingdom, without current coverage levels of OST and 100%NSP the chronic HCV prevalence could be 65% instead of 40%. However, increasing OST and 100%NSP coverage further is unlikely to reduce chronic prevalence to less than 30% over 10 years unless coverage becomes ≥80%. Scaling-up opiate substitution therapy and high coverage needle and syringe programmes can reduce hepatitis C prevalence among injecting drug users, but reductions can be modest and require long-term sustained intervention coverage. In high coverage settings, other interventions are needed to further decrease hepatitis C prevalence. In low coverage settings, sustained scale-up of both interventions is needed. © 2012 The Authors. Addiction © 2012 Society for the Study of Addiction.

  3. Attitudes toward opioid substitution therapy and pre-incarceration HIV transmission behaviors among HIV-infected prisoners in Malaysia: Implications for secondary prevention

    PubMed Central

    Bachireddy, Chethan; Bazazi, Alexander R.; Kavasery, Ravi; Govindasamy, Sumathi; Kamarulzaman, Adeeba; Altice, Frederick L.

    2011-01-01

    Background Pre-incarceration HIV transmission behaviors and current attitudes toward opioid substitution therapy (OST) among HIV-infected male prisoners in Malaysia have important implications for secondary HIV prevention efforts. Methods In June 2007, 102 HIV-infected male prisoners within 6 months of community-release were anonymously surveyed in Kota Bharu, Malaysia. Results Nearly all subjects (95%) met criteria for opioid dependence. Overall, 66% of participants reported sharing needles, and 37% reported unprotected sex in the 30 days prior to incarceration. During this period, 77% reported injection drug use, with 71% injecting daily and 65% injecting more than one substance. Injection of buprenorphine (28%), benzodiazepines (28%) and methamphetamines (49%) was reported. Nearly all (97%) reporting unprotected sex did so with someone not known to be HIV-infected. While 51% believed that opioid substitution therapy (OST) would be helpful, only 33% believed they needed it to prevent relapse after prison release. Most participants (70%) expressed interest in learning more about OST. Those reporting the highest injection risks were more likely to believe OST would be helpful (p<.05), to believe that it was needed to prevent relapse post-release (p<.05), and to express interest in learning more about OST (p<.01). Conclusions Secondary HIV prevention among prisoners in Malaysia is crucial to reduce community HIV transmission after release. Effectively reducing HIV risk associated with opioid injection will require OST expansion, including social marketing to improve its acceptability and careful monitoring. Access to sterile injection equipment, particularly for non-opioid injectors, and behavioral interventions that reduce sexual risk will also be required. PMID:21232882

  4. Immunoglobulin levels of vitiligo patients.

    PubMed

    Ali, Rubaiya; Ahsan, Mohammad Shamsul; Azad, Mohammad Abul Kalam; Ullah, Md Ashik; Bari, Wasimul; Islam, Sheikh Nazrul; Yeasmin, Sabina; Hasnat, Abul

    2010-01-01

    In the present study, the serum immunoglobulin profiles of vitiligo patients were compared with that of cohort control and evaluated the correlation between immunoglobulin level with their socioeconomic factors and nutritional status. Thirty vitiligo patients were recruited randomly from the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh for this study. Thirty healthy individuals as control group matched by age, sex, education and socioeconomic factors to the patient group were selected. Serum immunoglobulin concentrations were determined by turbidimetry method using immunoglobulin kit. The concentration of IgG and IgA decreased significantly (P<0.05), but the change of IgM was not significant. Socioeconomic data revealed that most of the patients were young and female. Moreover statistical analysis revealed that there was significant correlation between immunoglobulin (IgG and IgA only) concentrations and BMI and number of depigmented patches with IgG concentrations. Finally it can be concluded that the change of serum immunoglobulin concentration in vitiligo patients could be due to the disease condition as pathomechanism suggested the aberrations in cellular immunity. But study with larger number of population is required for further evaluation of the relationship between the immune response and disease state to confirm these findings.

  5. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment. The two other autoimmune diseases discussed in this session were immunobullous skin diseases, and secondary recurrent miscarriage (RM). In the former conditions, low levels of pathogenic autoantibodies can be achieved with adjuvant intravenous immunoglobulin (IVIg) therapy, usually in combination with an immunosuppressant. Secondary RM has an autoimmune basis, as shown by high tumour necrosis factor (TNF)-α levels and specific human leucocyte antigen (HLA) polymorphisms. Although the mechanism is not yet known, IVIg may also be an effective treatment, despite the generally low doses used in published studies. PMID:25546788

  6. Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications.

    PubMed

    Doucet, Christelle; Ernou, Isabelle; Zhang, Yizhou; Llense, Jean-Roch; Begot, Laurent; Holy, Xavier; Lataillade, Jean-Jacques

    2005-11-01

    Mesenchymal stem cells (MSCs) are considered as emergent "universal" cells and various tissue repair programs using MSCs are in development. In vitro expansion of MSCs is conventionally achieved in medium containing fetal calf serum (FCS) and is increased by addition of growth factors. However, for widespread clinical applications, contact of MSCs with FCS must be minimized since it is a putative source of prion or virus transmission. Therefore, because platelets are a natural source of growth factors, we sought to investigate in vitro MSC expansion in response to platelet lysates (PL) obtained from platelet-rich plasma. Human MSCs were expanded in FCS (+/-bFGF)- or PL-supplemented medium through a process of subculture. We demonstrated that PL-containing medium is enriched by growth factors (platelet-derived growth factors (PDGFs), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), insulin-like growth factor-1 (IGF-1) ...) and showed that PL is able to promote MSC expansion, to decrease the time required to reach confluence, and to increase CFU-F size, as compared to the FCS medium. Furthermore, we demonstrated that MSCs cultured in the presence of PL maintain their osteogenic, chondrogenic, and adipogenic differentiation properties and retain their immunosuppressive activity. Therefore, we propose that PL may be a powerful and safe substitute for FCS in development of tissue- and cellular-engineered products in clinical settings using MSCs.

  7. Substitute Solutions.

    ERIC Educational Resources Information Center

    Jones, Kevin R.; Hawkins, Amber

    2000-01-01

    In summer 1999, a group of Park City, Utah, school administrators, personnel directors, human-resource specialists, and substitute teacher coordinators brainstormed on improving the recruitment, training, and retention of substitute teachers. Providing effective preservice and on-the-job training and professional recognition are key suggestions.…

  8. [Bone substitutes].

    PubMed

    Jordana, Fabienne; Le Visage, Catherine; Weiss, Pierre

    2017-01-01

    Bone substitutes, used to fill a defect after a surgery or a trauma, provide a mechanical support and might induce bone healing. They constitute an alternative to autogenous bone grafts, the 'gold standard' which remains the reference despite its risk of postoperative complications. The clinician choice of a bone substitute is based on the required bone volume, the handling (injectability, malleability) and mechanical properties (setting time, viscosity, resorbability among others) of the material. Bone substitutes are commonly used in orthopedic surgery, neurosurgery, stomatology and dental applications. Their use increases steadily, with the recent clinical development of injectable forms. In addition, novel technologies by subtractive or additive techniques allow today the production of controlled architecture materials. Here, we present a bone substitutes classification according to their origin (natural or synthetic) and chemical composition, and the most common use of these substitutes. © 2017 médecine/sciences – Inserm.

  9. Skin Substitutes

    PubMed Central

    Howe, Nicole; Cohen, George

    2014-01-01

    In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes. PMID:25371771

  10. The Production Processes and Biological Effects of Intravenous Immunoglobulin

    PubMed Central

    Barahona Afonso, Ana Filipa; João, Cristina Maria Pires

    2016-01-01

    Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production. PMID:27005671

  11. Long-term monitoring of insulin sensitivity in growth hormone-deficient adults on substitutive recombinant human growth hormone therapy.

    PubMed

    Giavoli, Claudia; Porretti, Silvia; Ronchi, Cristina L; Cappiello, Vincenzo; Ferrante, Emanuele; Orsi, Emanuela; Arosio, Maura; Beck-Peccoz, Paolo

    2004-06-01

    Since the effects of recombinant human growth hormone (rhGH) replacement therapy on glucose metabolism are still a matter of debate, the aim of the present study was to evaluate the impact of long-term rhGH treatment on insulin sensitivity. Simple indices of insulin resistance (IR) and insulin sensitivity (IS), based on fasting glucose and insulin, such as the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin check index (QUICKI), were used to estimate the degree of IR and IS in 20 normoglycemic patients (11 men and 9 women; mean age, 44 +/- 14 years) with severe adult-onset GH deficiency (GHD). Measurements were determined at baseline and after 1 and 5 years of continuous rhGH therapy. Basal values were compared to those obtained in 20 healthy sex- and age-matched controls. Starting rhGH dose ranged from 3 to 8 microg/kg/d in keeping with sex and age, then doses were titrated according to insulin-like growth factor-I (IGF-I) levels. At baseline all patients had low IGF-I levels (10 +/- 5.4 nmol/L), high body mas index (BMI; 27.5 +/- 4 kg/m(2)), and elevated body fat percentage (BF%; 31.8 +/- 9.6). Fasting glucose and insulin levels, as well as HOMA-IR and QUICKI, did not differ significantly from those recorded in the control group. After 1 year of rhGH replacement therapy, normalization in IGF-I levels and a significant reduction in BF% were observed (P <.001), and these effects were maintained after 5 years of treatment. Fasting glucose increased from 79 +/- 10 to 87 +/- 13, and 87 +/- 12 mg/dL (P <.05) after 1 and 5 years of therapy, respectively. Fasting insulin significantly increased after 1 year, without further modifications in the long-term follow-up. HOMA-IR significantly increased from 2.1 +/- 1.7 to 2.5 +/- 1.7 (P <.05) after 1 year, then decreased to 2.3 +/- 1.5 (P = not significant [NS] v basal) after 5 years. A specular decrease in QUICKI from 0.37 +/- 0.05 to 0.34 +/- 0.03 (P <.01) occurred after 1 year, with

  12. A cost-effectiveness analysis of opioid substitution therapy upon prison release in reducing mortality among people with a history of opioid dependence.

    PubMed

    Gisev, Natasa; Shanahan, Marian; Weatherburn, Don J; Mattick, Richard P; Larney, Sarah; Burns, Lucy; Degenhardt, Louisa

    2015-12-01

    Although opioid substitution therapy (OST) immediately after prison release reduces mortality, the cost-effectiveness of treatment has not been examined. Therefore, we undertook a cost-effectiveness analysis of OST treatment upon prison release and the prevention of death in the first 6 months post-release. Population-based, retrospective data linkage study using records of OST entrants (1985-2010), charges and court appearances (1993-2011), prison episodes (2000-11) and death notifications (1985-2011). New South Wales, Australia. A cohort of 16,073 people with a history of opioid dependence released from prison for the first time between 1 January 2000 and 30 June 2011. OST treatment compared to no OST treatment at prison release. Mortality and costs (treatment, criminal justice system-court, penalties, prison-and the social costs of crime) were evaluated at 6 months post-release. Analyses included propensity score matching, bootstrapping and regression. A total of 13,468 individuals were matched (6734 in each group). Twenty (0.3%) people released onto OST died, compared with 46 people (0.7%) not released onto OST. The final average costs were lower for the group that received OST post-release ($7206 versus $14,356). The incremental cost-effectiveness ratio showed that OST post-release was dominant, incurring lower costs and saving more lives. The probability that OST post-release is cost-effective per life-year saved is 96.7% at a willingness to pay of $500. Opioid substitution treatment (compared with no such treatment), given on release from prison to people with a history of opioid dependence, is cost-effective in reducing mortality in the first 6 months of release. © 2015 Society for the Study of Addiction.

  13. Serum immunoglobulins in Nigerian neonates.

    PubMed

    Akinwolere, O A; Akinkugbe, F M; Oyewole, A I; Salimonu, L S

    1989-01-01

    Serum immunoglobulins G, M and A levels were studied in 187 Nigerian neonates. Estimations were done by the radial immunodifusion method of Mancini. Immunoglobulin G shows a fall in value in the first few days of life to about 62% of the value in the last days of the neonatal period. There is however a gradual increase in the level of IgM to about double at the end of the neonatal period. IgA level remained relatively constantly low throughout this period. The effect of maternal education on the levels of immunoglobulins of their neonates was also investigated. This had a positive influence at the secondary educational level, affecting only the IgG and IgA.

  14. The impact of needle and syringe provision and opiate substitution therapy on the incidence of hepatitis C virus in injecting drug users: pooling of UK evidence.

    PubMed

    Turner, Katy M E; Hutchinson, Sharon; Vickerman, Peter; Hope, Vivian; Craine, Noel; Palmateer, Norah; May, Margaret; Taylor, Avril; De Angelis, Daniela; Cameron, Sheila; Parry, John; Lyons, Margaret; Goldberg, David; Allen, Elizabeth; Hickman, Matthew

    2011-11-01

    To investigate whether opiate substitution therapy (OST) and needle and syringe programmes (NSP) can reduce hepatitis C virus (HCV) transmission among injecting drug users (IDUs). Meta-analysis and pooled analysis, with logistic regression allowing adjustment for gender, injecting duration, crack injecting and homelessness. Six UK sites (Birmingham, Bristol, Glasgow, Leeds, London and Wales), community recruitment. A total of 2986 IDUs surveyed during 2001-09. Questionnaire responses were used to define intervention categories for OST (on OST or not) and high NSP coverage (≥100% versus <100% needles per injection). The primary outcome was new HCV infection, measured as antibody seroconversion at follow-up or HCV antibody-negative/RNA-positive result in cross-sectional surveys. Preliminary meta-analysis showed little evidence of heterogeneity between the studies on the effects of OST (I2=48%, P=0.09) and NSP (I2=0%, P=0.75), allowing data pooling. The analysis of both interventions included 919 subjects with 40 new HCV infections. Both receiving OST and high NSP coverage were associated with a reduction in new HCV infection [adjusted odds ratios (AORs)=0.41, 95% confidence interval (CI): 0.21-0.82 and 0.48, 95% CI: 0.25-0.93, respectively]. Full harm reduction (on OST plus high NSP coverage) reduced the odds of new HCV infection by nearly 80% (AOR=0.21, 95% CI: 0.08-0.52). Full harm reduction was associated with a reduction in self-reported needle sharing by 48% (AOR 0.52, 95% CI: 0.32-0.83) and mean injecting frequency by 20.8 injections per month (95% CI: -27.3 to -14.4). There is good evidence that uptake of opiate substitution therapy and high coverage of needle and syringe programmes can substantially reduce the risk of hepatitis C virus transmission among injecting drug users. Research is now required on whether the scaling-up of intervention exposure can reduce and limit hepatitis C virus prevalence in this population. © 2011 The Authors, Addiction © 2011

  15. Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma.

    PubMed

    Kastritis, E; Zagouri, F; Symeonidis, A; Roussou, M; Sioni, A; Pouli, A; Delimpasi, S; Katodritou, E; Michalis, E; Michael, M; Hatzimichael, E; Vassou, A; Repousis, P; Christophoridou, A; Kartasis, Z; Stefanoudaki, E; Megalakaki, C; Giannouli, S; Kyrtsonis, M-C; Konstantopoulos, K; Spyroupoulou-Vlachou, M; Terpos, E; Dimopoulos, M A

    2014-10-01

    Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.

  16. 7th International Immunoglobulin Conference: Immunodeficiencies

    PubMed Central

    Schmidt, R E; Ochs, H D

    2014-01-01

    Awareness of the challenges involved in diagnosing and treating a heterogeneous group of immunodeficiency disorders is growing. The improvements in neonatal screening offer new methods to ensure that primary immunodeficiencies (PIDs) are diagnosed as early as possible, enabling accurate treatment and the prevention of life-threatening infections and other complications. Additionally, the need to individualize patient therapy in order to optimize both clinical outcomes and quality-of-life is obvious and is exemplified by the ability to switch between intravenous and subcutaneous immunoglobulin administration offering flexible treatment regimens. However, further research is crucial in order to determine the optimal treatment for secondary immunodeficiencies, and to gain greater understanding of the underlying causes of PIDs, including common variable immunodeficiency. The information relating to the growth of patient registries is encouraging, with approximately 25 000 patients with PIDs included in the two registries discussed. Registries such as this are vital for future research, as well as providing an educational resource. PMID:25546748

  17. True hyponatremia secondary to intravenous immunoglobulin.

    PubMed

    Nguyen, Minhtri K; Rastogi, Anjay; Kurtz, Ira

    2006-06-01

    Hyponatremia is characterized as either "true hyponatremia," which represents a decrease in the Na(+) concentration in the water phase of plasma, or "pseudohyponatremia," which is due to an increased percentage of protein or lipid in plasma, with a normal plasma water Na(+) concentration ([Na(+)]). Pseudohyponatremia is a known complication of intravenous immunoglobulin (IVIG). Because IVIG has been reported to result in post-infusional hyperproteinemia, IVIG-induced hyponatremia has been attributed to pseudohyponatremia. In this case report, we demonstrate that IVIG therapy can result in true hyponatremia, resulting from sucrose-induced translocation of water from the intracellular compartment (ICF) to the extracellular compartment (ECF), as well as the infusion of a large volume of dilute fluid, in patients with an underlying defect in urinary free water excretion.

  18. The substitutability of reinforcers

    PubMed Central

    Green, Leonard; Freed, Debra E.

    1993-01-01

    Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

  19. Intravenous Immunoglobulin in the Management of Lupus Nephritis

    PubMed Central

    Wenderfer, Scott E.; Thacker, Trisha

    2012-01-01

    The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

  20. The new generation of liquid intravenous immunoglobulin formulations in patient care: a comparison of intravenous immunoglobulins.

    PubMed

    Stein, Mark R

    2010-09-01

    Intravenous immunoglobulin (IGIV) replacement therapy is the standard of care for primary immunodeficiencies with impaired humoral immunity. It is also the immunomodulatory therapy of choice for some types of neuroimmunologic and autoimmune hematologic disorders and for immunomodulation in bone marrow and some solid organ transplants. Currently available IGIV products include older lyophilized formulations, 5% liquid products, and newer, liquid, ready-to-use, 10% formulations. Differences in the formulations, manufacturing processes, excipients, pH, and other physicochemical properties of IGIV products may affect their clinical efficacy and tolerability. Among at-risk patients, the possibility of serious complications such as renal insufficiency, heart failure, thrombotic events, and immunological reactions may be increased if an IGIV formulation has sugar as a stabilizer, has high sodium or immunoglobulin A (IgA) content, or is hyperosmolar. The 10% liquid formulations may offer advantages because of their lower IgA concentrations, optimal pH, glycine or proline stabilizers, low sodium content, and lower osmolality. Liquid formulations are more convenient for patients and health care providers due to shorter infusion times and easier preparation and administration.

  1. A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis.

    PubMed

    Shabaninejad, Hosein; Asgharzadeh, Asra; Rezaei, Nima; Rezapoor, Aziz

    2016-01-01

    Subcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients.

  2. A randomized multicenter study: safety and efficacy of mini-pool intravenous immunoglobulin versus standard immunoglobulin in children aged 1-18 years with immune thrombocytopenia.

    PubMed

    Elalfy, Mohsen; Reda, Marwa; Elghamry, Islam; Elalfy, Omar; Meabed, Mohamed; El-Ekiaby, Nada; El-Hawy, Mahmoud A; Goubran, Hadi; El-Ekiaby, Magdy

    2017-09-06

    Because there is a global shortage of intravenous immunoglobulin, there is a need for new products to fill the gap. This was a multicenter, open-label study investigating the safety and efficacy of a newly developed mini-pool intravenous immunoglobulin G for children with immune thrombocytopenia. Seventy-two patients ages 1 to 18 years with newly diagnosed (<1 month) immune thrombocytopenia who had platelet counts from 5 to 20 × 10(9) /L with no serious bleeding were recruited from four centers in Egypt. Eligible patients were randomized into three groups 1:1:1. Group A (n = 24) received blood group-specific mini-pool intravenous immunoglobulin in a dose equivalent to immunoglobulin 1 g/kg over 6 to 8 hours, Group B (n = 24) received standard intravenous immunoglobulin (approximately 1g/kg) as a single dose, and Group C (n = 24) did not receive any platelet-enhancing therapy. Parents signed informed consent. Of the patients who received mini-pool intravenous immunoglobulin, 14 achieved a complete response (CR) (58.8%), and four had a response (16.6%). Of the patients who received intravenous immunoglobulin G, 16 achieved a complete response (66.6%), and four had a response (16.6%). In Group C, eight patients achieved a complete response (33.3%), and four had a response (16.6%). The median time to response was 8, 9, and 21 days in Group A, B, and C, respectively, which was significantly higher in Group C than Groups A and B (p < 0.001). Patients in Groups A and B reported 16 adverse drug reactions. Mini-pool intravenous immunoglobulin G was well tolerated, presented no safety issues, and was effective in the treatment of immune thrombocytopenia, with efficacy comparable to that of the standard intravenous immunoglobulin G group, and it was significantly more effective than no treatment. © 2017 AABB.

  3. Therapy discontinuation or substitution in patients with cardiovascular disease, switching among different products of the same off-patent active substance: a ‘real-world’ retrospective cohort study

    PubMed Central

    Degli Esposti, Luca; Sangiorgi, Diego; Buda, Stefano; Degli Esposti, Ezio; Scaglione, Francesco

    2016-01-01

    Objective The present study investigated the effects of switching to different products of the same off-patent active substance (brand name or generic) on therapy discontinuation or substitution with another molecule of the same class, in patients with cardiovascular disease treated with statins and antihypertensives in a ‘real-world’ setting. Design A retrospective cohort study in a ‘real-world’ setting. Setting Analysis of data performed by integrating administrative databases that included approximately two million individuals who are assisted by the National Health System from three Local Health Units located in three different regions of Italy. Participants All patients aged ≥18 years with at least one prescription of simvastatin, ramipril or amlodipine in the period 1 January to 31 December 2010 were included and followed up for 2 years. Main outcome measures Prescription refills occurring during follow-up were evaluated. Frequency of discontinuation of therapy or substitution with another molecule of the same class (eg, from simvastatin to a different statin) during follow-up was identified. Results During follow-up, therapy discontinuation or substitution was found to be more frequent in patients switching to a different product of the same active substance compared with non-switching patients (11.5% vs 10.8% and 22.2% vs 20.8% (p=0.002), respectively, in the simvastatin group; 4.0% vs 3.5% and 24.6% vs 22.7% (p<0.001), respectively, in the amlodipine group). In the ramipril group, 8% of patients undertook a therapy substitution to another molecule; no trend towards a lower percentage of substitution was observed in the non-switching group, while 18% of patients discontinued treatment, with a significant difference in favour of patients not switching. These findings were partially confirmed by multivariate analysis. Conclusions Switches among products of the same active substance are quite common in patients with cardiovascular disease. Our

  4. Favorable outcome of Epstein-Barr virus-associated B-cell lymphoproliferative disorder complicated by immunoglobulin G4-related disease treated with rituximab-based therapy: a case report.

    PubMed

    Ueda, Koki; Ikeda, Kazuhiko; Ogawa, Kazuei; Sukegawa, Masumi; Sano, Takahiro; Kimura, Satoshi; Suzuki, Osamu; Hashimoto, Yuko; Takeishi, Yasuchika

    2016-08-24

    After acute infection of Epstein-Barr virus, Epstein-Barr virus-infected B cells survive but usually do not show clonal proliferation. However, Epstein-Barr virus-infected B cells occasionally acquire a proliferative capacity that provokes clonal lymphoproliferative disorders. We herein present a case with Epstein-Barr virus-infected CD30+ B cell and immunoglobulin G4+ plasmacytoid cell proliferation in the lymph nodes, suggesting a pathological and clinical interaction between Epstein-Barr virus-associated B-cell lymphoproliferative disorders and immunoglobulin G4-related disease. Immunoglobulin G4-related disease has been recognized as a benign disease with proliferation of IgG4-related disease+ plasmacytoid cells. Several studies have recently reported the coexistence of immunoglobulin G4-related disease+ plasmacytoid cells with Epstein-Barr virus-infected B cells in lymph nodes in some immunoglobulin G4-related disease cases. However, the pathogenic role of the clonal proliferation of Epstein-Barr virus-infected B cells in immunoglobulin G4-related disease, as well as the treatments for patients with both Epstein-Barr virus-infected B cells and immunoglobulin G4-related disease, have never been discussed. A 50-year-old Japanese man was referred to us for persistent fatigue and lymphadenopathy. His blood examination showed elevated IgG4, and detected high levels of Epstein-Barr virus DNA. A lymph node biopsy revealed IgG4+ plasmacytoid cells and infiltration of large lymphoid cells, which were positive for CD20, CD30, Epstein-Barr virus-related late membrane protein 1, and Epstein-Barr virus-encoded RNA, and were negative for IgG4. Based on the diagnosis of both Epstein-Barr virus-associated B-cell lymphoproliferative disorder and IgG4-related disease, the patient received eight cycles of rituximab combined with cyclophosphamide and prednisolone, which resulted in the complete disappearance of lymphadenopathy. Moreover, his serum IgG4 level was significantly

  5. The interactions of calreticulin with immunoglobulin G and immunoglobulin Y.

    PubMed

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz; Thaysen-Andersen, Morten; Liu, Yan; Palma, Angelina S; Feizi, Ten; Hansen, Paul R; Højrup, Peter; Houen, Gunnar

    2011-07-01

    Calreticulin is a chaperone of the endoplasmic reticulum (ER) assisting proteins in achieving the correctly folded structure. Details of the binding specificity of calreticulin are still a matter of debate. Calreticulin has been described as an oligosaccharide-binding chaperone but data are also accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin. The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins. Additionally, calreticulin peptide binding was examined with synthetic peptides covering the IgG Cγ2 domain demonstrating interaction with approximately half the peptides. Our results show that the dominant binding activity of calreticulin in vitro is toward the polypeptide moieties of IgG and IgY even in the presence of the monoglucosylated high mannose N-linked oligosaccharide on IgY.

  6. Solvent substitution

    SciTech Connect

    Not Available

    1990-01-01

    The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated.

  7. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    PubMed

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took <10 min. Linearity range (r(2) > 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps.

  8. The introduction of buprenorphine-naloxone film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations.

    PubMed

    Larance, Briony; Dietze, Paul; Ali, Robert; Lintzeris, Nicholas; White, Nancy; Jenkinson, Rebecca; Degenhardt, Louisa

    2015-11-01

    Buprenorphine-naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self-reported by BNX film clients, and (iii) dosing issues. Survey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined. Among the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was 'I am happy with my current treatment and do not see a reason to change' (53%). Some opioid substitution therapy clients and KE viewed transfers as 'forced' (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film-attributed adverse effects but clinic/prescriber-recommended transfer was not. The introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  9. Evaluation of buprenorphine dosage adequacy in opioid receptor agonist substitution therapy for heroin dependence: first use of the BUprenorphine-naloxone Dosage Adequacy eVAluation (BUDAVA) questionnaire.

    PubMed

    D'Amore, Antonio; Romano, Filomena; Biancolillo, Vincenzo; Lauro, Guglielmo; Armenante, Ciro; Pizzirusso, Anna; Del Tufo, Salvatore; Ruoppolo, Ciro; Auriemma, Francesco; Cassese, Francesco; Oliva, Patrizia; Amato, Patrizia

    2012-07-01

    The dosing of opioid receptor agonist medications adequately and on an individual basis is crucial in the pharmacotherapy of opioid dependence. Clinical tools that are able to measure dose appropriateness are sorely needed. The recently developed and validated Opiate Dosage Adequacy Scale (ODAS) comprehensively evaluates the main outcomes relevant for methadone dose optimization, namely relapse, cross-tolerance, objective and subjective withdrawal symptoms, craving and overdose. Based on the ODAS, we developed a new assessment tool (BUprenorphine-naloxone Dosage Adequacy eVAluation [BUDAVA]) for evaluating dosage adequacy in patients in treatment with buprenorphine-naloxone. The main goal of this observational study was to explore whether the BUDAVA questionnaire could be used to assess buprenorphine-based, long-term substitution therapy for heroin addiction. The study included heroin-dependent patients who had been in treatment with buprenorphine-naloxone for at least 3 months. Patients (n = 196) were recruited from 11 drug abuse treatment centres in Italy. Dosage adequacy was assessed with the BUDAVA questionnaire. Patients classified as inadequately treated had their dosage modified. After 1 week, they were again administered the questionnaire to assess the adequacy of the new dosage. The buprenorphine-naloxone dosage was found to be inadequate in 61 of the 196 patients. In 13 patients, the treatment scored as inadequate only in the subjective withdrawal symptoms item of the questionnaire and therefore no dosage adjustment was made in the 2 weeks that have characterized this work. The remaining 48 inadequately treated patients had their dosage modified (42 dose increases and six dose decreases). After 1 week on the modified dosage, in 24 of these patients the new regimen was found by the assessment with the questionnaire to be adequate. These preliminary results suggest that the BUDAVA questionnaire may be useful for guiding buprenorphine-naloxone maintenance

  10. Proteolysis of lymphocytic surface immunoglobulin.

    PubMed Central

    Hough, D W; McIlroy, B M; Stevenson, G T

    1977-01-01

    Limited proteolysis of lymphocytic surface immunoglobulins in guinea-pig, rabbit and man was investigated by immunofluorescence using conjugated antisera specific for immunoglobulin fragments. The cell surface IgM of guinea pig L2C leukaemic lymphocytes and rabbit blood lymphocytes was cleaved in situ at its hinge region by papain. The Fcmicron fragment remained attached to the membrane and could be stained with the appropriate anti-Fc conjugate. The surface IgD and IgM of human chronic lymphocytic leukaemia cells was cleared from the cell surface by papain, as shown by reagents directed against both Fab and Fc region determinants. This could be due either to proteolytic degradation of membrane bound Fc or to initial cleavage of Ig from the membrane at some point other than the hinge region. PMID:321347

  11. Automatic Substitute Computed Tomography Generation and Contouring for Magnetic Resonance Imaging (MRI)-Alone External Beam Radiation Therapy From Standard MRI Sequences.

    PubMed

    Dowling, Jason A; Sun, Jidi; Pichler, Peter; Rivest-Hénault, David; Ghose, Soumya; Richardson, Haylea; Wratten, Chris; Martin, Jarad; Arm, Jameen; Best, Leah; Chandra, Shekhar S; Fripp, Jurgen; Menk, Frederick W; Greer, Peter B

    2015-12-01

    To validate automatic substitute computed tomography CT (sCT) scans generated from standard T2-weighted (T2w) magnetic resonance (MR) pelvic scans for MR-Sim prostate treatment planning. A Siemens Skyra 3T MR imaging (MRI) scanner with laser bridge, flat couch, and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole-pelvis MRI scan (1.6 mm 3-dimensional isotropic T2w SPACE [Sampling Perfection with Application optimized Contrasts using different flip angle Evolution] sequence) was acquired. Three additional small field of view scans were acquired: T2w, T2*w, and T1w flip angle 80° for gold fiducials. Patients received a routine planning CT scan. Manual contouring of the prostate, rectum, bladder, and bones was performed independently on the CT and MR scans. Three experienced observers contoured each organ on MRI, allowing interobserver quantification. To generate a training database, each patient CT scan was coregistered to their whole-pelvis T2w using symmetric rigid registration and structure-guided deformable registration. A new multi-atlas local weighted voting method was used to generate automatic contours and sCT results. The mean error in Hounsfield units between the sCT and corresponding patient CT (within the body contour) was 0.6 ± 14.7 (mean ± 1 SD), with a mean absolute error of 40.5 ± 8.2 Hounsfield units. Automatic contouring results were very close to the expert interobserver level (Dice similarity coefficient): prostate 0.80 ± 0.08, bladder 0.86 ± 0.12, rectum 0.84 ± 0.06, bones 0.91 ± 0.03, and body 1.00 ± 0.003. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same dose prescription was found to be 0.3% ± 0.8%. The 3-dimensional γ pass rate was 1.00 ± 0.00 (2 mm/2%). The MR-Sim setup and automatic sCT generation methods using standard MR sequences generates realistic contours and

  12. 7th International Immunoglobulin Conference: Interlaken Leadership Awards.

    PubMed

    Dalakas, M C; Löscher, W N

    2014-12-01

    The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy.

  13. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients.

    PubMed

    Compagno, Nicolò; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo

    2014-06-01

    Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders.

  14. The vectorial release of nascent immunoglobulin peptides

    PubMed Central

    Bevan, Michael J.

    1971-01-01

    A microsomal preparation from a mouse plasmacytoma, MOPC 47A, that secretes immunoglobulin A was used to study the release of nascent immunoglobulin peptides in vitro. Nascent chains were released with puromycin and characterized with specific antiserum against the immunoglobulin product of the tumour. When the tissue had been prelabelled with [3H]leucine the experiments were complicated by the large background of completed radioactive polypeptides in the microsomal preparation. Up to one-third of the released radioactivity in the microsomal preparation could be recognized as immunoglobulin. With [3H]-puromycin as the radioactive label, however, the results are much easier to interpret, although the proportion of released radioactivity that can be identified as immunoglobulin is lower (up to one-tenth). Both types of experiment demonstrate that all of the recognizable nascent immunoglobulin chains remain in association with the microsomal vesicles after release from the ribosomes. PMID:5124814

  15. 7th International Immunoglobulin Conference: Immunodeficiencies

    PubMed Central

    Schmidt, R E; Ochs, H D

    2014-01-01

    Most primary immunodeficiency disorders (PID) are the result of single gene defects. Based on this fact, more than 240 different entities have been identified. Those PIDs with predominant antibody deficiency are treated with immunoglobulin (Ig) replacement therapy. This review focuses on the diagnosis, clinical characteristics and treatment of patients suffering from PID, or secondary immunodeficiency disorders (SID) caused, for instance, by irradiation, immunosuppressive drugs or thymectomy. Common variable immunodeficiency (CVID) is the most commonly diagnosed and least understood form of PID, with a heterogeneous range of symptoms and genotypes, requiring individualized treatment plans. This includes adjusting the dose and treatment interval, administrating Ig by intravenous or subcutaneous injection by either pump or push, and finally deciding which treatment options are best for a given patient. Ig therapy can also be used to treat immunodeficiencies resulting from lymphoproliferative and autoimmune diseases or immunosuppression following organ transplantation; however, there is an urgent need for research in this field. Accurate and early diagnosis of PID is important to ensure that optimal treatment is started early to maintain the patient's health. Detailed patient registries have been established to increase awareness of PID, as well as provide a valuable resource for further research. PMID:25546741

  16. Immunoglobulin A: magic bullet or Trojan horse?

    PubMed

    Heineke, Marieke H; van Egmond, Marjolein

    2017-02-01

    Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor Fc?RI (CD89), leading to pro- or anti-inflammatory responses. The aim of this review is to give a concise overview of the interplay between IgA, Fc?RI and neutrophils and to explore potential therapies for autoimmune diseases and cancer. Crosslinking of FcαRI by IgA-immune complexes yields potent neutrophil activation and pro-inflammatory effector functions, including the recruitment of neutrophils. This can lead to neutrophil accumulation and tissue destruction during IgA-autoantibody mediated diseases. Conversely, for cancer treatment, the myriad of powerful neutrophil effector functions after targeting FcαRI may contribute to effective immunotherapy. By interfering with or actively promoting the interaction between IgA and FcαRI, therapies for multiple maladies could be developed. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  17. Sporadic late onset nemaline myopathy and immunoglobulin deposition disease.

    PubMed

    Doppler, Kathrin; Knop, Stefan; Einsele, Hermann; Sommer, Claudia; Wessig, Carsten

    2013-12-01

    In monoclonal gammopathy, organ dysfunction can occur due to deposition of immunoglobulin fragments. A rare form of acquired myopathy often associated with monoclonal gammopathy is sporadic late onset nemaline myopathy (SLONM), which is characterized by nemaline rods in myofibers. The pathogenetic link between monoclonal gammopathy and SLONM has not yet been elucidated. Case report of a patient with monoclonal gammopathy who developed a progressive myopathy, finally diagnosed as SLONM. A muscle biopsy showed mild myopathic changes. A second biopsy 1 year after clinical onset demonstrated deposition of immunoglobulin light and heavy chains and the presence of nemaline rods. The patient experienced marked improvement of muscle strength after autologous stem cell transplantation and treatment with bortezomib, a therapy that is known to be effective in light chain deposition disease. We speculate that deposition of light and heavy chains, rather than nemaline bodies, has myotoxic effects on skeletal muscle. Copyright © 2013 Wiley Periodicals, Inc.

  18. Offending, custody and opioid substitution therapy treatment utilisation among opioid-dependent people in contact with the criminal justice system: comparison of Indigenous and non-Indigenous Australians.

    PubMed

    Gisev, Natasa; Gibson, Amy; Larney, Sarah; Kimber, Jo; Williams, Megan; Clifford, Anton; Doyle, Michael; Burns, Lucy; Butler, Tony; Weatherburn, Don J; Degenhardt, Louisa

    2014-09-06

    Although Indigenous Australians are over-represented among heroin users, there has been no study examining offending, time in custody, and opioid substitution therapy (OST) treatment utilisation among Indigenous opioid-dependent (including heroin) people at the population level, nor comparing these to non-Indigenous opioid-dependent people. The aims of this study were to compare the nature and types of charges, time in custody and OST treatment utilisation between opioid-dependent Indigenous and non-Indigenous Australians in contact with the criminal justice system. This was a population-based, retrospective data linkage study using records of OST entrants in New South Wales, Australia (1985-2010), court appearances (1993-2011) and custody episodes (2000-2012). Charge rates per 100 person-years were compared between Indigenous and non-Indigenous Australians by sex, age and calendar year. Statistical comparisons were made for variables describing the cumulative time and percentage of follow-up time spent in custody, as well as characteristics of OST initiation and overall OST treatment utilisation. Of the 34,962 people in the cohort, 6,830 (19.5%) were Indigenous and 28,132 (80.5%) non-Indigenous. Among the 6,830 Indigenous people, 4,615 (67.6%) were male and 2,215 (32.4%) female. The median number of charges per person against Indigenous people (25, IQR 31) was significantly greater than non-Indigenous people (9, IQR 16) (p < 0.001). Overall, Indigenous people were charged with 33.2% of the total number of charges against the cohort and 44.0% of all violent offences. The median percentage of follow-up time that Indigenous males and females spent in custody was twice that of non-Indigenous males (21.7% vs. 10.1%, p < 0.001) and females (6.0% vs. 2.9%, p < 0.001). The percentage of Indigenous people who first commenced OST in prison (30.2%) was three times that of non-Indigenous people (11.2%) (p < 0.001). Indigenous males spent less time in OST compared to non

  19. Immunoglobulins in human aqueous humour.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Saha, K.

    1977-01-01

    The immunoglobulin concentrations in human aqueous humour from 44 patients aged 35 to 85 years with cataracts were measured by a standard immunodiffusion method. IgG was found in all the samples (mean level 7-0 mg/100 ml. IgD, IgA or IgM could not be detected. There was no significant difference in IgG levels in aqueous humour between the two sexes, in different age groups, and in the different types of cataracts. PMID:403928

  20. WITHDRAWN: Immunoglobulin treatment for respiratory syncytial virus infection.

    PubMed

    Fuller, Hannah L; Del Mar, Chris B

    2010-09-08

    Respiratory syncytial virus (RSV) bronchiolitis and pneumonia hospitalise hundreds of thousands of infants every year. Treatment is largely supportive therapy, (for example, oxygen, fluids and occasionally mechanical ventilation). Ribavirin, an antiviral agent, is licensed for severe RSV infection, although systematic reviews find it of no benefit. Passive protection against RSV can be achieved through monthly intramuscular injections of the humanised monoclonal anti-RSV antibody palivizumab (Synagis), and yields a 55% reduction in RSV hospitalisation in susceptible infants. This review assesses immunoglobulin treatment of RSV infection rather than its role as a prophylactic measure. To assess the efficacy of adding human or humanised immunoglobulin therapy to supportive therapy in infants hospitalised with laboratory-determined RSV infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 1) which contains the Acute Respiratory Infections Group's specialized regsiter, MEDLINE (1966 to Week 4, January 2006) and EMBASE (1980 to September 2005). We also ran searches of reference lists of relevant trials and review articles and searches of personal files. We did not impose any language restrictions. We selected randomised controlled trials (RCTs) that compared immunoglobulin treatment with a placebo control in children hospitalised for RSV infection with bronchiolitis or pneumonia or other lower respiratory tract infection (LRTI) with laboratory-documented RSV infection. The primary outcomes of interest were mortality, length of hospitalisation, length of ventilation and oxygen dependence. Secondary outcome measures were pulmonary function and re-hospitalisations for recurrent breathing difficulties in subsequent years. Any adverse effects of the treatments were also noted, for example, hypersensitivity reactions. Data were extracted but cross-comparison was not possible due to the shortage of studies and

  1. Subcutaneous immunoglobulin: opportunities and outlook

    PubMed Central

    Misbah, S; Sturzenegger, M H; Borte, M; Shapiro, R S; Wasserman, R L; Berger, M; Ochs, H D

    2009-01-01

    Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future. PMID:19883424

  2. Blood Test: Immunoglobulin A (IgA)

    MedlinePlus

    ... to 2-Year-Old Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin A (IgA) Print A A A What's in this article? ... Questions en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA test measures the ...

  3. Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy.

    PubMed

    Kalbhenn, J; Wittau, N; Schmutz, A; Zieger, B; Schmidt, R

    2015-11-01

    Intracranial haemorrhage is a redoubtable complication during extracorporeal membrane oxygenation (ECMO) therapy. The underlying mechanisms of haemorrhagic diathesis are still not completely understood. This study was performed to evaluate a coagulation protocol for the regular analysis of acquired coagulation disorders and the systematic substitution of coagulation factors to reach predefined target values. We hypothesised that using this strategy would lead to the identification of acquired bleeding disorders which cannot be monitored with standard coagulation tests and that substitution of the respective factors in a target-controlled approach could have an impact on the incidence and severity of intracranial haemorrhage. A protocol for the analysis of acquired coagulation disorders and the subsequent administration of associated factor concentrates was introduced. Previously, coagulation management was mainly based on clinical bleeding signs as the trigger for the administration of blood products. In this investigation, nineteen consecutive patients before (control group) and twenty consecutive patients after the implementation of the protocol (intervention group) have been included in the study. Eighty-eight percent of the patients developed factor XIII deficiency, 79% acquired von Willebrand syndrome, 40% fibrinogen deficiency and 54% of the patients showed a decline in platelet count >20% within the first 24 hours of ECMO therapy. In 6 out of 19 (31%) patients in the control group and in 2 patients out of 20 (10%) in the intervention group, intracranial haemorrhage was detected. Whilst 5 of 6 patients in the control group died because of fatal bleeding, both of the patients in the intervention group recovered with a favourable neurologic outcome. Veno-venous ECMO therapy leads to thrombocytopenia, factor XIII and fibrinogen deficiency as well as acquired von Willebrand syndrome. The implementation of a coagulation protocol including a standardized

  4. [Serum immunoglobulin E level in bronchial asthma].

    PubMed

    Denchev, K; Radkov, M; Lipcheva, N

    1976-01-01

    Serum immunoglobulin E level was determined in 50 patients with bronchial asthma, treated in the out-patients department and clinical conditions at the Faculty Hospital--Varna. The quantitative determination of immunoglobulin E was carried out by radial immunodiffusion according to Mancini with monospecific anti-IgE globulin serum from Behringswerke (GFR). A considerable elevation of immunoglobulin E in the patients' sera was found, at an average of 394 IU (control 124 IU). A discrepancy in serum immunoglobulin E level was established with the different clinical forms of asthma. The highest are the values with infectious-allergic astmha-424 IU. High are the values both in the treated and not-treated with corticosteroids, without an essential difference between the two patient groups. Some of the rest immunoglobulins showed also an elevationppIgG 2620 mg% and IgA 366 mg%.

  5. Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers.

    PubMed

    Gonzalez-Quintela, Arturo; Gomez-Rial, Jose; Valcarcel, Catalina; Campos, Joaquin; Sanz, Maria-Luisa; Linneberg, Allan; Gude, Francisco; Vidal, Carmen

    2011-03-01

    N-glycans from plant and invertebrate allergens can induce extensive immunoglobulin-E (IgE) cross-reactivity in vitro. IgE antibodies against these N-glycans, also termed cross-reactive carbohydrate determinants or CCDs, are prevalent in alcohol drinkers. This study investigated the prevalence and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers. A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects. Eleven heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation with a glycoconjugate containing bromelain-type N-glycans. The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls. There was no relationship between immunoblot reactivity and consumption of any specific type of wine. No patient reported symptoms of hypersensitivity to Hymenoptera venom, food, or wine. In conclusion, heavy drinkers frequently show IgE reactivity to the N-glycans of wine glycoproteins. Glycans and wine glycoprotein extracts can induce basophil activation in sensitized alcoholics. The clinical significance of these findings remains to be elucidated.

  6. Coding strategy differences between constant and variable segments of immunoglobulin genes.

    PubMed Central

    Perrin, P

    1984-01-01

    Vertebrate immunoglobulin (Ig) mRNAs reveal intraspecies variation in codon usage distinct from that seen with yeast or bacterial genes. Comparison of all available Ig gene sequences shows that %(G + C) in codon position III is consistently lower in variable (V) segments than in constant (C) segments. I find an even lower %(G + C) in the hypervariable domains of V segments. This analysis suggests that base substitution in Ig genes correlates positively with local A + T content. PMID:6462913

  7. Polyomavirus BK Neutralizing Activity in Human Immunoglobulin Preparations

    PubMed Central

    Randhawa, Parmjeet S; Schonder, Kristine; Shapiro, Ron; Farasati, Nousha; Huang, Yuchen

    2011-01-01

    Background Polyomavirus BK (BKV) infection can cause nephropathy in the allograft kidney. No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness. Methods We tested five lots of commercially available IVIG preparations from two different suppliers for polyomavirus neutralizing activity. BKV and mouse polyomavirus were used to infect human and murine host cells, respectively, with or without prior treatment with IVIG. Neutralization activity was measured by quantitation of viral DNA after 7 days in culture. Results Coincubation of BKV but not mouse polyomavirus with clinically relevant concentrations of IVIG derived from healthy and hepatitis B vaccinated subjects caused more than 90% inhibition of viral DNA yield after 7 days in culture. Consistent with a direct neutralizing mechanism, this effect was significantly diminished if viral infection was performed in immunoglobulin pretreated cells or if immunoglobulin treatment was delayed 2 hr after addition of infectious virus. Conclusion Human IVIG preparations contain BKV neutralizing antibodies. Data on neutralizing capacity of these antibodies are presented to aid dose exploration in clinical trials seeking to validate the use of IVIG in patients with BKV infection. PMID:20568674

  8. Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y

    PubMed Central

    Millán Martín, Silvia; Wormald, Mark R.; Zapatero-Rodríguez, Julia; Conroy, Paul J.; O’Kennedy, Richard J.; Rudd, Pauline M.; Saldova, Radka

    2016-01-01

    Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases. PMID:27459092

  9. Clinical applications of intravenous immunoglobulins in neurology.

    PubMed

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-12-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.

  10. Clinical applications of intravenous immunoglobulins in neurology

    PubMed Central

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-01-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain–Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Aβ antibody titres associated with decreased Aβ peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way. PMID:19883422

  11. Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview.

    PubMed

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-03-01

    Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation.

  12. Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains.

    PubMed

    Muyldermans, S; Atarhouch, T; Saldanha, J; Barbosa, J A; Hamers, R

    1994-09-01

    We cloned 17 different PCR fragments encoding VH genes of camel (Camelus dromedarius). These clones were derived from the camel heavy chain immunoglobulins lacking the light chain counterpart of normal immunoglobulins. Insight into the camel VH sequences and structure may help the development of single domain antibodies. The most remarkable difference in the camel VH, consistent with the absence of the VL interaction, is the substitution of the conserved Leu45 by an Arg or Cys. Another noteworthy substitution is the Leu11 to Ser. This amino acid normally interacts with the CH1 domain, a domain missing in the camel heavy chain immunoglobulins. The nature of these substitutions agrees with the increased solubility behavior of an isolated camel VH domain. The VH domains of the camels are also characterized by a long CDR3, possibly compensating for the absence of the VL contacts with the antigen. The CDR3 lacks the salt bridge between Arg94 and Asp101. However, the frequent occurrence of additional Cys residues in both the CDR1 and CDR3 might lead to the formation of a second internal disulfide bridge, thereby stabilizing the CDR structure as in the DAW antibody. Within CDRs of the camel VH domains we observe a broad size distribution and a different amino acid pattern compared with the mouse or human VH. Therefore the camel hypervariable regions might adopt structures which differ substantially from the known canonical structures, thereby increasing the repertoire of the camel antigen binding sites within a VH.

  13. Atypical immunoglobulin light chain amyloidosis

    PubMed Central

    Wu, Xia; Feng, Jun; Cao, Xinxin; Zhang, Lu; Zhou, Daobin; Li, Jian

    2016-01-01

    Abstract Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce. Methods: Herein, we present 3 new cases of AL amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature. Results: Moreover, we observed overrepresentations of liver involvement and bone marrow involvement in AL amyloidosis with spontaneous vertebral compression fracture. Conclusion: We believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of AL amyloidosis can facilitate earlier diagnosis and earlier treatment. PMID:27603350

  14. HPLC chromatofocusing of human immunoglobulins.

    PubMed

    Waldrep, J C; Schulte, J R

    1989-03-31

    A method is described for fractionation and analysis of IgA, IgM, and IgG and antibodies in human serum and/or plasma using a combination of HPLC chromatofocusing and immunoassay. A pH 9.0-3.2 gradient is utilized to separate the major proteins in the complex biological samples and monoclonal antibody based ELISAs used to determine the isotype profiles. Antigen-specific ELISAs are subsequently utilized to determine the distribution of antibody species within the chromatofocused specimens. This method is versatile since multiple simultaneous assays can easily be run on each fraction generating extensive qualitative information regarding immunoglobulin classes, subclasses, and antibodies and their distribution profiles. Such spectra will prove useful for experimental kinetic analysis of the humoral immune status of humans and experimental animals.

  15. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56+, have been shown to decline after IVIg treatment [1-6]. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question. PMID:25546784

  16. Human immunoglobulin constant heavy G chain (IGHG) (Fcγ) (GM) genes, defining innate variants of IgG molecules and B cells, have impact on disease and therapy.

    PubMed

    Oxelius, Vivi-Anne; Pandey, Janardan P

    2013-12-01

    The distinguished alternative GM allotypes localized in immunoglobulin constant heavy G chain IGHG (Fcγ) (GM) genes on chromosome 14q32.3 define two unique variants of respectively IgG3, IgG1 and IgG2 subclasses, with different structures and functions. The IGHG allele (allotypes), expressed in homozygous or heterozygous forms, are assessed by new serological methods. Fixed combinations of γ3, γ1 and γ2 allotypes constitute the haplotypes, which are indirect markers of B cells. We highlight the role of homozygous IGHG genes with restricted qualities of IgG subclass molecules and B cells. These common Mendelian IGHG genes respond differently to allergens and infections, both bacterial and viral, and to active and passive immunotherapies. IGHG genes have an impact on diseases such as allergy, immunodeficiency, autoimmunity and malignancy. Association/linkage of different IGHG genes gives information about risk/protection, good or bad prognosis, for improvement of clinical care. The IGHG gene map of healthy Caucasians is registered. © 2013.

  17. The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients

    PubMed Central

    Bokharaei-Salim, Farah; Salehi-Vaziri, Mostafa; Sadeghi, Farzin; Esghaei, Maryam; Monavari, Seyed Hamidreza; Alavian, Seyed Moayed; Fakhim, Shahin; Keyvani, Hossein

    2016-01-01

    Background The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries. Objectives The aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients. Patients and Methods A total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Results In this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006). Conclusions The data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in

  18. Perspectives on Immunoglobulins in Colostrum and Milk

    PubMed Central

    Hurley, Walter L.; Theil, Peter K.

    2011-01-01

    Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk. PMID:22254105

  19. Intestinal immunoglobulins in children with coeliac disease

    PubMed Central

    Savilahti, E.

    1972-01-01

    The numbers of immunoglobulin-containing cells in jejunal biopsy specimens of 19 children with active coeliac disease aged 0·5 to 16·5 years were studied by direct immunofluorescence. Intestinal juice immunoglobulins were measured in 14 of these patients. The number of IgA-containing cells was twice and the number of IgM-containing cells 2·5 times that of age-matched controls. There were also more IgG-, IgE-, and IgD-containing cells in the jejunal mucosa of the coeliac patients, but the absolute numbers of these cells were low. The immunoglobulin content of the intestinal juice was not altered in coeliacs. A follow-up biopsy specimen was available from seven patients kept on a strict gluten-free diet for one to four months. A significant fall in the numbers of immunoglobulin-containing cells was seen, and they did not differ at that time from the controls. Two patients were followed until full normalization of the jejunal structure and they had normal numbers of immunoglobulin-containing cells. In children with coeliac disease in contrast to adult coeliacs, the study shows that the IgA-producing system is quantitatively stimulated during gluten challenge. The rapid drop in the numbers of immunoglobulin-containing cells after gluten withdrawal suggests that there is no quantitative abnormality in the local immunoglobulin-producing system of the gut in coeliac disease. ImagesFig. 3 PMID:4568803

  20. Accumulation of fetal IgG in immunoglobulin injection into the fetal abdominal cavity is proven.

    PubMed

    Yoshida, Masashi; Matsuda, Hideo; Hasegawa, Yuri; Yoshinaga, Yosuke; Asai, Kazuhiko; Kawashima, Akihiro; Furuya, Kenichi

    2011-01-01

    There have been a number of studies on immunoglobulin injection into fetuses or mothers during pregnancy for the treatment of congenital cytomegalovirus infection. However, no study has examined the effect of injected immunoglobulin on fetal hemodynamics. In this study, we examined the effect of immunoglobulin injection on fetal hemodynamics by retrospectively measuring the concentrations of several igg subclasses in stored umbilical cord blood sera collected during fetal therapy. Five patients who underwent immunoglobulin injection into the fetal abdominal cavity (IFAC) as a fetal therapy during pregnancy were included in this study. Frozen-stored umbilical venous blood samples collected from these patients during IFAC were measured for serum concentrations of each IgG subclass. The largest change was observed in the IgG2 concentration, with a mean increase of 221% following IFAC. The IgG4 concentration also showed a mean increase of 63%. In contrast, the concentration of IgG1, which has the strongest physiological activity of all IgG subclasses examined, only exhibited an overall mean increase of 1.4%. Our results confirmed that immunoglobulins are incorporated into the fetal circulation following IFAC. Copyright © 2010 S. Karger AG, Basel.

  1. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome.

    PubMed

    Patel, Kiran; Akhter, Javeed; Kobrynski, Lisa; Benjamin Gathmann, M A; Gathman, Benjamin; Davis, Onika; Sullivan, Kathleen E

    2012-11-01

    DiGeorge syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported. We found that 3% of patients with DiGeorge syndrome were receiving immunoglobulin replacement therapy and 6% of patients over the age of 3 years had hypogammaglobulinemia. We conclude that DiGeorge syndrome is associated with significant humoral immune deficiency.

  2. SU-C-213-01: 3D Printed Patient Specific Phantom Composed of Bone and Soft Tissue Substitute Plastics for Radiation Therapy

    SciTech Connect

    Ehler, E; Sterling, D; Higgins, P

    2015-06-15

    Purpose: 3D printed phantoms constructed of multiple tissue approximating materials could be useful in both clinical and research aspects of radiotherapy. This work describes a 3D printed phantom constructed with tissue substitute plastics for both bone and soft tissue; air cavities were included as well. Methods: 3D models of an anonymized nasopharynx patient were generated for air cavities, soft tissues, and bone, which were segmented by Hounsfield Unit (HU) thresholds. HU thresholds were chosen to define air-to-soft tissue boundaries of 0.65 g/cc and soft tissue-to-bone boundaries of 1.18 g/cc based on clinical HU to density tables. After evaluation of several composite plastics, a bone tissue substitute was identified as an acceptable material for typical radiotherapy x-ray energies, composed of iron and PLA plastic. PET plastic was determined to be an acceptable soft tissue substitute. 3D printing was performed on a consumer grade dual extrusion fused deposition model 3D printer. Results: MVCT scans of the 3D printed heterogeneous phantom were acquired. Rigid image registration of the patient and the 3D printed phantom scans was performed. The average physical density of the soft tissue and bone regions was 1.02 ± 0.08 g/cc and 1.39 ± 0.14 g/cc, respectively, for the patient kVCT scan. In the 3D printed phantom MVCT scan, the average density of the soft tissue and bone was 1.01 ± 0.09 g/cc and 1.44 ± 0.12 g/cc, respectively. Conclusion: A patient specific phantom, constructed of heterogeneous tissue substitute materials was constructed by 3D printing. MVCT of the 3D printed phantom showed realistic tissue densities were recreated by the 3D printing materials. Funding provided by intra-department grant by University of Minnesota Department of Radiation Oncology.

  3. Thermodynamic stability contributes to immunoglobulin specificity.

    PubMed

    Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2014-05-01

    Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies.

  4. Effect of flash-heat treatment on immunoglobulins in breast milk.

    PubMed

    Chantry, Caroline J; Israel-Ballard, Kiersten; Moldoveanu, Zina; Peerson, Jan; Coutsoudis, Anna; Sibeko, Lindiwe; Abrams, Barbara

    2009-07-01

    Heat-treated expressed breast milk is recommended by the World Health Organization as an option to reduce vertical HIV transmission in resource-poor regions. Flash-heat (FH) is a low technology pasteurization method developed for home use, but its effect on quantity and quality of breast milk immunoglobulins is unknown. To evaluate FH's effect on breast milk immunoglobulin levels and antigen-binding capacity. Fifty HIV+ mothers in South Africa provided breast milk. Part of each sample served as an unheated control; the remainder was flash-heated. Total and antigen-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent assay. Paired t test was performed on log-transformed data. FH significantly decreased total IgA and IgG concentrations [geometric mean (geometric SD) 318.0 (1.9) vs. 398.2 (1.9) microg/mL and 89.1 (2.7) vs. 133.3 (2.5) microg/mL, P < 0.001 each]. Similar decreases in anti-HIV-1 gp120 IgG, anti-pneumococcal polysaccharide, and anti-poliovirus IgA occurred (P < 0.001 each). Although the latter was most affected, FH retained 66% of the antigen-binding ability. In contrast, binding capacity of IgA and IgG to influenza increased after FH (P = 0.029 and 0.025, respectively). Most breast milk immunoglobulin activity survives FH, suggesting flash-heated breast milk is immunologically superior to breast milk substitutes. Clinical significance of this decreased immunoglobulin activity needs evaluation in prospective trials.

  5. Immunoglobulin G4-related sclerosing disease with orbital inflammation in a 12-year-old girl.

    PubMed

    Sane, Mona; Chelnis, James; Kozielski, Rafal; Fasiuddin, Airaj

    2013-10-01

    Immunoglobulin G4-related sclerosing disease is a rare but potentially debilitating cause of orbital inflammation, with a predilection for older males. We report the case of a 12-year-old African girl with immunoglobulin G4-related sclerosing disease, including possible extraorbital involvement. Because of an escalating severity of illness leading to oculomotor nerve palsy and cavernous sinus thrombosis that was resistant to steroids, systemic immunosuppressive therapy with rituximab was used to achieve disease remission. The diagnosis was histologically confirmed with a tissue biopsy. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  6. [Good response of scleromyxedema and dermato-neuro syndrome to treatment with intravenous immunoglobulins].

    PubMed

    Bielsa, I; Benvenutti, F; Guinovart, R M; Ferrándiz, C

    2012-05-01

    Scleromyxedema is a potentially serious disease that can have various systemic complications. One of the most frequent forms of central nervous system involvement is dermato-neuro syndrome. High-dose intravenous immunoglobulins are among the drug treatments that have been used for this syndrome. We describe 2 patients with scleromyxedema, one of whom developed dermato-neuro syndrome. Both patients responded well to treatment with high-dose intravenous immunoglobulins. We suggest this therapy as a suitable first-line treatment for scleromyxedema and for its neurological complications.

  7. Right Ventricular Outflow Tract Obstruction Due to Immunoglobulin G4-Related Disease.

    PubMed

    Ishida, Masaru; Sakaguchi, Taichi; Miyagawa, Shigeru; Nishi, Hiroyuki; Yoshikawa, Yasushi; Fukushima, Satsuki; Kawamura, Ai; Ueno, Takayoshi; Ishibashi-Ueda, Hatsue; Sawa, Yoshiki

    2017-03-01

    A 64-year-old man with extensive tumorous infiltration of the pulmonary valve underwent partial resection of a tumor of the right ventricular outflow tract and replacement of the affected valve. A diagnosis of immunoglobulin-G4 related disease of the heart was made based on the immunohistologic findings. One year after the surgical resection, growth of the tumorous mass was observed, and steroid therapy was initiated. He had no sign of tumor progression four years after the steroid therapy.

  8. Structure and Function of Immunoglobulins

    PubMed Central

    Schroeder, Harry W; Cavacini, Lisa

    2013-01-01

    Immunoglobulins are heterodimeric proteins composed of two heavy (H) and two light (L) chains. They can be separated functionally into variable (V) domains that binds antigens and constant (C) domains that specify effector functions such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events, and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each V domain can be split into three regions of sequence variability, termed the complementarity determining regions, or CDRs, and four regions of relatively constant sequence termed the framework regions, or FRs. The three CDRs of the H chain are paired with the three CDRs of the L chain to form the antigen binding site, as classically defined. There are five main classes of heavy chain C domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into four subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties; and IgA can similarly be split into IgA1 and IgA2. The constant domains of the H chain can be switched to allow altered effector function while maintaining antigen specificity. PMID:20176268

  9. Structure and function of immunoglobulins.

    PubMed

    Schroeder, Harry W; Cavacini, Lisa

    2010-02-01

    Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2.

  10. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    PubMed Central

    Jolles, Stephen

    2013-01-01

    Immunoglobulin (Ig)-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg) or subcutaneously (SCIg). While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20) has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg) infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. PMID:27471693

  11. Immunoglobulin M for Acute Infection: True or False?

    PubMed Central

    2016-01-01

    Immunoglobulin M (IgM) tests have clear clinical utility but also suffer disproportionately from false-positive results, which in turn can lead to misdiagnoses, inappropriate therapy, and premature closure of a diagnostic workup. Despite numerous reports in the literature, many clinicians and laboratorians remain unaware of this issue. In this brief review, a series of virology case examples is presented. However, a false-positive IgM can occur with any pathogen. Thus, when an accurate diagnosis is essential for therapy, prognosis, infection control, or public health, when the patient is sick enough to be hospitalized, or when the clinical or epidemiologic findings do not fit, IgM detection should not be accepted as a stand-alone test. Rather, whenever possible, the diagnosis should be confirmed by other means, including testing of serial samples and the application of additional test methods. PMID:27193039

  12. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

    PubMed Central

    Goudouris, Ekaterini Simões; Silva, Almerinda Maria do Rego; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso de Mello; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Segundo, Gesmar Rodrigues Silva; Barreto, Irma Cecília Douglas Paes; Dorna, Mayra de Barros; Barros, Myrthes Anna Maragna Toledo; Forte, Wilma Carvalho Neves

    2017-01-01

    ABSTRACT In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. PMID:28444082

  13. [Topical corticosteroids as a therapeutic alternative in linear immunoglobulin A bullous dermatosis in childhood: case report].

    PubMed

    Gil Sáenz, Francisco José; Durán Urdániz, Gabriel; Fernández Galar, Marta; Ballester, Juan Gimeno; Herrero Varasa, Ana; Garcés Bordege, Rosa

    2016-12-01

    Linear immunoglobulin A dermatosis of childhood is a rare autoimmune disorder. Its etiology remains unknown, although it has been linked to drugs, infections, immunological diseases and lymphoproliferative processes. We report the case of a 6 year old girl who consulted for perioral bullous lesions without other symptoms. Neither treatment with mupirocin nor methylprednisolone therapy achieved remission of cutaneous lesions. Skin biopsy showed a linear immunoglobulin A dermatosis. It was not possible to start treatment with dapsone because of a partial glucose-6-phosphate dehydrogenase deficiency, so topical treatment was maintained with good evolution of lesions. Linear immunoglobulin A dermatosis is a rare disease whose differential diagnosis includes other bullous diseases. Pathology is essential for diagnosis. When treatment with dapsone is not possible, topical corticosteroids may be an alternative, either alone or associated with other treatments.

  14. Unusual substitutions in HIV-1 vif from children infected perinatally without progression to AIDS for more than 8 years without therapy.

    PubMed

    De Maio, Federico A; Rocco, Carlos A; Aulicino, Paula C; Bologna, Rosa; Mangano, Andrea; Sen, Luisa

    2012-12-01

    The HIV-1 vif gene encodes for an accessory protein that is central for virus replication due mainly to its capacity to counteract the antiviral action of host APOBEC3 restriction factors. In order to evaluate whether HIV-1 vif alterations account for a delayed progression to AIDS in children infected perinatally, the vif genes from a group of 11 patients who exhibited an extremely slow disease progression (slow progressors) were studied by direct sequencing. In addition, the vif genes from a group of 93 children with typical disease progression (typical progressors) were analyzed for comparison. Phylogenetic analysis indicated that sequences from slow progressors did not have a common origin, discarding a shared ancestor of reduced virulence. There were no differences in the diversity between the vif genes from slow and typical progressors. No gross defects showing a clear distinction among sequences from both groups of children were found. However, in the deduced Vif proteins, changes V13I, V55T, and L81M were observed only in sequences from slow progressors. By analyzing sequences stored in databases, these mutations were determined as unusual substitutions occurring at highly conserved Vif sites across different HIV-1 clades, but were observed with an increased frequency in sequences from elite controllers. These mutations were in the Vif regions reported as relevant for protein activity. These findings suggest that the Vif sequences from slow progressors carry unusual substitutions, which may alter the protein function and may contribute to viral attenuation.

  15. Patterns of Somatic Mutations in Immunoglobulin Variable Genes

    PubMed Central

    Golding, G. Brian; Gearhart, Patricia J.; Glickman, Barry W.

    1987-01-01

    The mechanism responsible for somatic mutation in the variable genes of antibodies is unknown and may differ from previously described mechanisms that produce mutation in DNA. We have analyzed 421 somatic mutations from the rearranged immunoglobulin variable genes of mice to determine (1) if the nucleotide substitutions differ from those generated during meiosis and (2) if the presence of nearby direct and inverted repeated sequences could template mutations around the variable gene. The results reveal a difference in the pattern of substitutions obtained from somatic mutations vs. meiotic mutations. An increased frequency of T:A to C:G transitions and a decreased frequency of mutations involving a G in the somatic mutants compared to the meiotic mutants is indicated. This suggests that the mutational processes responsible for somatic mutation in antibody genes differs from that responsible for mutation during meiosis. An analysis of the local DNA sequences revealed many direct repeats and palindromic sequences that were capable of templating some of the known mutations. Although additional factors may be involved in targeting mutations to the variable gene, mistemplating by nearby repeats may provide a mechanism for the enhancement of somatic mutation. PMID:3557109

  16. Secretory immunoglobulin A and immunoglobulin G in horse saliva.

    PubMed

    Palm, Anna-Karin E; Wattle, Ove; Lundström, Torbjörn; Wattrang, Eva

    2016-11-01

    This study aimed to increase the knowledge on salivary antibodies in the horse since these constitute an important part of the immune defence of the oral cavity. For that purpose assays to detect horse immunoglobulin A (IgA) including secretory IgA (SIgA) were set up and the molecular weights of different components of the horse IgA system were estimated. Moreover, samples from 51 clinically healthy horses were tested for total SIgA and IgG amounts in saliva and relative IgG3/5 (IgG(T)) and IgG4/7 (IgGb) content were tested in serum and saliva. Results showed a mean concentration of 74μg SIgA/ml horse saliva and that there was a large inter-individual variation in salivary SIgA concentration. For total IgG the mean concentration was approx. 5 times lower than that of SIgA, i.e. 20μg IgG/ml saliva and the inter-individual variation was lower than that observed for SIgA. The saliva-serum ratio for IgG isotypes IgG3/5 and IgG4/7 was also assessed in the sampled horses and this analysis showed that the saliva-serum ratio of IgG4/7 was in general approximately 4 times higher than that of IgG3/5. The large inter-individual variation in salivary SIgA levels observed for the normal healthy horses in the present study emphasises the need for a large number of observations when studying this parameter especially in a clinical setting. Moreover, our results also indicated that some of the salivary IgG does not originate from serum but may be produced locally. Thus, these results provide novel insight, and a base for further research, into salivary antibody responses of horses.

  17. Cow's milk with active immunoglobulins against Campylobacter jejuni: effects of temperature on immunoglobulin activity.

    PubMed

    Riera, Francisco; Alvarez, Alejandro; Espi, Alberto; Prieto, Miguel; de la Roza, Begoña; Vicente, Fernando

    2014-04-01

    Adult Holstein cows were injected with an antiserum against Campylobacter jejuni and immunoglobulin activities in vitro were determined in blood and milk several weeks after injection. The immunoactivity of immunoglobulins in milk was measured by an ELISA after different temperature-time treatments (60-91°C and 4-3600 s) at laboratory and pilot-plant scales. Kinetic and thermodynamic parameters were determined. An increase in immunoglobulin activity in milk was detected several days after injection. Optical densities increased by three- to seven-fold in this period. The activity started to decay 4-5 weeks after injection. Immunoglobulins maintained most of their in vitro activity under pasteurisation conditions (72°C and 15 s) and were denatured following first-order kinetics. The injection protocol applied allows milk with specific immunoglobulins against Campylobacter jejuni to be obtained. Traditional pasteurisation did not reduce this activity. © 2013 Society of Chemical Industry.

  18. High-Dose Subcutaneous Immunoglobulin in Patients With Multifocal Motor Neuropathy: A Nursing Perspective.

    PubMed

    Rasutis, Vilija M; Katzberg, Hans D; Bril, Vera

    Multifocal motor neuropathy (MMN), an immune neuromuscular condition causing progressive weakness, usually responds to immune-mediated treatments, including intravenous immunoglobulin (IVIG). Fifteen patients with MMN receiving IVIG were enrolled in an open-label, single-center trial and switched to 20% subcutaneous immunoglobulin (SCIG) using a smooth transition protocol (ie, changing the therapy without interruption or impact on the intended outcome of the therapy). Patients received individualized training and support based on motivation and ability to learn, follow directions, and maintain compliance. Although some patients required assistance during the training phase, most managed self-infusion and reported satisfaction in managing therapy autonomously. Educating patients with neuropathies to self-infuse high-dose SCIG at home and with flexibility in dosing schedules was successfully demonstrated in this patient group.

  19. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy.

    PubMed

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-09-07

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

  20. Immunoglobulin classes of Aleutian disease virus antibody.

    PubMed Central

    Porter, D D; Porter, H G; Suffin, S C; Larsen, A E

    1984-01-01

    Aleutian disease virus (ADV) persistently infects mink and causes marked hypergammaglobulinemia. Immunoglobulin class-specific antisera were used to define the total immunoglobulin of each class by radial immunodiffusion and the immunoglobulin class of ADV-specific antibody by immunofluorescence in experimentally and naturally infected mink. Electrophoretic gamma globulin closely reflects the immunoglobulin G (IgG) level in mink, and the majority of the increased immunoglobulin and ADV antibody in infected mink is IgG. IgM becomes elevated within 6 days after infection, reaches peak levels by 15 to 18 days, and returns to normal by 60 days after infection. The first ADV antibody demonstrable is IgM, and most mink have virus-specific IgM antibody for at least 85 days postinfection. Serum IgA levels in normal mink are not normally distributed, and ADV infection causes a marked elevation of IgA. Low levels of ADV-specific IgA antibody can be shown throughout the course of infection. Failure of large amounts of virus-specific IgG antibody to inhibit the reaction of virus-specific IgM and IgA antibodies suggests that the various classes of antibodies are directed against spatially different antigenic determinants. The IgM and IgA were shown not to be rheumatoid factors. PMID:6319283

  1. Immunoglobulin isotypes in childhood asthma.

    PubMed

    Najam, F I; Giasuddin, A S; Shembesh, A H

    1999-01-01

    Immunoglobulin isotypes (IgG, IgA, IgM, IgD, IgE) in serum were investigated in 64 Libyan children with mild to moderately severe asthma (age: 1-12 years; sex: 39 males, 25 females) (Group A) and in 57 healthy Libyan children (age: 1-12 years; sex: 30 males, 27 females (Group B). The patients were classified according to age into three groups (A1: 1-3 years; A2: > 3-5 years; A3: > 5-12 years); according to disease activity into two groups (AA: active disease; NA: inactive disease); and according to age plus disease activity into six groups (AA1, NA1; AA2, NA2; AA3, NA3). The healthy children were also divided according to age into three groups (B1: 1-3 years; B2: > 3-5 years; B3: > 5-12 years). IgG, IgA, IgM and IgD were measured by radial immunodiffusion method and IgE was estimated by enzyme immunoassay technique utilizing immunokits from bioMerieux, France. Serum levels of IgG, IgD and IgE were elevated significantly in patients compared to controls (A vs B: p < 0.05) while IgA and IgM levels were normal (p > 0.05). IgG and IgD levels were raised in A3 (p < 0.05), while IgD levels were raised in both A2 and A3 (p < 0.05) and IgE was elevated in all age groups (p < 0.05). However, IgG was elevated significantly in AA only, while IgD and IgE levels were high in both AA and NA (p < 0.05) and IgE was even considerably higher in AA compared to NA (p < 0.02). Further elevated levels were observed for IgG in AA3 only (p < 0.05), for IgD in NA2 (p < 0.01), AA3 (p < 0.01) and NA3 (p < 0.05) and IgE was much higher in patients with active disease than with inactive disease in all age groups (p < 0.05). The fact that asthmatic attack in majority of our patients can be explained as mediated through IgE and the possibilities that IgG and IgD may play roles as aetiopathogenetic or protective regulatory factors in childhood asthma are discussed.

  2. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits complicated by immunoglobulin A nephropathy in the renal allograft.

    PubMed

    Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku

    2016-07-01

    Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.

  3. 7th International Immunoglobulin Conference: Mechanisms of action.

    PubMed

    Basta, M; Branch, D R

    2014-12-01

    Although intravenous immunoglobulin (IVIg) is widely used for replacement therapy in immunodeficiencies and to treat autoimmune and inflammatory diseases, its mechanisms of action are not fully understood. Examination of immunoglobulin (Ig) receptors, including the Fc-gamma receptors (FCγRs) and the neonatal Fc receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVIg treatment. However, the beneficial effect of IVIg encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C3a, C5a, C3b and C4b, by infused Ig molecules. This interaction prevents binding of complement fragments to their receptors on target cells, thus attenuating the immune damage. Additionally, anti-inflammatory effects may be facilitated by IgA via specific receptors and/or complement scavenging. Glycosylation of both the Fc- and Fab-fragments has also been implicated in the anti-inflammatory action of IVIg. Although there is evidence to support a role for sialylated IgG glycovariants in mediating the effect of IVIg, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in IgG glycosylation has been observed following IVIg treatment in Guillain-Barré syndrome patients, and this has been associated with improved clinical outcomes.

  4. IMMUNOGLOBULIN PATTERNS IN SCHIZOPHRENIC PATIENTS1

    PubMed Central

    Tiwari, S.G.; Lal, Narottam; Trivedi, J.K.; Sayeed, J.; Bahauguna, L.M.

    1984-01-01

    SUMMARY Immunoglobulins G, M and A were estimated in serum and cerebrospinal fluid (CSF) of 30 schizophrenics, 20 neurological controls and 20 surgical controls. Significant increased levels of serum Ig A and M were detected in schizophrenics. An association was observed between increasing levels of serum IgA and IgM with the duration of disease and the number of episodes. CSF IgG/TP% was also significantly increased with the severity of the disease. On the basis of viral aetiology of schizophrenia it can be concluded that the increase in immunoglobulins synthesis might be due to the persistent antigenic stimulation. PMID:21965989

  5. Estimation of bovine colostral immunoglobulins by refractometry.

    PubMed

    Molla, A

    1980-07-12

    The total protein of colostral whey from dairy cows as determined by a refractometer were compared with the immune globulin concentration obtained by cellulose acetate membrane electrophoresis and the immunoglobulin (IgA + IgG + IgM) contents determined by radial immunodiffusion. The coefficient of correlation between the results obtained by refractometry and electrophoresis was 0.98 (P < 0.001). The correlation between refractometry and radial immunodiffusion was 0.89 (P < 0.001), while that of electrophoresis and radial immunodiffusion was 0.87 (P < 0.001). Refractometry can be used as a simple, fast and inexpensive indirect method of assessing immunoglobulins in colostral whey.

  6. Switch Transcripts in Immunoglobulin Class Switching

    NASA Astrophysics Data System (ADS)

    Lorenz, Matthias; Jung, Steffen; Radbruch, Andreas

    1995-03-01

    B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG1) by the heterologous human metallothionein II_A promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.

  7. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

    Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)

  8. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

    Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)

  9. Therapeutic intervention of clinical sepsis with intravenous immunoglobulin, white blood cells and antibiotics.

    PubMed

    Fischer, G W; Weisman, L E

    1990-01-01

    Antibiotics are the mainstay of therapy for acute bacterial infections. However, recent studies have suggested that adjunctive therapy designed to augment host immunity, might reduce morbidity and mortality. Many bacterial pathogens such as Haemophilus influenzae, Streptococcus pneumoniae and Group B streptococcus are encapsulated and require opsonic antibody to promote efficient phagocytosis and killing by neutrophils. Children with bacterial sepsis may be deficient in both of these components of immunity. This is a particularly serious problem in premature babies who may not receive protective amounts of antibodies from their mothers, since most antibody crosses the placenta in the last 4-6 weeks of pregnancy. Septic infants may also deplete their neutrophil reserves and develop neutropenia during infection. Since efficient clearance of encapsulated bacteria require both neutrophils and antibody, these babies are at high risk for treatment failure even with appropriate antibiotic therapy. Several studies have analyzed the role of neutrophil transfusions and immunoglobulin therapy in septic infants. However, relatively few patients have been prospectively evaluated in controlled studies. In addition, the logistical problems related to rapidly collecting neutrophils for therapy of bacterial sepsis are considerable and have decreased the usefulness of this approach. The availability of intravenous immunoglobulin (IVIG) has made the use of immunoglobulin feasible even in rapidly progressing bacterial sepsis. Animal studies have demonstrated the potential usefulness of IVIG and studies in septic babies strongly suggest that IVIG as an adjunct to antibiotics might improve mortality in septic neonates. Further research is needed to improve the logistics of obtaining neutrophils and to improve the availability of pathogen-specific immunoglobulin preparations.

  10. Variations of serum carcinoembryonic antigen, alpha-fetoprotein and immunoglobulin levels in patients with breast cancer.

    PubMed

    Vântu, A; Bălănescu, I; Stafidov, N; Voiculeţ, N

    1982-01-01

    To find the marker value of the carcinoembryonic antigen, alpha-fetoprotein (AFP) and immunoglobulin levels in patients with breast cancer, stages I or II, these parameters were determined in 94 patients devided into two groups: group A of 57 patients operated on for extirpation of the tumor without preoperative treatment and group B of 37 patients subjected to cobalto-therapy prior to operation then having the tumor extirpated. In the first group the determinations were performed before operation, at 14 days, and 2 months, respectively after the operation. In the second group 5 determinations were performed: before cobalto-therapy, after therapy, before the operation, at 15 days and 2 months, respectively after the operation. CEA and AFP were determined by the RIA tests and the immunoglobulins by immunodiffusion. The results showed that in 7 out of 37 cases the levels of CEA were significantly raised before and after therapy sometimes reaching values as high as 1000-3000 ng/nl while AFP was not influenced at all by breast tumors. The immunoglobulin values were also uninfluenced by the disease, but in certain cases of breast cancer IgA reached values of 300-500 IU/ml. It is assumed that since the patients who presented high CEA values had also an unfavourable evolution of the disease, determination of this antigen might also have a predictive value.

  11. Efficacy of subcutaneous immunoglobulins in primary immunodeficiency with Crohn's-like phenotype: report of a case.

    PubMed

    Sanges, M; Spadaro, G; Miniero, M; Mattera, D; Sollazzo, R; D'Armiento, F P; De Palma, G D; Pecoraro, A; Borrelli, F; Genovese, A; D'Arienzo, A

    2015-01-01

    Common variable immune deficiency (CVID) is the most frequent primary immunodeficiency in adults. In CVID, the prevalence of gastrointestinal manifestations ranges between 2 and 50% with a complication-related morbidity second only to that of the respiratory tract. In some cases, clinical and endoscopic features are undistinguishable from those of inflammatory bowel disease (IBD). We describe the case of a 28-year-old man in which a diagnosis of Crohn's disease was firstly suspected. Subsequently, a diagnosis of Crohn's-like disease in a patient with CVID was made and a replacement therapy with human normal immunoglobulin intravenously was started. Unfortunately, serum IgG levels remained below 2.0 g/l in pre-infusional controls with persistence of gastrointestinal symptoms and malnutrition despite anti-inflammatory therapy (mesalazine, corticosteroids). Then, the patient began treatment with human normal immunoglobulins administered subcutaneously. The follow-up visits showed a progressive increase in serum IgG. Moreover, the patient reported improvement of gastrointestinal symptoms with reduction of diarrhoea, and laboratory tests showed a progressive and significant improvement. We confirm that therapy with subcutaneously administered immunoglobulins is safe and effective. In addition, our observations indicate that, for patients with CVID and enteropathic complications, replacement therapy with subcutaneous IgG may be the treatment of choice.

  12. Stress modulates intestinal secretory immunoglobulin A

    PubMed Central

    Campos-Rodríguez, Rafael; Godínez-Victoria, Marycarmen; Abarca-Rojano, Edgar; Pacheco-Yépez, Judith; Reyna-Garfias, Humberto; Barbosa-Cabrera, Reyna Elizabeth; Drago-Serrano, Maria Elisa

    2013-01-01

    Stress is a response of the central nervous system to environmental stimuli perceived as a threat to homeostasis. The stress response triggers the generation of neurotransmitters and hormones from the hypothalamus pituitary adrenal axis, sympathetic axis and brain gut axis, and in this way modulates the intestinal immune system. The effects of psychological stress on intestinal immunity have been investigated mostly with the restraint/immobilization rodent model, resulting in an up or down modulation of SIgA levels depending on the intensity and time of exposure to stress. SIgA is a protein complex formed by dimeric (dIgA) or polymeric IgA (pIgA) and the secretory component (SC), a peptide derived from the polymeric immunoglobulin receptor (pIgR). The latter receptor is a transmembrane protein expressed on the basolateral side of gut epithelial cells, where it uptakes dIgA or pIgA released by plasma cells in the lamina propria. As a result, the IgA-pIgR complex is formed and transported by vesicles to the apical side of epithelial cells. pIgR is then cleaved to release SIgA into the luminal secretions of gut. Down modulation of SIgA associated with stress can have negative repercussions on intestinal function and integrity. This can take the form of increased adhesion of pathogenic agents to the intestinal epithelium and/or an altered balance of inflammation leading to greater intestinal permeability. Most studies on the molecular and biochemical mechanisms involved in the stress response have focused on systemic immunity. The present review analyzes the impact of stress (mostly by restraint/immobilization, but also with mention of other models) on the generation of SIgA, pIgR and other humoral and cellular components involved in the intestinal immune response. Insights into these mechanisms could lead to better therapies for protecting against pathogenic agents and avoiding epithelial tissue damage by modulating intestinal inflammation. PMID:24348350

  13. Tissue-engineered skin substitutes.

    PubMed

    Mansbridge, Jonathan

    2002-01-01

    The last two years have seen new tissue-engineered skin substitutes come onto the market and begin to resolve the various roles to which each is best suited. It is becoming evident that some of the very expensive cell-based products have cost-benefit advantage despite their high price and are valuable within the restricted applications for which they are intended. The use of skin substitutes for testing purposes has extended from epidermal keratinocytes to other integumentary epithelia and into preparations containing multiple cell types in which reactions resulting from paracrine interactions can be examined. Challenges remain in the application of gene therapy techniques to skin substitutes, both the control of transgene expression and in the selection of suitable genes to transfect. A coming challenge is the production of tissue-engineered products without the use of animal products other than human cells. A challenge that may be diminishing is the importance of acute rejection of allogeneic tissue-engineered skin substitutes.

  14. Immunoglobulin production by human-mouse somatic cell hybrids.

    PubMed

    Smith, M; Hirschhorn, K

    1977-01-01

    Studies on immunoglobulin production in human-mouse somatic cell hybrids suggest: 1. The structural genes for heavy chain immunoglobulins are carried on chromsome 6, probably on the short arm or the proximal half of the long arm of the chromosome. 2. The structural gene for kappa light chain immunoglobulin may be carried on chromsome 11. 3. The occurrence of immunoglobulin molecules on the cell surface requires the presence of chromosome 2.

  15. Intestinal Absorption of Immunoglobulins by Newborn Infants

    PubMed Central

    Iyengar, Leela; Selvaraj, R. J.

    1972-01-01

    Intestinal absorption in newborn infants of immunoglobulins present in colostrum was studied by measuring the concentrations of immunoglobulins IgA, IgG, and IgM in cord blood and following the changes in the serum of the infant on the 5th day after birth. In infants who did not receive colostrum, a marked fall in IgG levels was observed on the 5th day after birth as compared to levels at birth. The concentrations of IgA and IgM showed marginal changes. In contrast, colostrumfed infants showed significant increases in the concentration of IgG. Levels of all 3 immunoglobulins on the 5th day were significantly higher in the serum of colostrumfed infants as compared to those who did not receive colostrum. It is suggested that immunoglobulins present in colostrum are to some extent absorbed from the intestinal tract of newborn infants, and this may have some physiological significance in the resistance to infection during the early neonatal period. PMID:4624594

  16. Anticonvulsant hypersensitivity syndrome treated with intravenous immunoglobulin.

    PubMed

    Dredge, David C; Parsons, Elizabeth C; Carter, Lindsay P; Staley, Kevin J

    2010-07-01

    Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed.

  17. Immunoglobulins in tears of normal Indian people.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Mani, K.; Saha, K.

    1976-01-01

    Immunoglobulin concentrations in tears from 50 healthy Indians aged from 14 to 50 years were measured by a standard immunodiffusion method. The levels of IgA were substantial; those of IgG were very low; and IgD and IgM were not present. The mean IgA level was 24-6 mg/100 ml. PMID:1276121

  18. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins

    PubMed Central

    Mukerji, Shibani S.; Lam, Alice D.

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins. PMID:26740855

  19. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins.

    PubMed

    Mukerji, Shibani S; Lam, Alice D; Wilson, Michael R

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins.

  20. Chronic myopathy due to immunoglobulin light chain amyloidosis

    PubMed Central

    Manoli, Irini; Kwan, Justin Y.; Wang, Qian; Rushing, Elisabeth J.; Tsokos, Maria; Arai, Andrew E.; Burch, Warner M.; Dispenzieri, Angela; McPherron, Alexandra C.; Gahl, William A.

    2013-01-01

    Amyloid myopathy associated with a plasma cell dyscrasia is a rare cause of muscle hypertrophy. It can be a challenging diagnosis, since pathological findings are often elusive. In addition, the mechanism by which immunoglobulin light-chain deposition stimulates muscle overgrowth remains poorly understood. We present a 53–year old female with a 10-year history of progressive generalized muscle overgrowth. Congo-red staining and immunohistochemistry revealed perivascular lambda light chain amyloid deposits, apparent only in a second muscle biopsy. The numbers of central nuclei and satellite cells were increased, suggesting enhanced muscle progenitor cell formation. Despite the chronicity of the light chain disease, the patient showed complete resolution of hematologic findings and significant improvement of her muscle symptoms following autologous bone marrow transplantation. This case highlights the importance of early diagnosis and therapy for this treatable cause of a chronic myopathy with muscle hypertrophy. PMID:23465863

  1. Calculating the Dose of Subcutaneous Immunoglobulin for Primary Immunodeficiency Disease in Patients Switched From Intravenous to Subcutaneous Immunoglobulin Without the Use of a Dose-Adjustment Coefficient

    PubMed Central

    Fadeyi, Michael; Tran, Tin

    2013-01-01

    Primary immunodeficiency disease (PIDD) is an inherited disorder characterized by an inadequate immune system. The most common type of PIDD is antibody deficiency. Patients with this disorder lack the ability to make functional immunoglobulin G (IgG) and require lifelong IgG replacement therapy to prevent serious bacterial infections. The current standard therapy for PIDD is intravenous immunoglobulin (IVIG) infusions, but IVIG might not be appropriate for all patients. For this reason, subcutaneous immunoglobulin (SCIG) has emerged as an alternative to IVIG. A concern for physicians is the precise SCIG dose that should be prescribed, because there are pharmacokinetic differences between IVIG and SCIG. Manufacturers of SCIG 10% and 20% liquid (immune globulin subcutaneous [human]) recommend a dose-adjustment coefficient (DAC). Both strengths are currently approved by the FDA. This DAC is to be used when patients are switched from IVIG to SCIG. In this article, we propose another dosing method that uses a higher ratio of IVIG to SCIG and an incremental adjustment based on clinical status, body weight, and the presence of concurrent diseases. PMID:24391400

  2. Manufacture of Immunoglobulin Products for Patients with Primary Antibody Deficiencies – The Effect of Processing Conditions on Product Safety and Efficacy

    PubMed Central

    Farrugia, Albert; Quinti, Isabella

    2014-01-01

    Early preparations of immunoglobulin (Ig) manufactured from human plasma by ethanol (Cohn) fractionation were limited in their usefulness for substitution therapy in patients with primary antibody deficiencies (PAD), as Ig aggregates formed during manufacture resulted in severe systemic reactions in patients when given intravenously. Developments in manufacturing technology obviated this problem through the capacity to produce concentrated solutions of intact monomeric Ig, revolutionizing PAD treatment and improving patient life expectancy and quality of life. As the need for Ig has grown, manufacturers have refined further manufacturing technologies to improve yield from plasma and produce therapies, which are easier and less expensive to deliver. This has led to the substitution, partly or wholly, of ethanol precipitation by other techniques such as chromatography, and has also stimulated the production of highly concentrated solutions capable of rapid infusion. Ig products have been associated, since their inception, with certain adverse events, including infectious disease transmission, hemolysis, and thromboembolism. The introduction of standardized manufacturing processes and dedicated pathogen elimination steps has removed the risk of infectious disease, and the focus of attention has shifted to other problems, which appear to have increased over the past 5 years. These include hemolysis and thromboembolism, both the cause for substantial concern and the subject of recent regulatory scrutiny and actions. We review the development of manufacturing technology and the emerging evidence that changes for the optimization of yield and convenience has contributed to the recent incidents in certain adverse events. Industry measures under development will be discussed in terms of their potential to improve safety and optimize care for patients with PAD. PMID:25566269

  3. Renal involvement of monoclonal immunoglobulin deposition disease associated with an unusual monoclonal immunoglobulin A glycan profile.

    PubMed

    Kaneko, Syuzou; Usui, Joichi; Narimatsu, Yoshiki; Ito, Hiromi; Narimatsu, Hisashi; Hagiwara, Masahiro; Tsuruoka, Shuichi; Nagata, Michio; Yamagata, Kunihiro

    2010-08-01

    A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-kappa gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-kappa deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient's serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-kappa staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient's serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.

  4. Elevated endoxin-like factor complicating a multifetal second trimester pregnancy: treatment with digoxin-binding immunoglobulin.

    PubMed

    Adair, C D; Buckalew, V; Taylor, K; Ernest, J M; Frye, A H; Evans, C; Veille, J C

    1996-01-01

    We report a case of a second trimester multifetal pregnancy with preeclampsia associated with an elevated digoxin-like immune factor. Due to the remoteness from viability the patient was offered therapy with digoxin-binding immunoglobulin. No untoward maternal effects were noted.

  5. Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections

    PubMed Central

    Kovacevic, Miro; Grant, Paul

    2015-01-01

    Abstract This is a case series describing 12 youths treated with intravenous immunoglobulin (IVIG) for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Although it is a clinically based series, the case reports provide new information about the short-term benefits of IVIG therapy, and are the first descriptions of long-term outcome for PANDAS patients. PMID:25658609

  6. Membrane-associated immunoglobulins of human lymphocytes in immunologic disorders

    PubMed Central

    Nicod, Isabelle; Girard, J. P.; Cruchaud, A.

    1973-01-01

    Membrane-associated immunoglobulins of peripheral blood lymphocytes were studied by indirect immunofluorescence for γ, α, μ, κ and λ chains in healthy subjects and patients with immunologic disease. In healthy subjects, heavy chains were found on 30·7% of lymphocytes (γ 15·3%, α 7·2% and μ 8·2%) and light chains on 32·8% of cells (κ 20·4% and λ 12·4%). Patients with humoral immune deficiencies had fewer immunoglobulin-bearing cells; sarcoidosis or thymectomy patients had normal or decreased immunoglobulin-bearing lymphocytes; cells with light chains were fewer than those with heavy chains on their lymphocytes. In some cases, normal levels of serum immunoglobulins were found in the absence of the corresponding immunoglobulin-bearing cells, and in others normal immunoglobulin-bearing lymphocytes were present in the absence of the corresponding serum immunoglobulins. These data suggest that (1) immunoglobulin-bearing lymphocytes in blood do not reflect the condition of immunoglobulin-synthesizing cells in peripheral lymphoid tissues, and (2) in certain immunologic disorders, either some B-lymphocytes do not synthesize immunoglobulins, or immunoglobulins are in such a situation that the whole molecule or part of the molecule is not visualized by current methods. PMID:4587505

  7. Stable synthetic bacteriochlorins for photodynamic therapy: role of dicyano peripheral groups, central metal substitution (2H, Zn, Pd), and Cremophor EL delivery.

    PubMed

    Huang, Ying-Ying; Balasubramanian, Thiagarajan; Yang, Eunkyung; Luo, Dianzhong; Diers, James R; Bocian, David F; Lindsey, Jonathan S; Holten, Dewey; Hamblin, Michael R

    2012-12-01

    A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)(2)BC and corresponding zinc chelate (NC)(2)BC-Zn and palladium chelate (NC)(2)BC-Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N-dimethylacetamide) into serum-containing medium was compared with the dilution of bacteriochlorin in Cremophor EL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24 h incubation and illumination with 10 J cm(-2) of near-infrared (NIR) light is (NC)(2)BC-Pd (LD(50)=25 nM) > (NC)(2)BC > (NC)(2)BC-Zn ≈ BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)(2)BC-Pd showed PDT-mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers.

  8. Stable Synthetic Bacteriochlorins for Photodynamic Therapy: Role of Dicyano Peripheral Groups, Central Metal Substitution (2H, Zn, Pd), and Cremophor EL Delivery

    PubMed Central

    Huang, Ying-Ying; Balasubramanian, Thiagarajan; Yang, Eunkyung; Luo, Dianzhong; Diers, James R.; Bocian, David F.; Lindsey, Jonathan S.; Holten, Dewey; Hamblin, Michael R.

    2012-01-01

    A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)2BC and corresponding zinc chelate (NC)2BC–Zn and palladium chelate (NC)2BC–Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N-dimethylacetamide) into serum-containing medium was compared with the dilution of bacteriochlorin in Cremophor EL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24 h incubation and illumination with 10 J cm−2 of near-infrared (NIR) light is (NC)2BC–Pd (LD50 = 25 nm) > (NC)2BC > (NC)2BC–Zn ≈ BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)2BC–Pd showed PDT-mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers. PMID:23065820

  9. Immunoglobulin expression and synthesis by human haemic cell lines.

    PubMed Central

    Gordon, J; Hough, D; Karpas, A; Smith, J L

    1977-01-01

    Twenty-six human cell lines derived from a variety of lymphoid and non-lymphoid malignancies, were investigated for their immunological markers, with special reference to the class of immunoglobulin expressed. Twenty-five of the lines stained positively for surface immunoglobulin and IgD together with IgM proved to be the major immunoglobulin classes on these cells. Six of the lines were chosen for a study of their immunoglobulin synthesis patterns over an 18-h period and the immunoglobulin produced was analysed on SDS-polyacrylamide gel electrophoresis. Patterns obtained from the cell lines were similar to that from normal lymph node lymphocytes and differed markedly to plasma cells. Two of the cell lines had abnormal immunoglobulin synthesis patterns characterized as free light chains in one case. The cell lines are evaluated for their usefulness as models of immunoglobulin synthesis and analogues of normal and neoplastic states. PMID:608682

  10. Treatment of rotavirus-associated diarrhea using enteral immunoglobulins for pediatric stem cell transplant patients.

    PubMed

    Williams, Devona

    2015-06-01

    Diarrhea is a common complication associated with allogeneic and autologous stem cell transplant patients. One potential cause of viral diarrhea is rotavirus gastroenteritis. This study represents a single-center experience of using multiple daily doses of enteral immunoglobulins in four pediatric hematopoietic stem cell transplant patients with confirmed rotavirus infections. Four courses of enteral immunoglobulin administration were included for analysis. Clinical characteristics recorded included duration of diarrhea symptoms, frequency of bowel movements, and consistency of stool. Four single courses of enteral immunoglobulins in four patients were included for analysis. Patient age range was from 10 months to 14 years. Three out of four courses observed displayed an improvement in diarrhea frequency and/or stool consistency. Median time from therapy initiation to symptom improvement was three days. At a median 22-month follow-up, one patient was diagnosed with gastrointestinal graft-versus-host disease. The time to rotavirus symptom resolution was decreased, compared to historical controls, and improvement in stool frequency and consistency was observed in three of four courses. One case of gastrointestinal graft-versus-host disease was observed after nearly two years of follow-up. Enteral administration of immunoglobulins may represent a valid clinical option for hematopoietic stem cell transplant patients with rotavirus diarrhea.

  11. Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies

    PubMed Central

    Beauté, J; Levy, P; Millet, V; Debré, M; Dudoit, Y; Le Mignot, L; Tajahmady, A; Thomas, C; Suarez, F; Pellier, I; Hermine, O; Aladjidi, N; Mahlaoui, N; Fischer, A

    2010-01-01

    Lifelong immunoglobulin replacement is the standard, expensive therapy for severe primary antibody deficiencies. This treatment can be administrated either by intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered at home or in an out-patient setting. This study aims to determine whether SCIG is cost-effective compared with IVIG from a French social insurance perspective. Because both methods of administration provide similar efficacies, a cost-minimization analysis was performed. First, costs were calculated through a simulation testing different hypothesis on costs drivers. Secondly, costs were estimated on the basis of field data collected by a questionnaire completed by a population of patients suffering from agammaglobulinaemia and hyper-immunoglobulin (Ig)M syndrome. Patients' satisfaction was also documented. Results of the simulation showed that direct medical costs ranged from €19 484 for home-based IVIG to €25 583 for hospital-based IVIG, with home-based SCIG in between at €24 952 per year. Estimations made from field data were found to be different, with significantly higher costs for IVIG. This result was explained mainly by a higher immunoglobulin mean dose prescribed for IVIG. While the theoretical model showed very little difference between SCIG and hospital-based IVIG costs, SCIG appears to be 25% less expensive with field data because of lower doses used in SCIG patients. The reality of the dose difference between both routes of administration needs to be confirmed by further and more specific studies. PMID:20041884

  12. Efficacy, safety and pharmacokinetics of a novel subcutaneous immunoglobulin, Evogam®, in primary immunodeficiency.

    PubMed

    Empson, Marianne B; Tang, Mimi L K; Pearce, Lisa K C; Rozen, Leon; Gold, Michael S; Katelaris, Constance H; Langton, David; Smart, Joanne; Smith, William B; Steele, Richard H; Ziegler, John B; Maher, Darryl

    2012-10-01

    This phase III, open-label, multi-centre study investigated the efficacy, safety, pharmacokinetics and quality of life impact of Evogam(®), a new chromatographically fractionated 16% subcutaneous immunoglobulin, utilising a 1:1 dose transition ratio from previous immunoglobulin therapy. Thirty-five previously treated patients with primary immunodeficiency received weekly Evogam over 36 weeks. Primary endpoints were rate of serious bacterial infections (SBIs) and steady-state serum immunoglobulin G (IgG) trough concentrations. No SBIs were reported during the study. Evogam produced significantly higher mean trough IgG concentrations with 1:1 dose conversion compared to previous immunoglobulin treatment (8.94 versus 8.27 g/L, p = 0.0063). Evogam was efficacious in the prevention of infections and maintenance of trough levels using a 1:1 dose conversion. It was well tolerated with no withdrawals due to adverse events and was preferred to IVIg by the majority of patients.

  13. Cytomegalovirus Hyper Immunoglobulin for CMV Prophylaxis in Thoracic Transplantation.

    PubMed

    Rea, Federico; Potena, Luciano; Yonan, Nizar; Wagner, Florian; Calabrese, Fiorella

    2016-03-01

    Cytomegalovirus (CMV) infection negatively influences both short- and long-term outcomes after cardiothoracic transplantation. In heart transplantation, registry analyses have shown that CMV immunoglobulin (CMVIG) with or without virostatic prophylaxis is associated with a significant reduction in mortality and graft loss versus no prophylaxis, particularly in high-risk donor (D)+/recipient (R)- transplants. Randomized comparative trials are lacking but retrospective data suggest that addition of CMVIG to antiviral prophylaxis may reduce rates of CMV-related events after heart transplantation, including the incidence of acute rejection or chronic allograft vasculopathy. However, available data consistently indicate that when CMVIG is used, it should be administered with concomitant antiviral therapy, and that evidence concerning preemptive management with CMVIG is limited, but promising. In lung transplantation, CMVIG should again only be used with concomitant antiviral therapy. Retrospective studies have shown convincing evidence that addition of CMVIG to antiviral prophylaxis lowers CMV endpoints and mortality. The current balance of evidence suggests that CMVIG prophylaxis reduces the risk of bronchiolitis obliterans syndrome, but a controlled trial is awaited. Overall, the relatively limited current data set suggests that prophylaxis with CMVIG in combination with antiviral therapy appears effective in D+/R- heart transplant patients, whereas in lung transplantation, addition of CMVIG in recipients of a CMV-positive graft may offer an advantage in terms of CMV infection and disease.

  14. False-positive serology following intravenous immunoglobulin and plasma exchange through transfusion of fresh frozen plasma in a patient with pemphigus vulgaris.

    PubMed

    Nomura, Hisashi; Honda, Haruki; Egami, Shohei; Yokoyama, Tomoaki; Fujimoto, Atsushi; Ishikawa, Makiko; Sugiura, Makoto

    2015-04-01

    Intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma are therapeutic options for patients with refractory pemphigus vulgaris. Passive acquisition of various clinically important antibodies through these therapies can occur, leading to false serology and negatively affecting patients' clinical care. It is recommended that dermatologists recognize the possibility of these phenomena and interpret them appropriately. Here, we report false-positive serology following intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma in a patient with refractory pemphigus vulgaris. We also discuss the measure for misinterpretation and unnecessary clinical intervention.

  15. The specific immunoglobulin in hydatid disease

    PubMed Central

    Matossian, R. M.; Kane, G. J.; Chantler, S. M.; Batty, I.; Sarhadian, H.

    1972-01-01

    The variation in the serum level of specific IgG, IgM and IgA antibodies during different stages of hydatid disease has been demonstrated by a technique of fluorescent microscopy that uses monospecific anti-human immunoglobulin conjugates and freeze-dried antigens. The technique is easy to perform and our results suggest that the test is sensitive and specific. Specific IgG antibodies are present in patients with either current or past infections. IgM antibodies, detected during periods of antigenic activity, disappear soon after removal of the cyst. In many cases IgA antibodies also disappear soon after removal of the cyst. Cross-reactions between the antigens and antibodies of hydatid disease and schistosomiasis are shown to be present mainly in the IgG immunoglobulin and only to a much smaller extent in the IgA. ImagesFIG. 1 PMID:4554745

  16. Chronic idiopathic thrombocytopenia treated with immunoglobulin.

    PubMed Central

    Mori, P G; Mancuso, G; del Principe, D; Duse, M; Miniero, R; Tovo, R; Bardare, M; Carnelli, V; de Mattia, D

    1983-01-01

    Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed. PMID:6685997

  17. Lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

    PubMed

    Khong, Peter; Enno, Alar; Darwish, Balsam

    2014-02-01

    We present the unusual case of a 33-year-old woman who presented with a 2 year history of amenorrhoea and an expanding sellar lesion. Initial MRI revealed a lesion in the pituitary fossa, thought to be a pituitary adenoma. One year later, the lesion had enlarged by 5mm, with associated enhancement of the dura of the planum sphenoidale and pituitary stalk. Histopathology revealed a lymphocytic and plasma cell inflammatory infiltrate suggestive of lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

  18. Intravenous immunoglobulins: evolution of commercial IVIG preparations.

    PubMed

    Hooper, John A

    2008-11-01

    Since its first use in 1952, human immunoglobulin has been used to treat people who have inherited antibody deficiencies. This article summarizes IVIG clinical development in primary immunodeficient patients and manufacturing improvements introduced over time. Manufacturing improvements include purification procedures that have reduced the incidence of adverse events and improved clinical efficacy, as well as virus inactivation and removal steps that have increased safety from blood-borne infections. Current manufacturing procedures, IVIG production trends, and recent clinical trial results are also reviewed.

  19. A de novo monoclonal immunoglobulin deposition disease in a kidney transplant recipient: a case report.

    PubMed

    Savenkoff, Benjamin; Aubertin, Perrine; Ladriere, Marc; Hulin, Cyril; Champigneulle, Jacqueline; Frimat, Luc

    2014-06-18

    Myeloma following kidney transplantation is a rare entity. It can be divided into two groups: relapse of a previous myeloma and de novo myeloma. Some of these myelomas can be complicated by a monoclonal immunoglobulin deposition disease, which is even less common. Less than ten cases of monoclonal immunoglobulin deposition disease after renal graft have been reported in the literature. The treatment of these patients is not well codified. We report the case of a 43-year-old white European man who received a renal transplant for a nephropathy of unknown etiology and developed a nephrotic syndrome with kidney failure at 2-years follow-up. We diagnosed a de novo monoclonal immunoglobulin deposition disease associated with a kappa light chain multiple myeloma, which is a very uncommon presentation for this disease. Three risk factors were identified in this patient: Epstein-Barr virus reactivation with cytomegalovirus co-infection; intensified immunosuppressive therapy during two previous rejection episodes; and human leukocyte antigen-B mismatches. Chemotherapy treatment and decrease in the immunosuppressive therapy were followed by remission and slight improvement of renal function. A relapse occurred 8 months later and his renal function worsened rapidly requiring hemodialysis. He died from septic shock 4 years after the diagnosis of monoclonal immunoglobulin deposition disease. This rare case of post-transplant lymphoproliferative disorder with an uncommon presentation illustrates the fact that treatment in such a situation is very difficult to manage because of a small number of patients reported and a lack of information on this disease. There are no guidelines, especially concerning the immunosuppressive therapy management.

  20. A de novo monoclonal immunoglobulin deposition disease in a kidney transplant recipient: a case report

    PubMed Central

    2014-01-01

    Introduction Myeloma following kidney transplantation is a rare entity. It can be divided into two groups: relapse of a previous myeloma and de novo myeloma. Some of these myelomas can be complicated by a monoclonal immunoglobulin deposition disease, which is even less common. Less than ten cases of monoclonal immunoglobulin deposition disease after renal graft have been reported in the literature. The treatment of these patients is not well codified. Case presentation We report the case of a 43-year-old white European man who received a renal transplant for a nephropathy of unknown etiology and developed a nephrotic syndrome with kidney failure at 2-years follow-up. We diagnosed a de novo monoclonal immunoglobulin deposition disease associated with a kappa light chain multiple myeloma, which is a very uncommon presentation for this disease. Three risk factors were identified in this patient: Epstein–Barr virus reactivation with cytomegalovirus co-infection; intensified immunosuppressive therapy during two previous rejection episodes; and human leukocyte antigen-B mismatches. Chemotherapy treatment and decrease in the immunosuppressive therapy were followed by remission and slight improvement of renal function. A relapse occurred 8 months later and his renal function worsened rapidly requiring hemodialysis. He died from septic shock 4 years after the diagnosis of monoclonal immunoglobulin deposition disease. Conclusions This rare case of post-transplant lymphoproliferative disorder with an uncommon presentation illustrates the fact that treatment in such a situation is very difficult to manage because of a small number of patients reported and a lack of information on this disease. There are no guidelines, especially concerning the immunosuppressive therapy management. PMID:24942882

  1. [Immunoglobulins in patients with Nocardia brasiliensis actinomycetoma].

    PubMed

    Méndez-Tovar, L J; Mondragón-González, R; Manzano-Gayosso, P; López-Martínez, R; Hernández-Hernández, F; Bonifaz, A; Anides Fonseca, A; Araiza, J; Vega-López, F

    2004-01-01

    Considering that some authors have reported an increasing of some immunoglobulins in actinomycetoma patients, in this study we propose to determine differential production of IgG1, IgG2, IgG3, IgG4 and IgGM in 25 patients with actinomycetoma and 25 healthy individuals from a mycetoma endemic area. Immunoglobulins were determined by ELISA technique. To sensibilize the plates, six Nocardia brasiliensis antigens were used: a crude antigen denominated NB and five derivatives (NB2, NB4, NB6, NB8 and NB10) obtained by their isoelectric point. Results showed that all IgG subclasses were higher in the patients' sera than in control sera, with a maximal difference to IgG3 and IgG4. To the latter subclass, six antigens were highly reactives. IgM levels were similar in both groups. As it occurs in other infections, in the actinomycetoma pathogenesis probably participate the increase or deficiency of a determined immunoglobulin class, as well as the relationship between different subclasses.

  2. [BIOLOGICAL AND IMMUNOCHEMICAL PROPERTIES OF POLYREACTIVE IMMUNOGLOBULINS].

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A previously unknown phenomenon of acquired polyreactivity for serum immunoglobulins, which were subjected either to solutions of KSCN (3.0-5.0 M), low/high pH (pH 2.2-3.0), or heating to 58-60 degrees C, was described by us in 1990 year. Much later, eleven years after that, similar data were published by others, which completely confirmed our results concerning the influence of either chaotropic ions or the drastic shift of pH on immunoglobulins polyreactive properties. Our further investigations of polyreactive serum immunoglobulins (PRIG) properties have shown that the mechanism of non-specific interaction between PRIG and antigens much differs from the mechanism of interaction between specific antibodies and corresponding antigens. Later we have shown that the increasing of PRIG reactivity could be induced in vivo, and PRIG are one of serum components for human or animal sera. Then, it could be suggested that PRIG can perform certain biological functions. Studying of PRIG's effect on the phagocytosis of microbes by peritoneal cells or the tumor growth have shown that PRIG can play a certain role in protecting the body from infections and probably can influence on the development of various pathological processes. Recently we have also found that PRIG IgG contents significantly increases in aged people. These data demonstrate that further investigations of PRIG's immunochemical properties and studying of their biological role in organism protection from various diseases is very intriguing and important.

  3. [Serum and secretory immunoglobulins in allergic diseases].

    PubMed

    Atovmian, O I; German, G P; Chernokhvostova, E V

    1985-07-01

    A total of 158 patients with pollinosis, bronchial asthma, urticaria and Quincke's edema were examined. The immunoglobulin and C3 levels in sera and the immunoglobulin and albumin levels in saliva were determined by the method of single radial immunodiffusion with the corresponding monospecific antisera. In all the groups of patients subjected to examination the presence of polyclonal hypergammaglobulinemia was detected, which was manifested by a rise in the levels of IgG, IgA and especially IgM; the level of IgD was low. A decrease in the level of C3 was detected in pollinosis patients in the absence of the exacerbation of the disease. No circulating immune complexes were detected. An essential increase in the level of IgG in saliva was revealed, which was due to the local synthesis of this immunoglobulin. In winter the level of salivary IgA in pollinosis patients was found to be essentially below normal, but at the period of exacerbation it increased twofold, probably in response to local stimulation with antigen-allergen. Patients with bronchial asthma and pollinosis were found to have a high level of free secretory component (SC); in pollinosis the level of free SC sharply increased during the stage of exacerbation, which was due to the increase of its synthesis and secretion by the epithelial cells of the mucous membranes. The importance of these data for the pathogenesis of allergic diseases are discussed.

  4. Antarctic teleost immunoglobulins: more extreme, more interesting.

    PubMed

    Coscia, Maria Rosaria; Varriale, Sonia; Giacomelli, Stefano; Oreste, Umberto

    2011-11-01

    We have investigated the immunoglobulin molecule and the genes encoding it in teleosts living in the Antarctic seas at the constant temperature of -1.86 °C. The majority of Antarctic teleosts belong to the suborder Notothenioidei (Perciformes), which includes only a few non-Antarctic species. Twenty-one Antarctic and two non-Antarctic Notothenioid species were included in our studies. We sequenced immunoglobulin light chains in two species and μ heavy chains, partially or totally, in twenty species. In the case of heavy chain, genomic DNA and the cDNA encoding the secreted and the membrane form were analyzed. From one species, Trematomus bernacchii, a spleen cDNA library was constructed to evaluate the diversity of VH gene segments. T. bernacchii IgM, purified from the serum and bile, was characterized. Homology Modelling and Molecular Dynamics were used to determine the molecular structure of T. bernacchii and Chionodraco hamatus immunoglobulin domains. This paper sums up the previous results and broadens them with the addition of unpublished data.

  5. Severe Periodontal Disease Associated with Long-Term Treatment with Intravenous Immunoglobulin

    PubMed Central

    Corrêa, Jôice Dias; Rocha, Amanda Leal; Costa, Lidiane Cristina Machado; Travassos, Denise; Castro, Wagner Henriques; Garlet, Gustavo Pompermaier; Gomez, Rodrigo Santiago; Teixeira, Antônio Lúcio; Silva, Tarcília Aparecida

    2014-01-01

    Intravenous immunoglobulin (IVIG) is used in the treatment of neuropathy. This case report presents, for the first time, a patient with severe periodontal destruction after chronic therapy with IVIG. The patient reported having extracted his maxillary anterior teeth himself due to high mobility. Clinical examination and radiographic images show a generalized and severe periodontitis. No significant alterations in genetic or microbiological features were observed. The present case suggests that periodontal disease aggravation could be considered a new adverse effect of IVIG therapy. Postulated mechanisms are immune complexes formation, complement activation, and a direct effect in osteoclasts. In conclusion, it is important that patients that will receive IVIG treatment underwent dental evaluation. PMID:25379295

  6. Association of mesenchymal cells and immunoglobulins with differentiating epithelial cells

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Keenan, Jeffrey A; Upadhyaya, Nirmala B; Van Meter, Stuart E; Wimalasena, Jay; Elder, Robert F

    2001-01-01

    Background Mesenchymal-epithelial interactions play an important role in the physiology and pathology of epithelial tissues. Mesenchymal cells either associate with epithelium basement membrane [pericytes and perivascular monocyte-derived cells (MDC)] or reside within epithelium (MDC and T cells). Although intraepithelial mesenchymal cells were suggested to contribute to the epithelium physiology, their association with particular steps in differentiation of epithelial cells, interactions among themselves, and their fate remain unclear. We studied epitopes of mesenchymal cells and their products (immunoglobulins) in stratified epithelium of uterine ectocervix, which is one of the prototypes of complete cellular differentiation from stem into the aged cells. Results Perivascular CD14 primitive MDC associated with basal (stem) epithelial cells. Thy-1 pericytes of microvasculature secreted intercellular vesicles, which associated with Ki67 postmitotic epithelial cells expressing MHC class I. Intraepithelial T cells showed an association with veiled type MDC [dendritic cell (DC) precursors] among parabasal cells, and exhibited fragmentation after entering intermediate (mature) epithelial layers. Mature DC secreted CD68 and exhibited fragmentation after reaching mid intermediate layers. Binding of IgM was detected at the top of each layer: in the upper parabasal, upper intermediate, and most surface epithelial cells. IgG was confined to the entire superficial layer. Conclusions These data suggest that the phylogenetically and ontogenetically developed hierarchy of mesenchymal cells (MDC, pericytes, T cells) and immunoglobulins (IgM, IgG) accompanies differentiation of epithelial cells from immature into the mature and aged phenotype. Further studies of an involvement of mesenchymal cells in the regulation of tissue homeostasis may bring novel approaches to the prevention and therapy of tissue dysfunctions characterized by permanent tissue immaturity (muscular dystrophy

  7. Efficacy of combined intravenous immunoglobulins and steroids in children with primary immune thrombocytopenia and persistent bleeding symptoms.

    PubMed

    Parodi, Emilia; Giordano, Paola; Rivetti, Elisa; Giraudo, Maria Teresa; Ansaldi, Giulia; Davitto, Mirella; Mondino, Anna; Farruggia, Piero; Amendola, Giovanni; Matarese, Sofia M R; Rossi, Francesca; Russo, Giovanna; Ramenghi, Ugo

    2014-07-01

    The aim of this study was to investigate the effect of the combined administration of intravenous immunoglobulins and steroids as a second-line therapy in 34 children with primary immune thrombocytopenia and persistent, symptomatic bleeding. Combined therapy (intravenous immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg daily on days 1-3) was administered to 12 patients with newly diagnosed ITP who did not respond to the administration of a single therapy (either intravenous immunoglobulins or steroids) and to 22 children with persistent and chronic disease who required frequent administrations (i.e. more frequently than every 30 days) of either immunoglobulins or steroids (at the same standard dosages) in order to control active bleeding. A response (i.e. platelet count >50×10(9)/L and remission of active bleeding) was observed in 8/12 (67%) patients with newly diagnosed ITP. The clinical presentation of responders and non-responders did not differ apparently. Patients in the chronic/persistent phase of disease had a significantly longer median period of remission from symptoms compared with the previous longest period of remission (p=0.016). The treatment was well tolerated. Our data suggest that the combined approach described is a well-tolerated therapeutic option for children with primary immune thrombocytopenia and persistent bleeding symptoms that can be used in both emergency and/or maintenance settings.

  8. The physiological effects of human immunoglobulin on severe bronchiolitis patients before and after treatment

    PubMed Central

    Shan, Yan-Hua; Zhang, Yong-Gang; Zhang, Jian-Hua; Wang, Dong; Li, Xiao-Xia; Zhang, Jie; Wang, Xi-Mei; Luo, Song-Yuan

    2015-01-01

    The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1–3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p < 0.05). As such, the CD8, IgA, IgG, IgM and IFN-γ levels were also significantly lower in the children with severe bronchiolitis than in the children in the healthy control group (p < 0.05). Furthermore, the CD4, IgE, IL-4, and IL-4/IFN-γ levels and CD4/CD8 ratio were dramatically higher than in the healthy control group (p < 0.05). Serum levels of the aforementioned indicators either increased or decreased after IVIG treatment. The amount of time required for coughing, wheezing, and pulmonary rales to seize, and the duration of illness for the children with the severe bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis. PMID:26308393

  9. The physiological effects of human immunoglobulin on severe bronchiolitis patients before and after treatment.

    PubMed

    Shan, Yan-Hua; Zhang, Yong-Gang; Zhang, Jian-Hua; Wang, Dong; Li, Xiao-Xia; Zhang, Jie; Wang, Xi-Mei; Luo, Song-Yuan

    2015-01-01

    The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1-3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p < 0.05). As such, the CD8, IgA, IgG, IgM and IFN-γ levels were also significantly lower in the children with severe bronchiolitis than in the children in the healthy control group (p < 0.05). Furthermore, the CD4, IgE, IL-4, and IL-4/IFN-γ levels and CD4/CD8 ratio were dramatically higher than in the healthy control group (p < 0.05). Serum levels of the aforementioned indicators either increased or decreased after IVIG treatment. The amount of time required for coughing, wheezing, and pulmonary rales to seize, and the duration of illness for the children with the severe bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis.

  10. A Hand to Substitutes

    ERIC Educational Resources Information Center

    Javernick, Ellen

    2005-01-01

    In the days before computers, passing on information to substitutes was difficult. Now teachers can individualize their lesson plans to guarantee that substitute teachers and the students will both have a good day. This article provides some plan-ahead procedures that have worked for the author.

  11. Working with Substitute Teachers.

    ERIC Educational Resources Information Center

    Wilson, Karen

    1999-01-01

    Resolving the perennial problem of substitute teachers' high turnover and low availability is feasible, if principals welcome, orient, and assign them properly. Regular teachers should prepare a folder containing class lists, daily schedules, seating charts, expectations of students, and meaningful lesson plans. Substitutes should be treated as…

  12. Florida's Substitute Teachers.

    ERIC Educational Resources Information Center

    Odutola, Adeniji A.; Etemadi, Judy N.

    2002-01-01

    Describes the statutory duties of the Florida Education Standards Commission, highlighting a study of the working conditions of Florida's substitute teachers. Researchers collected data on school board policies regarding substitutes' educational levels required, initial training and staff development opportunities required, salary schedules, and…

  13. Sustainability and substitutability.

    PubMed

    Fenichel, Eli P; Zhao, Jinhua

    2015-02-01

    Developing a quantitative science of sustainability requires bridging mathematical concepts from fields contributing to sustainability science. The concept of substitutability is central to sustainability but is defined differently by different fields. Specifically, economics tends to define substitutability as a marginal concept while fields such as ecology tend to focus on limiting behaviors. We explain how to reconcile these different views. We develop a model where investments can be made in knowledge to increase the elasticity of substitution. We explore the set of sustainable and optimal trajectories for natural capital extraction and built and knowledge capital accumulation. Investments in substitutability through knowledge stock accumulation affect the value of natural capital. Results suggest that investing in the knowledge stock, which can enhance substitutability, is critical to desirable sustainable outcomes. This result is robust even when natural capital is not managed optimally. This leads us to conclude that investments in the knowledge stock are of first order importance for sustainability.

  14. [Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].

    PubMed

    Arai, H; Rino, Y; Nishii, T; Andou, K; Kurosawa, R; Kuroki, F; Imagawa, T; Mori, M; Yokota, S; Oshiro, H; Takanashi, Y

    2006-03-01

    A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.

  15. Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies

    PubMed Central

    Gustafson, R; Gardulf, A; Hansen, S; Leibl, H; Engl, W; Lindén, M; Müller, A; Hammarström, L

    2008-01-01

    Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40·6 and 23·3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7·24 to 7·86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD. PMID:18341618

  16. Immunoglobulin patterns in humans over 95 years of age.

    PubMed Central

    Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

    1975-01-01

    Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

  17. Synthesis of immunoglobulins by human endocervix in organ culture.

    PubMed Central

    Cowan, M. E.; Buchan, A.; Skinner, G. R.

    1982-01-01

    The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6803822

  18. Synthesis of immunoglobulins by human endocervix in organ culture.

    PubMed

    Cowan, M E; Buchan, A; Skinner, G R

    1982-04-01

    The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects.

  19. Mechanisms of action of intravenous immunoglobulin in inflammatory muscle disease.

    PubMed

    Quick, Adam; Tandan, Rup

    2011-06-01

    Intravenous immunoglobulin (IVIG) is a unique immune-modulating therapy that has a wide range of effects on the immune system at multiple levels. This allows it to be used successfully in a variety of immune-mediated, systemic, and neurological disorders, including the inflammatory myopathies. It is likely that the specific action of IVIG varies depending on the underlying pathogenesis of a given disease. In dermatomyositis (DM), IVIG has been shown to diminish the activity of complement and deposition of membrane attack complex on capillaries and muscle fibers, the expression of adhesion molecules, and cytokine production. IVIG also appears to modify gene expression in the muscle of DM patients. The mechanism by which IVIG affects muscle in polymyositis and inclusion body myositis has not been well-studied. However, it may work via suppression of T-cell activation (including cytotoxic T cells) and migration into muscle tissue and alterations in cytokine production. IVIG generally yields the greatest therapeutic benefit in DM and is often of marginal utility in inclusion body myositis. It is generally considered as second-line or adjunctive therapy in the inflammatory myopathies.

  20. [Use of intravenous humana immunoglobulin in rheumatic diseases].

    PubMed

    Mussano, Eduardo D; Onetti, Laura B; Cadile, Isaac I; Onetti, Carlos M

    2012-01-01

    Preparations of intravenous immunoglobulin (IVIG) are used as treatment in different diseases such primary and secondary immunodeficiencies, autoimmune diseases, systemic inflammatory diseases, infectious diseases and allergic diseases among others. to present 13 of our cases with the use of IVIG in different rheumatic diseases. we retrospectively studied 13 patients (10 women and 3 men), mean age 29 years with different rheumatic diseases, that underwent conventional treatments without positive response. They received IVIG pulses, trying to improve or induce remission of their previous clinical situation. 6/13 patients met criteria for systemic lupus erythematosus (SLE), 2/13 had primary antiphospholipid syndrome (APL)one had polydermatomyositis (PDM), 1 juvenile arthritis, 1 panarteritis nodosa (cutaneous PAN), one Evans syndrome, and one with autoimmune uveitis. 7 of them had a positive response to therapy with IGEV evaluated by clinical and biochemical parameters. They remained with conventional treatments. One patient received a new IG EV pulse after 24 months, because of panniculitis reactivation. Clinical and biochemical response was poor in 4 of them, and 2 patients died. IVIg may be usefull in autoimmune rheumatic diseases when conventional therapies have failed. The therapeutic success is also limited. Only the 55 percent of our patients had a positive clinical response.

  1. Oxford classification of immunoglobulin A nephropathy: an update.

    PubMed

    Roberts, Ian S D

    2013-05-01

    This review summarizes the recommendations for reporting immunoglobulin A (IgA) nephropathy biopsies and their evidence base, discusses the limitations of the Oxford Classification study and presents the findings of recent validation studies. The Oxford Classification identified four histological lesions as independent prognostic factors: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S) and tubular atrophy/interstitial fibrosis (T). The MEST criteria predicted outcome in some, but not all, of 13 recent validation studies. M is of independent prognostic value in four out of 13 studies, S in four out of 13 and T in 10 out of 13. Apparently contradictory findings reflect differences in patient selection criteria, treatment and outcome measures. The Oxford Classification study provided indirect evidence that endocapillary hypercellularity is responsive to immunosuppressive therapy. This is confirmed in two validation studies. One study, which included patients with rapidly progressive disease, found glomerular crescents to be a significant prognostic marker. Immunohistological findings correlate with proliferative glomerular lesions but are not of independent prognostic value. The Oxford Classification is applicable to patients who were excluded from the original cohort, including those with rapidly progressive disease, and the prognostic value of proliferative glomerular lesions is influenced by immunosuppressive therapy. The Oxford schema will be reviewed in the light of recent findings.

  2. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

    PubMed Central

    Hoehn, Kenneth B.; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S. J.; Kaye, S.; Weber, J. N.; McClure, M. O.; Kellam, Paul; Pybus, Oliver G.

    2015-01-01

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. PMID:26194755

  3. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals.

    PubMed

    Hoehn, Kenneth B; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S J; Kaye, S; Weber, J N; McClure, M O; Kellam, Paul; Pybus, Oliver G

    2015-09-05

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4(+) count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection.

  4. May early intervention with high dose intravenous immunoglobulin pose a potentially successful treatment for severe cases of tick-borne encephalitis?

    PubMed Central

    2013-01-01

    Background Arthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins. Discussion To our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels. Summary Analogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible. PMID:23822550

  5. [Development and study of properties of immunoglobulins against Lassa fever].

    PubMed

    Krasnianskiĭ, V P; Gradoboev, V N; Borisevich, I V; Potryvaeva, N V; Lebedinskaia, E V; Chernikova, N K; Timan'kova, G D

    1997-01-01

    A horse may serve the producer of immune antiserum to Lassa virus. Specific immunoglobulin with at least 1:512 titer of virus-neutralizing antibodies to Lassa fever was obtained by alcohol sedimentation after Cohn from the blood serum of immunized horses. The preparation does not differ from heterologous commercial immunoglobulins. Preclinical studies of immunoglobulin to Lassa fever demonstrated its safety and a high specific activity. The agent can be injected both alone and in combination with virasole.

  6. Crystalline keratopathy due to intravenous immunoglobulin in a 12-year-old girl with Kawasaki disease.

    PubMed

    Viswanathan, Vijay; Agashe, Prachi; Jain, Vandana; Nair, Akshay Gopinathan

    2016-10-01

    Kawasaki disease (KD) is an acute, self-limiting, medium-vessel vasculitis that occurs predominantly in young children. The treatment of KD consists of intravenous immunoglobulin (IVIG) along with aspirin and, in IVIG-resistant cases, corticosteroids. Crystalline keratopathy with corneal deposition of the immunoglobulin is a rare complication of IVIG therapy. We report the case of a 12-year-old girl who received IVIG for KD and developed visual complaints, which were attributable to crystalline keratopathy and corneal edema. Cessation of IVIG and treatment with topical and systemic corticosteroids reversed the finding. At final follow-up, vision in both eyes was normal. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  7. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies.

    PubMed

    Leussink, Verena I; Hartung, Hans-Peter; Kieseier, Bernd C; Stettner, Mark

    2016-07-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients.

  8. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    PubMed Central

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  9. Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

    PubMed

    Fleenor, W A; Stott, G H

    1980-06-01

    A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use.

  10. Single radial immunodiffusion analysis for quantitation of colostral immunoglobulin concentration.

    PubMed

    Fleenor, W A; Stott, G H

    1981-05-01

    Relative accuracy of the single radial immunodiffusion technique to measure immunoglobulin concentrations of colostral preparations (whey, whole, or fat-free) has been assessed. Fresh colostrum samples were analyzed for major constituents. Gammaglobulin as a standard was compared to total immunoglobulin concentration derived from single radial immunodiffusion analysis of colostral preparations with no differences except between standard and whey. Differences were in part from either enhancement or interference of immunoglobulin diffusion by colostral constituents. Removal of casein and fat during whey preparations caused a concentrating effect upon immunoglobulin constituents resulting in exaggerated precipitin rings. Whey has produced unreliable results: therefore, whole colostrum is recommended for single radial immunodiffusion analysis.

  11. Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1.

    PubMed

    Sandberg, E; Daas, A; Behr-Gross, M-E

    2006-11-01

    A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size.

  12. Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency.

    PubMed

    Tachdjian, Raffi

    2013-12-01

    Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (<4.0). He only had 10 of 23 pneumococcal titers in the protective range post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed.

  13. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  14. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  15. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  16. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  17. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  18. Sugar substitutes during pregnancy

    PubMed Central

    Pope, Eliza; Koren, Gideon; Bozzo, Pina

    2014-01-01

    Abstract Question I have a pregnant patient who regularly consumes sugar substitutes and she asked me if continuing their use would affect her pregnancy or child. What should I tell her, and are there certain options that are better for use during pregnancy? Answer Although more research is required to fully determine the effects of in utero exposure to sugar substitutes, the available data do not suggest adverse effects in pregnancy. However, it is recommended that sugar substitutes be consumed in moderate amounts, adhering to the acceptable daily intake standards set by regulatory agencies. PMID:25392440

  19. Sugar substitutes during pregnancy.

    PubMed

    Pope, Eliza; Koren, Gideon; Bozzo, Pina

    2014-11-01

    I have a pregnant patient who regularly consumes sugar substitutes and she asked me if continuing their use would affect her pregnancy or child. What should I tell her, and are there certain options that are better for use during pregnancy? Although more research is required to fully determine the effects of in utero exposure to sugar substitutes, the available data do not suggest adverse effects in pregnancy. However, it is recommended that sugar substitutes be consumed in moderate amounts, adhering to the acceptable daily intake standards set by regulatory agencies. Copyright© the College of Family Physicians of Canada.

  20. Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

    NASA Technical Reports Server (NTRS)

    Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

    2002-01-01

    Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

  1. Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

    NASA Technical Reports Server (NTRS)

    Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

    2002-01-01

    Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

  2. [Dermatomyositis and Panniculitis: the function of immunoglobulins].

    PubMed

    Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah

    2016-01-01

    Panniculitis is an inflammatory disease of subcutaneous adipose tissue which is rarely associated with dermatomyositis. It can occur before, after or simultaneously with muscle damage. In most cases, the evolution of panniculitis and of other dermatomyositis affections is favorable with corticosteroids and/or immunosuppressants. We report the case of a 48 year-old patient who developed panniculitis lesions 2 months before having muscular signs. Skin involvement was resistant to corticosteroid treatment associated with immunosuppressants drugs. This led to the use of polyvalent immunoglobulin treatment improving both skin and muscle damage.

  3. [Secretory immunoglobulin A in amniotic fluid].

    PubMed

    Briese, V; Straube, W; Brock, J; Lorenz, U

    1983-01-01

    Secretory immunoglobulin A (S-IgA) was estimated in amniotic fluid samples by means of the single radial immunodiffusion according to Mancini. A monospecific antiserum against human secretory component was used. 163 amniotic fluid samples from normal pregnancies and risk pregnancies respectively were investigated. Within the 3rd trimenon the S-IgA content in amniotic fluid increased significantly. With respect to literature and examinations performed previously a connection between S-IgA content in amniotic fluid and fetal lung maturity seems to be possible.

  4. [Diabetes insipidus: approaches to desmopressin substitution therapy].

    PubMed

    Thanh, N C; Prokof'ev, A B

    2011-01-01

    There is a worldwide tendency toward the growing prevalence of diabetes insipidus due to the elevated frequency of its central form attributable to the large number of surgical brain interventions and craniocerebral injuries. The overall diabetes insipidus morbidity is estimated at 30%. During the last 100 years, the patients were treated first with pituitary posterior lobe extract then with synthetic arginine-vasopressin. The break-through came in 1974 with the advent of desmopressin, a synthetic analog of natural arginine-vasopressin, that antagonizes V2 receptors, lacks vasoconstrictor activity, and exerts strong long-term antidiuretic action.

  5. Evaluation of capillary zone electrophoresis for the determination of protein composition in therapeutic immunoglobulins and human albumins.

    PubMed

    Christians, Stefan; van Treel, Nadine Denise; Bieniara, Gabriele; Eulig-Wien, Annika; Hanschmann, Kay-Martin; Giess, Siegfried

    2016-07-01

    Capillary zone electrophoresis (CZE) provides an alternative means of separating native proteins on the basis of their inherent electrophoretic mobilities. The major advantage of CZE is the quantification by UV detection, circumventing the drawbacks of staining and densitometry in the case of gel electrophoresis methods. The data of this validation study showed that CZE is a reliable assay for the determination of protein composition in therapeutic preparations of human albumin and human polyclonal immunoglobulins. Data obtained by CZE are in line with "historical" data obtained by the compendial method, provided that peak integration is performed without time correction. The focus here was to establish a rapid and reliable test to substitute the current gel based zone electrophoresis techniques for the control of protein composition of human immunoglobulins or albumins in the European Pharmacopoeia. We believe that the more advanced and modern CZE method described here is a very good alternative to the procedures currently described in the relevant monographs.

  6. Synthesis of substituted pyrazines

    SciTech Connect

    Pagoria, Philip F.; Zhang, Mao Xi

    2016-10-04

    A method for synthesizing a pyrazine-containing material according to one embodiment includes contacting an iminodiacetonitrile derivative with a base and a reagent selected from a group consisting of hydroxylamine, a hydroxylamine salt, an aliphatic primary amine, a secondary amine, an aryl-substituted alkylamine a heteroaryl-substituted alkyl amine, an alcohol, an alkanolamine and an aryl alcoholamine. Additional methods and several reaction products are presented. ##STR00001##

  7. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell antibody-forming...

  8. Substitution of anticonvulsant drugs

    PubMed Central

    Steinhoff, Bernhard J; Runge, Uwe; Witte, Otto W; Stefan, Hermann; Hufnagel, Andreas; Mayer, Thomas; Krämer, Günter

    2009-01-01

    Changing from branded drugs to generic alternatives, or between different generic formulations, is common practice aiming at reducing health care costs. It has been suggested that antiepileptic drugs (AEDs) should be exempt from substitution because of the potential negative consequences of adverse events and breakthrough seizures. Controlled data are lacking on the risk of substitution. However, retrospective data from large medical claims databases suggest that switching might be associated with increased use of AED and non-AED medications, and health care resources (including hospitalization). In addition, some anecdotal evidence from patients and health care providers’ surveys suggest a potentially negative impact of substitution. Well-controlled data are needed to assess the real risk associated with substitution, allowing health care professionals involved in the care of patients with epilepsy to make informed decisions. This paper reviews currently available literature, based on which the authors suggest that the decision to substitute should be made on an individual basis by the physician and an informed patient. Unendorsed or undisclosed substitution at the pharmacy level should be discouraged. PMID:19707254

  9. [Glomerulopathies with organized monoclonal immunoglobulin deposits].

    PubMed

    Touchard, Guy; Bridoux, Frank; Goujon, Jean-Michel

    2016-02-01

    The spectrum of glomerular disorders with organized immunoglobulin (Ig) deposits is heterogeneous. It encompasses 2 mains categories: glomerulopathies with fibrillary deposits are mostly represented by immunoglobulinic amyloidosis (most commonly AL amyloidosis, characterized by monoclonal light chain deposits often of the lambda isotype), and pseudo-amyloid fibrillary glomerulonephritis in which deposits predominantly contain polyclonal IgG4. Glomerulopathies with microtubular deposits include cryoglobulinemic glomerulonephritis (type I and type II, with or without detectable serum cryoglobulin) and glomerulonephritis with organized microtubular monoclonal Ig deposits (GOMMID) also referred to as immunotactoid glomerulopathy. Pathological diagnosis requires meticulous studies by light microscopy (with systematic Congo red staining), immunofluorescence with specific conjugates, and electron microscopy. Ultrastructural studies are required to differentiate amyloid fibrils (8 to 10 nm in external diameter), pseudo-amyloid fibrils (15-20 nm) and microtubules (10 to 50 nm in external diameter, with a central hollow core). Glomerular deposits in type I cryoglobulinemic glomerulonephritis are arranged into parallel straight microtubules similar to those observed in GOMMID, but with different topography that allows distinction between the two entities. Glomerular substructures composed of circulating Igs should be distinguished from collagen fibrils that are commonly observed in glomerular disorders with or without deposition of monoclonal or polyclonal Igs. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  10. The Immunoglobulins of Cold-Blooded Vertebrates

    PubMed Central

    Pettinello, Rita; Dooley, Helen

    2014-01-01

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species. PMID:25427250

  11. Autoantibodies and immunoglobulins among atomic bomb survivors

    SciTech Connect

    Fujiwara, Saeko; Akahoshi, Masazumi; Kodama, Kazunori; Shimaoka, Katsutaro; Akiyama, Mitoshi; Carter, R.L.; Yamakido, Michio

    1994-01-01

    The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE. 32 refs., 2 figs., 3 tabs.

  12. Cloned transchromosomic calves producing human immunoglobulin.

    PubMed

    Kuroiwa, Yoshimi; Kasinathan, Poothappillai; Choi, Yoon J; Naeem, Rizwan; Tomizuka, Kazuma; Sullivan, Eddie J; Knott, Jason G; Duteau, Anae; Goldsby, Richard A; Osborne, Barbara A; Ishida, Isao; Robl, James M

    2002-09-01

    Human polyclonal antibodies (hPABs) are useful therapeutics, but because they are available only from human donors, their supply and application is limited. To address this need, we prepared a human artificial chromosome (HAC) vector containing the entire unrearranged sequences of the human immunoglobulin (hIg) heavy-chain (H) and lambda (lambda) light-chain loci. The HAC vector was introduced into bovine primary fetal fibroblasts using a microcell-mediated chromosome transfer (MMCT) approach. Primary selection was carried out, and the cells were used to produce cloned bovine fetuses. Secondary selection was done on the regenerated fetal cell lines, which were then used to produce four healthy transchromosomic (Tc) calves. The HAC was retained at a high rate (78-100% of cells) in calves and the hIg loci underwent rearrangement and expressed diversified transcripts. Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs.

  13. Passive transfer of colostral immunoglobulins in calves.

    PubMed

    Weaver, D M; Tyler, J W; VanMetre, D C; Hostetler, D E; Barrington, G M

    2000-01-01

    Passive transfer of colostral immunoglobulins has long been accepted as imperative to optimal calf health. Many factors, including timing of colostrum ingestion, the method and volume of colostrum administration, the immunoglobulin concentration of the colostrum ingested, and the age of the dam have been implicated in affecting the optimization of absorption. The practice of colostrum pooling, the breed and presence of the dam, and the presence of respiratory acidosis in the calf also may affect passive transfer. Various tests have been reported to accurately measure passive transfer status in neonatal calves. The radial immunodiffusion and the enzyme-linked immunosorbent assay (ELISA) are the only tests that directly measure serum IgG concentration. All other available tests including serum total solids by refractometry, sodium sulfite turbidity test, zinc sulfate turbidity test, serum gamma-glutamyl transferase activity, and whole blood glutaraldehyde gelation estimate serum IgG concentration based on concentration of total globulins or other proteins whose passive transfer is statistically associated with that of IgG. This paper presents a comprehensive review of the literature of passive transfer in calves including factors that affect passive transfer status, testing modalities, effects of failure of passive transfer on baseline mortality, consequences of failure of passive transfer, and some treatment options. Many previously accepted truisms regarding passive transfer in calves should be rejected based on the results of recent research.

  14. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-11-24

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species.

  15. Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

    PubMed

    Dejoie, Thomas; Attal, Michel; Moreau, Philippe; Harousseau, Jean-Luc; Avet-Loiseau, Herve

    2016-03-01

    Response criteria for multiple myeloma are based upon changes in monoclonal protein levels quantified using serum and/or urine protein electrophoresis. The latter lacks sensitivity at low monoclonal protein levels and since 2001, the serum free light chain test has been available and its clinical utility proven, yet guidelines have not recommended it as a replacement for urine assessment. Herein we evaluated responses using serum free light chain measurements and serum and urine electrophoresis after 2 and 4 cycles of therapy and after stem cell transplantation in 25 light chain and 157 intact immunoglobulin myeloma patients enrolled in the IFM 2007-02 MM trial. All 25 light chain patients had measurable disease by serum free light chain and urine methods at presentation. By contrast 98 out of 157 intact immunoglobulin patients had measurable disease by serum free light chain compared to 55 out of 157 by urine electrophoresis. In all patients there was substantial agreement between predicate (serum/urine protein electrophoresis) and test (serum protein electrophoresis and serum free light chain) methods for response assessment (Weighted Kappa=0.83). Urine immunofixation became negative in 47% light chain and 43% intact immunoglobulin patients after 2 cycles of therapy. At this time the serum free light chain ratio normalised in only 11% and 27% patients, respectively. In summary we found good agreement between methods for response assessment, but the serum free light chain test provided greater sensitivity than urine electrophoresis for monitoring. To our knowledge this is the first report comparing both methods for response assignment based on the International Myeloma Working Group guidelines. (Clinical Trials Register.eu identifier: 2007-005204-40).

  16. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial.

    PubMed

    Kobayashi, Tohru; Saji, Tsutomu; Otani, Tetsuya; Takeuchi, Kazuo; Nakamura, Tetsuya; Arakawa, Hirokazu; Kato, Taichi; Hara, Toshiro; Hamaoka, Kenji; Ogawa, Shunichi; Miura, Masaru; Nomura, Yuichi; Fuse, Shigeto; Ichida, Fukiko; Seki, Mitsuru; Fukazawa, Ryuji; Ogawa, Chitose; Furuno, Kenji; Tokunaga, Hirohide; Takatsuki, Shinichi; Hara, Shinya; Morikawa, Akihiro

    2012-04-28

    Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease. We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940. We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p<0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group. Addition of prednisolone to the standard regimen of intravenous

  17. Antiviral Therapy

    PubMed Central

    Stalder, Hans

    1977-01-01

    The current status of antiviral therapy is reviewed, including discussion of older approaches together with more recently developed chemotherapy. Following the introduction dealing with pathophysiological aspects of virus disease, the different approaches to antiviral therapy are presented. The reasons for the slow progress in antiviral therapy are discussed. These include: 1. the necessity of intracellular penetration of drugs acting on viral replication; 2. the severe toxicity of most antiviral drugs; 3. the narrow antiviral spectrum of most of these agents; 4. the difficulty of making a rapid etiological diagnosis in view of the necessity of starting (specific?) treatment early in the course of the disease; 5. the difficult evaluation of beneficial as compared with deleterious effects of antiviral therapy. After a detailed review of clinically tested substances, including immunoglobulins, synthetic antiviral drugs (amantadine, nucleoside analogs, thiosemicarbazones and photodynamic dyes) and interferon, a guide concerning indications and application of specific antiviral therapy is presented. Although at present there are few indications, clinicians should be aware of the (present and future) possibilities of antiviral therapy. PMID:341538

  18. Impact of vegetarian diet on serum immunoglobulin levels in children.

    PubMed

    Gorczyca, Daiva; Prescha, Anna; Szeremeta, Karolina

    2013-03-01

    Nutrition plays an important role in immune response. We evaluated the effect of nutrient intake on serum immunoglobulin levels in vegetarian and omnivore children. Serum immunoglobulin levels and iron status were estimated in 22 vegetarian and 18 omnivore children. Seven-day food records were used to assess the diet. There were no significant differences in serum IgA, IgM, and IgG levels between groups of children. Serum immunoglobulin levels were lower in vegetarian children with iron deficiency in comparison with those without iron deficiency. In the vegetarians, IgG level correlated positively with energy, zinc, copper, and vitamin B(6) intake. In the omnivores, these correlations were stronger with IgM level. Despite negligible differences in serum immunoglobulin levels between vegetarian and omnivore children, the impact of several nutrient intakes on IgM and IgG levels differed between groups. Low iron status in vegetarian children can lead to decreased immunoglobulin levels.

  19. Genomic structure and expression of immunoglobulins in Squamata.

    PubMed

    Olivieri, David N; Garet, Elina; Estevez, Olivia; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2016-04-01

    The Squamata order represents a major evolutionary reptile lineage, yet the structure and expression of immunoglobulins in this order has been scarcely studied in detail. From the genome sequences of four Squamata species (Gekko japonicus, Ophisaurus gracilis, Pogona vitticeps and Ophiophagus hannah) and RNA-seq datasets from 18 other Squamata species, we identified the immunoglobulins present in these animals as well as the tissues in which they are found. All Squamata have at least three immunoglobulin classes; namely, the immunoglobulins M, D, and Y. Unlike mammals, however, we provide evidence that some Squamata lineages possess more than one Cμ gene which is located downstream from the Cδ gene. The existence of two evolutionary lineages of immunoglobulin Y is shown. Additionally, it is demonstrated that while all Squamata species possess the λ light chain, only Iguanidae species possess the κ light chain.

  20. Polymyositis associated with severe interstitial lung disease: remission after three doses of IV immunoglobulin.

    PubMed

    Bakewell, Catherine J; Raghu, Ganesh

    2011-02-01

    Interstitial lung disease associated with polymyositis/dermatomyositis (ILD-PM/DM) often confers a poor prognosis, and optimal treatment of this condition is not well defined. This report describes a 63-year-old man with severe ILD-PM/DM who presented with 5 months of progressive dyspnea and weakness. He had an initial carbon-monoxide-diffusing capacity of 35% predicted and a creatine kinase level of 2,112 U/L. After three monthly doses of immunoglobulin at 2 gm/kg IV, he has sustained clinical remission for > 2 years. IV immunoglobulin has not previously been studied as a first-line agent for rheumatologic diseases, and it is currently used as a salvage therapy. However, if IV immunoglobulin is capable of inducing sustained remission after brief use as a treatment, as demonstrated in this patient, especially in the setting of significant pulmonary involvement, then it merits further consideration for investigation as a first-line therapeutic agent.

  1. Novel predictors of intravenous immunoglobulin resistance in Chinese children with Kawasaki disease.

    PubMed

    Fu, Pei-pei; Du, Zhong-dong; Pan, Yue-song

    2013-08-01

    The purpose of this study was to develop a predictive scoring system to identify intravenous immunoglobulin resistance in children with Kawasaki disease, to implement additional therapies early in the course of their illness and prevent coronary artery lesions. We performed a retrospective review of children with Kawasaki disease treated within 10 days of fever onset. To identify independent predictors of intravenous immunoglobulin resistance, multivariable logistic regression models were constructed using variables selected by univariable analysis. The independent predictors were combined into a new scoring system and compared with 2 existing systems. The discriminatory capacity of the scoring system was assessed using the area under the receiver operating characteristic curves. By logistic regression analysis, polymorphous exanthema, changes around the anus, days of illness at initial treatment, percentage of neutrophils, C-reactive protein levels, albumin levels, and total bilirubin proved to be independent predictors of intravenous immunoglobulin resistance. The new scoring system gave an area under the receiver operating characteristic curve of 0.672. In this scoring system, 2 risk strata were identified: low risk, with scores of 0-3, and high risk, with scores of ≥4. The sensitivity was 54.1% and the specificity was 71.2%. The new scoring system had a higher specificity and sensitivity for Chinese children, compared with the Kobayashi scoring system and the Egami scoring system, but, unfortunately, the new scoring system was not good enough to be widely used because of its low sensitivity.

  2. Dietary requirement for serum-derived bovine immunoglobulins in the clinical management of patients with enteropathy.

    PubMed

    Petschow, Bryon W; Burnett, Bruce P; Shaw, Audrey L; Weaver, Eric M; Klein, Gerald L

    2015-01-01

    A variety of human disease conditions are associated with chronic intestinal disorders or enteropathies that are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Such disruptions in the homeostasis of the gastrointestinal (GI) tract can lead to symptoms of abdominal pain and discomfort, bloating, abnormal bowel function, and malabsorption of nutrients. While significant advances have been made in understanding the factors that influence the complex and fragile balance between the gut microbiota, intestinal epithelial cell integrity, and the underlying immune system, effective therapies for restoring intestinal balance during enteropathy are still not available. Numerous studies have demonstrated the ability of oral immunoglobulins to improve weight gain, support gut barrier function, and reduce the severity of enteropathy in animals. More recently, studies in humans provide evidence that serum-derived bovine immunoglobulin/protein isolate is safe and improves nutritional status and GI symptoms in patients with enteropathy associated with irritable bowel syndrome or infection with the human immunodeficiency virus. This review summarizes studies showing the impact of enteropathy on nutritional status and how specially formulated bovine immunoglobulins may help restore intestinal homeostasis and nutritional status in patients with specific enteropathies. Such protein preparations may provide distinct nutritional support required for the dietary management of patients who, because of therapeutic or chronic medical needs, have limited or impaired capacity to digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or other special medically determined nutrient requirements that cannot be satisfied by changes to the normal diet alone.

  3. Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins.

    PubMed

    Figueiredo, Carlos R; Matsuo, Alisson L; Massaoka, Mariana H; Polonelli, Luciano; Travassos, Luiz R

    2014-09-01

    Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light- and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, they also exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. In this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. The present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs.

  4. Detection of specific immunoglobulin E in patients with toxoplasmosis.

    PubMed Central

    Pinon, J M; Toubas, D; Marx, C; Mougeot, G; Bonnin, A; Bonhomme, A; Villaume, M; Foudrinier, F; Lepan, H

    1990-01-01

    An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) in sera from adults with acute acquired infection or reactivation and from babies with congenital toxoplasmosis. The components of this assay were monoclonal antibody to human IgE, samples from patients, and T. gondii tachyzoites treated with Formalin. When T. gondii-specific IgE antibodies were present, visually detectable agglutination occurred. Sera, umbilical cord blood, fetal blood, cerebrospinal fluid, and amniotic fluid were tested by this method. Specific IgE antibodies were detected in sera from 25 (86%) of 29 adults who developed specific IgG antibody during pregnancy or had specific IgA and IgM antibodies. Specific IgE was present early during infection, at the time that IgM antibodies were present, and slightly preceding the presence of specific IgA antibodies. In 23 patients tested serially, IgE antibodies never persisted for longer than 4 months. No nonspecific anti-T. gondii IgE was detected in sera from uninfected individuals. Maternal IgE antibodies did not cross the placenta. In sera of patients with congenital toxoplasmosis, specific IgE antibodies were found at birth, during the first year of life, and during immunologic recrudescence following discontinuation of pyrimethamine-sulfonamide therapy. The IgE immunocapture assay is simple to perform. It is especially useful for determining when T. gondii was acquired by recently infected pregnant women. PMID:2203811

  5. Immunoglobulin G4-related ophthalmic disease presenting as uveitis.

    PubMed

    Prayson, Richard A

    2015-11-01

    This report documents a 47-year-old man who presented with back pain, uveitis and an elevated Westergren sedimentation rate. On biopsy, a paraspinal lesion showed a nonspecific chronic inflammatory cell infiltrate. The eye symptoms, after initially responding to immunosuppressive therapy, worsened and progressed to pain, resulting in an extirpation of the right eye. The histopathology of the excised eye showed an inflammatory pseudotumor marked by a lymphoplasmacytic infiltrate, areas of fibrosis, rare evidence of obliterative phlebitis and, focally, over 20 Immunoglobulin G4 (IgG4)-positive staining cells per high power microscopic field. IgG4-related ophthalmic disease is a relatively rare inflammatory lesion involving the eye and periorbital region. It is defined by a marked lymphoplasmacytic cell infiltrate, fibrosis obliterative phlebitis and increased IgG4 immunostaining (at least 10 cells per high power microscopic field in excised tissue). The entity is not unique to the eye, and has been described in other organs including the brain, endocrine organs, liver and kidney. The clinical presentation is often related to the location of the inflammatory infiltrates, and treatment involves the use of corticosteroids and other immunosuppressive agents. It is important to recognize IgG4-related ophthalmic disease because the condition appears to put patients at increased risk of developing lymphoma.

  6. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Eftimov, Filip; Winer, John B; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N

    2009-01-21

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of IVIg in CIDP. We searched the Cochrane Neuromuscular Trials Register, MEDLINE, EMBASE and ISI from January 1985 to May 2008. Randomised controlled studies testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP. Two authors reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. We contacted authors for additional information. Seven randomised controlled trials were considered eligible including 287 participants. These trials were homogeneous and overall quality was high. Five studies on 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange and one trial compared IVIg with prednisolone in 32 participants. A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (relative risk 2.40, 95% confidence interval 1.72 to 3.36). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used different disability scales and definitions of significant improvement. In three trials including 84 participants the disability could be transformed to the modified Rankin score, on which significantly more patients improved one point after IVIg treatment compared to placebo (relative risk 2.40, 95% confidence interval 0.98 to 5.83). Only one study included in this review had a long-term follow-up. The results of this study suggest that intravenous immunoglobulin improves disability more than placebo over 24 and 48 weeks. The

  7. Rapid method to detect rubella immunoglobulin M and immunoglobulin A antibodies.

    PubMed Central

    Schmitz, H; Shimizu, H; Kampa, D; Doerr, H W

    1975-01-01

    Immunoglobulin (Ig) G was removed from serum specimens by precipitation with gamma chain-specific anti-human IgG of rabbit origin. The remaining rubella virus-specific IgM (and IgA) antibodies were then detected by the rubella hemagglutination-inhibition test. This procedure has proven to be as reliable as estimations carried out with IgM fractions separated on a sucrose density gradient. PMID:1176596

  8. Serum immunoglobulin profile in normal Kashmiri adults.

    PubMed

    Bhat, G A; Mubarik, M; Bhat, M Y

    1995-01-01

    Serum levels of the immunoglobulins IgG, IgA and IgM were estimated in 102 apparently healthy Kashmiri adults in the age group of 16-60 years, using single radial immunodiffusion method of Mancini et al. The mean serum levels of IgG, IgA and IgM were observed to be 1289.19 +/- 234.9, 216.18 +/- 50.70 and 118.97 +/- 41.88 respectively. No significant difference in the mean serum levels was observed between the two sexes as such, but IgM showed a significant increase in females in the age group of 16-30 years. IgA showed a significant increase with age, with no such increase in case of IgG and IgM.

  9. Disodium cromoglycate inhibits production of immunoglobulin E.

    PubMed

    Seo, S B; Park, S J; Park, S T; Cho, C C; Park, B H; Lee, S J; Kim, H M; Kajiuchi, T; Shin, T Y

    2001-05-01

    Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells.

  10. Immunoglobulins in tear in trachoma patients.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Saha, K.

    1977-01-01

    Tear immunoglobulin concentrations have been measured in 100 healthy people and 62 patients in different stages of trachoma. In healthy people the average IgA level was 27-8 mg/100 ml. There was no significant difference in the IgA level in various age groups and between the sexes. IgG was detected in 92 samples, and it was less than 1 mg/100 ml. IgM in tears was detected in only one sample. IgD was not detected in any specimen. In tracoma cases, the mean IgA level was found to be significantly lower (22-0 mg/100 ml) than in healthy people. There was no significant difference in IgA level between different stages of trachoma, IgG, IgD, and IgM could not be detected in any sample from the trachoma cases. PMID:856248

  11. Immunoglobulins and the X-chromosome.

    PubMed

    Rhodes, K; Markham, R L; Maxwell, P M; Monk-Jones, M E

    1969-08-23

    Serum levels of immunoglobulins (Ig) G, M, and A were determined in 28 women with an additional X-chromosome (XXX), and in equal numbers of age-matched normal women and men. Mean IgM levels were found to be highest in the XXX group, intermediate in normal women, and lowest in men; these differences were statistically significant. Mean IgM values obtained from seven XXY and three XXXY cases were almost identical with those of normal women and XXX women respectively. No such sex linkage was observed for IgA and IgG levels. These results support the suggestion that the serum level of IgM is related to the number of X chromosomes present.

  12. Structural repertoire of immunoglobulin λ light chains.

    PubMed

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-05-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition.

  13. Intravenous immunoglobulin in pediatrics: A review

    PubMed Central

    Prasad, A.N.; Chaudhary, Sanjay

    2013-01-01

    There has been a rapid expansion of the use of intravenous immunoglobulin (IVIG) for an ever-growing number of conditions. IVIG is used at a ‘replacement dose’ (400–600 mg/kg/month) in antibody deficiencies and is used at a high dose (2 g/kg) as an ‘immunomodulatory’ agent in an increasing number of immune and inflammatory disorders.1 The limitations for IVIG are the cost of the preparation and the need for intravenous infusions. Due to the cost, shortages and growing use of IVIG there have been attempts to develop evidence-based guidelines for the use of IVIG in a wide variety of immune disorders in children and neonates. This commentary provides the recommendations and recent publication regarding the use of IVIG in various conditions in children. PMID:25378784

  14. Immunoglobulin Responses at the Mucosal Interface

    PubMed Central

    Chen, Kang; Chorny, Alejo

    2011-01-01

    Mucosal surfaces are colonized by large communities of commensal bacteria and represent the primary site of entry for pathogenic agents. To prevent microbial intrusion, mucosal B cells release large amounts of immunoglobulin (Ig) molecules through multiple follicular and extrafollicular pathways. IgA is the most abundant antibody isotype in mucosal secretions and owes its success in frontline immunity to its ability to undergo transcytosis across epithelial cells. In addition to translocating IgA onto the mucosal surface, epithelial cells educate the mucosal immune system as to the composition of the local microbiota and instruct B cells to initiate IgA responses that generate immune protection while preserving immune homeostasis. Here we review recent advances in our understanding of the cellular interactions and signaling pathways governing IgA production at mucosal surfaces and discuss new findings on the regulation and function of mucosal IgD, the most enigmatic isotype of our mucosal antibody repertoire. PMID:21219173

  15. Decreased serum levels of immunoglobulin A, immunoglobulin M and immunoglobulin G in a patient with primary biliary cirrhosis: A case report.

    PubMed

    Kawaguchi, Takumi; Tanaka, Toshimitsu; Hashiguchi, Michitoshi; Miyoshi, Hiroaki; Akiba, Jun; Kage, Masayoshi; Yano, Hirohisa; Ohshima, Koichi; Okamura, Takashi; Sata, Michio

    2014-10-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease with an elevated serum immunoglobulin (Ig)M level. Patients with PBC may develop extrahepatic manifestations, including hypogammaglobulinemia. However, hypogammaglobulinemia seldom occurs, and the associated changes of lymphocytes remain unknown. Furthermore, the impact of Ig on the progression of PBC is still unclear. Here, we describe a case of hypogammaglobulinemia developed in a female patient with PBC. The patient was diagnosed with PBC at the age of 46 years and treated with ursodeoxycholic acid and bezafibrate. At the age of 50 years, the patient developed bronchitis, and laboratory test results indicated a marked decrease in serum levels of IgA, IgM and IgG. Then, the patient was diagnosed as having idiopathic hypogammaglobulinemia and treated with Ig replacement therapy; however, respiratory infections recurred frequently, leading to the patient's death at the age of 53 years. An autopsy revealed hyperplastic bone marrow with CD3, CD20 and IgG positive lymphocytes. However, no CD79a, CD138, IgA and IgM positive lymphocytes were observed. Moreover, the severity of PBC progressed even after the onset of hypogammaglobulinemia. In addition, CD3 positive cells were seen around chronic non-suppurative destructive cholangitis in the autopsy specimen of the liver. Thus, the present case demonstrated changes of lymphocytes in hypogammaglobulinemia developed in patients with PBC. Furthermore, the clinical course of the present case of PBC may indicate that the Ig-mediated mechanisms may be non-essential for the progression of PBC. © 2013 The Japan Society of Hepatology.

  16. Aryl substitution of pentacenes

    PubMed Central

    Waterloo, Andreas R; Sale, Anna-Chiara; Lehnherr, Dan; Hampel, Frank

    2014-01-01

    Summary A series of 11 new pentacene derivatives has been synthesized, with unsymmetrical substitution based on a trialkylsilylethynyl group at the 6-position and various aryl groups appended to the 13-position. The electronic and physical properties of the new pentacene chromophores have been analyzed by UV–vis spectroscopy (solution and thin films), thermoanalytical methods (DSC and TGA), cyclic voltammetry, as well as X-ray crystallography (for 8 derivatives). X-ray crystallography has been specifically used to study the influence of unsymmetrical substitution on the solid-state packing of the pentacene derivatives. The obtained results add to our ability to better predict substitution patterns that might be helpful for designing new semiconductors for use in solid-state devices. PMID:25161729

  17. Neonatally measured immunoglobulins and risk of autism.

    PubMed

    Grether, Judith K; Croen, Lisa A; Anderson, Meredith C; Nelson, Karin B; Yolken, Robert H

    2010-12-01

    Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates. Archived newborn blood specimens were obtained from the California Genetic Disease Screening Program (GDSP) for N = 213 cases and N = 265 controls and assayed to determine levels of total IgG, antigen-specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive protein (CRP). We did not find measurable levels of total IgM or IgA in any neonate and measurable CRP was present in only a few. No antigen-specific IgG antibodies were elevated in cases compared to controls and total IgG levels were lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72 (95% CI 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed across increasing exposure quartiles of total IgG (P = 0.01). The finding of lower IgG in cases may indicate maternal immune dysfunction during gestation and/or impaired transplacental transfer of immunoglobulins. Further investigation of IgG levels in newborns and the mechanisms by which they might be associated with ASD are warranted. Copyright © 2010, International Society for Autism Research, Wiley Periodicals, Inc.

  18. Helicobacter pylori infection in patients with selective immunoglobulin E deficiency

    PubMed Central

    Magen, Eli; Schlesinger, Menachem; Ben-Zion, Itzhak; Vardy, Daniel

    2015-01-01

    AIM: To investigate the prevalence and clinical characteristics of Helicobacter pylori (H. pylori)-infected dyspeptic patients with selective immunoglobulin E deficiency (IgEd). METHODS: All individuals who underwent serum total immunoglobulin E (IgE) measurement at the Leumit Healthcare Services (Israel) in 2012 were identified in an electronic database search (n = 18487). From these, selected case group subjects were ≥ 12 years of age and had serum total IgE < 2 kIU/L (n = 158). The control group was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20 (n = 3160). Dyspeptic diseases, diagnosed no more than 5 years before serum total IgE testing, were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic codes. Results of C13-urea breath tests were used to identify subjects infected with H. pylori. Categorical variables between case and control subjects were analyzed using Fisher’s exact tests, whereas continuous variables were analyzed using χ2 tests. RESULTS: Dyspepsia was present in 27.2% (43/158) of case subjects and 22.7% (718/3160) of controls. Of these, significantly more case subjects (32/43, 74.4%) than controls (223/718, 31.1%) were positive for H. pylori (P < 0.01). Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects, revealing that gastritis was more prevalent in IgEd case subjects than in controls (57.9% vs 29.8%, P < 0.05). Furthermore, a significantly greater proportion of case subjects presented with peptic duodenal ulcers (63.2% vs 15.9%, P < 0.01). Histopathologic examination showed marked chronic inflammation, lymphoid follicle formation and prominent germinal centers, with polymorphonuclear cell infiltration of gastric glands, that was similar in case and control biopsy tissues. Finally, IgEd case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment

  19. Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis.

    PubMed Central

    Haque, K N; Remo, C; Bahakim, H

    1995-01-01

    In a prospective double-blind study, standard intravenous immunoglobulin (IVIG) was compared with an IgM-enriched IVIG in the treatment of neonatal sepsis. The two treatment groups were also compared with matched controls. One hundred and thirty babies (65 in each group) ranging from 0 to 24 days old, 480 to 4200 g in weight and born between 24 and 42 weeks of gestation who had, or were suspected of having, sepsis were given either standard IVIG or IgM-enriched IVIG (250 mg/kg per day) for 4 days in addition to supportive and antibiotic therapy. A further 65 babies who received similar supportive, antibiotic and fluids but not IVIG were used as matched controls. Mortality from infection in 'culture proven sepsis' was 3/44 (6.8%) in the IgM-enriched IVIG group, 6/42 (14.2%) in the standard IVIG group, and 11/43 (25.5%) in the control group (P = 0.017, IgM versus control, P = 0.19 standard IVIG versus control). There was no statistical difference in the outcome between the two immunoglobulin therapy groups (P = 0.25). The study indicates that IVIG improves outcome in neonatal sepsis when used as an adjunct to supportive and antibiotic therapy, but larger studies are required to confirm this. PMID:7648717

  20. "Half-half" blisters in bullous pemphigoid successfully treated with adjuvant high-dose intravenous immunoglobulin.

    PubMed

    Pacheco, David; Lopes, Leonor; Soares-Almeida, Luis; Marques, Manuel Sacramento; Filipe, Paulo

    2012-09-01

    Bullous pemphigoid is a rare, autoimmune blistering disease. Its clinical presentation is tense blisters that may arise on normal-appearing or erythematous skin. Bullous pemphigoid refractory to systemic corticosteroids in combination with immunosuppressants such as azathioprine and mycophenolate mofetil may benefit from adjuvant high-dose intravenous immunoglobulin (IVIg). We describe a particular case with an unusual clinical presentation unresponsive to systemic corticosteroids plus azathioprine, in which the addition of high-dose IVIg was successful. The combined therapy of systemic corticosteroids and azathioprine plus high-dose IVIg can be an option in refractory cases due to its efficiency and tolerability.

  1. The role of intravenous immunoglobulins in the treatment of rheumatoid arthritis.

    PubMed

    Katz-Agranov, Nurit; Khattri, Saakshi; Zandman-Goddard, Gisele

    2015-08-01

    Intravenous immunoglobulins (IVIGs) are beneficial and safe for various diseases other than primary immunodeficiencies. Over the years, IVIG has been given for autoimmune diseases as an off-label adjunct therapy. While other biologic agents are indicated for rheumatoid arthritis (RA), IVIG may have a role for specific subgroups of RA patients where anti-cytokine blockers or rituximab may be unwarranted. Such subgroups may include patients with vasculitis, overlap rhupus syndrome, severe infections with active disease, and pregnancy. In addition, IVIG may be considered for juvenile chronic arthritis (JCA) and adult Still's disease. We review the literature for IVIG treatment in RA patients and for these subgroups.

  2. Septic candidasis with intrahepatic cholestasis and immunoglobuline deficiency after renal transplantation.

    PubMed

    Zazgornik, J; Schmidt, P; Kopsa, H; Fill, W; Deutsch, E

    1975-10-01

    Two renal allograft recipients with acquired immunoglobulin deficiency had a disseminated infection with candida albicans. Septic fever, intrahepatic cholestasis and pulmonary mycotic disease were the prominent clinical symptoms. Recurrence of septic fever during the clinical course was associated with increase of intrahepatic cholestasis. On the other hand there was an amelioration of cholestasis when effective antimycotic therapy was instituted. In our patients there was no evidence that intrahepatic cholestasis was drug-related. It was assumed that toxic metabolits of candida albicans were responsible for intrahepatic cholestasis.

  3. Surface immunoglobulin of guinea-pig leukaemic lymphocytes.

    PubMed Central

    Stevenson, G T; Eady, R P; Hough, D W; Jurd, R D; Stevenson, F K

    1975-01-01

    The surface immunoglobulin of the transplantable L2C leukaemia of strain 2 guinea-pigs has been investigated. The immunoglobulin is seen to be synthesized when the cells are maintained in culture, indicating its intrinsic origin. Immunolabelling of the cell surface and immunochemical study of the Fab released by limited surface proteolysis indicate the presence of immunoglobulin of class IgM. IgG and free light chains were not detected, and there is unlikely to be an appreciable amount of immunoglobulin of any other class. The amount of immunoglobulin present, in terms of 4-chain monomers, is approximately 100,000 molecules per cell. Its half-life, calculated from the rate of reappearance in vitro of surface Fab after proteolytic clearing, is approximately 5 hours. Immunoglobulin secreted into the environment appears to arise predominantly or entirely from the cell surface: there is no evidence of an appreciable export of immunoglobulin which does not have a surface phase. Papain at 0.06 mg/ml rapidly removes the surface Fab. Residual Fcmu can then be detected by immunofluorescence, suggesting that papain cleaves surface IgM at a hinge region with the molecule in situ on the membrane. The released Fab is only moderately susceptible to degradation by papain at the enzyme: substrate ratio prevailing. It has been possible to isolate it from the papain digest by immuno-adsorption, with a notional yield of 75 mug per 10-10 cells, and then to prepare antisera against it. PMID:48498

  4. Case of twin pregnancy complicated by idiopathic thrombocytopenic purpura treated with intravenous immunoglobulin: Review of the literature.

    PubMed

    Zhao, W X; Yang, X F; Lin, J H

    2017-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acquired thrombocytopenia without other clear cause of thrombocytopenia. It is not common in a singleton pregnancy and less common in twin pregnancy. We report a 33-year-old ITP pluripara whose first pregnancy was uneventful. She carried twin pregnancy, complicated by recurrent very low platelets, and gave birth to preterm twins. This patient received multiple courses of intravenous immunoglobulin (IVIG) and showed a significant platelet count improvement with IVIG therapy.

  5. The influence of sodium perfluorooctanoate on the conformational transitions of human immunoglobulin.

    PubMed

    Messina, Paula V; Prieto, Gerardo; Salgado, Francisco; Varela, Carla; Nogueira, Montserrat; Dodero, Verónica; Ruso, Juan M; Sarmiento, Félix

    2007-07-19

    In the field of bioscience, the study of the interactions between blood proteins and fluorinated materials is very important from both theoretical and applied points of view. Fluorinated materials have potential use in drug delivery, as blood substitutes, and in biotechnology. Using a combination of ultraviolet-visible (UV-vis) and ultraviolet-circular dichroism (UV-CD) spectroscopies and ion-selective electrodes, the complete interaction of sodium perfluorooctanoate (SPFO) and the most important immunoglobulin (on a quantitative basis) in human serum, immunoglobulin G (IgG), has been evaluated. The study has been focused on bulk solution. By the application of an SPFO selective electrode, it was determined that there were true specific unions between surfactant molecules and IgG structure. The experimental data were presented as Koltz and Scatchard plots and analyzed on the basis of an empirical Hill equation. The conformational changes at the bulk solution were well characterized by UV-vis and UV-CD spectroscopies. As a consequence of these changes, the protein structure was affected.

  6. SAW: a graphical user interface for the analysis of immunoglobulin variable domain sequences.

    PubMed

    Elgavish, R A; Schroeder, H W

    1993-12-01

    The Sequence Analysis Workshop (SAW) is an interactive program for sequence analysis of immunoglobulin variable domains. Sequences for SAW can be obtained from GenBank or from a standard text file. SAW can compare a variable domain to as many as 100 different sequences, calculate the extent of homology, sort the sequences by their degree of similarity, translate the nucleotide codons into amino acids and then display the results in either a graphical or text format. These comparisons allow the investigator to determine the likely germ-line progenitors of a variable domain and to visualize how it differs from other antibody genes by functional region. SAW supports replacement and silent site substitution analysis by either codon or region, thus providing rapid insight into the forces that have shaped mutations. The sequence comparisons can be printed out as an aid for paper analysis or for preparation of figures for publication. SAW is written in Microsoft C for use with the Microsoft Windows graphics environment. The use of color and graphics, the generation of subsidiary windows that contain the results of specific analyses and the mouse-driven control of the program make SAW an easy-to-use tool for immunoglobulin sequence comparison.

  7. Effect of zinc supplementation on mycospecific immunoglobulins in tuberculosis patients.

    PubMed

    Chattopadhyay, Dipak Kumar; Maity, Chitta Ranjan; Nag, Debabrata

    2010-02-01

    The effect of zinc supplementation on the serum level of IgA, IgG, IgM mycospecific immunoglobulins in tuberculosis patients alongwith normal control and disease control subjects were studied. It was observed that with antituberculous drugs for one month (without zinc supplementation), the serum level of immunoglobulins in tuberculosis subjects although decreased significantly, but with zinc supplementation along with antituberculous drugs for one month the decrease in the level of immunoglobulins in serum was more significant. This may be attributed to the effect of zinc supplementation favouring the normal compartmentalisation state of iron and also to the immunomodulatory effect of zinc.

  8. A year in the life of the immunoglobulin superfamily.

    PubMed

    Williams, A F

    1987-01-01

    The superfamily of molecules with immunoglobulin-like domains has recently been gaining new members-largely on the basis of sequence homology. Here Alan Williams reviews this new work and reveals how the comparison of sequence patterns enables decisions on membership to be made. Accommodation of the new structures demands the provision of new categories, and forces the abandonment of the conserved disulphide bond as the last invariant characteristic of an immunoglobulin-type domain. They may, however, provide more dues to the origins and evolution of the immunoglobulin superfamily.

  9. [Successful Management by Immunoglobulin for Sunitinib-Induced Thrombocytopenia in a Patient with Advanced Metastatic Renal Cell Carcinoma].

    PubMed

    Okazaki, Satoshi; Hori, Jun-ichi; Watanabe, Masaki; Hashizume, Kazumi; Kobayashi, Shin; Azumi, Makoto; Kita, Masafumi; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2016-02-01

    An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

  10. Performing Substitute Teaching

    ERIC Educational Resources Information Center

    Bletzer, Keith V.

    2010-01-01

    Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

  11. The Age of Substitutability

    ERIC Educational Resources Information Center

    Goeller, H. E.; Weinberg, Alvin M.

    1976-01-01

    Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

  12. No cheap substitutes.

    PubMed

    Griffiths, Peter

    2016-06-15

    The Nuffield Trust report on reshaping the healthcare workforce was published last month. Its conclusions were widely reported as a recommendation to 'train up' nurses as a solution to junior doctor shortages, with support workers, in turn, substituting for registered nurses.

  13. The Age of Substitutability

    ERIC Educational Resources Information Center

    Goeller, H. E.; Weinberg, Alvin M.

    1976-01-01

    Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

  14. Performing Substitute Teaching

    ERIC Educational Resources Information Center

    Bletzer, Keith V.

    2010-01-01

    Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

  15. Screening Substitute Teachers.

    ERIC Educational Resources Information Center

    Kakkuri, Mark

    2000-01-01

    The screening process a school district uses in hiring substitute teachers is critical to striking a balance between required qualifications and immediate need. Typically, screening involves at least one of the following: pre-screening, paper and pencil screening, interviews, and background checks, each of which is used to different degrees…

  16. Organizing Substitute Teachers.

    ERIC Educational Resources Information Center

    Vail, Kathleen

    2000-01-01

    Many substitute teachers are underpaid, undertrained, and "invisible" employees lacking health benefits and respect from regular colleagues. Grass-roots organizing efforts have improved working conditions for subs in two Florida and California districts. Districts' improvement initiatives should be guided by concerns for student…

  17. [Colombian Guidelines of clinical practice for the use of immunoglobulins in the treatment of replacement and immunomodulation].

    PubMed

    Olivares, María Margarita; Olmos, Carlos E; Álvarez, Martha I; Fajardo, Adriana María; Zea-Vera, Andrés Felipe; Ortega, María Claudia; Medina, Diego; Pérez, Pahola Marcela; Beltrán, Delbert Giovanny; Duque, Beatriz; Álvarez, Carlos Arturo; Lenis, Germán; Solano, Juan Marcos; Gómez, Diana; Franco, José Luis; Díaz, María Claudia; Orrego, Julio César; Velásquez, Margarita María; Chaparro, Mauricio; Pinto, Jessica Liliana; Izquierdo, Álvaro; Ramírez, Sergio Francisco

    2017-01-01

    Immunoglobulins are heterodimeric proteins composed of 2 heavy chains and 2 light chains. Human immunoglobulin G (IgG) is a plasma derivative and contains more than 95% of IgG. The composition of IgG subclasses is similar to that of normal human plasma. Immunoglobulin therapy was first introduced more than 50 years ago, and its use has been described in numerous diseases. In Colombia, the importance of this immunomodulatory resource prompted the need for clinical practice guidelines to be available for its use. For this reason, a multidisciplinary group of experts was brought together and distributed in working groups, by specialties, in order to develop an initial manuscript. Systematic literature searches were undertaken; identified evidences were evaluated and classified to support a preliminary draft that was discussed, analyzed and amended. Recommendations were issued on the use of intravenous immunoglobulin in pathologies that include primary and secondary immunodeficiencies, autoimmune diseas es, neurological disorders, infections, transplants and miscellaneous conditions; grades were assigned to each one of them according to the GRADE system. The final result translated into recommendations that are put forth with the purpose to inform, guide and support on optimal use of this immunomodulatory resource.

  18. Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

    PubMed

    Lazzaro, Carlo; Lopiano, Leonardo; Cocito, Dario

    2014-07-01

    Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

  19. Substituted Hydroxyapatites with Antibacterial Properties

    PubMed Central

    Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Różycka, Dagmara

    2014-01-01

    Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency. PMID:24949423

  20. Substituted hydroxyapatites with antibacterial properties.

    PubMed

    Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Różycka, Dagmara

    2014-01-01

    Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency.

  1. Shared epitopes of avian immunoglobulin light chains.

    PubMed

    Benčina, Mateja; Cizelj, Ivanka; Berčič, Rebeka Lucijana; Narat, Mojca; Benčina, Dušan; Dovč, Peter

    2014-04-15

    Like all jawed vertebrates, birds (Aves) also produce antibodies i.e. immunoglobulins (Igs) as a defence mechanism against pathogens. Their Igs are composed of two identical heavy (H) and light (L) chains which are of lambda isotype. The L chain consists of variable (VL), joining (JL) and constant (CL) region. Using enzyme immunoassays (EIA) and two monoclonal antibodies (mAbs) (3C10 and CH31) to chicken L chain, we analysed their cross-reactivity with sera from 33 avian species belonging to nine different orders. Among Galliformes tested, mAbs 3C10 and CH31 reacted with L chains of chicken, turkey, four genera of pheasants, tragopan and peafowl, but not with sera of grey partridge, quail and Japanese quail. Immunoglobulins of guinea-fowl reacted only with mAb 3C10. Both mAbs reacted also with the L chain of Eurasian griffon (order Falconiformes) and domestic sparrow (order Passeriformes). Sera from six other orders of Aves did not react with either of the two mAbs. EIA using mAbs 3C10 and CH31 enabled detection of antibodies to major avian pathogens in sera of chickens, turkeys, pheasants, peafowl, Eurasian griffon and guinea-fowl (only with mAb 3C10). The N-terminal amino acid sequence of pheasant L chain (19 residues) was identical to that of chicken. Sequences of genes encoding the L chain constant regions of pheasants, turkey and partridge were determined and deposited in the public database (GenBank accession numbers: FJ 649651, FJ 649652 and FJ 649653, respectively). Among them, amino acid sequence of pheasants is the most similar to that of chicken (97% similarity), whereas those of turkey and partridge have greater similarity to each other (89%) than to any other avian L chain sequence. The characteristic deletion of two amino acids which is present in the L chain constant region in Galliformes has been most likely introduced to their L chain after their divergence from Anseriformes.

  2. Developing therapeutic immunoglobulins: European regulatory perspectives and implications.

    PubMed

    Kurz, Manfred

    2008-01-01

    Prepared from pooled human blood/plasma, therapeutic immunoglobulins contain the natural antibody spectrum of the entire donor population and mediate a range of therapeutic effects when administered to patients. They are particularly indicated for the prevention of serious and life-threatening infections in patients with immune systems failing to produce functional antibodies. Other than treatment of such rare primary immunodeficiencies (primary antibody deficiencies), therapeutic immunoglobulins are also used in certain inflammatory and autoimmune disorders, including immune thrombocytopenic purpura, Guillain Barré syndrome, and Kawasaki disease. The conditions for licensure of therapeutic immunoglobulins in the EU and the associated regulatory issues and procedures are reviewed. Regulatory expectations about the manufacture and control of immunoglobulins are highlighted and safety and efficacy requirements described. Although the main focus is on European pharmaceutical legislation, other applicable public information is considered.

  3. Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency.

    PubMed

    Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W

    2015-09-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin(®) ) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. © 2015 British Society for Immunology.

  4. Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency

    PubMed Central

    Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W

    2015-01-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin®) was compared with 20% SCIG (Hizentra®) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2–75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. PMID:25761372

  5. IMMUNOGLOBULIN SYNTHESIS AND SECRETION, III. INCORPORATION OF GLUCOSAMINE INTO IMMUNOGLOBULIN ON POLYRIBOSOMES*

    PubMed Central

    Sherr, Charles J.; Uhr, Jonathan W.

    1969-01-01

    Mouse myeloma cells were pulse-labeled in vitro with 3H-D-glucosamine and 14C-L-leucine. Analysis on sucrose gradients revealed incorporation of both isotopes into polyribosomes and release of most of such radioactivity after treatment of labeled cells in vitro with puromycin. A mixing experiment excluded the in vitro binding to unlabeled polyribosomes of 3H-glucosamine in labeled post-ribosomal material. Polyribosomes labeled with 3H-glucosamine were precipitated with antiserum specific for mouse immunoglobulin. By chromatography and gel filtration, the precipitable radioactivity was shown to be glucosamine covalently bound to heavy and light chains. PMID:5263020

  6. Immunoglobulin isotypes in Atlantic salmon, Salmo salar.

    PubMed

    Hordvik, Ivar

    2015-02-27

    There are three major immunoglobulin (Ig) isotypes in salmonid fish: IgM, IgD and IgT, defined by the heavy chains μ, δ and τ, respectively. As a result of whole genome duplication in the ancestor of the salmonid fish family, Atlantic salmon (Salmo salar) possess two highly similar Ig heavy chain gene complexes (A and B), comprising two μ genes, two δ genes, three intact τ genes and five τ pseudogenes. The μA and μB genes correspond to two distinct sub-populations of serum IgM. The IgM-B sub-variant has a characteristic extra cysteine near the C-terminal part of the heavy chain and exhibits a higher degree of polymer disulfide cross-linking compared to IgM-A. The IgM-B:IgM-A ratio in serum is typically 60:40, but skewed ratios are also observed. The IgT isotype appears to be specialized to mucosal immune responses in salmonid fish. The concentration of IgT in serum is 100 to 1000 times lower than IgM. Secreted forms of IgD have been detected in rainbow trout, but not yet in Atlantic salmon.

  7. Immunoglobulin A nephropathy complicating pulmonary tuberculosis.

    PubMed

    De Siati, L; Paroli, M; Ferri, C; Muda, A O; Bruno, G; Barnaba, V

    1999-10-01

    A 31-year-old man who presented with smear- and culture-negative pulmonary tuberculosis had associated macroscopic hematuria, elevation of serum creatinine and immunoglobulin A (IgA) levels, overt proteinuria, and peripheral edema. Renal biopsy revealed focal mesangial proliferation with IgA deposits, and a diagnosis of IgA nephropathy was made. The patient received treatment with isoniazide and rifampin. After 4 months, pulmonary lesions were almost completely healed, and a significant improvement of creatinine clearance with normalization of serum creatinine and IgA levels and disappearance of proteinuria were observed. Treatment with isoniazide and rifampin was discontinued after 6 months, without reappearance of either pulmonary or renal symptoms. Two years after the diagnosis of IgA nephropathy, the patient is in good general condition. Serum creatinine and IgA levels are normal, proteinuria is absent, and there is neither macrohematuria nor microhematuria. These findings suggest that IgA nephropathy may be a consequence of tuberculosis, possibly due to an abnormal IgA-mediated immune response against Mycobacterium tuberculosis with formation of nephrotoxic immune complexes.

  8. Immunological studies of an atypical (myeloma) immunoglobulin

    PubMed Central

    Johansson, S. G. O.; Bennich, H.

    1967-01-01

    An 8S myeloma component, isolated from serum of a patient with myelomatosis is described, which appears to have no antigenic determinants in common with human, α-, δ-, γ- or μ-polypeptide chains as revealed by immuno-electrophoresis and Ouchterlony gel diffusion analysis. The myeloma protein migrates in the fast γ-region on electrophoresis at pH 8.6 and has an elution volume on Sephadex G-200 similar to that of 6.5S IgA. The isolated myeloma component has an approximate molecular weight of 200,000 and a total carbohydrate content of 10.7 per cent. Reduction with β-mercaptoethanol and acid dissociation yields light polypeptide chains of Type L and a carbohydrate-rich component, in the ratio of 1:4. Antisera specific to determinants on the heavy chains of the myeloma protein showed no reaction with the immunoglobulins A, D, G or M. Instead unique determinants were found on the heavy polypeptide chains. ImagesFIG. 3FIG. 1FIG. 7FIG. 9FIG. 10 PMID:4168094

  9. Autoantibodies and immunoglobulins in collagenous colitis.

    PubMed Central

    Bohr, J; Tysk, C; Yang, P; Danielsson, D; Järnerot, G

    1996-01-01

    BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown. Autoimmunity has been suggested, but no serological findings have supported such a theory. AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38 matched healthy controls was analysed for autoantibodies--that is, antinuclear antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and microsomal antigen, together with antibodies to endomysium, gliadin, and cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and complement factors C3 and C4 were also determined. RESULTS: In patients with collagenous colitis the mean value of IgM was significantly increased 2.5 g/l (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p = 0.002). Antinuclear antibodies occurred in nine of 38 patients compared with three of 38 controls, this difference was not statistically significant (p = 0.11). The results of all other immunoglobulins, complement factors, and specific antibodies showed no statistical difference between patients and controls. CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is found in this study, although the findings of a positive ANA-titre in some patients and an increased IgM level might give some support for this hypothesis. PMID:8881813

  10. Immunoglobulin light chains, glycosaminoglycans and amyloid.

    SciTech Connect

    Stevens, F. J.; Kisilevsky, R.; Biosciences Division; Queen's Univ.

    2000-03-01

    Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as g2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the g peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normal protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue o shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans.

  11. Dermatomyosite et panniculite: place des immunoglobulines

    PubMed Central

    Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah

    2016-01-01

    La panniculite est une maladie inflammatoire du tissu adipeux sous-cutané rarement associée à la dermatomyosite. Elle peut survenir avant, après ou en même temps que l'atteinte musculaire. Dans la plupart des cas, l’évolution de la panniculite et des autres atteintes de la dermatomyosite est favorable sous traitement corticoïde et/ou immunosuppresseur. Nous rapportons le cas d'une patiente âgée de 48 ans ayant présenté des lésions de panniculite précédant de 2 mois les signes musculaires. L'atteinte cutanée était résistante au traitement corticoïde associés aux immunosuppresseurs ce qui a nécessité le recours au traitement par Immunoglobulines polyvalentes permettant ainsi une amélioration à la fois de l'atteinte cutanée et musculaire. PMID:27516827

  12. [Determination of serum immunoglobulins in asthmatic patients].

    PubMed

    Cabrera Jiménez, M; Valdés Sánchez, A F; Argüelles Sobrino, D; Gómez Echevarría, A H; Lastra Alfonso, G

    1989-01-01

    One hundred eighty one asthmatic patients were evaluated at the Allergy Consultation in Hermanos Ameijeiras Clinical Surgical Hospital. A case history was made for each of the patients, where the family background and personal history of allergy was collected; possible precipitating factors (such as inhalable, food, infectious, irritant, as well as climate factors) and physical and respiratory examinations. Serum immunoglobulin tests (by means of the ultramicroanalitic system (SUMA) and the rest of Igs: IgA, IgG, IgM by means of Mancini's simple radial immunodifusion method were made. Total eosinophil count was made to all of the patients in the study as well as serial studies of the faces. An increase in the IgE and IgM figures was found in asthmatic patients related to individual controls, and in relation to the normal figures for the adult population in our country. IgA and IgG determinations were normal both in the asthmatic and control groups, related to the standard figures.

  13. Immunoglobulin class-switch recombination deficiencies.

    PubMed

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

  14. Immunoglobulin: production, mechanisms of action and formulations

    PubMed Central

    Novaretti, Marcia Cristina Zago; Dinardo, Carla Luana

    2011-01-01

    Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs). There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented. PMID:23049343

  15. Ceftriaxone-induced hemolytic anemia in a child successfully managed with intravenous immunoglobulin.

    PubMed

    Vehapoğlu, Aysel; Göknar, Nilüfer; Tuna, Rümeysa; Çakır, Fatma Betül

    2016-01-01

    Drug-induced hemolytic anemia is an immune-mediated phenomenon that leads to the destruction of red blood cells. Here, we present a case of life-threatening ceftriaxone-induced hemolytic anemia (CIHA) in a previously healthy 3-year-old girl. We also reviewed the literature to summarize the clinical features and treatment of hemolytic anemia. Acute hemolysis is a rare side effect of ceftriaxone therapy associated with high mortality. Our patient had a sudden loss of consciousness with macroscopic hematuria and her hemoglobin dropped from 10.2 to 2.2 g/dl over 4 hours, indicating that the patient had life-threatening hemolysis after an intravascular dose of ceftriaxone who had previously been treated with ceftriaxone in intramuscular form for six days. CIHA is associated with a positive direct antiglobulin test, revealing the presence of IgG in all cases and C3d in most cases. Our patient's direct antiglobulin test was positive for IgG (3+) and for C3d (4+). The case was managed successfully with supportive measures and intravenous immunoglobulin therapy. Ceftriaxone is used very frequently in children; an early diagnosis and proper treatment of hemolytic anemia are essential to improve the patient outcome. The pathophysiological mechanism is the same as for non-drug autoimmune hemolytic anemia. However, there is still no consensus treatment for CIHA. Intravenous immunoglobulin can be used in clinical emergencies, such as our case, or in refractory cases.

  16. Therapeutic immunoglobulin should be dosed by clinical outcome rather than by body weight in obese patients.

    PubMed

    Hodkinson, J P; Lucas, M; Lee, M; Harrison, M; Lunn, M P; Chapel, H

    2015-07-01

    There are currently no data to support the suggestion that the dose of therapeutic immunoglobulin (Ig) should be capped in obese patients for pharmacokinetic (PK), safety and economic reasons. We compared IgG trough levels, increment and efficiency in matched pairs of obese and lean patients receiving either replacement or immunomodulatory immunoglobulin therapy. Thirty-one obese patients were matched with a clinically equivalent lean patient across a range of indications, including primary antibody deficiency or autoimmune peripheral neuropathy. Comprehensive matching was carried out using ongoing research databases at two centres in which the dose of Ig was based on clinical outcome, whether infection prevention or documented clinical neurological stability. The IgG trough or steady state levels, IgG increments and Ig efficiencies at times of clinical stability were compared between the obese and lean cohorts and within the matched pairs. This study shows that, at a population level, obese patients achieved a higher trough and increment (but not efficiency) for a given weight-adjusted dose compared with the lean patients. However at an individual patient level there were significant exceptions to this correlation, and upon sub-group analysis no significant difference was found between obese and lean patients receiving replacement therapy. Across all dose regimens a high body mass index (BMI) cannot be used to predict reliably the patients in whom dose restriction is clinically appropriate. © 2015 British Society for Immunology.

  17. Therapeutic immunoglobulin should be dosed by clinical outcome rather than by body weight in obese patients

    PubMed Central

    Hodkinson, J P; Lucas, M; Lee, M; Harrison, M; Lunn, M P; Chapel, H

    2015-01-01

    There are currently no data to support the suggestion that the dose of therapeutic immunoglobulin (Ig) should be capped in obese patients for pharmacokinetic (PK), safety and economic reasons. We compared IgG trough levels, increment and efficiency in matched pairs of obese and lean patients receiving either replacement or immunomodulatory immunoglobulin therapy. Thirty-one obese patients were matched with a clinically equivalent lean patient across a range of indications, including primary antibody deficiency or autoimmune peripheral neuropathy. Comprehensive matching was carried out using ongoing research databases at two centres in which the dose of Ig was based on clinical outcome, whether infection prevention or documented clinical neurological stability. The IgG trough or steady state levels, IgG increments and Ig efficiencies at times of clinical stability were compared between the obese and lean cohorts and within the matched pairs. This study shows that, at a population level, obese patients achieved a higher trough and increment (but not efficiency) for a given weight-adjusted dose compared with the lean patients. However at an individual patient level there were significant exceptions to this correlation, and upon sub-group analysis no significant difference was found between obese and lean patients receiving replacement therapy. Across all dose regimens a high body mass index (BMI) cannot be used to predict reliably the patients in whom dose restriction is clinically appropriate. PMID:25731216

  18. Intravenous immunoglobulin treatment of respiratory syncytial virus infections in infants and young children.

    PubMed Central

    Hemming, V G; Rodriguez, W; Kim, H W; Brandt, C D; Parrott, R H; Burch, B; Prince, G A; Baron, P A; Fink, R J; Reaman, G

    1987-01-01

    Respiratory syncytial virus (RSV)-infected cotton rats (Sigmadon hispidus) and owl monkeys (Aotus trivirgatus) showed significant reductions in RSV shedding from their respiratory tracts following parenteral therapy with human intravenous immunoglobulin (IVIG) containing high titers of RSV-neutralizing antibody. Because this therapy was well tolerated and appeared safe, a double-blind, placebo-controlled IVIG immunotherapy pilot study was performed on 35 hospitalized, RSV-infected infants and children. The treatment was well tolerated and resulted in significant reductions in nasal RSV shedding and in improvements in transcutaneous oximetry readings. However, the mean duration of hospitalization was not reduced by IVIG treatment. Followup to date has revealed no harmful effects resulting from immunotherapy of RSV infections. These studies appear to refute the hypothesis that passively acquired antibody may exacerbate RSV bronchiolitis or pneumonia in infants. Studies with larger numbers of seriously ill children will be required to determine if immunoglobulin G immunotherapy of RSV infections in infants is of clinical value. PMID:3439796

  19. Sensory Substitution for Wounded Servicemembers

    DTIC Science & Technology

    2009-10-28

    traumatic brain injury (TBI) and two civilians, all with partial visual impairment , evaluated the vision sensory substitution systems. The servicemember...Mobility Augmentation; Wounded Service Members; Human-Centered Computing; Vision Augmentation, Vision , Balance and Hearing; Sensory Substitution-enabled...mitigation of vision sensory and mobility losses. 2) Improved the usefulness of available sensory substitution technologies for injured military

  20. Treatment of multiple system atrophy using intravenous immunoglobulin.

    PubMed

    Novak, Peter; Williams, Arlene; Ravin, Paula; Zurkiya, Omar; Abduljalil, Amir; Novak, Vera

    2012-11-01

    Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA. This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. Nine subjects were enrolled, and seven (2 women and 5 men, age range 55-64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment. Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.

  1. Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies.

    PubMed

    Saadoun, D; Bodaghi, B; Bienvenu, B; Wechsler, B; Sene, D; Trad, S; Abad, S; Cacoub, P; Kodjikian, L; Sève, P

    2013-05-01

    Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcet's disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcet's disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

  2. Infantile immunoglobulin A nephropathy showing features of membranoproliferative glomerulonephritis.

    PubMed

    Kurosu, Akira; Oka, Noriko; Hamaguchi, Takeshi; Yoshikawa, Norishige; Joh, Kensuke

    2012-01-01

    Immunoglobulin A nephropathy (IgAN) showing predominant IgA and complement 3 (C3) deposition on the mesangium is an immune complex-mediated glomerulonephritis. This renal disease is the most common primary glomerular disease worldwide. However, infantile onset of IgAN is rare. In the present patient, urinary protein and occult blood were detected in a girl aged 1 year and 8 months on urinalysis at a nursery school. Despite being young, a kidney biopsy was performed for diagnosis and the correct choice of therapy. Glomerular mesangial cell proliferation and a double contour of the glomerular basement membrane (GBM) resembling a railroad track were noted on light microscopy. Therefore, the patient was diagnosed morphologically with membranoproliferative glomerulonephritis (MPGN), because mesangial hypercellularity and thickening of the GBM were identified. However, on immunofluorescent staining, the deposition of immune complexes mainly consisting of IgA, IgG, and C3 was noted in the mesangial region and glomerular capillary loops. On electron microscopy, electron-dense deposits were recognized in the subendothelial and paramesangial regions associated with mesangial cell interposition into the subendothelial space. Autoimmune diseases and infection-associated secondary glomerulonephritis were clinically excluded, because there were no relevant signs or symptoms. Steroid treatment was initiated and findings of urinalysis were normalized within 8 months. This patient was finally diagnosed with IgA nephropathy showing the features of MPGN. The present patient was the youngest among reported cases of IgA nephropathy, suggesting that early onset of IgAN is associated with an MPGN-like lesion. The present report provides information for pathogenesis of IgA nephropathy.

  3. Treatment of multiple system atrophy using intravenous immunoglobulin

    PubMed Central

    2012-01-01

    Background Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA. Methods This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. Results Nine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment. Conclusions Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed. PMID:23116538

  4. Anti-Proteinuric Effect of Sulodexide in Immunoglobulin A Nephropathy

    PubMed Central

    Bang, Kitae; Chin, Ho Jun; Chae, Dong Wan; Joo, Kwon Wook; Kim, Yon Su; Kim, Suhnggwon; Ju, Kyung Don; Kim, Hwajung; Ahn, Curie

    2011-01-01

    Purpose We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy. Materials and Methods A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value. Results At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38±0.77 at baseline to 5.98±0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not. Conclusion A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients. PMID:21623600

  5. Anti-sulfatide/galactocerebroside antibodies in immunoglobulin M paraproteinemic neuropathies.

    PubMed

    Boso, F; Ruggero, S; Giannotta, C; Benedetti, L; Marfia, G A; Ermani, M; Campagnolo, M; Salvalaggio, A; Gallia, F; De Michelis, C; Visentin, A; Bianco, M; Ruiz, M; Mataluni, G; Nobile-Orazio, E; Briani, C

    2017-08-07

    Anti-sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme-linked immunosorbent assay testing compared to sulfatide alone was assessed. Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti-myelin-associated glycoprotein (anti-MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control. Thirty-three patients showed increased titers of anti-sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy (P < 0.0001). When evaluating the reactivity for the combination Sulf/GalC, 57/229 patients were found to be positive, including 36/73 (49%) with IgM paraproteinemic neuropathy (P < 0.0001). Patients with known anti-sulfatide antibodies also showed anti-Sulf/GalC reactivity, with increased titers in 48.5% of the cases. Testing for anti-Sulf/GalC antibodies allowed 24 additional patients to be detected (eight with IgM paraproteinemic neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti-MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside. Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti-sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy.

  6. A double blind randomized experimental study on the use of IgM-enriched polyclonal immunoglobulins in an animal model of pneumonia developing shock.

    PubMed

    Vaschetto, Rosanna; Clemente, Nausicaa; Pagni, Aline; Esposito, Teresa; Longhini, Federico; Mercalli, Francesca; Boggio, Elena; Boldorini, Renzo; Chiocchetti, Annalisa; Dianzani, Umberto; Navalesi, Paolo

    2017-09-08

    Patients with severe pneumonia often develop septic shock. IgM-enriched immunoglobulins have been proposed as a potential adjuvant therapy for septic shock. While in vitro data are available on the possible mechanisms of action of IgM-enriched immunoglobulins, the results of the in vivo experimental studies are non-univocal and, overall, unconvincing. We designed this double blinded randomized controlled study to test whether IgM-enriched immunoglobulins administered as rescue treatment in a pneumonia model developing shock, could either limit lung damage and/or contain systemic inflammatory response. Thirty-eight Sprague Dawley rats were ventilated with injurious ventilation for 30min to prime the lung. The rats were subsequently randomized to received intratracheal instillation of either lipopolysaccharide (LPS) (12mg/kg) or placebo followed by 3.5h of protective mechanical ventilation. IgM-enriched immunoglobulins at 25mg/h (0.5mL/h) or saline were intravenously administered in the last hour of mechanical ventilation. During the experiment, gas exchange and hemodynamic measurements were recorded. Thereafter, the animals were sacrificed, and blood and organs were stored for cytokines measurements. Despite similar lung and hemodynamic findings, the administration of IgM-enriched immunoglobulins compared to placebo significantly modulates the inflammatory response by increasing IL-10 levels in the bloodstream and by decreasing TNF-α in bronchoalveolar lavage (BAL) fluid. Furthermore, in vitro data suggest that IgM-enriched immunoglobulins induce monocytes production of IL-10 after LPS stimulation. In an in vivo model of pneumonia developing shock, IgM-enriched immunoglobulins administered as rescue treatment enhance the anti-inflammatory response by increasing blood levels of IL-10 and reducing TNF-α in BAL fluid. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

    PubMed Central

    Berstein, R M; Schluter, S F; Shen, S; Marchalonis, J J

    1996-01-01

    All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution. Images Fig. 1 Fig. 3 PMID:8622930

  8. Successful multimodality treatment of recalcitrant necrobiotic xanthogranuloma using electron beam radiation and intravenous immunoglobulin.

    PubMed

    Nambudiri, V E; McLaughlin, C; Lo, T C M; Zembowicz, A; Moschella, S

    2016-03-01

    Necrobiotic xanthogranuloma (NXG) is a rare dermatosis with a poorly understood pathophysiology. Studies comparing treatments for such lesions are limited. We present the case of a patient with a 30-year history of NXG refractory to several individual therapeutic interventions [excision, intravenous immunoglobulin (IVIg), systemic chemotherapies and immunosuppressants, cryotherapy and laser therapy], who ultimately responded to a combination of treatment with electron beam radiation therapy (EBRT) in conjunction with IVIg. This combined treatment resulted in flattening of the NXG lesions and a reduction of symptomatic pruritus within the treatment zone. EBRT may represent a potent treatment for NXG, and formal trials evaluating its effectiveness may yield insights into the management of NXG. © 2015 British Association of Dermatologists.

  9. Immunoglobulin G4-Related Retroperitoneal Fibrosis Treated with Hochuekkito, a Kampo Medicine, following Steroid Treatment.

    PubMed

    Fukuchi, Minoru; Sakurai, Shinji; Kogure, Toshiaki; Naitoh, Hiroshi; Kuwano, Hiroyuki

    2014-05-01

    We report a case of immunoglobulin G4 (IgG4)-related retroperitoneal fibrosis (RF) with complete remission and no relapses after therapy with steroids and Hochuekkito, a Kampo (i.e. traditional Japanese herbal) medicine. A 62-year-old Japanese man was admitted to our hospital for treatment of a retroperitoneal mass detected by computed tomography. The mass had a maximum diameter of 11.0 cm; it involved the left ureter and was associated with left hydronephrosis. After inserting a ureteral stent, we performed a biopsy by laparotomy. Histopathology revealed IgG4-related RF. The lesion disappeared after 7 months of steroid therapy. We subsequently used Hochuekkito as an alternative maintenance treatment because of steroid-related complications. The patient has not relapsed in the 3 years since starting the medication. To the best of our knowledge, this is the first case of IgG4-related RF treated with Hochuekkito as a maintenance treatment.

  10. An aortoduodenal fistula as a complication of immunoglobulin G4-related disease

    PubMed Central

    Sarac, Momir; Marjanovic, Ivan; Bezmarevic, Mihailo; Zoranovic, Uros; Petrovic, Stanko; Mihajlovic, Miodrag

    2012-01-01

    Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm, which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level. A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula. The patient received antibiotics and other supportive therapy, and the postoperative course was uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein were noted, which normalized after the introduction of steroid therapy. Control computed tomography angiography showed no endoleaks. The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair. PMID:23155348

  11. Restoration of Retarded Influenza Virus-specific Immunoglobulin Class Switch in Aged Mice

    PubMed Central

    Zhang, Yongxin; Wang, Ying; Zhang, Monica; Liu, Lin; Mbawuike, Innocent N

    2016-01-01

    Objective The declined immune response to infection causes significant higher morbidity and mortality in aging in spite of the coexisted hyperimmunoglobulinemia (HIG). This study is to reveal the cellular basis of HIG and mechanism of weakened HA-specific IgG response in aged mice and to test cell therapy in the treatment of age-related IgG antibody production deficiency with immunocyte adoptive transfer. Methods BALB/c mice was immunized with Influenza A/Taiwan vaccine and challenged with the same strain of virus. ELISA was used to assess the levels of total immunoglobulins and antigen specific antibody response. The flow cytometry and ELISPOT were used to evaluate the frequencies of total immunoglobulin- and specific antibody-producing and secreting B lymphocytes. In vitro expanded mononuclear cells, CD4+ T lymphocytes and CD20+ B lymphocytes from old and young mice were adoptively transferred into influenza virus-challenged aged mice, and HA-specific IgG responses were observed. Results It is found that old mice exhibited higher levels of total serum IgG, IgM and IgA, higher frequencies of IgG+, IgM+ and IgA+ cells, and greater antigen-specific IgM and IgA responses to influenza infection, in comparison to young mice. However, influenza antigen- specific IgG and its subclass responses in old mice were significantly lower. Conclusion The retarded specific IgG response could be attributed to an insufficiency of immunoglobulin class switch in aging. Correlation analysis indicated that HIG and deficient specific IgG production in aged mice could be independent to each other in their pathogenesis. Correction of deficient specific IgG production by adoptive transfer of in vitro expanded and unexpanded CD4+ cells from immunized young mice suggests the CD4+ cell dysfunction contributes to the insufficiency of immunoglobulin class switch in aged mice. The transfusion of in vitro expanded lymphocytes could be a potential effective therapy for the age

  12. Current therapies in primary immune thrombocytopenia.

    PubMed

    Pels, Salley G

    2011-09-01

    Immune thrombocytopenia (ITP) has long been characterized as an autoimmune disease that exhibits antibody-mediated destruction of platelets. Many of the therapies have targeted reducing the antibody production and/or the platelet destruction process within the reticuloendothelial system, including steroids, immunoglobulin, anti-RhD immunoglobulin, splenectomy, and rituximab. Relatively new insights into the pathophysiology of this disorder have led to the introduction of new therapies, such as the use of thrombopoietic agents to enhance platelet production. This review outlines many of the most commonly used therapeutic agents for the treatment of severe thrombocytopenia associated with both newly diagnosed and chronic ITP. Thieme Medical Publishers.

  13. Methodologies in Creating Skin Substitutes

    PubMed Central

    Nicholas, Mathew N; Jeschke, Marc G; Amini-Nik, Saeid

    2016-01-01

    The creation of skin substitutes has significantly decreased morbidity and mortality of skin wounds. Although there are still a number of disadvantages of currently available skin substitutes, there has been a significant decline in research advances over the past several years in improving these skin substitutes. Clinically most skin substitutes used are acellular and do not use growth factors to assist wound healing, key areas of potential in this field of research. This article discusses the five necessary attributes of an ideal skin substitute. It comprehensively discusses the three major basic components of currently available skin substitutes: scaffold materials, growth factors, and cells, comparing and contrasting what has been used so far. It then examines a variety of techniques in how to incorporate these basic components together to act as a guide for further research in the field to create cellular skin substitutes with clinically better results. PMID:27154041

  14. Immunoglobulin VH determinants defined by monoclonal antibodies.

    PubMed

    Kubagawa, H; Mayumi, M; Kearney, J F; Cooper, M D

    1982-10-01

    Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts.

  15. Immunoglobulin VH determinants defined by monoclonal antibodies

    PubMed Central

    1982-01-01

    Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts. PMID:6185604

  16. Systemic sclerosis and prevalence of monoclonal immunoglobulin.

    PubMed

    Trad, Salim; Nosbaum, Audrey; Musset, Lucile; Ghillani-Dalbin, Pascale; Launay, David; Costedoat-Chalumeau, Nathalie; Saadoun, David; Cabane, Jean; Hachulla, Eric; Hanslik, Thomas; Frances, Camille

    2014-12-01

    The purpose of this study was to estimate the prevalence of monoclonal immunoglobulin (MIg) among patients with systemic sclerosis (SSc) according to the capillary electrophoresis or immunofixation method of detection and to search for any related clinical correlations. Retrospective multicenter comparison of capillary electrophoresis and immunofixation results in SSc patients and of the characteristics of patients with and without MIg. The study included 244 SSc patients (216 women and 28 men, mean age: 55±14 years). Median time since SSc diagnosis was 51 months [0-320]; disease was diffuse in 48% of cases. Ten percent of patients had cancer, including Waldenström macroglobulinemia (n=1) and multiple myeloma (n=3). Capillary electrophoresis showed a γ-globulin anomaly in 41% of cases, and immunofixation in 18%: MIg (13.5%) and restriction of heterogeneity (4.5%). Capillary electrophoresis failed to detect 60% of the 33 MIg patients. Measurable MIg concentrations were obtained from 7 patients. MIg patients were significantly older at SSc diagnosis than those without MIg (p=0.002), had a lower diffusing capacity (p=0.002), a higher prevalence of pulmonary hypertension and cancer (p=0.002) and were more frequently positive for anti-mitochondrial and anti-beta2-glycoprotein-I antibodies (p=0.03 and p=0.02, respectively). Multivariate analyses showed that only age at test [hazard ratio 1.03 (95% CI, 1.00-1.07, p=0.04)] and presence of cancer [hazard ratio 4.46 (95% CI, 1.6-12.4, p=0.004)] were associated with MIg. Immunofixation detected a high prevalence of MIg among SSc patients especially in patients aged 50-years or older. MIg was not detected by the standard capillary electrophoresis in 60% of cases and was significantly associated with cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Helicobacter pylori-related immunoglobulins in sarcoidosis.

    PubMed

    Herndon, Betty L; Vlach, Victoria; Dew, Michelle; Willsie, Sandra K

    2004-03-01

    The purpose of this study was to determine serum antibody titers against a common bacterial antigen, Helicobacter pylori (H. pylon), in subjects with sarcoidosis, comparing those titers to those present in a healthy population. With the approval of the Institutional Review Board of the University of Missouri-Kansas City, patients with sarcoidosis (pulmonary and extrapulmonary) who visited the Truman Medical Center-Hospital Hill pulmonary clinic were recruited to enter the study. A serum sample was frozen at -70 degrees C for later testing (n = 20). Specific information collected on subjects included corticosteroid use, use of histamine2 blockers and antacids, date of first diagnosis, and stage of sarcoidosis. Normal controls and demographically matched individuals who lacked pulmonary diseases, including sarcoidosis, were also recruited. Serum samples were processed as above. Antibody capture enzyme immunoassay was completed for H. pylori and urease antigens by serum dilution assay for each subject, from which titers for antigen-specific immunoglobulin (Ig)G and IgA were calculated. Nonspecific serum IgE was also measured. An increased incidence of high-titer IgG antibody directed against H. pylori antigens was found in subjects with sarcoidosis compared with controls. The sarcoidosis and control groups were significantly different with respect to IgG and IgA against H. pylori, both at p = .001. IgG directed against urease was also significantly different between sarcoidosis and control patients (p = .001), but IgA directed against urease was very low in all subjects and did not yield significant differences between groups. Specific H. pylori and urease IgG antibodies exceeded those expected in the population studied. The data suggest that in pulmonary sarcoidosis, the relationship of H. pylori and its products to sarcoid granuloma formation warrants further investigation.

  18. Immunoglobulin heavy chains in medaka (Oryzias latipes)

    PubMed Central

    2011-01-01

    Background Bony fish present an immunological system, which evolved independently from those of animals that migrated to land 400 million years ago. The publication of whole genome sequences and the availability of several cDNA libraries for medaka (Oryzias latipes) permitted us to perform a thorough analysis of immunoglobulin heavy chains present in this teleost. Results We identified IgM and IgD coding ESTs, mainly in spleen, kidney and gills using published cDNA libraries but we did not find any sequence that coded for IgT or other heavy chain isotypes described in fish. The IgM - ESTs corresponded with the secreted and membrane forms and surprisingly, the latter form only presented two constant heavy chain domains. This is the first time that this short form of membrane IgM is described in a teleost. It is different from that identified in Notothenioid teleost because it does not present the typical splicing pattern of membrane IgM. The identified IgD-ESTs only present membrane transcripts, with Cμ1 and five Cδ exons. Furthermore, there are ESTs with sequences that do not have any VH which disrupt open reading frames. A scan of the medaka genome using transcripts and genomic short reads resulted in five zones within a region on chromosome 8 with Cμ and Cδ exons. Some of these exons do not form part of antibodies and were at times interspersed, suggesting a recombination process between zones. An analysis of the ESTs confirmed that no antibodies are expressed from zone 3. Conclusions Our results suggest that the IGH locus duplication is very common among teleosts, wherein the existence of a recombination process explains the sequence homology between them. PMID:21676244

  19. Immunoglobulin negative follicle centre cell lymphoma.

    PubMed Central

    Gregg, E. O.; Al-Saffar, N.; Jones, D. B.; Wright, D. H.; Stevenson, F. K.; Smith, J. L.

    1984-01-01

    Immunoglobulin (Ig) could not be detected on the surface or in the cytoplasm of neoplastic cells from five cases of follicle centre cell lymphoma with centroblastic/centrocytic follicular histology when examined by immunohistology of frozen or wax embedded sections. Examination by fluorescein labelled antibodies of cells in suspensions prepared from the biopsies revealed a monotypic surface Ig positive population in one case and a surface or cytoplasmic Ig kappa:lambda light chain imbalance in a further two cases consistent with neoplastic B cell involvement: in all cases the proportion of cells failing to express Ig or T cell markers ranged from 24 to 75%. The monoclonal antibodies B1 (Pan B cell), FMC4 (HLA class II) and J5 (cALL antigen) stained the majority of cells in suspension with residual cells staining with UCHT1 or OKT11 (T cell monoclonal antibodies). In frozen sections, neoplastic follicular cells did not stain with UCHT1. However, in the one case tested these cells stained with the antibodies B1 and FMC4. In paraffin sections J chain could be demonstrated in the cytoplasm of three out of five cases. Cells from four cases were cultured in vitro for Ig production: two failed to produce Ig and monotypic light chains were the sole Ig product of the remaining two cases. The failure to express Ig by the majority of the neoplastic cells from the cases described in this report is at variance with the follicular histology of these neoplasms. Mechanisms responsible for this failure are discussed with reference to current models of B cell differentiation. Images Figure 1 PMID:6437429

  20. Nucleotide sequences of immunoglobulin eta genes of chimpanzee and orangutan: DNA molecular clock and hominoid evolution

    SciTech Connect

    Sakoyama, Y.; Hong, K.J.; Byun, S.M.; Hisajima, H.; Ueda, S.; Yaoita, Y.; Hayashida, H.; Miyata, T.; Honjo, T.

    1987-02-01

    To determine the phylogenetic relationships among hominoids and the dates of their divergence, the complete nucleotide sequences of the constant region of the immunoglobulin eta-chain (C/sub eta1/) genes from chimpanzee and orangutan have been determined. These sequences were compared with the human eta-chain constant-region sequence. A molecular clock (silent molecular clock), measured by the degree of sequence divergence at the synonymous (silent) positions of protein-encoding regions, was introduced for the present study. From the comparison of nucleotide sequences of ..cap alpha../sub 1/-antitrypsin and ..beta..- and delta-globulin genes between humans and Old World monkeys, the silent molecular clock was calibrated: the mean evolutionary rate of silent substitution was determined to be 1.56 x 10/sup -9/ substitutions per site per year. Using the silent molecular clock, the mean divergence dates of chimpanzee and orangutan from the human lineage were estimated as 6.4 +/- 2.6 million years and 17.3 +/- 4.5 million years, respectively. It was also shown that the evolutionary rate of primate genes is considerably slower than those of other mammalian genes.

  1. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted...

  2. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted...

  3. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substitut