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Good?s syndrome is defined by the association of thymoma, hypogammaglobulinemia and recurrent infections especially bronchopulmonary and sinus. We report the case of a 53 years old man , with a history of recurrent respiratory infections, hospitalized in June 2017 for bronchial syndrome dragging with radiographic front chest presence of bilateral alveolar syndrome and lat?rotrach?ale opacity right, supplemented by a thoracic scan, which objectified the chance discovery of a regular meditational tissue mass without locoregional malignancy, with no clinical and electrophysiological signs of myasthenia gravis. The patient was operated for his m?diatisnal mass which histological study was in favor of a thymoma type A, the outcome was favorable. In our patient the association between thymoma and hypogammaglobulinemia and bronchopulmonary infection severe and recurrent led to the diagnosis of Good\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s syndrome. The patient was put under appropriate antibiotic therapy combined with weekly infusions of intravenous immunoglobulin, with a positive trend, achieving significant clinical improvement, biological and radiological. Good?s syndrome represents only 5% of parathymiques diseases, but its research is essential because it allows effective treatment of infections, avoiding lung destruction and the use of lung surgery.

Intravenous Ig (IVIg) products are used in various medical conditions. Differences in excipients account for most adverse events (AE). Reports of complications including acute myocardial infarction (AMI) and acute renal failure (ARF) have emerged. Herein is described one institution's experience with IVIg-related complications. This study is a retrospective analysis of infusion-related AE that are associated with various IVIg products. Infusion-related AE were monitored during and after the administration of three IVIg products: Gamimune-N 10% (n = 76), Polygam (n = 105), and Carimune (n = 98). AE segregated to specific IVIg products. No patients who received Gamimune-N experienced AMI or ARF. Five (4.7%) patients (P0.01) in the Polygam group experienced AMI. Eight (8.2%) patients (P0.0001) in the Carimune group developed ARF. IVIg was safe to give on hemodialysis. IVIg products differ in osmolality, pH, and sugar and sodium content; this results in specific AE. Polygam resulted in no ARF but an increase in AMI. Carimune products at 9% concentration resulted in an increase in ARF. Gamimune-N 10% and other IVIg products were frequently associated with headaches. Administration of IVIg to patients who are on hemodialysis seems to be safe and effective.

The first therapeutic indication, and still currently the most applied of gamma globulin, is the one which uses its substitutive capacity in patients with antibodies deficiencies. Its immunomodulatory effectiveness with pro and anti-inflammatory activity holds a second place in their indications, in autoimmune and inflammatory illnesses. The first gamma globulin to be used in patients with agammaglobulinemia in the 50’s, were of intramuscular administration, with significant limitations on the volume and the infusion’s amount, as well as being painful . For over 20 years intravenous immunoglobulin (IVIG) has been widely used in human pathology. The first proteolytic enzyme-treated intravenous immunoglobulins allowed large doses infusions, thereby getting higher levels of IgC circulating in plasma, a subclass profile similar to the normal population, as well as a much higher average life expectancy. The pharmaceutical industry efforts brought about new more purified and viral safer immunoglobulins. The Cohn and cold ethanol methods were quickly supplemented with ulterior procedures that strengthened the viral safety of these products. The application of molecular techniques to the screening study of plasma donors, as well as incorporating new viral inactivation procedures during its manufacture, have made of IVIG a safe product whose consumption has exponentially increased in recent years. IVIG’s high cost, the hypothetical plasma supply problems and risks associated to its administration made essential the writing of usage protocols for official agencies, which, besides, hospitals also adopted.

though intravenous gammaglobulin (IVIG) with aspirin is effective therapy for most children with acute KD, its mechanism of action is unknown, and some children do not respond. In the present era of sophisticated medicine, this conversation, with all its unknowns, is very unsettling both to me and to the family. In addition, when I diagnose acute KD in a child during the first week of fever and promptly administer IVIG and aspirin therapy but the child fails to respond and coronary aneurysms develop and worsen despite additional therapies, I ponder the sobering reality that even those of us who have devoted a great deal of our careers to the study of KD cannot always stop this process. All of this leads directly to the question: what is the cause of this disease? Finding the cause of KD is a pediatric infectious diseases research priority. Identification of the causative agent(s) would be the most promising step toward developing a diagnostic test and specific therapy and, ultimately, preventing the disease. Therefore, a study by Esper et al. [1] from Yale, published in the Journal of Infectious Diseases in February 2005, that implicated an association between the new human coronavirus (HCoV) NL-63 and KD, was met with great interest. Those investigators reported detection of the virus in respiratory samples from 8 of 11 patients with KD and 1 of 22 control subjects by reverse transcription-polymerase chain reaction (RT-PCR). As a result of that article, laboratories around the world performed additional studies to determine whether an association between KD and HCoV NL-63 could be confirmed. This

Guillain-Barre syndrome (GBS) is an eponym for a heterogeneous group of immune-mediated peripheral neuropathies. We describe a case of GBS in a patient who recieved intravenous streptokinase therapy for acute anterior myocardial infarction. Clinical symptoms are thought to result from streptokinase-antibody complex mediated damage to the local blood-nerve barrier. Patient was treated with 5-days course of intravenous gammaglobulin and his outcome was good.

Intravenously administered immune globulin therapy has been reported to be an effective treatment for serious patients with verotoxin-producing Escherichia coli infections while an efficacy for VT2 are under discussion. We therefore examined in vitro commercially available immune globulin preparations for the presence of anti-VT neutralizing antibodies in expectation of protecting a patient from serious complications as HUS. We examined 47 lots of gamma-globulin prepared by 5 pharmaceutical companies in Japan. Of them 29 lots were prepared from imported blood and 18 lots were from Japanese donors' blood. They were prepared in each company following their own manufactures' process. Neutralizing activity for VT1 and VT2 were determined by means of cytotoxicity using ACHN (renal adenocarcinoma, human) cells. All lots of gamma-globulin preparations from imported blood completely neutralized 125 pg/ml VT1 at the concentration of 12.5 mg/ml, and no significant difference was found in the manufactures' process. On the other hand gamma-globulin preparations from Japanese donors' blood neutralized VT1 five times less than the former. None of all preparations neutralized VT2. Gammaglobulin preparations were produced from pooled human plasma. To know the difference of neutralizing activities in the source, we examined randomly selected 239 human plasma samples of which 51 were from Japanese donors' blood and 188 were from imported blood. Prevalences of neutralizing activity of VT1 in imported plasma and domestic plasma were 10.6% and 2.0%, respectively. The prevalence of neutralizing antibody in these plasma samples reflects the different neutralizing activity of VT1 in gamma-globulin preparations prepared from imported blood and Japanese donors' blood. From these results, by selecting the lot of gamma-globulin preparations or the material of plasma with highly neutralizing activity, intravenously administered immune globulin therapy may be effective for VT1. The lack of VT2-neutralizing activity in any gamma-globulin preparation promotes us to develop humanized anti-VT2-monoclonal antibody for the prevention of HUS in high risk children.

Intravenous gammaglobulins are used for the treatment of various auto-immune hematological disorders. Renal failure is a relatively rare, but an increasingly recognized side effect of gammaglobulin therapy. Although the renal failure is usually reversible, renal replacement therapy is required occasionally. A high index of suspicion, early recognition and appropriate intervention can prevent this complication. We herewith describe two patients with an immune hematological disorder, who developed acute renal failure after treatment with intravenous gammaglobulins. A brief review of the possible risk factors, pathophysiology and management of this complication is provided.

On July 27, 1989, the International Conference on Molecular Aspects of Immune Response and Infectious Diseases devoted a symposium to the subject of the use of intravenous gamma globulin (IVIG) in acquired immunodeficiency syndrome (AIDS). The information presented confirmed that IVIG benefits human immunodeficiency virus (HIV)-infected children with recurrent infections and that much remains to be learned about the influence of IVIG in adult AIDS. The symposium participants recognized the urgent need to develop randomized clinical trials using a control group to assess the efficacy of a treatment with IVIG in PGL (persistent generalized lymphadenopathy), ARC (AIDS-related complex), and AIDS. To prepare this report, a committee was established, including individuals with expertise in immunology, immunopharmacology, microbiology, virology, infectious diseases, general medicine, and pediatrics and representing research experience in academia and hospitals. After an introduction to the report with a summary of immunotherapeutic agents under evaluation to treat HIV infection, section 1 lays out the present understanding of the disease pathogenesis. Section 2 then outlines the treatment of HIV-seropositive individuals, discussing the uncertainties that any treatment entails. Section 3 discusses the rationale for treating HIV-infected individuals with WIG, and Section 4 examines the major differences between IVIG and hyperimmuneglobulins for the treatment of HIV infection. Section 5 looks at IVIG as a mean to delay the emergence of opportunistic infections and restore immunocompetence in AIDS and related illnesses, and Sections 6 and 7 suggest a pilot protocol on the use of WIG in association with low-dose or standard-dose zidovudine (AZT). Limited time precluded the committee's addressing certain important aspects, and it must be remembered that, since this report represents the committee evaluations as of July 1989, the use of WIG in adults infected with HIV should be studied on a continuous basis according to more up-todate knowledge of HIV infection.

Gabexate Mesilate (FOY) as a New Additional Therapy to High Dose Intravenous Gammaglobulin for High Risk Kawasaki Disease

Background: In Kawasaki disease (KD), administration of intravenous gammma-globulin (IVGG) reduced frequency of coronary artery lesion (CAL) from 25% to 8%. However, approximately 500 children still develop CAL every year in Japan. We evaluated the efficacy and safety of plasma exchange (PE) for children with KD intractable to IVGG therapy. Patients and Methods: Among 255 children with KD treated with initial IVGG, 119 children were identified at high risk for CAL according to the increases in fractional changes (FC) of white blood cell count, neutrophils, and CRP between baseline and 1 to 2 days after IVGG treatment. Seventy-five were administered additional IVGG, and finally 50 of them were underwent the PE therapy in 3 consecutive days. All the children were serially monitored for the development of CAL by echocardiography during the course of the disease until days 28-30. The incidence of CAL was compared among the children treated and those untreated with PE. Results: The demographic differences between the treated and untreated children were not significant on admission. The PE therapy was safely performed without any adverse reactions, and has completed in each child. Out of 50 children treated PE, only 10 (20.0%) had CAL, including temporary dilatation in 7, persistent CAL in 1, and giant aneurysms in 2 children. In contrast, 24 children (40.7%) among 69 without PE were affected with CAL, including giant aneurysm in 5 (P < 0.0004). Conclusions: We suggested that PE therapy performed within 10 days after the onset of the disease should be effective and safe for the children with KD intractable to the IVGG therapy. The PE therapy may be applied as soon as possible when the fractional increases in inflammatory markers after the initial IVGG are determined.

Summary We report the case of a teenage boy with thrombocytopenia complicating varicella infection, which responded promptly to treatment with intravenous immunoglobulin therapy. Such treatment is well recognized in the management of immune thrombocytopenia, particularly where steroids are contra-indicated, but we have not found any previous case reports of the use of immunoglobulin in this condition.

In a patient with idiopathic thrombocytopenic purpura (ITP), the hemostatic control is considerably troublesome. When a tooth extraction is required in such a case, platelet rich plasma and/or fresh whole blood transfusion has been usually practiced. Though oral surgical treatmant has become convenient with this therapy, serious problems such as a new production of antibodies against platelet happens. Since these antibodies invalidate the effect of transfusiontherapy in lethal bleeding, its use must be deliberate. So we are looking forward to a more suitable method in minor treatments of oral surgery or dentistry.It was revealed by Imbach et al. in 1981 that high-dose intravenous gammaglobulin therapy was able to increase the number of platelets in ITP. Thereafter the usefulness of this therapy has been ascertained at various clinics and it is considered a new treatment for ITP. By this time no important side effects through this therapy are reported. We consider this therapy is also very useful on our clinics.We have recently experienced two cases of tooth extraction with this therapy in a patient with ITP and obtained good results. From these experiences we have come to the conclusion that systematic oral or dental care is most imprtant in a patient with ITP or hemorrhagic diathesis.

KANOH, T., OHNO, T., HARADA, S. and FUJII, H. An Unsuccessful Attempt to Isolate Human Immunodeficiency Virus (HIV) from Patients with Primary Immunodeficiency Diseases. Tohoku J. exp. Med., 1987, 152 (4), 391-395 -Isolation of the human immunodeficiency virus (HIV) was performed in 5 seronegative patients with primary immunodeficiency diseases (IDDs) who had no or little ability to produce antibodies and received a large amount of intravenous gammaglobulin (IVG) for a long period. In this study cultured cells were considered to be infected if the following 2 criteria were met: (1) They produced revers etranscriptase (RT) activity in the supernatant fluid and (2) expressed viral antigens. Under experimental conditions, virus was demonstrated by both RT activity and viral antigen expression detectable by immunofluorescence technique in lymphocyte cultures from 2 seropositive patients with acquired immunodeficiency syndrome-related complex who were examined as controls. There was no evidence of HIV infection in cultures of lymphocytes from all of the 5 patients with primary IDDs and from 2 healthy subjects. The above patients did not show the extremely low numbers of target T4+ cells, which make isolation of the virus in lymphocytes difficult. The present results suggest that current methods of IVG preparation either remove or inactivate HIV.

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000–790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3–4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2–10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.

Ten patients with idiopathic thrombocytopenic purpura (ITP) were studied before and following a rise in circulating platelets subsequent to infusions of intravenous gammaglobulin (400 mg/kg/day x 5 days). We quantitated the amount of circulating IgG capable of binding to normal donor platelets in vitro using an 125I-monoclonal anti-human IgG assay, as well as the amount of IgG associated with the patients' platelets before and following therapy. We found no evidence for a decrease in platelet-specific IgG antibodies in these patients undergoing an acute response to therapy. These data suggest that the short-term efficacy of intravenous gammaglobulin is due to effects other than a substantive reduction in platelet reactive antibodies, such as the alteration of IgG-coated platelet destruction.

Fourteen adults with idiopathic thrombocytopenic purpura suffered a relapse after treatment with steroids, vinca alkaloids, or intravenous gammaglobulin. Splenic sequestration of platelets labelled with 111In-oxine was assessed, and the patients then underwent splenectomy. During follow up of four to 47 months (mean 20.7) none of the patients required further treatment, including three of 14 who showed partial relapses. Splenic sequestration patterns did not predict relapses, but an unexpected finding was that patients who relapsed had significantly smaller spleens. It is concluded that splenectomy is beneficial in most adult patients with idiopathic thrombocytopenic purpura and that radiological techniques to measure the size of the spleen may be useful in predicting which patients may relapse.

Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months' treatment with the weekly intramuscular preparation and six months' treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.

An infant with severe, isoimmune thrombocytopenia secondary to maternal anti-Pla 1 immunisation was treated successfully by intravenous gammaglobulin (400 mg/kg per day for five days). This treatment compared with Pla 1 negative platelet transfusions is discussed.

phase radioimmunoassay for platelet-associated immunoglobulin G. J Lab Clin Med 101:392, 1983. 5. Singer DB: Postsplenectomy sepsis. In Rosenberg HS, Bolande RP, editors: Perspectives in pediatric pathology, vol 1. Chicago, 1973, Year Book Medical Publishers, p 285. 6. Venetz U, Willi P, Hirt A, lmbach P, Wagner HP: Chronic idiopathic thrombocytopenic purpura in childhood. Helv Paediatr Acta 37:27, 1982. 7. Fehr J, Hofmann V, Kappeler V: Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gammaglobulin. N Engl J Med 306:1254, 1982. 8. Picozzi V J, Roeske WR, Greger WP: F~ te of therapy failures in adult idiopathic thrombocytopenic purpura. Am J Med 69:690, 1980. 9. Lammi AT, Lovric VA: Idopathic thrombocytopenic purpura: An epidemiologic study. J PEDIATR 83:31, 1973. 10. Williams W J, Beutler E, Erslev A J, Rundles RW, editors: Hematology. New York, 1972, McGraw-Hill. II. Cohen P, Gardner FH: The thrombocytopenic effect of sustained high-dosage prednisone therapy in thrombocytopenic purpura. N Engl J Med 265:611, 1961.

This work was supported in part by a grant-in-aid from the Japan Medical Research Foundation and by Scientific Research Grants (project No. 57770632) from the Ministry of Education, Science and Culture of Japan.

IVGG has been used as an alternative to splenectomy (SPL) in children 6 months (J Peds 10/83). Decision analysis was used to compare the benefits and costs of IVGG vs. SPL in the initial management of chronic ITP. Published reports and a survey of 11 pediatric hematology centers provided data for the analysis. For IVGG, the experience of the first 25 patients treated at Cornell was used: (1) THERAPY/COSTS: induction IVGG dose of 73 grams/pt (2 gms/kg) at $40/gm=$3,000, avg maintenance IVGG dose in a subsequent 6 month period of 117 gms/pt $5,000, office visits & CBC's=$780. (2) OUTCOME/MANAGEMENT: 5 remissions, 6 stable without IVGG, 4 infrequent (