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Absence of seroconversion following treatment with hepatitis B immune globulin containing antibody to human immunodeficiency virus.

Recent studies have demonstrated that commercial preparations of hepatitis B immune globulin often contain antibody to the human immunodeficiency virus. The presence of this antibody has aroused concerns that treatment with hepatitis B immune globulin might passively induce human immunodeficiency virus antibody seropositivity, leading to incorrect diagnoses of human immunodeficiency virus exposure. We studied a group of 16 normal volunteers who received an intramuscular dose of hepatitis B immune globulin (0.06 ml per kg) which was later discovered to contain human immunodeficiency virus antibody. None of the subjects had human immunodeficiency virus antibody before receiving hepatitis B immune globulin. Serum specimens collected at 1 to 4, 6, 8, 12, 16, 20 and 24 weeks after the injection were consistently negative for human immunodeficiency virus antibody. There was no detectable human immunodeficiency virus antibody in any specimen from any subject. We conclude that intramuscular therapy with hepatitis B immune globulin in the recommended dose does not appear to place patients at risk of passive seroconversion to human immunodeficiency virus antibody positivity, despite the presence of antibody in the injected material.

Adult↗

Immunoglobulin A concentrations in commercial immune globulins.

Commercial immune globulins contain varying concentrations of IgA as a minor constituent. For patients who are both IgA deficient and IgA hypersensitive, the administration of most immune globulins is contraindicated due to potentially lethal anaphylactic reactions. We have measured the IgA levels in a broad range of commercial immune globulin preparations by means of a competitive-binding solid-phase radioimmunoassay. Of the products tested, all immune globulins intended for intramuscular administration and most immune globulins for intravenous use had IgA levels of over 150 micrograms/ml. Only two of the intravenous products had IgA concentrations in the range of 10 micrograms/ml or less.

Humans↗

Intravenous immune globulin therapy in hypogammaglobulinemia. A review.

An immune globulin preparation specifically modified for intravenous administration has been employed therapeutically in 30 patients with primary immunodeficiency disease. Our results of this long-term study are summarized within three major categories: (1) Levels of serum IgG produced and maintained after intravenously administered serum immune globulin infusions of 100 to 500 mg/kilo. The disappearance pattern of infused IgG is outlined and individual patient variations emphasized. (2) The therapeutic effects of intravenously administered serum immune globulin therapy are reported and related to dosages of intravenously administered serum immune globulin administered and serum levels of IgG maintained. (3) The incidence and nature of detrimental side effects are outlined, and methods to reduce this problem are indicated. It is recommended that patients with primary immunodeficiency be given from 150 to 200 mg/kilo intravenously administered serum immune globulin, every four weeks, as prophylactic therapy to reduce acute infectious complications. A method to establish an optimum therapy for a specific patient is presented.

Agammaglobulinemia↗

Efficacy and safety of high-dose intravenous immune globulin therapy for antibody deficiency syndromes.

Ten patients with antibody deficiency syndromes were admitted to a treatment protocol in which the dose of intravenous immune serum globulin was increased from 100 mg/kg to a maximum of 250 mg/kg each four weeks. The dose increases were determined by recurrence of infection during treatment and by IgG trough levels of less than 400 mg/dl. Infectious episodes during intravenous immune serum globulin treatment responded well to 10 to 20 day long periods of antibiotic treatment, and prolonged infection-free periods were achieved in all patients. Only one hospital admission was necessary during the entire study period. The increase in intravenous immune serum globulin dose to 200 mg/kg did not significantly reduce the recurrence of infections. Infections also occurred in patients whose IgG trough levels were persistently above 400 mg/dl. High doses of intravenous immune serum globulin were well tolerated, and all patients are still receiving intravenous immune serum globulin treatment. A generalized pruritic rash was observed in two patients. In no patient have clinical or laboratory signs of deficiency in cell-mediated immunity developed.

Adolescent↗

Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa. Treatment with intravenous immune globulin.

Intravenous immune globulin was used to treat Pseudomonas aeruginosa infected, burned mice. Protection was dose-related and large amounts of intravenous immune globulin administered early in the infection process were necessary for full protection. Intravenous immune globulin is processed differently in unburned, burned, and burned, infected mice with significantly lower plasma levels in the burned, infected animals 36 hours after a standard dose is given. At 30 hours post-treatment, bacterial counts in the skin and liver tissue of untreated, burned, infected mice are significantly higher than in mice given a protective dose of intravenous immune globulin. Adsorption of intravenous immune globulin with heat-killed cells reduces its protective effects; adsorption with formalin-killed cells reduces its protective effects even more.

Animals↗

Intravenous gamma globulin in the treatment of chronic idiopathic thrombocytopenic purpura in adults.

Eight adult patients with chronic idiopathic thrombocytopenic purpura have been treated with an intravenous gamma globulin preparation. All patients received at least one "induction" course of intravenous gamma globulin for five consecutive days at a dose of 400 mg/kg per day. There were a total of 12 induction treatments. In five instances, patients also received single "maintenance" infusions of intravenous gamma globulin at the same dose. The mean peak increment in platelet count (X 10(3)/microliters) after induction was 87.3 +/- 42.37; after maintenance therapy it was 62.2 +/- 12.99. In only one instance was the platelet count increment less than 50 X 10(3)/microliters. In 13 of 17 intravenous gamma globulin treatments (both induction and maintenance), the platelet count returned to baseline or near-baseline levels within one to two weeks. In four instances, more prolonged remissions were observed. Measurements of platelet-associated IgG demonstrated the following: when platelet-associated IgG was greater than 100 ng/10(6) platelets, platelet-associated IgG usually decreased markedly after intravenous gamma globulin therapy. When platelet-associated IgG was less than 20 ng/10(6) platelets, platelet-associated IgG usually increased with therapy. There was no correlation between starting platelet-associated IgG levels or changes in platelet-associated IgG levels with therapy and the increment in the patient's platelet count.

Adult↗

Intravenous gamma globulin treatment for chronic idiopathic thrombocytopenic purpura in children.

Six children, five to 16 years of age, with the chronic, autoimmune form of idiopathic thrombocytopenic purpura were given intravenous gamma globulin (Gamimune, Cutter Biological, Berkeley, California) in a dose of 400 mg/kg per day for five consecutive days as six-hour infusions. Two of the six children had undergone splenectomy but the other four had not. Three of six children had a good or excellent response to the first five-day course of intravenous gamma globulin. The peak platelet count occurred within 12 days of the start of therapy in all. All three have required booster doses of intravenous gamma globulin to maintain platelet counts at a safe level. All children had marked increases in serum IgG following intravenous gamma globulin, except one who had undergone splenectomy and who had chronic idiopathic thrombocytopenic purpura with high baseline levels of immunoglobulin G (IgG). The significance of the observed increase in platelet-associated IgG during treatment is not clear. No untoward reactions necessitating cessation of therapy were encountered during this study. Our short-term observations in six children with chronic idiopathic thrombocytopenic purpura indicate that high-dose intravenous gamma globulin is an effective form of treatment for certain children with this condition.

Adolescent↗

Improved response of patients refractory to random-donor platelet transfusions by intravenous gamma globulin.

Because of frequent unavailability of HLA-compatible platelets or their inefficiency in increasing platelet counts in patients requiring platelet transfusions, platelet refractoriness remains a major problem. Since human gamma globulin has been shown to interfere with the binding of platelet-reactive immunoglobulin G (IgG) to platelets in vitro, and since gamma globulin has proved effective in reversing destruction of platelets in idiopathic thrombocytopenic purpura, we decided to investigate intravenous gamma globulin as an adjunct to random-donor platelet transfusions. We studied three patients, one with acute T-cell leukemia, and two with aplastic anemia. When a total dose of 2 g/kg of body weight of intravenous gamma globulin was infused over five to six days in these patients, two of them showed a remarkable increment in platelet counts and improved hemostasis with random-donor platelet transfusions. We conclude that intravenous gamma globulin may be used in critical situations to improve the response of patients refractory to random-donor platelet transfusions.

Adult↗

Re-treatment of aplastic anemia with antithymocyte globulin or antilymphocyte serum.

Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. The median age was 42 (eight to 73 years); the male:female ratio was 8:14. Nineteen patients had severe aplastic anemia, and three had moderate disease. Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. There were seven responses (31.8 percent) to the first course with four complete responses and three partial responses. Six of 15 patients who received fluoxymesterone showed a response, compared with zero of five treated without androgens (p less than 0.05). Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). Overall, 10 of 22 patients (45 percent) had a response (six complete responses, four partial responses). Median survival for those without a response is six months. Median survival for those with a response has not been reached, with follow-up ranging from 18 to 70 months. This study shows the benefit of a second cycle of antilymphocyte serum or antithymocyte globulin and a possible role for concomitant androgens in this treatment of aplastic anemia.

Adult↗

Sheep thyroxine-binding globulin: cDNA sequence and expression.

A full-length thyroxine-binding globulin clone was isolated from a sheep liver cDNA library. The nucleotide sequence consisted of 1379 nucleotides and contained the coding region of 1236 nucleotides. The deduced sequence of the mature protein was 396 amino acids long. The similarity of the sheep thyroxine-binding globulin amino acid sequence with those of human and rat were 80% and 76%, respectively. Expression of the thyroxine-binding globulin gene was investigated by Northern analysis. The gene was not expressed in choroid plexus nor at other extrahepatic sites. The expression of the thyroxine-binding globulin gene was also studied during sheep foetal development. Thyroxine-binding globulin mRNA was already detected in livers of 1 cm long foetuses and levels similar to those found in liver from adult sheep were reached half way through pregnancy.

Amino Acid Sequence↗

Effect of long-chain fatty acids on the binding of thyroxine and triiodothyronine to human thyroxine-binding globulin.

The effect of long-chain fatty acids on the binding of thyroxine to highly purified human thyroxine-binding globulin has been studied by equilibrium dialysis performed at pH 7.4 and 37 degrees C. At a fixed molar ratio of 2000:1 of fatty acid to thyroxine-binding globulin, the degree of binding inhibition based on the percent change in nK value relative to the control as determined from Scatchard plots was: palmitic, 0%; stearic, 0%; oleic, 76%; linoleic, 69%; and linolenic, 61%. At a 500:1 molar ratio of oleic acid to thyroxine-binding globulin, equivalent to 0.125 mM free fatty acid in serum, thyroxine binding was inhibited by 18%, increasing to 93% at a 4500:1 molar ratio. At molar ratios of oleic acid to thyroxine-binding globulin of 1000:1, 2000:1 and 4000:1, the degree of inhibition of triiodothyronine binding was 24%, 41% and 76%, respectively. The results indicate that the unsaturated long-chain fatty acids are potent inhibitors of thyroxine binding to thyroxine-binding globulin, whereas the saturated fatty acids have little or no effect on thyroxine binding.

Fatty Acids↗

A prospective trial of prophylactic intravenous immune globulin for the prevention of infections in severely burned patients.

A prospective randomized double-blind study evaluated the efficacy of i.v. immune globulin in preventing infectious complications in severely burned patients. Fifty patients were randomized to receive either i.v. immune globulin or placebo. Each group of patients was treated with twice weekly infusions for either 5 weeks or until the patients' wounds were covered. Patients treated with the immune globulin had an immediate correction of their depressed serum IgG levels, however there was no change in the infection or mortality rates. No adverse effects were noted with the immune globulin treatments. One potential weakness of this study was the greater burn surface area and a higher incidence of inhalation injury in adult patients treated with i.v. immune globulin compared to controls.

Adolescent↗

Effect of prenatal betamethasone administration on maternal and fetal corticosteroid-binding globulin concentrations.

OBJECTIVE: This study was undertaken to examine the effects of prenatal betamethasone administration on corticosteroid-binding globulin concentrations in maternal and fetal plasma and amniotic fluid. STUDY DESIGN: Two groups of patients with preterm labor at 24 to 35 weeks' gestation who were receiving prenatal betamethasone (2 intramuscular doses of 12 mg) were studied. Maternal plasma was obtained before and at variable intervals until 1 week after betamethasone administration. Umbilical cord blood and amniotic fluid samples were collected at the time of delivery. Samples were also collected from patients at risk for preterm delivery who did not receive glucocorticoids. RESULTS: Betamethasone suppressed maternal cortisol concentration by >70% within 24 hours of injection but did not significantly alter corticosteroid-binding capacity or relative concentrations of corticosteroid-binding globulin isoforms in either maternal or umbilical cord plasma. Betamethasone reduced corticosteroid-binding capacity in amniotic fluid within 24 hours of injection, and values remained suppressed 1 week after treatment. CONCLUSION: Maternal and fetal plasma corticosteroid-binding globulin concentrations were unchanged after maternal betamethasone administration at 24 to 32 weeks' gestation but amniotic fluid corticosteroid-binding globulin concentrations decreased significantly, suggesting different sites of either corticosteroid-binding globulin production or regulation or both.

Amniotic Fluid↗

The influence of anti-theta-globulin treatment on the growth of mastocytoma in mice.

DBA/2 mice were treated with four successive subcutaneous injections of rabbit anti-theta-gamma-globulin followed by the subcutaneous implantation of chemically induced mastocytoma (P-815-X2). Another series of animals received rabbit anti-thymus-gammaglobulin according to the same schedule and still another series of animals served as non-treated controls. A definite augmentation of the tumor growth, as evidenced by the dissemination of the tumor into the spleen, liver and kidney, was evident in the globulin-treated series. Such dissemination was not observed in the control animals, where the metastases were limited to the reginal lymph nodes. The studied gammaglobulins were different in two important respects; the death rate of animals and the frequency of thymic metastases were higher in the anti-theta-globulin series. These findings advocate the conclusion that anti-theta-globulin, prepared against the brain tissue, is the more specific and more potent T-lymphocyte suppressor of these two globulins studied. T-lymphocyte population seems to play an important role in host resistance against experimental neoplasia.

Animals↗

Anticytotoxin-neutralizing antibodies in immune globulin preparations: potential use in hemolytic-uremic syndrome.

The pathogenesis of primary (classic) hemolytic-uremic syndrome (HUS) is thought to be related to cytotoxin-producing enteric pathogens such as Shigella dysenteriae serotype 1 and Escherichia coli serotypes O157:H7 and 026:H11. The relevant cytotoxins include Shiga toxin and the closely related Shiga-like toxins (SLTs) produced by some E. coli strains. Intravenously administered immune globulin (IVIG) therapy has been reported to be beneficial in a few children with HUS. We therefore examined commercially available immune globulin preparations for the presence of anticytotoxin-neutralizing antibodies. Cytotoxicity and neutralization of the HUS-associated cytotoxins were quantitatively determined by means of a (3H)thymidine-labeled HeLa cell assay. The immune globulin preparations tested almost completely neutralized Shiga toxin (produced by S. dysenteriae 1) and SLT-I (produced by E. coli serotype 026:H11). Twofold dilutions of the preparations showed significant (p less than 0.01) neutralizing titers of 1:64 to 1:128. No significant neutralization (greater than 20%) of SLT-II (produced by E. coli strain C600 (933W] was noted. The IVIG preparation lost its inhibitory activity when passed through a protein A-Sepharose column, which bound immune globulin, indicating that its neutralizing effect is related to the antibody content. We also examined sera from 30 children without diarrhea or HUS; only one child had neutralizing titers against Shiga toxin (1:64) and SLT-I (1:128). Immune globulin preparations contain anticytotoxin-neutralizing antibodies, a finding that warrants further investigation of the therapeutic role of these preparations in early treatment of children with HUS related to Shiga toxin and SLT-I.

Adolescent↗

Effect of intravenous immune globulin on the coagulopathy of Kawasaki syndrome.

We studied the effects of immune globulin and aspirin versus aspirin alone on platelet count, platelet activation, and factor-mediated coagulation in patients with Kawasaki syndrome. Coagulation tests were performed on the day of admission to the study and 4 to 6 days later. Twenty-three patients were enrolled; 12 received immune globulin intravenously plus aspirin, and 11 received aspirin alone. At initiation of the study the groups were comparable with regard to age, sex, race, and time from onset of illness to study entry. Coagulation values were similar at entry with the exception that the aspirin group had a geometric mean platelet count that was higher than the platelet count in the aspirin-immune globulin group (p = 0.02). Four days after entry there were no significant differences between the two groups in any coagulation studies. Although the immune globulin preparation used has been effective in reducing the prevalence of coronary artery aneurysms, it appears to have no early effect on reduction of platelet activation or other measures of coagulopathy. The mechanism of action of immune globulin in patients with Kawasaki syndrome remains to be elucidated.

Adolescent↗

Improved survival-rates in presensitised recipients of kidney transplants by immunosuppression with maternal-source gamma-globulin.

The effect on cadaver-kidney transplant survival-rates of a gamma-globulin concentrate, prepared from clotted blood centrifugally expressed from placental tissue recovered from postpartum women, was evaluated in a prospective controlled trial in 195 patients who were also given a standard immunosuppressive regimen. Allograft-survival rates were analysed according to whether or not the recipient had lymphocytotoxic antibodies before transplantation (responders) and whether the graft was a first or second transplant. The graft-survival rate was improved in responder-type recipients of first transplants who had received the gamma-globulin concentrate as adjunctive therapy (control group 28.8+/-10.1% vs. gamma-globulin 55.5 + 9.7% at 2 years, p less than 0.05). The survival-rate of grafts in non-responders was not affected by administration of gamma-globulin and data on its use in recipients of a second graft were insufficient for analysis. These results suggest that the gamma-globulin concentrate was suppressing immunological responses associated with humoral-type rejection.

Adult↗

Intravenous immune globulin in the therapy of peripartum cardiomyopathy.

OBJECTIVES: We sought to evaluate the effect of therapy with intravenous immune globulin on recovery of left ventricular function in women presenting with peripartum cardiomyopathy. BACKGROUND: Peripartum cardiomyopathy is a rare complication of pregnancy that results in significant morbidity and mortality in women of childbearing age. Intravenous immune globulin has been reported to improve left ventricular systolic function in patients with acute dilated cardiomyopathy and myocarditis, but its effectiveness in peripartum cardiomyopathy is unknown. METHODS: In this retrospective study, we compared the clinical outcomes of six women with peripartum cardiomyopathy treated with intravenous immune globulin (2 g/kg) with those of 11 recent historical control subjects. All women in the study were referred between 1991 and 1998 with class II to IV heart failure and a left ventricular ejection fraction of <0.40. Left ventricular ejection was reassessed during early follow-up (6.1+/-2.9 months). RESULTS: The two groups did not differ in terms of baseline left ventricular ejection fraction, left ventricular end-diastolic diameter, months to presentation, age or multiparity. The improvement in left ventricular ejection fraction in patients treated with immune globulin was significantly greater than in the conventionally treated group (increase of 26+/-8 ejection fraction units vs. 13+/-13, p = 0.042). CONCLUSIONS: In this small retrospective study of women with peripartum cardiomyopathy, patients treated with immune globulin had a greater improvement in ejection fraction during early follow-up than patients treated conventionally. Given the poor prognosis of women with peripartum cardiomyopathy who do not improve, this therapy merits further study.

Adolescent↗