Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product.
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Adolescent↗
Biomedical subjects
R H Kobayashi
Publications and source records attributed to R H Kobayashi.
Extended-release albuterol in the treatment of 6- to 12-year-old asthmatic children.
BACKGROUND: Albuterol sulfate, in the syrup and tablet form for oral administration, has been an effective treatment for adults and children with bronchial asthma. Extended-release albuterol sulfate tablets (Proventil Repetabs, Schering Corp.) provide a convenient, twice-daily dosing regimen, but are indicated only for patients > or = 12 years of age. OBJECTIVE: This study was undertaken to determine whether patients 6 to 12 years of age could be effectively and safely treated with extended-release albuterol tablets. METHODS: This was a randomized, double-blind, placebo-controlled, parallel group study of 157 patients in five centers. Patients were randomized to 4 weeks' treatment with extended-release albuterol tablets, 4 mg twice daily (q 12h), increasing up to 12 mg q 12h, or placebo. Efficacy was evaluated based on pulmonary function tests (PFTs), physician and patient evaluations, and data collected from patients' diaries on PEFR, asthma symptoms, number of nighttime awakenings, and number of tablets taken. The primary efficacy parameter was area under the curve (AUC) for FEV1, evaluated for 8 to 12 hours post-dosing. Safety was evaluated based on vital signs, electrocardiograms, and adverse events. RESULTS: Mean AUCs for FEV1 were significantly greater in the albuterol group at days 1 and 8 (P < or = .03). The albuterol group showed consistently lower severity scores for asthma symptoms. Physicians' and patients' global evaluations favored the albuterol group over the placebo group. No serious, treatment-related adverse events were reported. There were no clinically meaningful changes from baseline in either treatment group for vital signs or electrocardiograms. CONCLUSIONS: Extended-release albuterol tablets (4 mg), administered to children 6 to 12 years old in divided doses of up to 24 mg/day, improved pulmonary function and asthmatic symptoms and were well tolerated.
Adolescent↗
Topical nasal sprays: treatment of allergic rhinitis.
Topical nasal sprays, especially steroids, have regained favor as treatment for allergic rhinitis. Nasal steroids are widely used and are as safe and effective as antihistamines in controlling symptoms of rhinitis. However, if improperly used, steroids can have side effects. It is essential that patients learn correct techniques for administering nasal steroids and understand complications that can result from nasal steroid use. New steroid drugs, such as budesonide, tripedane and fluticasone, are being evaluated and will be available in the near future. Other topical drugs, such as cromolyn and ipratropium, are also effective. Over-the-counter decongestants are helpful in reducing nasal congestion and allowing other topical medicines to penetrate effectively into the nasal cavity, but their use should be limited to no more than three days. Prolonged use of topical nasal decongestants has no place in the treatment of allergic rhinitis and can be associated with significant side effects.
Administration, Intranasal↗
Hypersensitivity to therapeutic murine monoclonal antibodies.
OBJECTIVE: To determine the predictive value of pre-treatment skin tests and in vitro IgE/IgG4 anti-murine monoclonal antibodies in patients treated with murine monoclonal antibodies. DESIGN: Patients treated at two cancer institutions were evaluated by skin testing and solid phase immunoassays to detect IgE and IgG4 specific anti-murine monoclonal antibodies. Skin testing by scratch and intradermal skin testing was done on patients before treatment with murine monoclonal antibodies. IgE & IgG4 specific anti-murine monoclonal antibodies were determined before treatment in all patients and at 1, 7, 14 and 21 days post-treatment in 1 patient. SETTING: Cancer patients undergoing murine monoclonal antibody treatment in two university medical centers were recruited for the study. PARTICIPANTS: Twelve patients, aged 41-75 years with gastrointestinal cancers (colon, stomach, pancreas or liver) with metastatic disease, who had relapses or conventional therapy were enrolled. Some patients had previous exposure to rodents, either as laboratory personnel or had kept them as pets. INTERVENTION: One patient who experienced an anaphylactic reaction to murine monoclonal antibody infusion was desensitized so therapy could continue. MAIN OUTCOME MEASURES: Skin tests, immunoassays, and patient history were correlated with adverse reactions to infusions of murine monoclonal antibodies. MAIN RESULTS: Skin tests (scratch method) and/or in vitro immunoassays may predict allergic outcomes in patients receiving infusions of murine monoclonal antibodies. Intradermal skin testing with murine monoclonal antibodies may result in false positive reactions and have less predictive value. Specific IgE or IgG4 were elevated in the two patients who experienced severe adverse reactions to murine monoclonal antibodies but not in those patients with no reactions and therefore, may have some predictive value. A history of past exposure to mice may also increase the risk of adverse reactions. In one patient, intravenous desensitization enabled treatment to proceed. CONCLUSION: Scratch skin tests, in vitro IgE and/or IgG4 immunoassays together with a past history of previous exposure to murine antigen(s) may predict potential allergic reaction to therapy with murine monoclonal antibodies.
Adult↗
What is the current status of management of the patient with exercise-induced asthma?
Exercise-induced asthma (EIA) is a very common and troublesome disease frequently impairing optimal athletic performance. Although described as early as the second century A.D. and widely known since 1972, EIA often goes unrecognized by both patient and physician. The goals of treatment are to minimize symptoms thus allowing the athlete to participate fully in a broad array of activities and to utilize the most effective pharmacologic drugs available. The recognition and treatment of exercise-induced asthma (EIA) have made significant progress since 1972 when United States swimmer, Rick Demont had his Olympic gold medal award rescinded because of traces of ephedrine were detected in his urine. Lessons from this episode paid dividends subsequently; in preparation for the 1984 Olympic games in Los Angeles, the U.S. Olympic Committee developed a screening program which identified 67 U.S. team members with EIA. Astoundingly, several of these world-class athletes did not realize they had asthma. Affected individuals were counseled on the prevention of asthma and also on the effective use of medications; 41 won medals in various competitions including track and field, wrestling, basketball, cycling, swimming and rowing. Despite this resounding success, many athletes at all levels of competition still suffer from unrecognized or under-treated EIA despite knowledge of the problem since the second century A.D.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Agonists↗
Suppression of an antibody to adenosine-deaminase (ADA) in an ADA-deficient patient receiving polyethylene glycol modified adenosine deaminase.
An adenosine deaminase (ADA) deficient patient with severe combined immunodeficiency (SCID) developed resistance to therapeutic injections of bovine ADA conjugated to polyethylene glycol (PEG-ADA). This 18-year-old girl was diagnosed as having partial ADA deficiency at age 7 years, and was started on bovine conjugated PEG-ADA at age 15 years. The weekly dose of 15 U/kg led to clinical improvement with resolution of sinusitis and bronchitis within 2 months and normalization of some T cell functions. After 5 months, however, she developed an inhibitory antibody to ADA, became refractory to treatment with PEG-ADA, and clinically and immunologically deteriorated. This antibody was successfully suppressed over a 4-month period with a combination of prednisone (2 mg/kg/day), intravenous immunoglobulin (2 g/kg/dose), and discontinuing the PEG-ADA injections for 7 weeks. The PEG-ADA injections were then restarted at a higher dose (20 U/kg/dose, twice a week). With the suppression of the inhibitory antibody, her clinical and immunologic status improved to previously achieved level. She has subsequently continued treatment for over 36 months, receiving a single weekly dose of PEG-ADA (20 U/kg/week) with sustained clinical and immunologic improvement, including weakly positive antigen-specific T cell proliferative responses to tetanus and Candida.
Adenosine Deaminase↗
Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase deficiency.
Adenosine deaminase (ADA) deficiency and its biochemical consequences cause severe combined immunodeficiency (SCID). Treatment strategies, designed to correct the biochemical abnormalities, include transplantation of matched bone marrow or haploidentical bone marrow stem cells, repeated partial exchange transfusions with frozen irradiated human red blood cells (RBC), or weekly injection of polyethylene glycol-modified bovine ADA (PEG-ADA). To evaluate the effect of these therapeutic options, we studied in vitro T-cell function and in vivo antibody responses to the T-cell-dependent neoantigen, bacteriophage phi X174, in 10 children with ADA-deficient SCID. In untreated patients, T-cell function was severely depressed, and only minute amounts of antibacteriophage antibody were produced. Transplantation of bone marrow from a matched sibling (one patient) or a phenotypically matched parent (one patient) resulted in a stable graft, normal T-cell function, and substantial but subnormal antibody titers to bacteriophage, with reduced memory and impaired switch from IgM to IgG. Patients receiving T-cell-depleted haploidentical bone marrow stem cells had markedly depressed antibody responses for as long as 3 years posttransplantation, despite rapidly improving T-cell function that became normal in two of four patients. Two methods of enzyme replacement were explored. During treatment with human RBC transfusions, antibody responses to bacteriophage were as severely depressed as in untreated ADA-deficient patients. Treatment with weekly injections of PEG-ADA resulted in normalization of T-cell numbers in all four patients, normal or near-normal T-cell function in two, and mildly but variably improved T-cell function in the other two patients. Quantitatively and qualitatively normal antibody responses to bacteriophage were observed in three of four patients. Assessment of antibody responses to immunization with bacteriophage phi X174 is a useful method to monitor humoral immune function in treated ADA-deficient patients and can be used to estimate when intravenous immunoglobulin (IVIG) prophylaxis may be safely discontinued.
Adenosine Deaminase↗
Exercise-induced asthma.
Exercise-induced asthma affects approximately 10 percent of the exercising population but often goes undiagnosed. Diagnosis is generally simple if the physician is aware of the subtle symptoms that may present during or after exercise. Preventive treatment, using a combination of exercise strategies and inhaled medications, is often successful. For patients with underlying chronic asthma that is exacerbated by exercise, long-term medication with preexercise doses is recommended.
Adrenergic alpha-Agonists↗
Exercise-induced asthma, anaphylaxis, and urticaria.
Exercise-induced asthma is a common but frequently undiagnosed problem. The patient may not wheeze, but rather have shortness of breath, chest tightening, and coughing. The coach and the physician must be particularly alert to the signs and symptoms of exercise-induced asthma to recognize this syndrome. Proper conditioning, warming up, inducing refractoriness, participating in sports less likely to provoke exercise-induced asthma, and the aggressive use of appropriate medications allow patients to enjoy sports and compete effectively. A rare but potentially fatal syndrome is exercise-induced anaphylaxis. Accurate diagnosis and differentiation from other exertion-related syndromes are critical, and appropriate precautions are necessary. A third clinical entity, exercise-induced cholinergic urticaria, although not life-threatening, can be quite annoying. Aggravating factors, such as increased heat, compound the problems. In summary, exercise-induced allergic phenomena are common and should be recognized by the practicing physician.
Anaphylaxis↗
Home-based immunoglobulin infusion therapy: quality of life and patient health perceptions.
Thirty-seven antibody-deficient patients who were participating in a multicenter trial evaluating home-based, self-administered IVIG therapy anonymously completed questionnaires regarding beliefs concerning health control, quality of life, and attitudes toward active participation in medical care. Their responses were compared with a group of 29 patients undergoing traditional IVIG therapy in a medical clinic setting. A subsample of the home-based group who later returned to clinic-based IVIG therapy allowed comparison of responses given by the same patients in both settings. Home-based therapy was preferred to clinic-based therapy. Independence, convenience, comfort, decreased disruption of activities, travel time, and costs were specific factors rated most favorably. On the Health Belief Questionnaires, patients preferred informed, self-involved medical care regardless of the setting for their IVIG treatments.
Adult↗
Respiratory failure in a seven-month-old baby: an unusual presentation of severe immunologic disease.
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Agammaglobulinemia↗
Home self-administration of intravenous immunoglobulin therapy in children.
Twelve children with primary immunodeficiency, aged 2 to 17 years (mean +/- 1 SD = 9.8 +/- 5.3), were enrolled in a 9-month study to evaluate the feasibility and safety of home self-infusion of intravenous immunoglobulin (IVIg). An initial 2-month training and supervisory period was followed by a 6- to 7-month period during which the children or their parents infused IVIg in a home setting. Eight children received an average dose of 204 +/- 12 mg/kg every 2 weeks, two children received a dose of 400 mg/kg every month, and an additional two children received 240 to 250 mg/kg every 10 days. Peak and trough levels varied from 946 +/- 20 mg/dL and 627 +/- 16 mg/dL, respectively, in children receiving IVIg every 2 weeks. The peak-trough values for the children receiving IVIg every month were 1105 +/- 94 mg/dL and 457 +/- 78 mg/dL, while those of children receiving IVIg every 10 days were 840 +/- 24 mg/dL and 553 +/- 109 mg/dL. A total of 224 infusions were administered, with only two minor reactions occurring (reaction rate of 0.9%). There was no difference in the frequency of infections and antibiotic use during the study compared with the previous phase. The results demonstrate that home self-infusion of IVIg in children is safe and feasible.
Adolescent↗
Interferon-gamma in a family with X-linked lymphoproliferative syndrome with acute Epstein-Barr virus infection.
A 20-month-old male with fulminant infectious mononucleosis and the X-linked lymphoproliferative syndrome (XLP) was studied. Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA) and EBV DNA were detected in various tissues. Despite a combined treatment with acyclovir, immunoglobulin, and methylprednisolone, the patient deteriorated rapidly. Following treatment with recombinant interferon-gamma (IFN-gamma), defervescence occurred and circulating EBNA-positive cells markedly decreased. IFN-gamma prior to treatment ranged from 10.8 to 24.5 U/ml in the patient's serum and increased linearly post exogenous IFN-gamma treatment. His natural killer (NK)-cell activity remained in the normal range throughout his illness but autologous EBV-infected cells were not killed in vitro by his peripheral blood lymphocytes (PBL). These results suggest that patients with the fatal infectious mononucleosis phenotype of XLP may produce endogenous IFN-gamma. Defective cytotoxic T cells against EBV-infected cells seem to be responsible for the fulminant infectious mononucleosis in this patient.
Acute Disease↗
Beclomethasone dipropionate aqueous nasal spray for seasonal allergic rhinitis in children.
A 3-week double-blind, parallel group study comparing the effectiveness and safety of an aqueous formulation of beclomethasone dipropionate (BDP-AQ) versus placebo was undertaken in 101 patients. Children aged 5 to 13 years with a diagnosis of seasonal allergic rhinitis received one spray in each nostril twice daily of either BDP-AQ (42 micrograms/spray) or an identical placebo spray. Patient assessment at the end of treatment indicated statistically significant improvement in nasal symptoms for BDP-AQ patients. The physicians overall evaluation of treatment indicated that the BDP-AQ-treated patients experienced significantly greater (P = .012) improvement as compared with placebo-treated patients. There was no difference in the incidence of adverse events between the two treatments. The results demonstrate the effectiveness and safety of BDP-AQ nasal spray in the treatment of seasonal allergic rhinitis in children.
Adolescent↗
Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.
We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.
Adenosine Deaminase↗
Circulating immune complexes in cystic fibrosis and their correlation to clinical parameters.
Circulating immune complexes (CIC) have been found to be elevated in individuals with cystic fibrosis (CF). Previous investigators, using a variety of assays, have reported high levels of CIC in as many as 86% of these patients. Our study followed the progress of 25 patients with CF over a period of 10 months to determine which, if any, clinical parameters correlated with the occurrence and/or concentration of CIC. Immune complex determinations were performed using a coprecipitation method with equine rheumatoid-complement complex. One hundred percent of the CF patients had CIC elevated above normal levels, however, levels of CIC did not correlate with the severity of an individual's acute exacerbation. Clinical parameters including pulmonary function tests, vital signs, total serum IgG levels, and other laboratory studies, were obtained on each individual and analyzed with respect to their relationship to CIC. Only four of 38 parameters examined had p less than 0.05. Factors that showed significant correlation to elevated CIC's in the highly elevated portion of our CIC population were poor NIH score, increased patient age, low peak expiratory flow rate, and elevated total serum IgG. These clinical values are associated more with the measurement of chronic disease. These data suggest that CICs cannot be used as an indication of short-term prognosis or as a monitor to follow the course of acute severe lung infections in the CF patient. Of interest was the observation that all patients who died during the course of the investigation had CIC levels greater than 80 micrograms/ml.
Adolescent↗
Pharmacologic management of asthma in infants and young children.
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Asthma↗
Evaluation of a sustained-release theophylline tablet in young asthmatics.
A sustained-release theophylline (SRT) tablet was evaluated in 15 children with moderately severe asthma between the ages of 3 and 5 years (4.2 +/- 0.83 years). They received a mean daily dose of 20.4 mg/kg given q12h for 3 or more weeks with daily symptom scores and twice daily peak flow rates (PFR) measured. Serum theophylline levels (STL) were then obtained at 0, 1, 2, 4, 6, 8, 10, and 12 hr (eight children had 24-hr samples obtained), along with PFRs every 3 hr. The mean peak STL (x +/- SD) was 16.6 +/- 4.4 and the trough was 5.9 +/- 2.8, with a peak-trough difference of 10.6 +/- 3.9. The average time to peak level was 3.9 hr. The mean +/- SD clearance was 1.42 +/- 0.63 ml/kg per min and the apparent T1/2 was 5.11 +/- 1.34 hr. The average weekly morning PFR for the 3-week period ranged from 116.8 +/- 41.2 to 127.4 +/- 37.4 L/min, and the evening PFT ranged from 126.5 +/- 38.4 to 137.0 +/- 40.9 L/min. In conclusion, the SRT tablet is effective in treating many young asthmatics on a 12-hr dosage schedule. For some children who experience excessive peak-trough differences, an 8-hr dosage schedule may be indicated.
Asthma↗