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.

Candida esophagitis and laryngitis in chronic mucocutaneous candidiasis.

Five children (aged 11 to 19 years) with lifelong chronic mucocutaneous candidiasis had 12 episodes of esophageal and/or laryngeal candidiasis documented by endoscopy. Symptoms included hoarseness (8/12), dysphagia (6/12), and hemoptysis (1/12). There was poor correlation between oral lesions and esophageal or laryngeal involvement. On fiberoptic endoscopy, the esophagus was involved alone in four episodes (33%), the larynx in two episodes (17%), and both structures in six episodes (50%). In six of eight instances, the esophagram was nondiagnostic or markedly underestimated the extent of inflammation. Intravenous amphotericin B or miconazole resulted in the resolution of these infections for variable periods of time. Repeat endoscopy was used to follow the course of the disease. Aerosolized amphotericin B was effective on one occasion in clearing candidal lesions of the larynx and one small area of the left mainstem bronchus. Oral topical therapy was not beneficial. Since the signs and symptoms of laryngitis or esophagitis are often minimal or absent and complications, including strictures, may arise from chronic inflammation, periodic endoscopy and systemic therapy may be necessary.

Prostaglandin E1 therapy. Is it associated with a higher incidence of wound infection in the cyanotic neonate?

Prostaglandin (PGE1) may be used to maintain ductal patency in the infant with cyanotic congenital heart disease, but the risk of infection may be increased. Between October, 1976 and December, 1982, 38 neonates with complex cyanotic congenital heart disease required operations creating systemic-to-pulmonary artery shunts. Of 13 patients who did not receive PGE1 therapy, none developed a wound infection. Of 25 patients who did receive PGE1 therapy, four (16 percent) developed a significant wound infection. The two patient groups were similar when compared by age and weight at operation, by severity of heart disease and by the presence of other congenital anomalies. Pathogenic Staphylococcus epidermidis was recovered from all infected wounds, all of which responded favorably over a period of two to four weeks with a short course of antibiotics and wound debridement.

Triamcinolone acetonide aqueous nasal spray for the treatment of patients with perennial allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled study.

In this multicenter, randomized, double-blind, placebo-controlled study, 178 patients with symptoms of perennial allergic rhinitis (PAR) were treated with either triamcinolone acetonide (TAA) Aqueous nasal spray (220 micrograms once daily) or placebo for 4 weeks. Symptoms of PAR (nasal stuffiness, nasal discharge, sneezing, nasal index, and nasal itching) were evaluated throughout the treatment period through the use of patient diaries. In addition, both patients and physicians completed independent global evaluations of treatment efficacy at the conclusion of the study. TAA Aqueous provided clinically and statistically (P < or = 0.05) greater improvements in nasal stuffiness, sneezing, nasal index, and nasal itching over the 4-week study period than did placebo. Significant improvements in sneezing (P = 0.022) were observed as early as the first day (within 12 to 16 hours based on treatment in the morning and assessment of symptoms at bedtime), and in the nasal index (P = 0.009) by the third day after treatment with TAA Aqueous. Patients' and physicians' global evaluations of overall efficacy were concordant: 65% of patients rated their nasal symptoms greatly or somewhat improved with TAA Aqueous compared with 48% in the placebo group; physicians rated 66% of patients as having greatly or somewhat improved symptoms with the study drug compared with 48% of patients who received placebo. Adverse events were mild and the incidences were comparable for both groups; no significant changes in vital signs or clinical laboratory parameters were observed. This study demonstrated that TAA Aqueous administered once daily was well tolerated and provided relief of PAR symptoms in adults and adolescents.

Ovarian teratomas in early childhood.

The ovary is second only to the sacroccygeal area as the commonest anatomic site for the occurrence of teratomas (including dermoid cysts) in infancy and childhood. While virtually all sacrococcygeal teratomas are present at birth or appear within the first 24 mo of life, ovarian teratomas are quite rare within the first 24 mo of life and seldom appear before 6 yr of age. Teratomas comprise half the surgically significant lesions of the ovary in infancy and childhood and carry a mean malignancy incidence of approximately 14% in this age group. Seven cases of ovarian teratoma in the first 2 yr of life have been reported. All of these have been seen in the second 12 mo of life. They differ from those occurring after 2 yr of age in the lesser incidence of abdominal pain, the higher incidence of an abdominal mass and the absence of reported malignancy.

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.

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.

Immunologic maturation in an infant born to a mother with agammaglobulinemia.

An infant born to a mother with agammaglobulinemia was followed up since birth to study immunologic maturation uninfluenced by circulating maternal antibodies. Immunoglobulin levels remained low and antibodies to immunizing antigens appeared late. These observations, together with findings in two other reported infants born to agammaglobulinemic mothers, suggest that transplacental maternal antibodies play little or no role in modulating newborn igG production and that the delay in achieving normal levels of IgG are probably due to the immaturity of newborn B lymphocytes.

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.

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)

Galactose inhibition of neonatal neutrophil function.

To investigate possible causes for the significantly increased incidence of sepsis observed in galactosemic neonates, the in vitro effect of galactose on neutrophil function in healthy newborns was studied. Neutrophils from 25 normal newborns and 23 normal adult volunteers were incubated with 100 mg of glucose per dl, 300 mg of galactose per dl and 300 mg of galactose plus 100 mg of glucose per dl, respectively. Tests for neutrophil function included chemiluminescence (CL), chemotaxis (CTX) and adherence. Neutrophil CL (measure of bactericidal activity) was significantly depressed by galactose in both adults (30.2%) and newborns (59.5%); however, neonatal neutrophil function (CL) was depressed to a much greater extent than in adults. CTX was also significantly depressed by galactose in newborns but not in adults. Supplementing the galactose-containing medium with glucose restored both CL and CTX function to normal in adults. However, only CTX was restored in newborns, while CL remained markedly depressed. Neutrophil adhesion, a function which is not energy-dependent, was not affected by galactose in both adults and newborns. These findings indicate that depressed neutrophil function by galactose or its metabolites may contribute to the high incidence of sepsis in galactosemic neonates.

Serum theophylline levels in young children receiving a sustained-release theophylline tablet.

This study indicates that a sustained-release tablet may be used in certain young children on an every-12-hr dosing schedule with acceptable serum theophylline fluctuation. Many young children are able to swallow the tablet and dosing increments are convenient.

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.

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.

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.

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.

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.

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.

Long-term safety and efficacy of triamcinolone acetonide aqueous nasal spray for the treatment of perennial allergic rhinitis.

This 12-month, multicenter, open-label study to assess the long-term safety and efficacy of triamcinolone acetonide (TAA) aqueous nasal spray for perennial allergic rhinitis (PAR) symptom relief was a continuation of a 4-week, double-blind study. Patients who received TAA Aqueous (220 micrograms/day) during the 4-week, double-blind study continued with the same treatment for the open label study; those randomized to placebo during the 4-week, double-blind study received TAA Aqueous (220 micrograms/day) for the open-label study. Dose reduction to 110 micrograms/day was allowed if it was felt that symptom relief would be maintained. Safety was assessed by daily diary entries and clinical laboratory results. Long-term efficacy was assessed by visual analog scale (VAS). Of the 172 patients who began the open-label study, 94.2 percent completed 3 months of treatment, 83.6 percent completed 6 months, and 62 percent completed 12 months. PAR symptom relief improved progressively throughout the study. Adverse events were generally mild or moderate and consistent with long-term use and winter symptoms. The most common adverse events were pharyngitis (32 percent of patients), rhinitis (28.5 percent), headache (22.1 percent), and epistaxis (18 percent). Adverse events related to the local effects of the study medication were similar to those observed in long-term studies with TAA aerosol. The aqueous nasal spray formulation of triamcinolone acetonide was well tolerated and continued to relieve nasal symptoms with long-term use in adolescent and adult patients with PAR.