Biomedical subjects
Publications and source records attributed to J A Church.
Four patients are reported who experienced seizures in association with serum theophylline concentrations which were in the mildly toxic range. In three patients, erythromycin administration was a probable factor contributing to the elevated theophylline levels. One patient suffered severe neurologic damage as a result of the seizure.
Ninety-one children with acute asthma were studied to determine the extent of incremental improvement in pulmonary function afforded by successive doses of subcutaneous epinephrine, and by a bronchodilator aerosol in those patients refractory to epinephrine. A significant proportion of patients (69%), as expected, responded to the first injection. Among those who did not respond to the first injection a significant proportion (30%) responded to the second injection. Markedly fewer patients responded to subsequent bronchodilator treatments, including aerosols, if they did not improve significantly after the first two treatments. Patients with higher initial peak flow rates (PEFR) generally required fewer epinephrine injections, and achieved higher maximal PEFR than those with lower initial PEFR. Most asthmatic patients who required hospital admission had lower initial peak flow rates, were less responsive to epinephrine injections, and achieved lower maximal rates than those who could be discharged home.
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The acquired immune deficiency syndrome (AIDS) has been reported in hemophiliacs . We examined lymphocyte numbers and functions in 28 patients with hemophilia and 16 healthy adults. Healthy hemophiliacs who had received fewer than 150 commercial factor concentrate (CFC) infusions had normal T-cell numbers, T-cell subsets, and mitogen responses. Healthy hemophiliacs who had received more than 250 CFC infusions had a decreased number of Leu 3+ "helper" T cells, a decreased Leu 3-Leu 2 ratio, and decreased pokeweed mitogen responses. Hemophiliacs who had received greater than 250 CFC infusions and who had persistent lymphadenopathy had decreased Leu 3+ cells, increased Leu 2+ "suppressor" T cells, a decreased Leu 3-Leu 2 ratio, and decreased phytohemagglutinin responses. Abnormal results of T-cell studies were found in 67% of healthy hemophiliacs who had a high degree of CFC exposure and 100% of clinically abnormal hemophiliacs. These findings suggest that hemophiliacs are at risk for the development of the immunologic changes that characterize AIDS and that this risk is related to CFC exposure.
A variety of phagocytic cell and lymphocyte assays were employed to evaluate the immune status of four patients with methylmalonicaciduria . One patient had a depressed absolute granulocyte count and two patients had depressed neutrophil and monocyte chemotactic responses. All subjects had normal neutrophil phagocytic and bactericidal activities. One patient had a decreased T-cell number; blastogenic responses to phytohaemagglutinin and pokeweed mitogen were normal in all subjects. B lymphocyte measurements were variably abnormal; two children had decreased B-cell numbers; two had marginally decreased IgG levels; a third had an undetectable rubella titre; and two had elevated serum IgE concentrations. In vitro exposure of normal cells to methylmalonic acid concentrations up to 50 mg/100 ml did not affect chemotactic or lymphoproliferative responses. In conclusion, although B-cell function may be affected, no consistent abnormality of lymphocyte or phagocytic cell functions could be attributed to the metabolic disorder.
Two preterm infant boys not known to be at risk developed clinical, laboratory, and pathologic features of acquired immune deficiency syndrome (AIDS) after receiving multiple blood transfusions in the neonatal period. Their clinical courses were characterized by failure to thrive, recurrent otitis media, hepatomegaly, and fatal interstitial pneumonia. Laboratory evaluation revealed progressive lymphopenia, reversed T helper/suppressor ratios, increased percentages of B-lymphocytes, decreased lymphoproliferative responses to mitogens, hyperimmunoglobulinemia, and high levels of circulating immune complexes. At postmortem examination thymic involution, lymphocyte depletion in spleen and lymph nodes, and micronodular mineralization in the central nervous system were seen. The findings were not specific for other known congenital immune deficiencies and were most indicative of AIDS. The lack of other risk factors suggests transmission of AIDS via blood transfusions in the neonatal period.
High dose factor VIII concentrate was infused over 12 months in a 3-year-old child with hemophilia A and a high-titer inhibitor. This regimen was successful in producing clinical tolerance to the factor VIII and was associated with a fall of inhibitor titer from 85 BU to less than 1 BU. Subsequently, a rise in inhibitor to peak at 3.5 BU correlated with a decrease in infusion dose. In vitro studies using a microdroplet assay for immunoglobulin synthesis in the presence of varying concentrations of factor VIII was carried out prior to the clinical trial. This system indicated that the patient's peripheral blood mononuclear cells were stimulated to release IgG by 0.01 U/ml factor VIII coagulant activity and inhibited at 0.9 U/ml FVIIIc. Lymphocyte subsets were monitored during the course of therapy. The ratio of Leu-3a+/Leu-2a+ (helper/suppressor) varied considerably, fluctuating between a peak of 4.4 and low point of 0.6, with the initial pretrial ratio being 1.2.
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The critical role of the spleen in protecting subjects from systemic bacterial infection is well known. Plasma fibronectin (PF), cold-insoluble globulin, and opsonic alpha2 surface binding glycoprotein, has regulatory influence on reticuloendothelial system clearance activity and it is important for maximal phagocytosis. Ascorbic acid (AA) also appears to play an important role in phagocytic cell function. The purposes of this study were to determine the effects of splenectomy and splenectomy with autoimplantation, with and without dietary AA supplementation, on PF levels. Six-week-old male Sprague-Dawley rats were divided into four experimental groups of 20 animals each: Nonoperated controls, sham-operated controls, totally splenectomized animals, and splenectomized animals with intraperitoneal autoimplantation. Each group was further randomly divided into two subgroups of 10 animals, those receiving dietary AA supplementation and those not receiving AA. PF levels were measured with a colorimetric assay immediately prior to and at 4 and 8 weeks after operation. Plasma AA determinations documented the effectiveness of dietary AA supplementation. PF levels in nonoperated and sham-operated controls increased significantly during the 8 weeks of experimentation. In contrast, PF levels decreased significantly following total splenectomy from 328 +/- 46 mcg/mL (mean +/- S.D.) to 285 +/- 46 at 4 weeks and rose to 303 +/- 77 at 8 weeks postoperatively in non-AA supplemented animals. Splenic autoimplantation eliminated this decrease in PF levels at 4 weeks. AA supplementation also protected against the decrease in PF levels in the splenectomized group. In the intragroup comparisons, AA supplementation did not produce a significant elevation of PF.(ABSTRACT TRUNCATED AT 250 WORDS)
It has been suggested that the effectiveness of bronchodilators administered from metered-dose inhalers (MDI) may be improved by altering the inhalation technique with which they are taken. The efficacy of the traditional closed-mouth technique of MDI use was compared with one in which the mouth remained open throughout inhalation. Eighteen asthmatics, aged seven to 16 years whose peak expiratory flow rates (PEFR) were less than 70% predicted, were studied. PEFR was measured before and 5, 10 and 15 minutes after a single inhalation of isoetharine using the open-mouth and closed-mouth techniques on separate days. There was no significant difference in PEFR improvement at any time when the two techniques were compared. Routine re-training of pediatric patients already using the traditional closed-mouth method successfully is not warranted on the basis of these findings.
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Suppressor cell dysfunction has been suggested as a cause of the heightened IgE responses seen in human atopic disease and allergy immunotherapy has been shown to be associated with the generation of antigen-specific suppressor cells. In an attempt to simulate immunotherapy, the in vitro effects of grass antigen exposure upon non-control subjects were treated with preincubation, concanavalin A or varying concentrations of a crude grass antigen preparation. The effects of the generated suppressor activities upon phytohemagglutinin-induced proliferation of fresh, autologous lymphocytes were measured. All three treatments resulted in significant suppression. There was no over-all difference in suppression between atopic and control groups. However, grass antigen exposure enhanced suppression by cells from atopic subjects (p. 05) but only to levels seen in concanavalin A treated cells from the same individuals. Further, the grass antigen preparation appeared to act in a non-specific fashion, resulting in similar mitogenic responses in cells from atopic and control groups. These findings bring into question the role of non-specific suppressor cells, as currently measured, in the pathogenesis of atopic disease. Allergy immunotherapy with crude antigen preparations likely results in non-specific immunologic perturbations which may enhance or depress its clinically valuable, antigen-specific, effects.
A four-week structured experience for pediatric residents in allergy-clinical immunology is described. Outlined are the educational goals and objectives developed by the teaching faculty in three areas: clinical allergy, clinical immunology and clinical laboratory aspects of allergy-immunology. Finally, assessment is made of the effectiveness of this approach to resident training.
Eighteen children in status asthmaticus, six to 14 years of age, were systematically studied to compare the efficacy of aerosolized isoetharine and isoproterenol. The studies were conducted in a randomized, double-blind fashion. Five inhalations of 1% isoetharine and 0.5% isoproterenol were administered via a wall-mounted air/O2 nebulizing unit. Pulse, respiratory rate, blood pressure, FVC, PEFR, FEV1 and FEF25-75 were measured at the patient's bedside. Isoetharine produced significantly less cardiac side effect and tended to produce a greater improvement in pulmonary function than did isoproterenol. In addition, no change from baseline was noted in any of the parameters at 120 minutes following treatment with either medication.
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Lymphoid interstitial pneumonitis is an uncommon process, and an association with hypogammaglobulinemia in children is rare. Three patients, a 10-yr-old boy (Patient 1), a 17-yr-old girl (Patient 2), and a 13-yr-old boy (Patient 3) were evaluated for progressive interstitial pneumonitis and hypogammaglobulinemia. At presentation, symptoms or signs of lung disease had been present for 9, 6, and 1.5 yr and consisted of severe exertional dyspnea asymptomatic pneumonitis on roentgenogram, and mild exertional dyspnea, respectively. Serum immunoglobulin deficiencies were variable with IgG and IgA being depressed in all patients and IgM being within normal limits in Patient 2. In vitro neutrophil function and T lymphocyte number and mitogen responses were normal. Measurement of in vitro immunoglobulin production suggested a primary B lymphocyte dysfunction. Pulmonary function testing revealed restrictive lung disease in Patient 1, arterial hypoxemia in Patients 1 and 2, and increased alveolar-arterial oxygen differences in all patients. Microscopic examination of lung specimens from each patient revealed diffuse lymphoid parenchymal infiltration with formation of follicles with occasional germinal centers, varying degrees of fibrosis, and negative examinations for viruses, bacteria, and fungi. The factors responsible for the cessation of antibody production and for the striking lympho-proliferative process seen in these patients remain to be identified.
A structured program designed to enhance self-treatment was successfully implemented in a residential center for asthmatic children. The ultimate objective of the program was to improve compliance with therapeutic regimens, which was felt to be a factor that had necessitated placement of many of the patients. The program was designed to educate the patient and the patient's family regarding the nature of asthma, its treatment and the importance of self-help. Efforts were also made to enhance the emotional maturity of the child. Patients remembered to take their medication over 90% of the time within 1 month of implementation of the program. a similar program was instituted for outpatient use.
Circulating immune complexes (CICs) were measured in the sera of clinically stable and acutely infected patients with cystic fibrosis (CF). Twenty CF patients were studied when clinically stable; and additional 18 patients were studied during an acute exacerbation of pulmonary infection as evidenced by fever, tachypnea, increased white blood cell count, increased sputum production, and acute chest x-ray film changes. Three methods for determining CICs were employed: polyethyelene glycol precipitation, a C1q phase assay, and the Raji cell radioimmune assay. Ten of 20 clinically stable CF patients had one or two positive assays for CICs; two of 20 had two positive assays. In contrast, 16 of 18 acutely infected CF patients had a positive CIC test, and 12 of these were positive with two or three of the assays employed. Serum C3 and C4 concentrations and total hemolytic complement activity did not correlate with the presence of CICs in either patient group. These findings suggest that immune complex formation may mediate some of the tissue damage characteristic of CF, although this usually does not involve intravascular complement activation.