Immunologic evaluation of the child with recurrent otitis media.
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Acute Disease↗
Biomedical subjects
J A Church
Publications and source records attributed to J A Church.
Acquired protein S deficiency in children infected with human immunodeficiency virus.
OBJECTIVES: To determine the prevalence of an acquired deficiency of protein S, a coagulation inhibitor, in children infected with the human immunodeficiency virus (HIV) and to identify clinical and laboratory features associated with this coagulation abnormality. METHODS: A convenience sample of HIV-infected children, ages 2 to 18 years, was evaluated for total, free and functional protein S; total and functional protein C; prothrombin and activated partial thromboplastin times; fibrinogen; antithrombin III activity; dilute Russell viper venom time; IgG anticardiolipin antibodies; von Willebrand factor antigen; C4b-binding protein; CD4+ T lymphocyte counts; HIV p24 antigen concentration; and serum beta 2-microglobulin concentrations. RESULTS: Thirty-four subjects were evaluated. Twenty-four subjects were infected perinatally and 10 by transfusion. Nine of the subjects were CDC Class N (asymptomatic), 13 were Class A/B (symptomatic without AIDS-defining condition) and 12 were Class C (AIDS). None had previously documented thrombosis, nephrosis or significant hepatic dysfunction. Twenty-six subjects (76.5%) had decreased free protein S, and 19 (55.9%) had functional protein S < 2 SD below the mean of laboratory controls. Decreased functional protein S was seen in 33.3% of Class N, 53.8% of Class A/B and 75.0% of Class C subjects. The prevalence of decreased total and functional protein S was greater in those with absolute CD4+ T lymphocyte counts < 200/mm3 compared to those with CD4+ counts > or = 200/mm3 (75.0% vs. 38.9%; chi square, 4.48, P = 0.034). A trend toward negative correlation was observed between protein S and duration of HIV infection only for Class N subjects. No linear correlation was seen between protein S and CD4+ T lymphocyte counts; and no significant relationships were observed between protein S values and CMV status, HIV p24 antigen, C4b-binding protein, von Willebrand factor antigen, IgG anti-cardiolipin antibodies or serum beta 2-microglobulin values. CONCLUSIONS: Acquired protein S deficiency is common in HIV-infected children. The high prevalence of this anticoagulant abnormality suggests an increased risk for thrombotic complications in this population.
Adolescent↗
Systemic gaseous microemboli during left atrial catheterization: a common occurrence?
OBJECTIVE: Gaseous microemboli during cardiac surgery have been implicated as a potential cause of postoperative neurologic injury. Any monitoring technique that exposes the systemic circulation to atmospheric pressure could introduce gaseous microemboli, causing cerebral microembolization. The incidence of carotid artery gaseous microemboli was studied during left atrial catheter insertion. DESIGN: Prospective clinical study. SETTING: Tertiary care university hospital. PARTICIPANTS: Twelve patients undergoing elective cardiac surgery. INTERVENTIONS: Perioperatively, a 5-MHz continuous wave Doppler probe was positioned over the left carotid artery to maximally record blood flow signals. The criteria used for detecting a gaseous microembolus were a sudden increase in the amplitude of the visual signal by 30% and a characteristic audible sound. MEASUREMENTS AND MAIN RESULTS: Numbers of microemboli at three timepoints (before and during left atrial catheter insertion and during catheter flushing) were assessed using the Friedman test. No emboli were detected before left atrial catheter insertion. When compared with the preinsertion time period, statistically (p < 0.05) significant numbers of gaseous microemboli were found in six patients during catheter insertion (3 +/- 1 microemboli; range 1 to 7 microemboli) and in five patients during catheter flushing (5 +/- 2 microemboli; range 1 to 12 microemboli). There was a tendency for patients with lower filling pressures to entrain more microemboli during insertion (r = 0.44; p = 0.149). No patient showed evidence of gross neurologic dysfunction postoperatively, although sensitive neurologic testing was not performed. CONCLUSIONS: Left atrial catheter insertion and flushing can cause systemic gaseous microemboli in more than 50% of patients. Although the number of microemboli introduced is relatively small, extreme care should be used during left atrial catheter insertion.
Adult↗
A rapid and sensitive chemiluminescence assay for evaluation of functional opsonic activity of Haemophilus influenzae type b-specific antibodies.
Luminol-enhanced chemiluminescence (CL) of heterologous neutrophils was used to assess the capacity of a 1-ng/ml concentration of Haemophilus influenzae type b (Hib)-specific antibodies to induce opsonization of Hib with autologous heat-inactivated sera from children immunized with Hib capsular polysaccharide-polyribosylribitolphosphate (Hib-PRP) conjugate vaccine. Serum samples from 15 of 36 children (42%) vaccinated with Hib-PRP conjugate vaccine had protective levels of Hib-specific antibodies of > or = 1,000 ng/ml. Ten of these 15 (67%) had poor or nonfunctional opsonic activity. Of the 10 children whose sera lacked opsonic activity, 5 (50%) presented with recurrent Hib infection. In contrast, none of the sera of 20 healthy adults lacked opsonic capability. CL intensity was proportional to the concentration of anti-Hib antibodies used for opsonization. Furthermore, the titers of Hib-PRP-specific antibody in children and adults did not correlate with opsonic activity. These results suggest that luminol-enhanced CL as described here with minute concentrations of antibody for opsonization can be used to assess functional capacity of anti-Hib antibodies after vaccination or natural infection in the evaluation of patients with recurrent infections.
Antibodies, Bacterial↗
A phase I/II evaluation of stavudine (d4T) in children with human immunodeficiency virus infection.
OBJECTIVES: To determine the pharmacokinetic properties, tolerance, safety, and preliminary activity of stavudine in human immunodeficiency virus (HIV)-infected children. DESIGN: Phase I/II, open and dose-ranging (0.125 to 4 mg/kg/day in two divided doses). PATIENTS: Thirty-seven HIV-infected children (median age, 5.5 years; range, 7 months to 15 years) with a median CD4+ lymphocyte count at baseline of 242 cells/microL (range 2 to 2290 cells/microL). Thirty children had symptomatic HIV disease at entry; seven had HIV-related immunosuppression alone. Twenty-nine subjects had a history of prior zidovudine (ZDV) therapy. RESULTS: As compared with adults receiving the same weight-adjusted doses, the children we studied had lower maximum observed stavudine plasma concentrations (CMAX) and area under the plasma concentration versus time curves (AUC), and more rapid stavudine elimination. The absolute oral bioavailability of the drug ranged from 61% to 78%. There was no plasma accumulation of the drug between day 1 and week 12. Week 12 cerebrospinal fluid stavudine concentrations in seven subjects, obtained approximately 2 to 3 hours after oral doses, ranged from 16% to 97% of concomitant plasma concentrations. Stavudine was well-tolerated and there were no dose-related clinical or laboratory adverse events. One subject with baseline neurologic abnormalities experienced a transient episode of apparent pain or discomfort in her fingers, possibly related to stavudine. All other adverse events were attributed to underlying disease. Stavudine activity, measured indirectly by CD4+ lymphocyte count and serum p24 antigen concentration changes, was observed in some subjects. Progression of HIV disease and survival correlated with prior ZDV therapy, HIV disease classification, baseline CD4+ lymphocyte count, and weight growth velocity. CONCLUSIONS: Stavudine appears to hold promise for the treatment of HIV infection in children. Its pharmacokinetic properties are consistent and predictable, and it appears to be remarkably well-tolerated and safe. Although our study was not designed to assess the drug's efficacy, preliminary clinical and laboratory evidence of activity was observed.
Administration, Oral↗
Pharmacokinetic evaluation of the combination of zidovudine and didanosine in children with human immunodeficiency virus infection.
As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m2 per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0 mumol.hr per liter at the 180 mg/m2 level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications for the future utility of therapeutic drug monitoring with these agents.
Adolescent↗
The diagnostic challenge of the child born "at risk" for HIV infection.
Standard serologic tests for human immunodeficiency (HIV)-specific antibodies are difficult to interpret in young infants born "at risk" for HIV infection owing to transplacentally acquired maternal IgG. This article reviews the treatment advantages of early diagnosis of HIV infection, the indications for HIV testing in children, the general principles and use of individual HIV assays, and an idealized evaluation schedule for infants born "at risk" for HIV infection.
AIDS Serodiagnosis↗
Immunologic and virologic effects of glucocorticoids on human immunodeficiency virus infection in children: a preliminary study.
The immune dysfunction in human immunodeficiency virus (HIV) infection is complex and cannot be explained solely on the basis of numerical depletion of T lymphocytes. Inappropriate, uncontrolled activation of the immune system may be involved. In a test of this hypothesis, five HIV-infected children were prospectively treated with prednisone and selected immunologic and virologic indices were analyzed. Subjects had marked T lymphopenia (CD4+ T lymphocytes < 500 cells/ml) and antigenemia (serum p24 antigen > 30 pg/ml) and were free of opportunistic infections. There was a significant drop in serum p24 antigen concentrations from baseline (60.2 +/- 10.1% SEM; P < 0.005) 4 weeks after initiation of prednisone, which returned to baseline concentrations as the prednisone was tapered. Concomitant with this decrease, there was decreased expression of cell surface activation markers (HLA-DR, CD25 (interleukin 2 receptor) and CD26 (Ta-1)) in peripheral T lymphocytes. There was no significant change in either T lymphocyte subset numbers or mitogen and antigen-specific lymphoproliferation. A regulatory dysfunction of the immune system, allowing inappropriate activation of T lymphocytes, may be involved in the pathogenesis of HIV disease, and further studies involving selective immunosuppression in HIV disease are warranted.
CD4-CD8 Ratio↗
A comparative study of transfusion-acquired human immunodeficiency virus-infected children with and without disseminated Mycobacterium avium complex.
For identification of the features of disseminated Mycobacterium avium complex (DMAC) in human immunodeficiency virus (HIV)-infected children, a retrospective medical record review of 31 long-term survivors with transfusion-acquired HIV was conducted. Nine patients developed DMAC defined as positive isolation of M. avium complex from peripheral blood. DMAC was diagnosed in patients 51 to 132 months of age (mean, 101). The time from HIV-infecting transfusion to DMAC diagnosis ranged from 37 to 132 months (mean, 92) and survival from the time of DMAC diagnosis ranged from 4 to 21 months (mean, 10). Selected laboratory and clinical measures in DMAC-positive and DMAC-negative subjects were compared. DMAC-positive patients had significantly lower CD4+ T cell counts and higher HIV p24 antigen concentrations than DMAC-negative patients at comparable times. Increased percentages of circulating leukocyte band forms and increased aspartate aminotransferase values were seen more often in DMAC-positive patients. Fever and abdominal pain were the only clinical features seen more often in DMAC-positive than in DMAC-negative patients. At the end of the study period overall survival of DMAC-positive patients was less than that of DMAC-negative children, at 33% vs. 73%. DMAC occurs in profoundly immunocompromised children with advanced HIV disease and significantly affects survival. The clinical and laboratory features of DMAC are relatively nonspecific and a high index of suspicion in patients with markedly reduced CD4+ T cells is essential.
AIDS-Related Opportunistic Infections↗
The use of revised habituation in the treatment of obsessive-compulsive disorders.
The effectiveness of the technique of revised habituation (Salkovskis & Westbrook, 1989) has received limited attention in the literature. This paper describes a clinical example which demonstrates both the utility and power of this intervention in complex cases of obsessive-compulsive disorder.
Adult↗
Sinusitis in status asthmaticus.
The relationship between sinusitis and status asthmaticus (SA) remains obscure. The purposes of this study were to determine the prevalence of abnormal sinus radiographs (SXRs) and investigate possible risk factors among unselected children admitted with SA. Eighty-eight patients over 2 years of age (range 2 to 16 years) consecutively admitted with SA were studied. The principal investigator, blinded to SXR findings, interviewed and examined the patients with respect to 10 physical parameters and 14 historical parameters. Two staff radiologists, blinded to the clinical findings, interpreted the SXRs. Relationship of historical and physical findings with positive SXRs was determined by statistical analysis. Twenty-seven percent of patients were found to have abnormal SXRs, manifesting two thirds or greater opacification of the sinuses. The mean age, sex, and race of patients with abnormal SXRs was not significantly different from those with normal films. A history of two or more admissions per year for SA, and, in children under 5 years of age, a history of chronic otitis media, and the physical finding of otitis media were significantly more frequent among patients with abnormal SXRs. Although not found to be statistically significant, a history of sinusitis and cough occurred more frequently in association with abnormal SXRs.
Adolescent↗
Oral zinc supplementation in the treatment of HIV-infected children.
Primary zinc (Zn) deficiency has been reported to cause immune dysfunction; secondary Zn deficiency has been noted in HIV-infected adults; and in vitro studies have suggested that Zn may have antiviral activity. Zn supplementation was studied in HIV-infected children to evaluate selected clinical and laboratory responses. Thirteen clinically stable HIV-infected children (five females, eight males, 1.5-10 years of age, mean 6 years) with CD4+ counts < 500/mm3 were supplemented with oral elemental zinc at 1.8-2.2 mg/kg/day for 3 to 4 weeks. HIV p24 antigen (p24) levels, T-cell subsets, and serum Zn and copper (Cu) levels were measured before and at the end of Zn supplementation. Clinical assessment of appetite, sense of well being, weight change, and days of fever over 38 degrees C was performed at these times. Baseline serum Zn levels were abnormally low in nine (69%) HIV-infected children. After oral elemental Zn supplementation, six had increased their serum Zn level into the normal range. However, only two patients had increased CD4+T-cell numbers and none of the seven patients with positive p24 had decreased p24 levels. Clinical scores improved in only four patients. This study does not demonstrate impressive short-term benefit from oral Zn supplementation in HIV-infected children.
Administration, Oral↗
Mycobacterium avium complex in HIV-infected children.
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AIDS-Related Opportunistic Infections↗
Clinical aspects of HIV infection in children.
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Child↗
Chronic arthritis in a 3-year-old boy.
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Anti-Inflammatory Agents, Non-Steroidal↗
An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins.
A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs.
Actin Cytoskeleton↗
Complications of central venous catheters in pediatric patients with acquired immunodeficiency syndrome.
Medical records of 18 pediatric acquired immunodeficiency syndrome patients with 24 central venous catheters (CVCs) were reviewed to determine the rates and types of CVC complications and to evaluate the influence of selected social factors, absolute granulocyte counts and CD4+ T cell counts on the rate of CVC infections. CVCs were in place for a total of 4233 days. CVCs were used for blood sampling, administration of blood products and infusions of intravenous immune globulin, parenteral nutrition and medications. Complications included catheter-related infections (8 episodes; with a rate of 1.9/1000 CVC days), occlusions (15 episodes) and unplanned catheter removals (9 episodes). Reduced CD4+ T cell counts were not predictive of CVC infection. The CVC infection rate in our pediatric acquired immunodeficiency syndrome patients was similar to rates reported in children with cancer and adults with cancer and acquired immunodeficiency syndrome.
Acquired Immunodeficiency Syndrome↗