Interleukin-6-associated laboratory parameters and immunohistochemistry in symptomatic stage A and B nodular sclerosing Hodgkin's disease in children.

Interleukin (IL)-6-associated laboratory parameters obtained at diagnosis on 17 children with histologically confirmed nodular sclerosing Hodgkin's disease (NSHD) are reported. When these patients were grouped as either symptomatic stage A or B, they were found to be similar in extent of disease, age, and gender. However, statistically significant differences between these two groups were observed for the means of the following IL-6-associated laboratory parameters: hematocrit (p = 0.019), platelet count (p = 0.009), serum albumin (p = 0.001), and ferritin (p = 0.037) concentrations. Moreover, trend analysis of abnormalcy revealed an increasing frequency of anemia, thrombocytosis, hypoalbuminemia, and hyperferritinemia between stage A and B patients and, when available, febrile controls (p values = 0.0012, 0.0009, 0.0406, and 0.0011, respectively). Correspondingly, IL-6 immunohistochemistry performed on archival material from representative cases in each group showed greater overall reactivity in specimens from stage B patients. A variety of cells accounted for this positivity for IL-6 antigen including Reed-Sternberg cells and their variants, lacunar cells, dendritic interdigitating cells, endothelial cells, fibroblasts, and vascular smooth muscle cells. In summary, greater and more frequent abnormalities in IL-6-associated laboratory parameters and increased immunohistochemical reactivity for IL-6 antigen coincide with the presence of fever in helping to identify children with clinical stage B NSHD.

Aluminum-induced microcytosis in a child with moderate renal insufficiency.

A child with moderate renal failure, on high doses of aluminum compounds for treatment for hyperphosphatasemia, presented with unexplained microcytosis. The patient also had psychomotor delay. On discontinuation of aluminum, microcytosis reversed in 2 months. Four months later, psychomotor development improved. Children with renal failure, on aluminum supplementation, should be carefully monitored for toxicity. Microcytosis may be a clue to aluminum toxicity in such patients.

Value of screening umbilical cord blood for hemoglobinopathy.

Foremost among the beneficial effects of screening umbilical cord blood is the optimized quality of care that can follow the immediate involvement of an infant with sickle cell disease and his or her family in an appropriate health care system. This is exemplified by the reduction in the case fatality rate of pneumococcal septicemia that has been achieved. Appropriate follow-up of screening also includes transmission of information about the diagnosis of a hemoglobinopathy trait or alpha-thalassemia to affected families and their physicians, with ready availability of education and counseling.

Parvovirus B19 infection associated with reticulocytopenia and chronic autoimmune hemolytic anemia.

A previously healthy 11-year-old white female presented with a Coomb's positive hemolytic anemia and reticulocytopenia. The patient was treated with prednisone (6.4 mg/kg/day) and had a stable hemoglobin with subsequent recovery of reticulocytes by 7 days. Bone marrow aspiration showed hypercellularity with arrest of red cell maturation. The patient's serum contained specific IgM and IgG antibodies to parvovirus B19. Our report confirms parvovirus B19 as a cause of reticulocytopenia at presentation in autoimmune hemolytic anemia. Immunosuppressive therapy with prednisone did not appear to significantly prolong the course of the B19 infection.

Severe anemia caused by human parvovirus in a leukemia patient on maintenance chemotherapy.

A 6-year-old boy on maintenance chemotherapy for acute lymphocytic leukemia developed severe hypoplastic anemia during chemotherapy previously well tolerated. The hypoplastic episode persisted for approximately 30 days. Human parvovirus (B19), the etiologic agent of aplastic crisis in persons with underlying hemolytic syndromes, was detected in the patient's serum 25-30 days after onset of hemoglobin decrease, and B19 IgM seroconversion occurred 1 week later. The patient's hypoplastic anemia was presumably caused by prolonged B19 infection resulting from a blunted immune response. An immune response to the B19 infection and resolution of the illness were temporally associated with brief cessation of chemotherapy.

Methemoglobinemia and hemolytic anemia associated with Campylobacter jejuni enteritis.

A 7-week-old infant with methemoglobinemia, hemolytic anemia, and inadequate weight gain was found to have a Campylobacter jejuni gastrointestinal tract infection. Known etiologies of methemoglobinemia such as oxidative drug exposure, deficiency of NADH-methemoglobin reductase, and hemoglobin M disorder were excluded. The patient had a twin brother (probably identical) who had neither methemoglobinemia nor stool cultures positive for C. jejuni. The twin essentially served as an experimental control, making other environmental or genetic causes of methemoglobinemia unlikely in the patient. Both the methemoglobinemia and the C. jejuni infection responded to adequate treatment with erythromycin. The association of a C. jejuni infection with methemoglobinemia is discussed in light of previous associations of enteritis and methemoglobinemia in infants.

Pregnancy associated with both insulin-dependent diabetes mellitus and sickle cell disease. A report of two cases.

Two pregnant women were treated for both insulin-dependent diabetes and sickle cell disease. Careful application of treatments developed for each of these conditions allowed both pregnancies to be successfully carried to term.

Direct evidence that decreased serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in sickle cell disease is related to antibody deficiency.

Two approaches were used to demonstrate that reduction in serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in children with sickle cell disease is related to a deficiency of antibodies to pneumococcal capsular polysaccharide. First, opsonization of S. pneumoniae mediated by the alternative pathway in patients' sera was restored to normal by addition of the purified IgG or IgM fraction of goat antiserum to capsular polysaccharide of the homologous serotype. Secondly, IgG antibody titers to capsular polysaccharide in patients' sera correlated significantly with alternative pathway-mediated opsonization; the correlation between titers of IgM anticapsular antibodies and opsonization approached statistical significance. The sum of the IgG and IgM anticapsular antibody titers correlated most significantly with opsonization. Our results suggest that reduction in alternative pathway-mediated opsonization in sera from children with sickle cell disease is related to low levels of both IgG and IgM anticapsular antibodies.

Lack of a requirement for the Fc region of IgG in restoring pneumococcal opsonization via the alternative complement pathway in sickle cell disease.

Children with sickle cell disease have reduced serum opsonization of Streptococcus pneumoniae. Our previous studies have suggested that opsonization mediated by both the alternative and classic complement pathways is reduced because of a deficiency of IgG antibodies to pneumococcal capsular polysaccharide. This study compares the ability of purified IgG (fractionated from goat antiserum to pneumococcal capsular polysaccharide) and F(ab')2 fragments of the IgG preparation to restore alternative pathway-mediated opsonization of S. pneumoniae to sera from patients with sickle cell disease. Both the whole IgG preparation and F(ab')2 fragments of this preparation restored opsonization to normal levels and concomitantly increased alternative pathway-mediated deposition of C3 onto the pneumococci to a supranormal level. These results suggest that enhancement of opsonization is mediated by the F(ab')2 region of IgG antibody to capsular polysaccharide and is associated with an increase in complement deposition on the bacterial surface.

Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial.

Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia.

Relation between serum opsonic activity for Streptococcus pneumoniae and complement function in sickle cell disease.

Opsonic activity for Streptococcus pneumoniae mediated by the alternative and classic complement pathways and concomitant binding of activated C3 to the bacteria were measured in sera from children with sickle cell disease and normal siblings of similar age. Uptake of radiolabeled serotypes 7F, 10A, 15B, and 24F by normal human polymorphonuclear leukocytes and intracellular killing were the parameters used to assess opsonization. C3 fixation was quantitated by radioimmunoassay under conditions identical to those used for opsonic measurements. Both classic and alternative pathway-mediated opsonic activities were significantly reduced in a subset of patients. These alterations were associated with reduction in C3 fixation by way of the classic pathway and normal C3 fixation by way of the alternative pathway. The data implicate auxiliary serum factors rather than an intrinsic defect in the complement system in the opsonic alterations. Retrospective data were suggestive of an increased incidence of pneumococcal bacteremia occurring in association with reduction in opsonic activity.

Treatment of occult bacteremia: a prospective randomized clinical trial.

Antibiotic therapy for children without foci of infection and at risk for bacteremia is controversial. A prospective randomized clinical trial was conducted using expectant antibiotic therapy in children at risk for bacteremia. A total of 96 children (aged 6 to 24 months) with temperature of more than 40 degrees C, no identifiable source of infection, and a leukocyte count greater than or equal to 15,000/microL and/or sedimentation rate greater than or equal to 30 were enrolled. The following tests were performed on all children: blood culture, chest roentgenogram, urinalysis, and urine culture. A lumbar puncture was performed if a child was 12 months or less. Patients were randomized to receive either no antibiotic therapy or Bicillin C-R, 50,000 U/kg intramuscularly, followed by penicillin V, 100 mg/kg/d, orally four times a day for three days. Patients were examined at 24 and 72 hours. Fifty patients were treated expectantly and 46 received no antimicrobial therapy. Ten of the 96 patients were bacteremic (nine had Streptococcus pneumoniae, one had Haemophilus influenzae). Four of the five children treated for bacteremia showed improvement at the first follow-up visit (afebrile and no obvious focus of infection). The five untreated patients showed no improvement; four patients developed focal infections (two had meningitis, two had otitis media) (P less than or equal to .05, Fisher exact test). No complications of expectant therapy were detected. Thus, expectant antibiotic therapy for children who have no obvious source of infection and who meet these criteria associated with occult bacteremia is warranted.

Evaluation of clinical severity in sickle cell disease.

For a severity classification of sickle cell disease to be accepted, it is necessary that clinicians agree upon relative disease severity between patients. This condition was shown to be satisfied for a randomly selected group of patients evaluated by four persons. All rank correlation coefficients between observer pairs were highly significant. Representative severity indices based on history and recent hospital events also correlated significantly with evaluator ranking. The results show that, in principle, a classification of sickle cell disease patients by severity is possible. Such a classification would be most useful to evaluate the prognostic significance of particular signs or symptoms, or the success of various treatments in affecting severity of disease.

Pediatric hematologic and oncologic emergencies.

Acute hematologic-oncologic problems fall into two groups, those that require immediate assessment, diagnosis, and therapy, and those that require attention but are not life threatening if treated appropriately. Both types are considered in this article, which discusses hemorrhagic disorders; anemias, with special emphasis on patients with sickle cell disease; an approach to fever and infection in the immunocompromised child; and oncologic disorders that may be life threatening.

Nocturnal oxygen desaturation in patients with sickle cell anemia.

The sleep of two patients with sickle cell disease was punctuated by periods with notably reduced arterial O2 saturation despite simultaneous normal respiratory rates. The O2 levels returned to baseline during intermittent wakefulness. Gas exchange patterns during sleep may contribute to the morbidity of sickle cell disease.

Clinicopathologic characteristics of septicemia in sickle cell disease.

Bacterial septicemia occurred in 22 of 210 pediatric patients with sickle cell disease over a nine-year period, an attack rate of 10.5%. Children less than 2 1/2 years old with hemoglobin SS were at greatest risk; Streptococcus pneumoniae was the most common pathogen. Although sudden febrile illness developed in nine patients, in 13 a gradual prodrome was associated with symptoms for more than 24 hours before evaluation. Both initial body temperature and WBC count were highly variable. In all six fatal cases, autopsy disclosed adrenal hemorrhagic necrosis, which in three was diffuse and typical of that seen in the Waterhouse-Friderichsen syndrome. Recommendations in patients with sickle cell disease and fever, even if only of moderate degree, include the rapid initiation of antibiotic therapy and the use of corticosteroids at the first sign of circulatory insufficiency.

Otolaryngologic manifestations of sickle cell disease.

Sickle cell disease is a common hereditary hematologic disorder characterized by the presence of a structurally abnormal hemoglobin molecule. Physicochemical properties of sickle hemoglobin result in a chronic hemolytic anemia and in vaso-occlusive episodes with ischemic injury of many tissues. In patients with sickle cell disease the otolaryngologist may be confronted with lesions affecting the ear, the bones and soft tissues, and the nervous system. Surgery and anesthesia also present special problems. An outline and discussion of these clinical concerns are presented.

Restoration by normal human immunoglobulin G of deficient serum opsonization for Streptococcus pneumoniae in sickle cell disease.

Supplementation of sera from four children with sickle cell disease with untreated or heated normal human serum or with normal human immunoglobulin G restored opsonic activity for serotype 10 Streptococcus pneumoniae, whereas supplementation with normal human immunoglobulin M did not.