Esophagitis: a frequent consequence of gastroesophageal reflux in infancy

A control group of infants was evaluated to determine criteria for the diagnosis of histologic esophagitis. Based on our observations, histologic esophagitis was defined as four or more intraepithelial neutrophils or one eosinophil per high power field or both. Esophageal biopsy specimens from 33 consecutive infants younger than 2 years who had been examined for clinically significant gastroesophageal reflux (GER) were reviewed for histologic esophagitis. Endoscopy had been performed in each patient, and 4.1 +/- 1.1 (mean +/- SD) biopsy specimens had been obtained above the distal 20% of the esophagus. Twenty (61%) infants had histologic esophagitis, including 15 with intraepithelial eosinophils alone, one with intraepithelial neutrophils alone, and four with both. Older infants (7 to 24 months) with histologic esophagitis were more likely to have moderate to severe inflammation than were infants younger than 7 months of age (P = 0.01). Endoscopic evidence for gross esophagitis was found in six (18%) infants; of these, five had abnormal biopsies, including four with moderate to severe inflammation. Among the 27 infants with a grossly normal esophagus, 14 (52%) had histologic esophagitis, including nine (33%) with moderate to severe inflammation. We conclude that in infants with clinically significant GER: (1) esophagitis is common, (2) histologic esophagitis frequently occurs in the absence of gross endoscopic findings, (3) the likelihood of moderate to severe inflammation increases after 6 months of age, and (4) intraepithelial eosinophils are a sensitive marker for acute inflammation in association with GER.     

Inhibitory effects of bilirubin on cellular immune responses in man.

A significant depression in cell-mediated immunity as measured by lymphoproliferative responses to phytohemagglutinin and responsiveness to mixed lymphocyte culture was observed when adult lymphocytes or cord blood lymphocytes were incubated with increasing concentrations of bilirubin. The inhibitory effect of bilirubin could only be demonstrated with suboptimal concentrations of PHA (0.01 and 0.005%) and was more marked in premature infants than in term neonates or adults. This effect was partially reversible after short preincubation with bilirubin, but was more protracted with preincubations of 24 hours or more. Inhibition of MLC responsiveness of 80.1 plus or minus 5.1% was also demonstrated at a bilirubin concentration of 20 mg/dl. Specific cytotoxicity to rubella virus-infected cells, measured by a 51Cr-release microassay, was not found to be depressed. Bilirubin thus appears to have an inhibitory effect on immune responsiveness which is greater on the afferent limb than on the effrent limb of immunity.     

Glycosylated albumin and transferrin: short-term markers of blood glucose control

Serum was collected from children with type 1 diabetes mellitus before and 10 days after attending a camp session in which blood glucose concentrations were carefully controlled. Glycosylated and nonglycosylated proteins were separated, and levels of albumin and transferrin were determined on each of these fractions. Glycosylated hemoglobin was also determined and ranged from 4.6% to 14.6% (mean +/- SEM 8.1% +/- 0.2%). Mean initial glycosylated albumin in 73 children was 16.4% +/- 0.6%, which was elevated compared with the mean of levels in 20 nondiabetic controls (8.7% +/- 0.3%) and correlated well with levels of glycosylated hemoglobin (r = 0.71). After 10 days mean glycosylated albumin fell to 14.6% +/- 0.5% (P less than 0.00001), near the predicted final value of 13.4% if control had been ideal. Initial levels of glycosylated transferrin in 44 of these children ranged from 4.5% to 22.3% (11.4 +/- 0.6%) and was significantly higher than the mean of 3.8% +/- 0.3% in 20 nondiabetic controls. Mean final glycosylated transferrin fell to 8.2% +/- 0.3% (P less than 0.00001), near the predicted final mean of 7.0% +/- 0.2%. The mean of each subject's blood glucose determinations performed throughout the study period correlated with final levels of both glycosylated albumin (r = 0.55, P less than 0.001) and glycosylated transferrin (r = 0.54, P less than 0.001). Both glycosylated albumin and glycosylated transferrin appear to be reliable markers of short-term glycemic control; glycosylated transferrin (half-life 8 days) was more sensitive than glycosylated albumin over this 10-day period.     

Localized intestinal perforations after enteral administration of indomethacin in premature infants

Four very-low-birth-weight infants developed localized intestinal perforations after enteral administration of indomethacin. The clinical picture and histologic findings were unlike those seen in necrotizing enterocolitis.     

Diagnostic value of surgical testicular biopsy after therapy for acute lymphocytic leukemia

Inasmuch as several cooperative research groups currently require routine testicular biopsy in boys with acute lymphocytic leukemia before cessation of therapy, we performed bilateral open wedge biopsies in 38 boys aged 4 1/2 to 18 years, all of whom were completing 3 years of therapy, were apparently in complete remission, and had palpably normal testes. Biopsy specimens from two other patients were examined during therapy for specific clinical indications. Among the 40 patients, one biopsy revealed leukemia bilaterally; 39 patients had negative biopsy results, three of whom had overt, biopsy-proved testicular relapse 6 weeks to 17 months after normal biopsy. All four patients with testicular relapse are in complete remission six to 50 months after testicular irradiation. We conclude that random sampling during routine testicular biopsies may fail to demonstrate occult leukemia, and that the high rate of complete remissions following retrieval therapy after overt testicular relapse makes routine biopsies before cessation of therapy unnecessary.     

Induction of tolerance to factor VIII in a child with a high-titer inhibitor: in vitro and in vivo observations

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.     

Improvement of left ventricular dysfunction after control of persistent tachycardia

Five children are described who had persistent, chronic tachycardia and left ventricular dysfunction manifested by decreased left ventricular percent fractional shortening on echocardiogram (five patients) cardiomegaly on chest roentgenogram (three), ventricular or atrial hypertrophy on ECG (three), and symptoms of congestive heart failure (three). After antidysrhythmia therapy and control of the tachycardia, signs and symptoms of congestive heart failure resolved in two infants. Moreover, in each patient signs of cardiomegaly resolved on chest roentgenogram, hypertrophy resolved on ECG, and the fractional shortening improved to normal (mean 20.2% +/- 2.4% SEM before vs 36.2% +/- 2.4%, P = 0.02, after treatment). Evaluation in the child who has dilated cardiomyopathy should include assessment of heart rate and rhythm. Moreover, when persistent tachycardia is found in an asymptomatic child, evaluation of left ventricular function is indicated.     

Early manifestations of multiple sulfatase deficiency

We describe two boys, presenting by 1 year of age, with developmental delay from birth, mildly coarse facial features, and hepatomegaly. These clinical features were most suggestive of a mucopolysaccharidosis, particularly MPS II. Biochemical studies, including sulfate incorporation in fibroblasts and lysosomal enzyme analyses in fibroblasts, leukocytes, and serum, showed abnormalities in both sulfatide and mucopolysaccharide metabolism and led to the diagnosis of multiple sulfatase deficiency. With time, both patients developed an ichthyotic rash and profound intellectual deterioration. We conclude that findings in the first year of life in some patients with MSD may closely resemble those in patients with a MPS disorder rather than the late infantile form of metachromatic leukodystrophy, as is classically described. Thus, MSD should be considered in the young patient suspected of having a MPS disorder.