High Prevalence of Developmental Disabilities in Children Admitted to a General Pediatric Inpatient Unit

Objective: Evaluate a) the prevalence of developmental disabilities (DD) in children admitted to a general pediatrics inpatient unit, and b) the number of children admitted to the unit with previously undiagnosed developmental disability. Methods: Prevalence was evaluated through retrospective record review. Subjects: One hundred ninety children older than five months of age admitted to a general pediatric unit. Results: Of 190 children admitted, 155 (81.6%) had adequate developmental screening documented in the record. Forty-nine (25.7% of total, 31.6% of screened) had a developmental disability, 22 (12.1% of total, 14.8% of screened) had a previously unrecognized disability. Sample prevalence of DD was: cerebral palsy (6.8%), developmental delay or mental retardation (8.4%), language delay (4.6%), learning disability (8.2%), and hearing loss (1.5%). New diagnoses included: three children with probable mental retardation (MR), nine with learning disability (may include mild MR), seven with language delay, three with abnormal motor skills (fine and/or gross motor), one each of: neurofibromatosis type I, hearing loss, cerebral palsy, dysphagia. Some children had more than one new diagnosis. Conclusion: The prevalence of disabilities in a general pediatrics inpatient unit is much higher than the prevalence in the community. Because almost half of the disabilities were previously unrecognized, acute hospitalization is an excellent opportunity to conduct developmental screening.     

The Epstein-Barr virus latent membrane protein 1 induces interleukin-10 in Burkitt's lymphoma cells but not in Hodgkin's cells involving the p38/SAPK2 pathway

Infection of B cells with Epstein-Barr Virus (EBV) induces interleukin-10 (IL-10) production, which may contribute to transformation. IL-10 can modulate the immune response at certain levels, playing a crucial role in balancing humoral and cellular responses. Moreover, it can function as a growth and differentiation factor for B cells. However, the mechanism of IL-10 induction is still unclear. Here we demonstrate that IL-10 was specifically induced by the EBV-latent membrane protein 1 (LMP1) in Burkitt's lymphoma (BL) cell lines BL2 and BL41. In two T cell lines (Jurkat, MOLT3), two NHL cell lines (U266, MHH-PREB1), or three Hodgkin's disease (HD) cell lines (L428, L540, and KMH2), LMP1 did not induce IL-10 expression. In contrast, LMP1 activated CD40 or CD54 (ICAM1) expression in the analyzed cell lines. LMP1 derivatives lacking the C-terminal activation regions (CTAR), by deletion of the amino acids between 187 and 351 (Delta CTAR1) or 232 and 386 (Delta CTAR2), alone, or together induced IL-10 at very low amounts compared to wild-type LMP1. Inhibition of LMP1-mediated NF kappa B activation by constitutive repressive I kappa B-alpha only marginally impaired IL-10 expression in BL2 cells, while SB2035080 at 5 microM (a specific p38/SAPK2 inhibitor) led to reduced IL-10 expression. Our findings confirm the role of LMP1 in transactivation of cellular genes possibly important for tumor immunoescape but show that more than one signaling pathway is involved in this activation and suggests the necessity of a defined conformation of CTARs to activate IL-10 involving p38/SAPK2.     

Structural characterisation of the distal 5' flanking region of the human interleukin-10 gene

Interleukin-10 (IL-10) is an important immunoregulatory cytokine. The recent characterisation of the proximal 5' flanking region of IL-10 led to the identification of the promoter region. Two polymorphic dinucleotide repeats and 10 single nucleotide polymorphisms (SNPs) have been identified and suggested to be useful genetic markers in several diseases. We have sequenced a further 5275 bp from -9296 to -4021 of the distal part of the 5' flanking region of the human IL-10 gene from the cosmid clone pWE15-4/11. Our sequence analysis reveals a high density of Alu-repeats within the IL-10 gene locus, including three novel, related structures which we term Alu-IL10 (A-C). Using three overlapping PCR products spanning 5110 bp of this distal part of the IL-10 gene the following single base pair substitutions were identified: at -8571 C/T, -8531 G/A, -6752 A/T, -6208 G/C, -5402 C/G. In addition a heterozygous three base pair deletion at -7400 was observed. The SNPs at -8571 C/T and -8531 G/A are contained within an Alu-repeat. These data should further the understanding of how the IL-10 gene is controlled in man and how its function may vary between individuals.     

Dark spots in late-phase indocyanine green angiographic studies in a patient with presumed ocular histoplasmosis syndrome

Purpose: We analyzed indocyanine green (ICG) angiograms in a patient with presumed ocular histoplasmosis syndrome (POHS) complaining about “seeing spots” and decreased visual acuity in order to identify the pathologic process. · Patients and methods: A 30-year-old caucasian man with clinical signs of POHS who had previously undergone laser photocoagulation for secondary choroidal neovascularization developed visual disturbances primarily in his temporal visual field. We performed fundus photography, fluorescein angiography and ICG angiography before, during and after the episode of visual disturbance. ICG angiographic findings were correlated to fundus photographs and fluorescein angiograms. · Results: Fundus examination, fluorescein angiograms and early-phase ICG angiograms were unremarkable at all time points. However, during the phase of visual disturbance, late-phase ICG angiographic study revealed hypofluorescent lesions in the area representing the visual disturbances. At 1 week follow-up, these hypofluorescent lesions were reduced in size and number; at 6 months follow-up they had completely resolved. · Conclusions: Late-phase ICG angiographic study can provide additional information in inflammatory retinal disease by virtue of identifying areas of choroidal alterations while standard diagnostic examination remain unremarkable. Received: 12 August 1998 Revised version received: 29 September 1998 Accepted: 29 September 1998     

CAT/CLAMS: its use in detecting early childhood cognitive impairment

The Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS), a neurodevelopmental tool for the cognitive assessment of infants and toddlers, correlates well with the Bayley Scales of Infant Development. In 1993 the Bayley Scales were revised and the second edition published (BSID-II). This study was designed to determine how well the CAT/CLAMS correlates with the BSID-II and its utility in identifying mild and severe cognitive impairment. Sixty-eight infants and toddlers (age range = 14-48 months), referred for suspected developmental delays, were administered the CAT/CLAMS and BSID-II and the results compared. The correlation between the two instruments was strong (r = 0.89, P<0.0001). The CAT/CLAMS was sensitive (81%) and specific (85%) for detecting overall cognitive impairment (BSID-II less than 70) and was even more sensitive (100%) and specific (96%) in detecting severe cognitive impairment (BSID-II less than 50). The physician using the CAT/CLAMS formulated a clinical impression of cognitive impairment that was sensitive (95%) and specific (84%) compared with formal psychologic testing. The CAT/CLAMS correlates well with the BSID-II. It is useful for detecting and quantifying mild and severe cognitive impairment. It permits the physician to formulate an accurate clinical impression of cognitive impairment consistent with possible mental retardation.     

The Significance of Meckel’s Diverticulum in Appendicitis — A Retrospective Analysis of 233 Cases

Conflicting reports are found in the literature concerning whether to remove an incidentally discovered Meckel’s diverticulum (MD). Between 1.1.1974 and 31.12.2000, at a single center, the perioperative data associated with appendectomy (AE) were recorded consecutively and analyzed retrospectively. All patients in whom an MD was discovered during an AE were included in the study. The clinical presentation, postoperative course, and follow-up in all MDs left in place were analyzed. During the course of 7927 AE, 233 MD (2.9%) were detected. Of these 80.7% (n = 188) were removed and 19.3% (n = 45) were left untouched. In 9% (n = 21) of all detected diverticula pathological changes were found. Ectopic tissue was seen in 12.2% (n = 23) of the MDs removed. The postoperative complication rates did not differ significantly between patients in whom the MD was removed (9.5%; n = l8) and those in whom it was not (17.7%; n = 8); in the latter group the appendicitis was of the more acute type (gangrenous or perforated) (24.4% vs. 4.3%). In 18 patients (40.0%) with non-removed MDs, a follow-up period of 14.1 ± 5.8 years was achieved. Complications associated with a non-removed MD were not observed. If during the course of an AE a MD is detected, the present data, as well as those in the literature, suggest that an individualized approach should be taken. Meckel’s diverticulum with obvious pathology should always be removed. In cases of gangrenous or perforated appendicitis, an incidentally discovered MD should be left in place, whereas in an only mildly inflamed appendix it should be removed.     

Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used

Interleukin-10 (IL-10), a cytokine involved in many aspects of the immune response shows interindividual variations in their expression. However, genetic variations of the 5'-flanking region of the IL-10 gene (PIL-10) are poorly characterised with respect to different stimuli. New extended haplo- and genotypes are identified present at differing frequencies in three geographically separated populations. Their influence on IL-10 expression have been assessed in vitro after stimulation of leukocytes with lipopolysaccharide (LPS), dibutyryl-cAMP or following immortalisation with Epstein-Barr virus (lymphoblastoid cell line (LCL)). Interindividual differences of IL-10 production were found to be related to single-nucleotide polymorphisms (SNP) haplotype -6752/-6208 in LCLs (P<0.02), and for haplotypes comprising SNPs -6752/-6208/-3538 after LPS stimulation (P<0.03). Carriers of the IL10.G microsatellite with 22, 24 or 26 dinucleotide repeats linked with the -1087G SNP, exhibited the highest levels of IL-10 expression. Contrasting IL-10 secretion patterns were found for IL10.R microsatellite alleles characterised by 15 dinucleotide repeats: after LPS stimulation this allele was associated with high IL-10 production (P<0.007), but with low IL-10 levels in LCLs (P< 0.038). Thus, the effects of mosaics of genetic elements in the PIL-10 on the capacity of leukocytes to produce IL-10 depend on the agent inducing IL-10 expression.