Investigation of EEG changes before and after phototherapy in infants with severe hyperbilirubinemia.

BACKGROUND: Despite the known effect of hyperbilirubinemia in neonates, the effect of phototherapy on electroencephalography (EEG) remains unknown. Therefore, we aimed to determine the alteration of electroencephalography in infants with hyperbilirubinemia before and after phototherapy. METHODS: This cross-sectional study was performed on infants of≥35 weeks of gestation with hyperbilirubinemia. Information including age, sex, birth weight, hemoglobin levels, and treatment measures was recorded. In all studied infants, an EEG was performed before (in the first eight hours of hospitalization) and after treatment (after phototherapy or blood transfusion). The required duration of phototherapy, hospitalization and adverse effects were assessed then EEG of the neonates was compared before and after treatment. RESULTS: A total of 52 infants (44% female and 56% male) were included in this study. Mean gestational age, weight, and bilirubin were 38.6±1.53 weeks, 3150±625 g, and 23.87±4.36 mg/dl, respectively. The most common findings before phototherapy were Frontal Theta (21 patients, 40.4 percent) and Delta Brush (14 patients, 26.9%), while the most common findings after phototherapy were Frontal Theta (20 patients, 38.5%) and Delta Brush (19 patients, 36.5%). Mean±SD of bilirubin in infants with and without Delta Brush was 21.30±1.67 mg/dl and 19.95±0.94 mg/dl, respectively. CONCLUSIONS: Hyperbilirubinemia in newborns may be linked to altered EEG findings. After phototherapy, the Frontal theta was reduced, but the Delta brush was intensified. Bilirubin levels were higher in infants with Delta Brush in their EEG compared to infants without this finding.

Severe obstructive sleep apnoea syndrome in an adult patient with Laron syndrome.

A 68 year old patient with Laron syndrome (primary growth hormone (GH) resistance-insensitivity due to a molecular defect of the GH receptor) and severe obstructive sleep apnoea syndrome is described. Treatment with continuous positive air pressure therapy resulted in improved nocturnal sleep, daytime alertness and cognitive functions.

Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy.

OBJECTIVES: We studied the clinical and genetic features of hypertrophic cardiomyopathy (HCM) caused by mutations in the myosin-binding protein C gene (MYBPC3) in 110 consecutive, unrelated patients and family members of European descent. BACKGROUND: Mutations in the MYBPC3 gene represent the cause of HCM in approximately 15% of familial cases. MYBPC3 mutations were reported to include mainly nonsense versus missense mutations and to be characterized by a delayed onset and benign clinical course of the disease in Japanese and French families. We investigated the features that characterize MYBPC3 variants in a large, unrelated cohort of consecutive patients. METHODS: The MYBPC3 gene was screened by single-strand conformational polymorphism analysis and sequencing. The clinical phenotypes were analyzed using rest and 24-h electrocardiography, electrophysiology, two-dimensional and Doppler echocardiography and angiography. RESULTS: We identified 13 mutations in the MYBPC3 gene: one nonsense, four missense and three splicing mutations and five small deletions and insertions. Of these, 11 were novel, and two were probably founder mutations. Patients with MYBPC3 mutations presented a broad range of phenotypes. In general, the 16 carriers of protein truncations had a tendency toward earlier disease manifestations (33 +/- 13 vs. 48 +/- 9 years; p = 0.06) and more frequently needed invasive procedures (septal ablation or cardioverter-defibrillator implantation) compared with the 9 carriers of missense mutations or in-frame deletions (12/16 vs. 1/9 patients; p < 0.01). CONCLUSIONS: Multiple mutations, which include missense, nonsense and splicing mutations, as well as small deletions and insertions, occur in the MYBPC3 gene. Protein truncation mutations seem to cause a more severe disease phenotype than missense mutations or in-frame deletions.

Serologic evidence for Cryptococcus neoformans infection in early childhood.

OBJECTIVE: Cryptococcus neoformans is an important cause of central nervous system infection in adults with acquired immunodeficiency syndrome (AIDS) but an unusual cause of disease in children with AIDS. The basis for this age-related difference in incidence is not known but may be caused by differences in exposure or immune response. The objective of this study was to determine whether the low prevalence of cryptococcal disease among children is related to a lack of exposure to C neoformans. METHODS: Sera were obtained from 185 immunocompetent individuals ranging in age from 1 week to 21 years who were being evaluated in an urban emergency department. Sera were analyzed for antibodies to C neoformans and Candida albicans proteins by immunoblotting. Immunoblot patterns were compared with those obtained from sera of patients with cryptococcosis (n = 10) and workers in a laboratory devoted to the study of C neoformans. The specificity of our results was confirmed by several approaches, including antibody absorption and blocking studies. Sera were also analyzed for the presence of cryptococcal polysaccharide by both enzyme-linked immunosorbent assay and latex agglutination assays. RESULTS: Sera from children 1.1 to 2 years old demonstrated minimal reactivity to C neoformans proteins. In contrast, the majority of sera from children >2 years old recognized many (>/=6) C neoformans proteins. For children between 2.1 and 5 years old, 56% of sera (n = 25) reacted with many proteins, whereas for children >5 years old (n = 120), 70% of samples reacted with many proteins. Reactivity was decreased by absorbing sera with C neoformans extracts or by preincubating blots with sera from experimentally infected but not from control rats. Reactivity to C neoformans proteins did not correlate with reactivity to C albicans proteins, which was common in sera from children between the ages of 1.1 and 2 years. Cryptococcal polysaccharide was detected at a titer of 1:16 (~10 ng/mL) in the sera of 1 child, a 5.6-year-old boy who presented to the emergency department with vomiting. CONCLUSIONS: Our findings provide both indirect and direct evidence of C neoformans infection in immunocompetent children. Our results indicate that C neoformans infects a majority of children living in the Bronx after 2 years old. These results are consistent with several observations: the ubiquitous nature of C neoformans in the environment, including its association with pigeon excreta; the large number of pigeons in urban areas; and the increased likelihood of environmental exposure for children once they have learned to walk. The signs and symptoms associated with C neoformans infection in immunocompetent children remained to be determined. Primary pulmonary cryptococcosis may be asymptomatic or produce symptoms confused with viral infections and, therefore, not recognized as a fungal infection. Our results suggest that the low incidence of symptomatic cryptococcal disease in children with AIDS is not a result of lack of exposure to C neoformans. These findings have important implications for C neoformans pathogenesis and the development of vaccine strategies.

CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus.

BACKGROUND: Recent studies have reported an increased incidence of squamous intraepithelial lesions in women infected with the human immunodeficiency virus (HIV). However, to the authors' knowledge there are scarce data regarding the relation between the CD4 T-lymphocyte count (CD4+), HIV viral load, and the development of cervical dysplasia as evidenced by cervicovaginal cytology. The objective of the current study was to examine the association between cervicovaginal smears (with and without squamous lesions) from HIV-infected women and their CD4+ counts and HIV viral load. METHODS: Two hundred ninety-six cervicovaginal smears from 108 HIV-infected women were reviewed and classified according to the Bethesda system. Abnormal cytologies (n = 74) were followed by colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the time of the cytologic evaluation. Statistical analysis was performed using the Student t test and the Mann-Whitney U test. RESULTS: The control group (n = 222) had significantly higher CD4+ counts (378 vs. 246 cells/microL; P < 0.001) compared with the group with cervical lesions. There was no apparent difference between the CD4+ counts from women with low grade lesions and those from women with high grade lesions. The HIV viral load was significantly higher in patients with cytologic abnormalities than in those with negative Papanicolaou smears (P = 0.006). CONCLUSIONS: The degree of immunosuppression may contribute to the development of intraepithelial lesions in HIV-positive women, but once the lesion is established disease progression may not be affected by the CD4+ counts.

Circadian rhythm sleep disorders as a possible side effect of fluvoxamine.

Sleep problems, day somnolence, and fatigue as a result of psychotropic drugs are very common. Psychiatrists usually consider these effects a result of insomnia and treat them by prescribing sleeping pills or other benzodiazepine agents. We describe here 10 cases of circadian rhythm sleep disorders (CRSD)--and not merely insomnia--as a possible side effect of fluvoxamine (FVA). Two other serotonin reuptake inhibitors, fluoxetine and clomipramine, did not induce CRSD in any of these 10 patients. We speculate that FVA-induced CRSD is caused by the effect of FVA on serotonin and melatonin levels in the central nervous system. CRSD as a side effect of FVA can be treated by replacing the suspected FVA or adding melatonin to a beneficial FVA treatment. Thus, it is important to be aware of possible iatrogenic CRSD in order to treat appropriately. Prospective studies are needed to confirm our observation and to study the influence of other psychotropic drugs on sleep-wake schedule.

Sleep-wake schedule disorder disability: a lifelong untreatable pathology of the circadian time structure.

Certain sleep-wake schedule disorders (SWSDs) cannot be successfully managed clinically using conventional methods of sleep therapy. We describe two cases of SWSD, the first following head trauma and the second originating during childhood, that had been misdiagnosed by physicians for many years. After conventional treatment for SWSD with light therapy and melatonin failed to bring about substantial improvement, it was determined that they were suffering from an incurable disability. Hence, we propose new medical terminology for such cases--SWSD disability. SWSD disability is an untreatable pathology of the circadian time structure. Patients suffering from SWSD disability should be encouraged to accept the fact that they suffer from a permanent disability, and that their quality of life can only be improved if they are willing to undergo rehabilitation. It is imperative that physicians recognize the medical condition of SWSD disability in their patients and bring it to the notice of the public institutions responsible for vocational and social rehabilitation.

A pneumococcal capsular polysaccharide vaccine induces a repertoire shift with increased VH3 expression in peripheral B cells from human immunodeficiency virus (HIV)-uninfected but not HIV-infected persons.

The molecular mechanism of pneumococcal vaccine failure in human immunodeficiency virus (HIV)-infected persons is not fully understood. A polymerase chain reaction ELISA was used to determine the proportion of peripheral IgG, IgA, and IgM CD19-positive B cells expressing 6 immunoglobulin heavy-chain variable region (VH) subgroups before and 7 days after pneumococcal vaccination of 12 HIV-infected and 12 HIV-uninfected subjects. Significant postvaccination increases in the expression of the VH3 subgroup by IgG and IgA and a greater serologic response to vaccination were observed in the HIV-uninfected group. In contrast, the HIV-infected group had reduced prevaccination IgG VH3 and a postvaccination increase in IgG VH5. These results demonstrate that pneumococcal vaccination changes the pattern of B cell VH gene expression and support the concept that aberrant VH3 expression may translate into a poor antipneumococcal response in the setting of HIV infection.

Antibodies reactive with the cryptococcal capsular polysaccharide glucuronoxylomannan are present in sera from children with and without human immunodeficiency virus infection.

Antibodies reactive with the cryptococcal polysaccharide glucuronoxylomannan (GXM) are present in sera from both human immunodeficiency virus (HIV)-uninfected and -infected adults. However, the prevalence of these antibodies in US children is unknown. An antigen-capture ELISA was used to determine the presence, serotype specificity, isotype, and IgG subclass distribution of antibodies to GXM in sera from 27 HIV-uninfected and 34 HIV-infected children. The children were of similar age and socioeconomic background. IgG and IgM to GXM were present in sera from all children, although HIV-uninfected children had significantly higher titers. HIV-uninfected children had IgG1 and IgG2 to GXM and significantly greater IgG2 than in HIV-infected children. These findings of type-specific antibodies to GXM in early childhood suggest that exposure to or subclinical infection with Cryptococcus neoformans may be an early childhood event.

Cryptococcosis in children with AIDS.

We compiled the clinical and immunologic features of Cryptococcus neoformans infections in human immunodeficiency virus (HIV)-infected children from 1985 to 1996 in a retrospective case series. Thirty cases of cryptococcosis were identified. These children had a median age of 9.8 years, a median CD4+ cell count of 54/microL at the time of diagnosis, and either a culture positive for C. neoformans or cryptococcal antigen in serum or cerebrospinal fluid. Sixty-three percent of the cases occurred in children vertically infected with HIV and in children between 6 and 12 years of age. The clinical and laboratory characteristics of this pediatric cohort were similar to those of adults with AIDS and cryptococcosis. On the basis of a subset of the cases, a 10-year point prevalence of cryptococcosis among children with AIDS of approximately 1% was estimated.

Human antibodies elicited by a pneumococcal vaccine express idiotypic determinants indicative of V(H)3 gene segment usage.

Human immunodeficiency virus (HIV)-infected persons manifest decreased antibody responses to pneumococcal polysaccharide vaccines. Since human antibody responses to polysaccharides are often restricted, the molecular structure of antibodies elicited by a 23-valent pneumococcal vaccine was analyzed. Anti-idiotypic reagents were used to detect V(H)1, V(H)3, and V(H)4 gene usage by antibodies to pneumococcal capsular polysaccharides in HIV-uninfected and HIV-infected subjects by ELISA. HIV-uninfected persons generated beta-mercaptoethanol-sensitive and -resistant antibodies to pneumococcal capsular polysaccharides expressing V(H)3 determinants recognized by the D12, 16.84, and B6 monoclonal antibodies; antibodies expressing V(H)1 determinants were not detected, and V(H)4 determinants were expressed by beta-mercaptoethanol-sensitive antibodies only; and HIV-infected subjects had significantly lower capsular polysaccharide-specific and V(H)3-positive antibody responses. These findings confirm decreased antibody responses to pneumococcal vaccination in HIV-infected persons and suggest that their poor responses may result from HIV-associated depletion of restricted B cell subsets.

Fc gammaRIIa polymorphism in human immunodeficiency virus-infected children with invasive pneumococcal disease.

Invasive pneumococcal disease (IPD) occurs frequently in HIV-infected children and adults. Defects in complement function, opsonic capsular antibodies, and Fc receptor antibody-mediated phagocytosis could contribute to impaired host defense against Streptococcus pneumoniae. The objective of this study was to define the distribution of the three Fc gammaRIIa genotypes in HIV+ children, including those with IPD. Forty-eight HIV+ Hispanic children, including eight with IPD, followed at Bronx-Lebanon Hospital Center, Bronx, New York, nine HIV+ adults with IPD, and 56 HIV- Hispanic control subjects were studied. The children and adults were identified retrospectively except for one child who developed IPD during the study. Fc gammaRIIa genotypes were determined by PCR amplification of the Fc gammaRIIa locus from genomic DNA samples and hybridization of the PCR products with allele-specific oligonucleotides. Naturally occurring serum antibodies reactive with four pneumococcal polysaccharide serotypes were determined by ELISA in seven of eight children with IPD. There were no statistical differences in Fc gammaRIIa genotypes between HIV+ children with and without IPD, HIV+ adults with IPD, or HIV- Hispanics. The predominant IgG subclass of pneumococcal polysaccharide binding antibodies in the seven HIV+ children with IPD studied was IgG1. The distribution of Fc gammaRIIa genotypes in HIV+ children with and without IPD is similar to that of the normal Hispanic population. The prospect of passive immunotherapy with specific anticapsular antibodies might be a promising alternative for the treatment and/or prevention of IPD in HIV+ children and other immunodeficient groups.

Actinomyces chorioamnionitis and preterm labor in a twin pregnancy: a case report.

A case of premature delivery of a twin gestation with evidence of Actinomyces chorioamnionitis is presented. This unusual infection of the placenta was associated with preterm labor.

Relationship between neonatal behavior and subsequent temperament.

The validity of the neonatal behavioral assessment scale in predicting later infant temperament is of theoretical and clinical importance. The scale was administered to 47 full-term healthy neonates. Of these, 40 were followed and the infant characteristics questionnaire was given at four months of age. Significant correlations were revealed between the neonatal assessment items from the clusters of orientation and motor maturity and the temperament factors "fussy-difficult" and "unpredictable". Items from the cluster of autonomic stability correlated with the temperament factor "unadaptable." These correlations possibly indicate that perceived temperament does reflect intrinsic infant qualities.

Neonatal behavior of Panamanian and Israeli infants: a cross-cultural study.

The behavior of third-generation Israeli neonates belonging to two ethnic groups--Ashkenazic infants (n = 20) and Sephardic infants (n = 20)--and the behavior of a group of full-term Panamanian infants (n = 30) were compared in order to examine cross-cultural and interethnic predispositions. The Israeli and Panamanian infants differed on 5 of a total of 27 neonatal behavioral assessment items: the difference in 3 of these items, representing the autonomic stability and motor clusters, exceeded 1 scale score. A comparison of the two Israeli ethnic subgroups with the Panamanian group (Duncan's multiple-range test) revealed significant differences between Ashkenazic and Sephardic infants on 2 auditory habituation items, whereas the Panamanian infants differed significantly from both Israeli subgroups on 10 of the items, representing the motor, range of state, and autonomic stability clusters. These results corroborate previous observations concerning cross-cultural neonatal behavioral differences and the possible role of environmental factors in the ongoing modeling process of human behavioral traits and personality.

Comparison of early neonatal behavior in two Israeli ethnic groups.

A review of the literature on differences between Israeli children born to parents of North African and of European descent revealed only a few studies concerning child development. Two trends emerged: a) these developmental differences seemed to resolve gradually over time; and b) there appeared to be an early general developmental precocity in the infants of North African descent, while in later childhood, European children generally performed better in all developmental areas. The present study compared the early behavior of 40 second-generation Israeli neonates from these two ethnic groups. The results indicated a few statistically significant behavioral differences between the groups, all in favor of the North African group. The auditory habituation item was dependent on maternal education, a result which may be attributed to genetic and/or intrauterine environmental factors fostering the development of a protective mechanism in a potentially over-stimulatory future environment. The small-scale differences between the neonates of the two ethnic groups may represent the already documented tendency and gradual resolution of interethnic variations and the early North African precocity during infancy.