Evidence of a reduced role for circumscribed interests in the social attention patterns of children with Autism Spectrum Disorder.

Reduced social attention is characteristic of Autism Spectrum Disorder (ASD). It has been suggested to result from an early onset and excessive influence of circumscribed interests (CIs) on gaze behaviour, compared to typically developing (TYP) individuals. To date, these findings have been mixed. The current eye-tracking study utilised a visual preference paradigm to investigate the influence of CI versus non-CI objects on attention patterns in children with ASD (aged 3-12 years, n = 37) and their age-matched TYP peers (n = 30). Compared to TYP, social and object attention was reduced in the ASD group irrespective of the presence of CIs. Results suggest a reduced role for CIs and extend recent evidence of atypical attention patterns across social and non-social domains in ASD.

A transdiagnostic examination of anxiety and stress on executive function outcomes in disorders with social impairment.

BACKGROUND: Executive function (EF) difficulties characterise a number of psychiatric conditions and EF impairment may be a predisposing factor and/or consequence of anxiety and stress. The aim of the study was to examine EF factors in a mixed clinical cohort (Autism Spectrum Disorder and Social Anxiety Disorder) characterised by social impairment and investigate the influence of trait anxiety and state-based depression, anxiety and stress. METHODS: In Study 1, a factor analysis identified EF and non-EF latent factor structures (N=205). In Study 2, (N=137) multiple regression analyses investigated the association between trait anxiety and state based depression, anxiety and stress, on EF and non-EF cognitive domains and on the two composite indices of the Behavioural Rating Inventory of Executive Function (BRIEF). RESULTS: Trait anxiety was associated with better performance on neuropsychological measures of EF while state-based stress was associated with lower EF performance. A dissociation was observed between trait anxiety and state stress on the two behavioural indices of the BRIEF. Depression, anxiety and stress did not predict performance on non-EF cognitive domains. LIMITATIONS: The cross-sectional design precludes cause-effect conclusions, further only self-report measures of affect were utilised and our performance measures of EF did not include a working memory test. CONCLUSIONS: The results demonstrate that trait anxiety and state-based stress influence EF processes across disorders with social impairment. The transdiagnostic efficacy of this finding can facilitate remediation strategies, it may also contribute to individuals with Autism Spectrum Disorder gaining better access to mental health services.

Autism, early psychosis, and social anxiety disorder: understanding the role of social cognition and its relationship to disability in young adults with disorders characterized by social impairments.

Impairments in social cognition are believed contribute to disability, particularly for disorders characterized by difficulties in social interaction. There has been little transdiagnostic investigation of this across social cognition domains in young adults. A total of 199 young adults diagnosed with autism spectrum disorder (ASD; N = 53), early psychosis (EP; N = 51), and social anxiety disorder (SAD; N = 64) were compared against neurotypical controls (NT; N = 31) on a battery of lower and higher-order and self-report social cognition measures. For both ASD and EP, participants showed impaired performance on all lower-order emotion recognition tasks and one higher-order social cognition test. Self-reports of empathy were reduced in all clinical groups and particularly in ASD. For SAD, despite showing no objective social cognition impairment, self-reported empathy was reduced to the same level as EP. Discriminant analysis revealed that self-reported empathy and lower-order emotion recognition tests provide best capacity to differentiate groups. Regressions predicting disability revealed depression as the strongest predictor across all disability measures. Empathy provided additional predictive value for social disability and social interaction anxiety. Overall, results support a similar social-cognitive development profile across ASD and EP. While self-reported empathy differentiated between groups, discrepancy between objective social cognition test performance and self-reported empathy in the SAD group suggests probable threat-related self-monitoring report biases that likely further influence all group outcomes. As depression and empathy were the most important predictors of disability, regardless of diagnostic group, research is required to explore targeted interventions for difficulties in these domains to reduce disability.

Utilization of herpes simplex PCR assays for cerebrospinal fluid in a pediatric health care setting.

An assessment was made of the utilization and impact of a diagnostic polymerase chain reaction (PCR) assay for the diagnosis of herpes simplex viruses (HSV) 1 and 2 in cerebrospinal fluid of children who attended a Canadian pediatric referral centre. One hundred and three assays were performed on specimens from 103 patients during the period August 1997 to September 1998. Patient ages ranged from newborn to 16 years. Indications for HSV PCR included seizures with or without fever (56.3%), aseptic meningitis (16.5%), and encephalopathy with or without fever (10.7%). Only 2 of 103 (1.9%) assays were positive, including one each for HSV1 and HSV2. Control specimens that were seeded with virus indicated inhibition for 24.3, 8.8, and 6.8% of assays for HSV1, HSV2, and both HSV1 and HSV2, respectively. The mean turn-around time for HSV PCR was 2.5 days, and 90.3% were completed in less than 5 days. Acyclovir was administered to 78.6% of the patients overall; the results of the HSV PCR impacted on the treatment courses for 36 individuals. Nevertheless, 16.5% of patients continued to receive extended courses of antiviral therapy despite negative HSV PCR assays. Although it is desirable to decrease the frequency of PCR inhibitions and to further decrease the interval to assay completion, HSV PCR does have a significant impact on antiviral use in this setting.

Postpericardiotomy syndrome: no evidence for a viral etiology.

BACKGROUND: Postpericardiotomy syndrome has been considered a disorder induced by viral infection. This conclusion is based on serologic criterions, but these may be unreliable following either cardiopulmonary bypass or transfusion therapy. Previous studies have not verified the proposed etiology either by isolation of viruses, or by detection of their genome. We sought, therefore, to clarify the role, if any, of viruses in this syndrome. METHODS AND RESULTS: We studied prospectively 149 children aged from 6 months to 16 years who were undergoing open heart surgery. Blood samples were collected from all prior to operation, and again 7 to 10 days post-operatively, and 47 were sampled at the time of development of symptoms of pericardial involvement. Serums were analyzed for the presence of IgM and IgG antibodies to cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. The polymerase chain reaction was used for amplification when assessing the genome of the enteroviruses. Cultures for viruses were established on samples of stool, urine, and throat swabs collected 7 days post-operatively, and at the time of postpericardial symptoms. Pericardial fluid obtained from 5 patients with the syndrome was cultured for viruses, and tested for enterovirus genome. On the basis of clinical and echocardiographic findings, 34 children were determined to have definite evidence of the syndrome, 13 were considered to have possible evidence, and the results from these patients were compared to those from patients with no pericardial symptoms, the latter being matched for age and transfusion status. We isolated viruses from one or more sites in five patients with definite evidence (16%), from one (9%) of those with possible evidence, and from seven (19%) of the controls. All serums and pericardial samples were negative for enterovirus genome. IgM antibodies were found in only 5 patients, three with symptoms of pericardial involvement and two without. Rates of seroconversion to IgG for the viruses were lower in the patients with symptoms of pericardial involvement compared to controls, but were strongly influenced by transfusion status. CONCLUSION: Our study has provided no evidence to support a viral etiology for the postpericardiotomy syndrome.

Differences in resistance to herpes simplex virus type 1 (HSV-1) among oligodendroglia derived from different strains of mice are determined after viral adsorption but prior to the expression of immediate early (IE) genes.

The nature of an innate cellular resistance to HSV-1 of cultured murine oligodendrocytes (OLs) in three strains of mice (C57BL/6J, Balb/cByJ and A/J) was investigated. The expression of immediate early (ICP4), early (ICP8) and late (gC) antigens in primary OL cultures was studied using an indirect immunofluorescence (IF) technique. HSV-1 infected OLs from C57BL/6J mice showed no viral antigens at 24 h post infection (p.i.) but rather a marked delay in antigen expression beginning at 60 h p.i. In contrast all three proteins were expressed in A/J OLs at 24 h p.i. while Balb/cByJ OLs showed an intermediate protein expression pattern. These results suggest that the innate cellular resistance to HSV-1 is determined prior to the expression of immediate early viral antigens. To further study these differences, the adsorption capacity between the three mouse strains was compared using dextran purified, [3H]thymidine labelled virus. No differences in HSV-1 adsorption were identified. Results from viral penetration studies approached statistical significance suggesting that penetration may be impaired in C57BL/6J and Balb/cByJ OLs when compared to A/J OLs and is likely fusion independent. The selective differences in HSV-1 resistance mediated by OLs, reflect differences in virus host cell interactions, that likely contribute to differences in mortality, viral spread, and the ability of virus to induce central nervous system (CNS) demyelination.

Basal ganglia infarction associated with HHV-6 infection.

A 6 year old boy presented with meningoencephalitis and was found to have serological evidence of acute human herpes virus-6 (HHV-6) infection. He did not develop symptomatic seizures or the rash of exanthum subitum (roseola). His course was marked by severe spastic quadriparesis associated with radiological evidence of basal ganglia infarction. HHV-6 infection should be considered in any child with acute meningoencephalitis.

Diagnosis of viral respiratory tract infections in children by using a reverse transcription-PCR panel.

Reverse transcription-PCR (RT-PCR) is a sensitive method for detection of RNA virus nucleic acid sequences in clinical respiratory specimens. Previous studies have focused on RT-PCR for a single virus, but this approach is limited by the inability to establish a specific etiology when the RT-PCR result is negative and by the inability to document simultaneous infections involving more than one virus. The purpose of this study was to apply a panel of RT-PCR protocols for respiratory syncytial virus, parainfluenza virus, and picornaviruses to respiratory specimens from 80 children suspected to have acute viral respiratory tract infections and to correlate RT-PCR results with viral culture results and clinical diagnosis. In comparison with viral culture, the RT-PCR panel had a sensitivity of over 94% and showed evidence of simultaneous infections in a significantly greater proportion of specimens (20.0% versus 3.8%; P < 0.002). For specimens in which no viruses were detected by culture, the proportion of specimens with positive picornavirus RT-PCR results was significantly greater than the proportion of specimens with positive respiratory syncytial virus or parainfluenza virus RT-PCR results (P < 0.001). There were no statistically significant associations between RT-PCR results and clinical diagnosis. In summary, the RT-PCR panel provides an improved approach to obtain new insights into acute viral respiratory tract infections in children.

Occurrence of chickenpox during pregnancy in women seropositive for varicella-zoster virus.

In a group of 21 women counseled after exposure to chickenpox during pregnancy, 4 developed varicella despite initial studies showing that preinfection sera were varicella-zoster virus (VZV)-seropositive by fluorescent anti-membrane antibody, latex agglutination, ELISA, and VZV glycoprotein immunoblot assay. Further investigations showed that 2 of the 4 had low-titer (1/100), low-avidity, VZV-reactive IgG3 antibodies by ELISAs of preinfection sera. After chickenpox, these women developed primary-like serologic responses to VZV. Two women with high-titer (1/1600, 1/3200), high-avidity, IgG1 antibodies showed anamnestic serologic responses after reinfection. The criteria of protective VZV immunity remain ill-defined.

Acute encephalopathy and status epilepticus associated with human herpes virus 6 infection.

A previously healthy 22-month-old boy presented in status epilepticus with high fever. He was comatose, with upper respiratory-tract infection. The seizures responded to anticonvulsant therapy. The boy's temperature returned to normal within 24 hours and he recovered slowly from his encephalopathy. On the third hospital day, he exhibited the characteristic rash of reseola infantum. Acute infection with human herpes virus 6 (HHV-6) was established serologically by enzyme immunoassay. HHV-6 DNA was not detected by polymerase chain reaction in CSF or serum at the onset of illness, but was found three months later in the child's saliva. The pathogenesis of the patient's encephalopathy is discussed. It is concluded that HHV-6 infection should be considered in infants and young children with febrile status epilepticus.

The utility of latex agglutination assays in the diagnosis of pediatric viral gastroenteritis.

To design a rapid and efficient protocol for processing pediatric stool specimens, the authors used 434 specimens to evaluate two commercial latex assays to detect rotavirus (Meritec-Rotavirus and Rotalex) and one to detect adenovirus (Adenolex). Rotavirus latex assay results were compared with electron microscopic examination and adenovirus latex assay results with virus culture. Ninety-two specimens (21%) were positive for rotavirus and 28 (6.5%) for adenovirus; 5 (1%) had both viruses. The sensitivity, specificity, positive predictive values, and negative predictive values for the three assays were, respectively, as follows: Meritec-Rotavirus (97%, 99%, 97%, 99%), Rotalex (91%, 99%, 94%, 98%), and Adenolex (46%, 99%, 77%, 97%). For primary rotavirus screening, the Meritec-Rotavirus and Rotalex latex assays offer a good alternative to electron microscopic examination. For primary adenovirus screening, the low sensitivity of the Adenolex latex assay precludes its use as a routine screen. Its excellent specificity, however, makes it a useful tool for culture confirmation.

Contrasting effects of immunosuppression on herpes simplex virus type I (HSV I) induced central nervous system (CNS) demyelination in mice.

We previously reported that lip inoculation of Herpes simplex virus type I (HSV I) in specific strains of mice would induce multifocal brain demyelination (MBD). The mechanisms mediating the development of MBD are unknown. In this study, five inbred strains of mice (C57BL/6J, Balb/cByJ, A/J, SJL/J, PL/J) immunosuppressed with either irradiation (IR), cyclophosphamide (CY), or cyclosporin A (CP) along with three immune deficient strains (C57BL/6J nu/nu, Balb/cByJ nu/nu, C57BL/6J bg/bg) were lip inoculated with HSV I to determine the effect of immunosuppression on viral spread throughout the brain and the development of demyelination during the acute stage of infection. Mortality increased in all groups when compared with controls but was greatest in A/J, SJL/J, and PL/J strains, where all mice died before day 6 PI. In contrast with immunocompetent C57BL/6J mice where virus is restricted to the brainstem, virus spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, and C57BL/6J bg/bg mice. Despite viral spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, Balb/cByJ and Balb/cByJ nu/nu mice, MBD did not develop. MBD did develop however, in both HSV I infected C57BL/6J bg/bg and CP treated Balb/cByJ mice. Immunosuppression of HSV I infected Balb/cByJ mice prevents the development of demyelination at the trigeminal root entry zone (TREZ) of the brainstem while in Balb/cByJ nu/nu mice, the extent of demyelination at TREZ was reduced and delayed when compared with immunocompetent controls. These results suggest that the immune system plays an important role in limiting viral spread in the brain as well as in the development of demyelination at TREZ and of MBD throughout the brain during the acute phase of infection. Virus alone does not induce MBD in this animal model of virus induced CNS demyelination but is a prerequisite for its development.

Reye syndrome associated with subclinical varicella zoster virus and influenza A infection.

An association is reported between Reye syndrome and varicella zoster virus (VZV) infection in a 10-year-old boy who had serologic evidence of coinfection with VZV and influenza A H3N2, and exposure to salicylates. He developed VZV reinfection without skin lesions after family exposure and influenza A was community-acquired. Recent chickenpox contact should initiate VZV serologic studies in Reye syndrome patients, regardless of the chickenpox history or evidence of infection with other viruses.

Herpes simplex virus type I (HSV I)-induced multifocal central nervous system (CNS) demyelination in mice.

Multifocal central nervous system (CNS) demyelination develops in the brains of SJL/J, PL/J, and A/J mice following lip inoculation with a specific strain of herpes simplex virus I (HSV I). The lesions in all three inbred strains of mice share similar characteristics including demyelination, relative preservation of axons, and a mononuclear cell (MNC) infiltrate. The lesions, developing during the early phase of demyelination, also appear sequentially in the CNS (trigeminal root entry zone of the brainstem greater than cerebellum greater than cerebral hemispheres) of all three strains of mice but differ in the time of their initial appearance following infection as well as their morphology. In SJL/J mice, new areas of demyelination are observed for only 24 days following lip inoculation with virus. Late stage multifocal CNS demyelination persists throughout 28 weeks postinoculation (pi) in PL/J mice while in A/J mice the development of new areas of demyelination are restricted to 8 weeks pi. Although mononuclear inflammatory cells are present in the new areas of demyelination in either PL/J or A/J mice, viral antigens are not detected in the CNS beyond 12 days pi. In contrast, in situ hybridization studies using 35S-cDNA HSV probes and performed beyond day 12 pi identify probe-positive cells central to a number of the multifocal CNS demyelinating lesions in A/J mice. Results from studies with inbred and congenic strains of mice indicate that the major histocompatibility complex (H-2) does not determine the development of multifocal CNS demyelination following lip inoculation with HSV I but does influence the morphological appearance of the lesions that do develop.

Comparison of urea treatment with established methods of sorghum grain preservation and processing on site and extent of starch digestion by cattle.

To determine the effect of dry (D); reconstituted and ensiled (R); reconstituted and acid-treated (A); and urea-treated, high-moisture (U) sorghum grain on starch digestibility, four Angus x Hereford steers (means BW = 350 kg) with duodenal and ileal cannulas were used in a 4 x 4 Latin square design. Diets consisting of 69% ground sorghum grain were fed every 2 h in equal portions (8.2 kg/d). Diets averaged 46.5% starch and 12% CP, except for U, which averaged 14% CP due to urea treatment. Ytterbium attached to sorghum was used as a particulate marker. Duodenal, ileal, and fecal samples were taken 1 h postfeeding after a 14-d adaption to diets. Whole samples were analyzed. Preduodenal starch digestion (%) was 89, 83, 76, and 70, and starch digestion over the total tract was 99, 97, 95 and 91 for R, U, A, and D, respectively. Starch digestion proximal to each site (duodenum and ileum) was enhanced (P less than .05) by R and U compared with D. Within the small intestine, there was a linear relationship (P less than .003) between starch digestion and daily starch supply. However, digestibility of starch in the small intestine (mean = 45%) was not different among diets. Apparent digestibility of starch in the large intestine was not significantly different from digestibility in the small intestine. Urea-treated sorghum grain was equivalent to reconstituted, ensiled sorghum in digestion characteristics and was superior to dry sorghum.

Epstein-Barr virus shedding in breast milk.

One hundred healthy women already donating to the Children's Hospital Breast Milk bank consented to provide a sample of breast milk for this study. Using a DNA-DNA hybridization dot-blot assay Epstein-Barr virus (EBV) genome (Bam HIW region) was detected in cells shed into breast milk of 46 out of 100 women studied and in 60 out of 132 (46%) of samples donated overall. The prevalence of EBV shedding increased postnatally to a peak of 74% (26/35 positive samples) between 3 and 12 weeks postdelivery. Women delivering prematurely had an initially lower prevalence of shedding with only six out of 30 (20%) positive samples in the first week after delivery, compared to 16 out of 35 (46%) for women delivering at term. Of the 18 women donating more than one sample, 13 showed consistently positive (n = 8) or negative (n = 5) results, and the remaining five had intermittent shedding detected. Only seven out of 42 (17%) breast milk samples studied were EBV-IgG antibody positive, and none showed IgM or IgA-EBV antibodies. Further studies and prospective followup of infants are needed to confirm that breast milk is a significant source for early EBV infection of infants, as indicated by serologic studies.

Variation in resistance to herpes simplex virus type 1 of oligodendrocytes derived from inbred strains of mice.

Primary oligodendrocyte (OL) cultures from three inbred strains of mice with known differences in resistance to herpes simplex virus type 1 (HSV-1) infection in vivo (A/J, susceptible; BALB/cByJ, moderately resistant; C57BL/6J, resistant), also display a similar pattern of resistance in vitro. The nature of the in vitro resistance at the cellular level was investigated. Virus production at different m.o.i.s indicated that the differences in HSV-1 replication are m.o.i.-dependent. Overall, virus yield from the OL cultures infected at a multiplicity of 1 increased 48 h post-infection (p.i.); no additional enhancement occurred 72 h p.i. However, the difference in the replication capacity of the three OL cultures observed at 24 h p.i. persisted at 48 and 72 h p.i. Serial electron microscopy studies on infected OL cultures derived from the different murine strains suggested that the resistance to HSV-1 infection occurs at different stages during the replicative cycle. Virus was detected at the nuclear membrane 5 min p.i. in A/J cells, but was not observed until 120 min p.i. in BALB/cByJ cells, whereas virus could not be detected at the nuclear membrane of C57BL/6J cells, even at 24 h p.i. Virus adsorption, determined by assay of residual non-adsorbed virus infectivity and cell-associated, radiolabelled HSV-1, did not differ in the OL cultures. The cumulative data suggest that A/J cells display the same replication pattern as permissive CV-1 cells, whereas the major replicative blocks in the other two murine strains occur at the level of the cytoplasmic membrane in C57BL/6J OLs, and at the level of the nuclear membrane in BALB/cByJ cells.

Recurrent varicella-zoster virus infections in apparently immunocompetent children.

Fourteen generally healthy children (5 females, 9 males, ages 18 months to 13 years) who have developed 2 to 5 attacks of chickenpox are described. Herpes zoster also occurred in 2 of 14 children. No case of chickenpox was severe or associated with complications. General studies of immunoglobulins, specific antibodies to immunization agents, complement and lymphocyte subpopulation number and function indicated that 1 of 14 had low serum IgA and 3 of 14 lacked antibody to 1 (n = 2) or 2 (n = 1) immunization agents. Varicella-zoster virus (VZV)-specific immune studies showed that the children developed VZV-antibody titers by enzyme-linked immunosorbent assay of 1:640 to 1:10 240. By immunoblot assay all appeared to develop a normal spectrum of antibodies to individual VZV proteins. All but one developed VZV cellular immune responses with stimulation indices ranging from 3.6 to 174. Sequential follow-up of 8 patients revealed 1 who became seronegative and 2 who lost VZV cell-mediated immune responses. Chickenpox may recur more frequently than is generally recognized. General and VZV-specific immune investigations are unlikely to indicate a reason.

Comparison of two rapid methods for detection of respiratory syncytial virus (RSV) (Testpack RSV and ortho RSV ELISA) with direct immunofluorescence and virus isolation for the diagnosis of pediatric RSV infection.

The ability of two commercial immunoassays to detect respiratory syncytial virus (RSV) in respiratory specimens was evaluated as follows: 152 specimens were tested by TestPack RSV (Abbott), and 72 were tested by Ortho RSV ELISA (Ortho). Test outcomes were compared with those of virus isolation alone, direct immunofluorescence assay (DFA) alone, or virus isolation and/or DFA. TestPack RSV versus virus isolation showed 91% sensitivity, 96% specificity, 93% positive predictive value (PPV), and 95% negative predictive value (NPV). TestPack RSV versus DFA showed 89% sensitivity, 97% specificity, 96% PPV, and 93% NPV. When TestPack RSV performance was compared with that of virus isolation and DFA, the sensitivity was 87% and the specificity was 100%. Ortho RSV ELISA versus virus isolation showed 88% sensitivity, 87% specificity, 79% PPV, and 93% NPV. Ortho RSV ELISA versus DFA showed 91% sensitivity, 88% specificity, 81% PPV and 95% NPV. When Ortho RSV ELISA performance was compared with that of virus isolation and DFA, the sensitivity was 86%, the specificity was 89%, the PPV was 86%, and the NPV was 89%. The accuracy of the TestPack RSV in combination with ease of performance and no need for specialized equipment or special skills make it an attractive alternative to DFA for rapid direct detection of RSV.