Serum IGFBP-2 levels are associated with reduced insulin sensitivity in obese children.

Insulin-like growth factor binding protein 2 (IGFBP-2) may represent a critical link between body composition and insulin sensitivity. We investigated the relationship between circulating IGFBP-2 levels, body composition, insulin sensitivity, energy intake and physical activity in children with obesity. Children were recruited via the Weight Management Service at the Royal Children's Hospital, Melbourne, as part of the Childhood Overweight BioRepository of Australia (COBRA). Comprehensive anthropometric, biochemical and environmental data were collected and compared to serum IGFBP-2 levels (measured by enzyme-linked immunosorbent assay). Multiple regression modelling was used to assess the influence of circulating IGFBP-2 levels on anthropometric and biochemical measures. One hundred and ninety-four children were included in this study (46% male). Circulating IGFBP-2 negatively correlated with age, anthropometric measures, blood pressure and insulin concentration. Positive associations were observed between insulin sensitivity index-homeostasis model assessment (ISI-HOMA) and serum IGFBP-2. In multiple regression modelling, IGFBP-2 significantly contributes to variance in systolic blood pressure (-19%, P < 0.05), circulating triglycerides (-16%, P < 0.05) and ISI-HOMA (18%, P < 0.05). No associations were observed between dietary energy intake or physical activity and IGFBP-2 levels. Circulating IGFBP-2 levels in children with obesity correlate inversely with body mass and markers of metabolic dysfunction, and positively with insulin sensitivity. These findings suggest that reduced levels of IGFBP-2 may play an important role in the pathogenesis of obesity complications in early life.

Subjective and Objective Numerical Outcome Measure Assessment (SONOMA). A combined outcome measure tool: findings on a study of reliability.

OBJECTIVE: To determine the reliability of a combined tool, namely that of Subjective and Objective Numerical Outcome Measure Assessment (SONOMA). METHODS: Testing was conducted, limited to patients with neck, midback, or lower back pain, with or without radiculopathy, in an outpatient chiropractic office setting. Test-retest reliability of the objective analysis of SONOMA was carried out on the same day (n = 50) with an interval time period of less than 60 minutes. Between-day reliability of the subjective analysis of SONOMA was carried out with an interval time period of 24 hours (n = 50). Individual and combined parameter reliability was established for the tool. RESULTS: Short-term objective and between-day subjective reliability coefficients were high. The Pearson correlation coefficient for the combined tool was .96, and the coefficient for the individual parameters ranged from .55 through .93. All these correlations were statistically significant, with a P value not more than .0001. CONCLUSIONS: The SONOMA combined numerical outcome measure tool demonstrated a high degree of reliability. This outcome tool measures directly and therefore reflects patient pain perception, functional status, and provider-driven objective assessment. We believe this tool provides the unique combination of both subjective and objective functional capacity assessment. It should be valuable for day-to-day practical application, as well as considered for future clinical trials and quality-of-care studies. This combined tool shows promise as having a high degree of reliability and, hence, may demonstrate a comprehensive representation of the patient-clinical picture, particularly in regard to functional capacity assessment.

Molecular characterization of the polymerase gene and genomic termini of Nipah virus.

In 1998, Nipah virus (NV) emerged in peninsular Malaysia, causing fatal encephalitis in humans and a respiratory disease in swine. NV is most closely related to Hendra virus (HV), a paramyxovirus that was identified in Australia in 1994, and it has been proposed that HV and NV represent a new genus within the family Paramyxoviridae. This report describes the analysis of the sequences of the polymerase gene (L) and genomic termini of NV as well as a comparison of the full-length, genomic sequences of HV and NV. The L gene of NV is predicted to be 2244 amino acids in size and contains the six domains found within the L proteins of all nonsegmented, negative-stranded (NNS) RNA viruses. However, the GDNQ motif found in most NNS RNA viruses was replaced by GDNE in both NV and HV. The 3' and 5' termini of the NV genome are nearly identical to the genomic termini of HV and share sequence homology with the genomic termini of other members of the subfamily Paramyxovirinae. At 18,246 nucleotides, the genome of NV is 12 nucleotides longer than the genome of HV and they have the largest genomes within the family Paramyxoviridae. The comparison of the structures of the genomes of HV and NV is now complete and this information will help to establish the taxonomic position of these novel viruses within the family Paramyxoviridae.

Molecular biology of Hendra and Nipah viruses.

The structure and genetic organization of Hendra and Nipah viruses places them in the subfamily Paramyxovirinae. However, low homology with other subfamily members and several novel biological and molecular features such as genome length and F(0 )cleavage site suggest classification in a new genus within the Paramyxovirinae.

Molecular characterization of Nipah virus, a newly emergent paramyxovirus.

Recently, a new paramyxovirus, now known as Nipah virus (NV), emerged in Malaysia and Singapore, causing fatal encephalitis in humans and a respiratory syndrome in pigs. Initial studies had indicated that NV is antigenically and genetically related to Hendra virus (HV). We generated the sequences of the N, P/C/V, M, F, and G genes of NV and compared these sequences with those of HV and other members of the family Paramyxoviridae. The intergenic regions of NV were identical to those of HV, and the gene start and stop sequences of NV were nearly identical to those of HV. The open reading frames (ORFs) for the V and C proteins within the P gene were found in NV, but the ORF encoding a potential short basic protein found in the P gene of HV was not conserved in NV. The N, P, C, V, M, F, and G ORFs in NV have nucleotide homologies ranging from 88% to 70% and predicted amino acid homologies ranging from 92% to 67% in comparison with HV. The predicted fusion cleavage sequence of the F protein of NV had a single amino acid substitution (K to R) in comparison with HV. Phylogenetic analysis demonstrated that although HV and NV are closely related, they are clearly distinct from any of the established genera within the Paramyxoviridae and should be considered a new genus.

Nipah virus: a recently emergent deadly paramyxovirus.

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Ebola virus selectively inhibits responses to interferons, but not to interleukin-1beta, in endothelial cells.

Ebola virus infection is highly lethal and leads to severe immunosuppression. In this study, we demonstrate that infection of human umbilical vein endothelial cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expression of the major histocompatibility complex class I (MHC I) family of proteins and inhibited the induction of multiple genes by alpha interferon (IFN-alpha) and IFN-gamma, including those coding for MHC I proteins, 2'-5' oligoadenylate synthetase [2'-5'(A)N], and IFN regulatory factor 1 (IRF-1). Induction of interleukin-6 (IL-6) and ICAM-1 by IL-1beta was not suppressed by infection with EZ, suggesting that the inhibition of IFN signaling is specific. Gel shift analysis demonstrated that infection with EZ blocked the induction by IFNs of nuclear proteins that bind to IFN-stimulated response elements, gamma activation sequences, and IFN regulatory factor binding site (IRF-E). In contrast, infection with EZ did not block activation of the transcription factor NF-kappaB by IL-1beta. The events that lead to the blockage of IFN signaling may be critical for Ebola virus-induced immunosuppression and would play a role in the pathogenesis of Ebola virus infection.

Induction of intercellular adhesion molecule 1 gene expression by measles virus in human umbilical vein endothelial cells.

The expression of intercellular adhesion molecule 1 (ICAM-1) by endothelial cells is important for the regulation of adhesion and transendothelial migration of a variety of leukocytes that express the integrins lymphocyte function-associated antigen 1 (LFA-1) and/or Mac-1. Here, we demonstrate strain-specific differences in the ability of measles virus (MV) to induce ICAM-1 expression. The vaccine strain Moraten (Mor) rapidly induced high levels of ICAM-1 mRNA and protein expression, whereas the vaccine strain CAM-70 and the Edmonston wild type (Ed-wt) strain were far less effective, even when they were used at very high multiplicities of infection (MOIs). Strain-specific differences in the induction were not a consequence of differences in the ability to infect ECs. Furthermore, induction of ICAM-1 by Mor was not dependent on de novo expression of MV or cellular proteins. Dual-immunofluorescence analysis indicated that there was no association between the expression of either MV nucleocapsid or hemagglutinin protein and the induction of ICAM-1 expression. Some human umbilical vein endothelial cells (HUVECs) that expressed high nucleocapsid protein in response to either Mor or CAM-70 failed to express elevated ICAM-1, whereas some HUVECs that were incubated with Mor expressed high ICAM-1 prior to expression of MV nucleocapsid protein. Strain-specific differences in the ability of Mor and CAM-70 to induce ICAM-1 correlated with their ability to activate the latent transcription factor NF-kappaB. These studies suggest a preexisting component of MV particles that leads to strain-specific differences in the activation of NF-kappaB and the induction of ICAM-1 gene expression.

Ebola virus inhibits induction of genes by double-stranded RNA in endothelial cells.

Fatal cases of filoviral infection are accompanied by a marked immunosuppression. Endothelial cells play a vital role in the host immune response through the expression of several immunomodulatory genes in addition to the expression of the antiviral genes, 2',5'-oligoadenylate synthetase [2'-5'(A)N], and the double-stranded RNA (dsRNA)-activated protein kinase (PKR). dsRNA, an intermediate generated during viral replication and gene transcription of many viruses, leads to the induction of immunomodulatory genes in endothelial cells. In this report, we show that induction of the major histocompatibility complex class I family of genes, 2'-5'(A)N, interleukin-6 (IL-6), PKR, interferon (IFN)-regulatory factor-1, and intercellular adhesion molecule-1 (ICAM-1) by dsRNA in human umbilical vein endothelial cells is suppressed by infection with the filovirus Ebola-Zaire (EZ). In contrast, induction of IL-6 and ICAM-1 by IL-1 is intact in EZ-infected cells. Gel shift analysis demonstrates that dsRNA-induced protein binding to IFN-responsive elements is strongly suppressed by EZ-IFN, whereas NF-kappa B activation by dsRNA remains intact. We previously reported that IFN signaling is suppressed by EZ infection, and these data strongly suggest that elements shared between IFN and dsRNA signaling are being inhibited by EZ. Inhibition of IFN and dsRNA responsiveness could play a role in the immunosuppression seen in EZ infections and would play a role in the pathogenesis of disease caused by EZ.

Psychosocial aspects of chronic lower leg ulceration in the elderly.

The perceived health of a group of elderly people with chronic lower leg ulceration was compared with health perceptions of a matched group of controls. The perceived psychological well-being, self-esteem, life satisfaction, and social supports of the two groups were also compared. The people with leg ulceration described significantly more problems with activity and mobility, pain, and health worries and concerns than the control group. The groups did not differ significantly in their general evaluations of their health status, the experience of physical symptoms, or the numbers of diagnosed medical problems present. The leg ulcer group reported significantly lower levels of self-esteem and higher levels of negative affect, but the groups did not differ significantly on the other psychological variables. Leg ulcers are a serious problem for those affected by them, and health care providers need to be more informed about the effect of chronic health problems on elderly persons.

Occipitalization of the atlas.

This paper discusses occipitalization of the atlas and its relationship to the chiropractic practitioner. Patients commonly consult a chiropractor with complaint of headache, suboccipital stiffness, restricted motion, dizziness and other symptoms related to the upper cervical region. Differential diagnosis of the exact etiological factor of these symptoms must be made via a thorough history, physical examination, and roentgenological examination. If occipitalization of the atlas is detected on the initial roentgenological examination, then follow-up magnetic resonance imaging, computerized tomography or linear tomographic studies may be warranted to rule out concomitant diverse osseous and/or neural anomalous conditions of the cervical spine which may easily mimic symptoms of disorders commonly treated by the chiropractic practitioner. The chiropractic practitioner must obtain appropriate roentgenological and other diagnostic imaging studies to ensure proper evaluation of the structural integrity of the cervical spine before appropriate treatment can be rendered.

Survival of patients following second eye cataract extraction.

One hundred and seventy-seven patients aged 65 years or older were studied retrospectively following second eye cataract extraction, having already had successful surgery to their first eye. The period of follow up was 5 to 13.5 years and during this period 109 (62 per cent) patients had died. Analysis of the data showed being male was the only risk factor influencing survival, with female patients living significantly longer. The five year survival of the 60 male patients was 47 per cent while that of 117 female patients was 75 per cent. The figures reflect the shorter life expectancy of males found in the general population and also support the hypothesis that the development of cataract reflects an ageing process in the patient as a whole.

Superior oblique muscle surgery.

The anatomy and actions of the superior oblique muscle are discussed as a basis for logical surgical procedures. Weakening procedures are indicated for overaction or for a short superior oblique tendon. Tenectomy is performed nasal to the superior rectus while selective tenotomies for bilateral overaction are performed temporal to the superior rectus. Recession of the whole tendon on an adjustable suture is preferred for unilateral superior oblique overaction. Tendon tucking for unilateral superior oblique palsy is performed temporal to the superior rectus and inevitably causes a degree of pseudo-Brown's syndrome. Tucks may be used bilaterally in bilateral cases. Alternatively, anterior tendon advancement corrects tensional symptoms. It may be graded from a maximum advancement to the upper border of the lateral rectus to suit the degree of tension. Adjustable sutures may be used. Superior oblique tendon transfer for long-standing third nerve palsies may produce paradoxical eye movements in the long-term due to scarring.

Cataract surgery in childhood.

A simple aspiration technique with maintenance of the anterior chamber in a "closed" system by simultaneous introduction of isotonic fluid is preferred when the lens is soft and easily broken up. Otherwise the lens needs to be fragmented, and this can be achieved either by ultrasonic probe or by some type of lensectomy machine.

Natural history and associations of dissociated vertical divergence.

One hundred patients with dissociated vertical divergence (DVD) have been followed up for an average of 7.3 years. In contrast to some other reports, none of them has worthwhile binocular vision. There has been a constant association with nystagmus, often manifest, and the DVD has always been noted later than the nystagmus. In no case has the degree of DVD decreased significantly with age. The dissociation has only rarely caused a serious cosmetic problem, and then it has been markedly asymmetrical and has been improved by combined superior rectus recession and Faden procedure. DVD can simulate inferior oblique overactions, but is more commonly associated with an A phenomenon, and can be distinguished by careful cover/uncover testing. The common occurrence of associated congenital defects, especially of the central nervous system, is noted.