Anti-N-methyl-d-aspartate receptor encephalitis in Maori and Pacific Island children in New Zealand.

AIM: To investigate the incidence and severity of anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis in children from New Zealand. METHOD: A retrospective case series was undertaken of all children (≤18y) diagnosed with anti-NMDA receptor encephalitis from January 2008 to October 2015. RESULTS: Sixteen patients were identified with anti-NMDA receptor antibodies in the cerebrospinal fluid, three of whom had an associated teratoma. Fifteen children had Maori and/or Pacific Island ancestry. The incidence of anti-NMDA receptor encephalitis in Maori children was 3.4 per million children per year (95% confidence interval [CI] 1.4-7.0) and the incidence in Pacific children was 10.0 per million children per year (95% CI 4.3-19.8) compared with 0.2 per million children per year (95% CI 0.0-1.0) in children without Maori or Pacific Island ancestry. Sixty-seven per cent of children had a good outcome (modified Rankin Score ≤2) at 2 years' follow-up. This compares unfavourably with other cohorts despite a shorter median time to first-line immunotherapy (13d; range 4-89) and a higher proportion of children being treated with second-line therapy (50%). INTERPRETATION: Maori and Pacific Island children have a higher incidence of anti-NMDA receptor encephalitis and possibly a more severe phenotype. These data suggest a genetic predisposition to anti-NMDA receptor encephalitis in these populations.

Efficacy, safety and pharmacokinetics of a novel subcutaneous immunoglobulin, Evogam®, in primary immunodeficiency.

This phase III, open-label, multi-centre study investigated the efficacy, safety, pharmacokinetics and quality of life impact of Evogam(®), a new chromatographically fractionated 16% subcutaneous immunoglobulin, utilising a 1:1 dose transition ratio from previous immunoglobulin therapy. Thirty-five previously treated patients with primary immunodeficiency received weekly Evogam over 36 weeks. Primary endpoints were rate of serious bacterial infections (SBIs) and steady-state serum immunoglobulin G (IgG) trough concentrations. No SBIs were reported during the study. Evogam produced significantly higher mean trough IgG concentrations with 1:1 dose conversion compared to previous immunoglobulin treatment (8.94 versus 8.27 g/L, p = 0.0063). Evogam was efficacious in the prevention of infections and maintenance of trough levels using a 1:1 dose conversion. It was well tolerated with no withdrawals due to adverse events and was preferred to IVIg by the majority of patients.

Harmonic oscillators: the quantization of simple systems in the old quantum theory and their functional roles in biology.

This article introduces quantum physics into biology in an intuitive and non-intimidating manner. It extends the quantum aspects of harmonic oscillators, and electromagnetic fields, to their functional roles in biology. Central to this process are the De Broglie wave-particle duality equation, and the adiabatic invariant parameters, magnetic moment, angular momentum and magnetic flux, determined by Ehrenfest as imposing quantum constraints on the dynamics of charges in motion. In mechanisms designed to explain the generation of low-level light emissions in biology we have adopted a biological analog of the electrical circuitry modeled on the parallel plated capacitor, traversed by helical protein structures, capable of generating electromagnetic radiation in the optical spectral region. The charge carrier required for the emissions is an accelerating electron driven, in a cyclotron-type mechanism, by ATP-induced reverse electron transfer with the radial, emission, components, mediated by coulombic forces within the helical configurations. Adenine, an essential nucleotide constituent of DNA, was examined with its long wavelength absorption maximum determining the energetic parameters for the calculations. The calculations were made for a virtual 5-turn helix where each turn of the helix emits a different frequency, generating a biological quantum series. The components of six adiabatic invariant equations were found to be embedded in Planck's constant rendering them discrete, finite, non-random, non-statistical-Planck's constant precludes probability. A mechanism for drug-induced hallucination is described that might provide insights as to the possible role of electromagnetic fields in consciousness. Sodium acceleration through a proposed nerve membrane helical channel generated electromagnetic emissions in the microwave region in confirmation of reported microwave emission for active nerves and may explain saltatory nerve conduction. Theoretical calculations for a helical DNA system gave a conduction resistance in agreement with a experimentally determined parameter.

Diagnostic accuracy of coeliac serological tests: a prospective study.

OBJECTIVE: The best way to test serologically for coeliac disease (CD) remains controversial, with endomysial (EMA), transglutaminase (TTG), and gliadin antibodies (AGA) being assessed in various combinations with no apparent standardization. The objective of this study was to evaluate whether TTG-IgA+/-TTG-IgG could be used as a replacement for endomysial antibodies as a reliable screen for CD in patients presenting to a major Australian tertiary referral hospital for assessment of symptoms consistent with CD. METHODS: Individuals referred for gastroscopic assessment of possible CD were prospectively evaluated by duodenal biopsy assessment. The following diagnostic methods were compared: dual-isotype transglutaminase (TTG-dual), combined-isotype transglutaminase (TTG-IgA+G), TTG-IgA, combined-isotype gliadin antibodies (AGA-IgA+G), AGA-IgA, and endomysial antibody assays. Clinical performance characteristics (sensitivity, specificity, area under the curve for receiver-operating characteristic analysis; AUROC) were assessed for all kits. RESULTS: The correlation between transglutaminase kits was generally good, with the best transglutaminase kit demonstrating high correlation (r=0.86) with endomysial antibodies. A comparison of different types of endomysial antibody assays displayed variable diagnostic performance (sensitivity 61.90-68.42%; specificity 80.00-98.57%; AUROC 0.71-0.83). Sensitivity (90.48-92.31%), specificity (80.77-82.89%) and AUROC values (0.92-0.94) for dual-isotype transglutaminase kits displayed narrow ranges. AGA assays were less sensitive (AGA-IgA: 42.31-46.15%; AGA-IgG: 61.54%) and less specific (AGA-IgA: 85.09-87.73%; AGA-IgG: 82.46-84.09%). Dual-isotype transglutaminase testing was diagnostically equivalent to transglutaminase-IgA (AUROC 0.92 versus 0.91, P=0.33). CONCLUSIONS: Our study suggests that transglutaminase screening (using the IgA+/-IgG isotype) is a sensitive and specific alternative to endomysial antibody testing in the serological assessment of CD. On the basis of our findings, AGA antibody testing no longer appears to be an essential part of the diagnostic strategy for adult CD.

Hypersensitivity reactions to the polysorbate contained in recombinant erythropoietin and darbepoietin.

The following case reports are of two patients who have developed hypersensitivity reactions to the red cell growth hormones, darbepoietin and erythropoietin. The subsequent skin testing and clinical course suggested that the cause of these reactions was due to the excipient polysorbate 80. This finding might have implications in the recent increase in the incidence of pure red cell aplasia.

Consensus guidelines on anti-cardiolipin antibody testing and reporting.

UNLABELLED: Consensus guidelines on anti-cardiolipin antibody (aCL) testing have been developed to help minimise laboratory variation in the performance and reporting of aCL assays. These guidelines include minimum, optimum and optional recommendations for the following aspects of aCL testing and reporting: (1) isotype of aCL tested; (2) specimen type; (3) controls and assay precision; (4) calibrators; (5) patient samples; (6) rheumatoid factors and IgM aCL testing; (7) reporting of results; (8) cut-off values; and (9) interpretative comments. ABBREVIATIONS: aCL, anti-cardiolipin antibodies; APS, anti-phospholipid antibody syndrome; ASCIA, Australasian Society of Clinical Immunology and Allergy; ASTH, Australasian Society of Thrombosis and Haemostasis; beta2-GPI=beta2-glycoprotein I; ELISA, enzyme-linked immunosorbent assay; NCCLS, National Committee for Clinical Laboratory Standards; HSANZ, Haematology Society of Australia and New Zealand; QAP, Quality Assurance Program; RCPA, Royal College of Pathologists of Australasia; %CV, inter-assay inter-run coefficient of variation.

Antibody and genetic testing in coeliac disease.

The description of a range of antibodies associated with coeliac disease has been an important development in the ability to test for this common and treatable condition non-invasively. However, the detection of these antibodies remains unstandardised and the appreciation of the clinical utility of each is evolving. In view of the advances in the diagnosis and understanding of coeliac disease, we discuss: (1) the relative advantages, disadvantages and comparative diagnostic utility of the different antibody tests including the confounding effect of selective IgA deficiency; (2) various technical aspects of these tests; (3) HLA-DQ typing as a supplementary tool to antibody testing; (4) areas of controversy resulting from insufficient or conflicting published data; and (5) potential testing strategies.

Electromagnetic field generation by ATP-induced reverse electron transfer.

This paper describes a mechanism to explain low-level light emission in biology. A biological analog of the electrical circuitry, modeled on the parallel plate capacitor, traversed by a helical structure, required to generate electromagnetic radiation in the optical spectral range, is described. The charge carrier required for the emissions is determined to be an accelerating electron driven by an ATP-induced reverse electron transfer. The radial velocity component, the emission trajectory, of the moving charges traversing helical protein structures in a cyclotron-type mechanism is proposed to be imposed by the ferromagnetic field components of the iron in the iron-sulfur proteins. The redox systems NADH, riboflavin, and chlorophyll were examined with their long-wavelength absorption maxima determining the energetic parameters for the calculations. Potentials calculated from the axial velocity components for the riboflavin and NADH systems were found to equal the standard redox potentials of these systems as measured electrochemically and enzymatically. The mechanics for the three systems determined the magnetic moments, the angular momenta, and the orbital magnetic fluxes to be adiabatic invariant parameters. The De Broglie dual wave-particle equation, the fundamental equation of wave mechanics, and the key idea of quantum mechanics, establishes the wavelengths for accelerating electrons which, divided into a given radial velocity, gives its respective emission frequency. Electrons propelled through helical structures, traversed by biologically available electric and magnetic fields, make accessible to the internal environment the optical spectral frequency range that the solar spectrum provides to the external environment.

Mean cell volume (MCV) changes in HIV-positive patients taking nucleoside reverse transcriptase inhibitors (NRTIs): a surrogate marker for adherence.

To assess whether changes in mean cell volume (MCV) could be used as a surrogate marker of adherence, the percentage rise from the baseline MCV (%MCV rise) was compared to an independent marker of adherence, the number of days of medications dispensed in a 24-week period. Nucleoside analogues were found to differ in the extent to which they affect the MCV. The correlation between zidovudine (AZT) (30 subjects) and stavudine (D4T) (41 subjects) with adherence based on prescriptions was 0.82 (P<0.05) and 0.55 respectively (P<0.05). When adherence was categorized into 10% intervals, there was a progressive rise in the average MCV with increasing adherence that plateaus at 70% adherence. Plotting %MCV rise on time charts appears to detect those subjects with adherence of less than 70%. In conclusion, changes in MCV for HIV-positive patients taking either AZT or D4T may be a useful surrogate marker for adherence to anti-retroviral medications.