Dystrophia myotonica: combined spinal-epidural anaesthesia for caesarean section

Patients with dystrophia myotonica requiring caesarean section pose significant problems for the anaesthetist. This report describes the successful use of a combined spinal-epidural technique for anaesthesia and postoperative analgesia in such a patient.     

A method for the construction of disposable cylindrical diffusing fibre optic tips for use in photodynamic therapy

A simple method for the manufacture of disposable, cylindrical, diffusing fibre tips is described. The method is suitable for plastic clad silica fibres with core diameters in the range 200–600m. Light diffusing tips up to 40 mm in length have been constructed. The method is highly reproducible, construction is typically less than five minutes and the financial cost is negligible. The diffusers are highly efficient, delivering an amount of light at least equal to that transmitted by a plane cut fibre of the same core diameter. The uniformity of light emission along the diffuser can be modified to meet the requirements of any given treatment. The diffusers have been successfully used in interstitial photodynamic therapy.     

Unexpected functional consequences of xenogeneic transgene expression in β-cells of NOD mice

We describe unexpected alterations in the non-obese diabetic (NOD/Lt) mouse model of type 1 diabetes (T1D) following forced β-cell expression of non-mammalian genes ligated to an insulin promoter sequence. These include the jellyfish green fluorescent protein (GFP), useful for β-cell identification, and the bacteriophage P1 Cre recombinase, necessary for β cell–specific ablation of a gene using a Cre- loxP system. Homozygous expression of GFP, driven by the mouse insulin 1 gene promoter (MIP-GFP) in a single transgenic line of NOD mice, produced T1D in postnatal mice that was not associated with insulitis, but rather β cell–depleted islets. Hemizygous transgene expression suppressed spontaneous autoimmune T1D in females, and produced a male glucose intolerance syndrome associated with age-dependent declines in plasma insulin content. Among lines of transgenic NOD/Lt mice expressing Cre recombinase driven by the rat insulin 2 promoter (RIP-Cre), high, non-mosaic expression correlated with suppressed T1D development. These findings emphasize the need for careful characterization of genetically manipulated NOD mouse stocks to insure that model characteristics have not been compromised.     

A recombinant heavy chain antibody approach blocks ART2 mediated deletion of an iNKT cell population that upon activation inhibits autoimmune diabetes

The ectoenzyme ADP-ribosyltransferase 2.2 (ART2.2) can apoptotically delete various T-cell subsets. Depending on the involved apoptotic T-cell subset, enhanced ART2.2 activity could result in immunosuppression or autoimmunity. Diminished activity of the CD38 ectoenzyme that normally represents a counter-regulatory competitor for the NAD substrate represents one mechanism enhancing ART2.2 activity. Hence, it would be desirable to develop an agent that efficiently blocks ART2.2 activity in vivo. While the llama derived recombinant s+16 single domain antibody overcame the difficulty of specifically targeting the ART2.2 catalytic site potential therapeutic use of this reagent is limited due to short in vivo persistence. Thus, we tested if a modified version of s+16 incorporating the murine IgG1 Fc tail (s+16Fc) mediated long-term efficient in vivo suppression of ART2.2. We reasoned an ideal model to test the s+16Fc reagent were NOD mice in which genetic ablation of CD38 results in an ART2.2 mediated reduction in already sub-normal numbers of immunoregulatory natural killer T-(NKT) cells to a level that no longer allows them when activated by the super-agonist alpha-galactosylceramide (α-GalCer) to elicit effects inhibiting autoimmune type 1 diabetes (T1D) development. Treatment with s+16Fc efficiently mediated long-term in vivo inhibition of ART2.2 activity in NOD.CD38^null mice, restoring their iNKT cell numbers to levels that upon α-GalCer activation were capable of inhibiting T1D development.