Putative paraneoplastic pemphigus and myasthenia gravis in a cat with a lymphocytic thymoma.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare and severe autoimmune blistering skin disease of humans. It is associated mainly with haematopoietic neoplasia and a unique autoantibody profile. At this time and in animals, PNP has only been reported in dogs. OBJECTIVES: To report clinical, histological and immunological findings in a cat with suspected thymoma-associated PNP. ANIMAL: An 8-year-old female spayed Himalayan cat. RESULTS: The cat presented with a thoracic mass diagnosed as a lymphocytic thymoma. Two weeks postremoval, the cat developed myasthenia gravis, which was controlled with prednisolone and pyridostigmine. The myasthenia gravis resolved, but the cat developed severe cutaneous erosions and ulcers primarily affecting the caudal ventral abdomen and perineum, but also the ventral chest, axillae and medial pinnae. Histopathological analysis revealed changes consistent with pemphigus vulgaris and erythema multiforme, a combination of lesions highly suggestive of PNP. Direct immunofluorescence revealed intercellular epidermal IgG deposition in the lower epidermis, especially in areas of suprabasal clefts. Indirect immunofluorescence revealed antikeratinocyte IgG to basal keratinocytes and bladder epithelial cells. Immunological results supported a diagnosis of PNP. Skin lesions were treated with prednisolone and chlorambucil and, after clinical remission was obtained, the drugs were tapered and eventually discontinued without further recurrence of skin lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: In this cat, clinical, microscopic and immunological findings were consistent with a diagnosis of PNP, with thymoma being the suspected cause.

Characterisation of very low frequency oscillations in laser Doppler perfusion signals with a singular spectrum analysis.

Laser Doppler (LD) perfusion signals consist of a number of superimposed frequencies that span a wide range. Singular spectrum analysis (SSA) was used to characterise the very low frequency (VLF) components as this method can extract frequencies of interest from the time domain. Its utility is demonstrated on a sex health clinical data set where the focus was on VLF oscillations. A significant change in this frequency range can be measured with SSA when the subject is undergoing erotic stimulation.

Fitting E(max) models to clinical trial dose-response data.

We consider fitting Emax models to the primary endpoint for a parallel group dose­response clinical trial. Such models can be difficult to fit using Maximum Likelihood if the data give little information about the maximum possible response. Consequently, we consider alternative models that can be derived as limiting cases, which can usually be fitted. Furthermore we propose two model selection procedures for choosing between the different models. These model selection procedures are compared with two model selection procedures which have previously been used. In a simulation study we find that the model selection procedure that performs best depends on the underlying true situation. One of the new model selection procedures gives what may be regarded as the most robust of the procedures.

Conscious wireless electroretinogram and visual evoked potentials in rats.

The electroretinogram (ERG, retina) and visual evoked potential (VEP, brain) are widely used in vivo tools assaying the integrity of the visual pathway. Current recordings in preclinical models are conducted under anesthesia, which alters neural physiology and contaminates responses. We describe a conscious wireless ERG and VEP recording platform in rats. Using a novel surgical technique to chronically implant electrodes subconjunctivally on the eye and epidurally over the visual cortex, we are able to record stable and repeatable conscious ERG and VEP signals over at least 1 month. We show that the use of anaesthetics, necessary for conventional ERG and VEP measurements, alters electrophysiology recordings. Conscious visual electrophysiology improves the viability of longitudinal studies by eliminating complications associated with repeated anaesthesia. It will also enable uncontaminated assessment of drug effects, allowing the eye to be used as an effective biomarker of the central nervous system.

Comparing activity analyses for improved accuracy and sensitivity of drug detection.

Activity (or locomotion) can be one of the most sensitive and broadly affected translatable biomarkers of drug or disease. However activity data often have variance heterogeneity and periods with zero activity, and thus is usually not normally distributed giving the possibility of false interpretation of the data. We attempt to address this issue by developing and comparing different analysis techniques. These include transforming the data (square root and ln) as well as determining the probability of activity. In order to comprehensively assess these analysis techniques they are applied to a variety of different activity data sets, which have varying pharmacological manipulation or diurnal cycle state. These analyses indicate that activity data can firstly be improved by a square root transform of the data, which reduces variance heterogeneity. A further improved step is to analyse the "probability of moving", which is the most sensitive methodology to detect a change in activity. Thus analysis of the powerful non-invasive physiological marker activity and locomotion can be easily and simply modified to improve accuracy and sensitivity in disease or drug detection.