The assessment of locomotor function in spinal cord injured rats: the importance of objective analysis of coordination

The Basso, Beattie and Bresnahan (BBB) locomotor rating scale is the most widely used open field test and has been accepted as a valid way to assess locomotor function after spinal cord contusion injury in the rat. A limitation within the BBB locomotor rating scale is the correct assessment of forelimb (FL)-hindlimb (HL) coordination. This limitation can have major implications for the final assessment of locomotor function. In the present study, we show an objective method to assess coordination based on the regularity index (RI), achieved through the use of the CatWalk method. The RI grades the degree of coordination as the result of the number of normal step sequence patterns multiplied by four and divided by the total amount of paw placements. Using the RI, single walkway crossings can be objectively analyzed on coordination. Integration of the CatWalk based coordination into the BBB scale indicates that objective analysis of coordination results in reliable and more sensitive assessment of locomotor function. This new method has been tested successfully in determination of positive effects of enriched housing on functional recovery after spinal cord injury (SCI).     

Thyroid hormone, but not parathyroid hormone, partially restores glucocorticoid-induced growth retardation

Growth retardation is a serious side effect of long-term glucocorticoid (GC) treatment. In order to prevent or diminish this deleterious effect, a combination therapy including growth hormone (GH), a stimulator of bone growth, is often recommended. Parathyroid hormone (PTH) and thyroid hormone (T₄) are important hormonal regulators of bone growth, and might also be helpful anabolic agents for counteracting the negative effects of GCs. Therefore, we studied the interaction of GCs in combination with a single dose of either PTH or T₄ on GC-induced growth retardation. Dexamethasone (Dex) treatment of mice for four weeks induced a significant growth inhibition of body length and weight and weights of several organs. PTH or T₄ alone did not affect the normal growth pattern. However, T₄ could partially restore the Dex-induced growth inhibition, whereas PTH could not. Although PTH did not affect total body growth, it did affect the height of the proliferative zone, which could be counteracted by Dex. This contrasts with T₄ treatment alone or in combination with Dex, which both resulted in a disturbed morphology of the growth plate. IGF-I mRNA, one of the mediators of longitudinal bone growth, was present in proliferative and hypertrophic chondrocytes. However, its expression was not affected by any of the treatments. In conclusion, T₄ but not PTH can partially counteract the effects of Dex on general body growth, with possible implications for future treatments of GC-induced growth retardation. Additionally, both T₄ and PTH, alone or in combination with Dex, have differential effects on the morphology of the growth plate.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany     

Modulation of the immune response by antibacterial antibodies

Antibodies induced by the gram+ bacteria Micrococcus lysodeikticus exhibit different carbohydrate specificities and hence might cross-react with membrane glycoproteins and/or glycolipids of mammalian cells. Using a T cell derived lymphoid line, these antibodies were found to detect a membrane marker which is only exposed in confluent culture conditions on non-dividing cells. Such confluence related antigen (Cag) is a cryptic membrane antigen, which can be unmasked through membrane perturbating agents such as p-formaldehyde or through interactions with macrophages and macrophage derived factors. Anti-micrococcus antibodies appear also to affect functionally normal T lymphocytes. Thus such reagents drastically inhibit the murine T cell reactivity towards mitogens such as Con A and PHA provided, however, the mitogenic signal is delivered through peritoneal macrophages. Furthermore, anti-micrococcus antibodies induce activated T lymphocytes into mitogenesis, but not unprimed resting T cells. Hence the physiological activity of anti-micrococcus antibodies depends on the state of activation of the T lymphocyte, indicating the involvement of cryptic membrane molecules. The relevance of such phenomena to host-bacteria and host-parasite interaction will be discussed.     

Multispectral analysis of magnetic resonance images

Magnetic resonance (MR) imaging systems produce spatial distribution estimates of proton density, relaxation time, and flow, in a two dimensional matrix form that is analogous to that of the image data obtained from multispectral imaging satellites. Advanced NASA satellite image processing offers sophisticated multispectral analysis of MR images. Spin echo and inversion recovery pulse sequence images were entered in a digital format compatible with satellite images and accurately registered pixel by pixel. Signatures of each tissue class were automatically determined using both supervised and unsupervised classification. Overall tissue classification was obtained in the form of a theme map. In MR images of the brain, for example, the classes included CSF, gray matter, white matter, subcutaneous fat, muscle, and bone. These methods provide an efficient means of identifying subtle relationships in a multi-image MR study.     

Pain assessment in intellectually disabled people: non-verbal indicators

BACKGROUND: Although important progress has been made during the past decade, research on pain in people with intellectual disabilities is still scarce. Pain assessment in people with intellectual disabilities is a frequent and difficult problem, especially for nurses working with people with intellectual disabilities on a daily basis. Gathering more information about pain in people with intellectual disabilities is of major importance and relevance for nursing, and adds to the developing body of knowledge. OBJECTIVE: To investigate the nature and relative importance of non-verbal indicators used by nurses to assess pain in people with a severe or profound intellectual disability. METHODS: A questionnaire consisting of 158 indicators of pain was used. A total of 135 nurses from nine institutions specializing in the care of people with intellectual disability were asked to rate each indicator on a scale of 1-10 to show which non-verbal expressions they considered important in diagnosing pain. RESULTS: A total of 109 nurses responded. All 158 indicators were mentioned as being important to indicate pain. All except four had a range of 9. Seven (moaning during manipulation, crying during manipulation, painful facial expression during manipulation, swelling, screaming during manipulation, not using (affected) body part, and moving the body in a specific way of behaving) were reported as 'very important' by more than 50% of nurses. The lowest score (median 5.5; minimum 1, maximum 10) was given to the indicator 'waving arm movements'. The pain of people with severe intellectual disability appeared to be assessed differently from that of people with profound intellectual disability. Indicators belonging to the 'physiological' category scored relatively higher in the group of nurses specializing in profound disability. In contrast, indicators belonging to the 'social-emotional' category were scored relatively higher by nurses specializing in severe disability. CONCLUSION: Nurses used a wide range of indicators to assess pain in people with intellectual disability. Functional abilities and level of disability seem to influence the indicators used.     

Sciatic nerve regeneration in mice and rats: recovery of sensory innervation is followed by a slowly retreating neuropathic pain-like syndrome

Peripheral nerve regeneration has been studied extensively in the sciatic nerve crush model, at the level of both function and gene expression. The crush injury allows full recovery of sensory and motor function in about 3 weeks as assessed by the foot reflex withdrawal test and De Medinacelli walking patterns. We used the recently developed CatWalk paradigm to study walking patterns in more detail in mice and rats. We found that, following the recovery of sensory function, the animals developed a state of mechanical allodynia, which retreated slowly over time. The motor function, although fully recovered with the conventional methods, was revealed to be still impaired because the animals did not put weight on their previously injured paw. The development of neuropathic pain following successful sensory recovery has not been described before in crush-lesioned animals and may provide an important new parameter to assess full sensory recovery.