Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13

Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior born cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the so-me chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.

Intra-abdominal pressure response to multidirectional support-surface translation

A complex response of the trunk muscles occurs to restore equilibrium in response to movement of the support surface. Intra-abdominal pressure (IAP) is considered to contribute to control of the trunk. This study investigated the contribution of IAP to the postural response to multidirection support-surface translation. IAP was recorded with a thin-film pressure transducer inserted via the nose into the stomach and trunk motion was recorded with an optoelectronic system with markers over the spinous process of L1. A pattern of trunk movement was recorded in response to the support-surface translations that was consistent with a 'hip' strategy of postural control. The trunk moved in a manner appropriate to move the centre of gravity over the new base of support. IAP was increased with movement in each direction, but varied in timing and amplitude between translation directions. In general, the IAP was greater with translations in the sagittal plane compared to the frontal plane and was initiated earlier for translations in the backward direction. These data indicate that IAP contributes to the postural response associated with support-surface translation and suggest that this is consistent with stiffening the spine. (C) 2003 Elsevier B.V. All rights reserved.

Satisfaction with medical rehabilitation after spinal cord injury

Study Design. Retrospective Objective. To predict satisfaction with medical rehabilitation. Summary of Background Data. While spinal cord injury (SCI) patient satisfaction with life and community services has been investigated, satisfaction with medical rehabilitation has not. Methods. Information submitted to the Uniform Data System for Medical Rehabilitation ( 1998 - 2001) by 134 hospitals/rehabilitation facilities in the United States (n = 6,205 patients with SCI) was examined. Predictors were sociodemographic variables, Case Mix Groupings (CMG) ( 401 - 505, 5001), length of stay, rehospitalization, followup therapy, and health maintenance. Satisfaction was assessed at a mean of 92.2 days (SD 11.9 days) postdischarge. Data were analyzed according to who reported the outcome ( patient, n = 3,858 or family/other, n = 1,869). Statistical modeling was conducted using logistic regression. Results. High overall satisfaction was reported (94%). Significant predictors for the patient report data were CMG and rehospitalization. Compared with CMG 5001 ( short stay,

Sagittal movement of the medial longitudinal arch is unchanged in plantar fasciitis

Background: Although a lowered medial longitudinal arch has been cited as a causal factor in plantar fasciitis, there is little experimental evidence linking arch motion to the pathogenesis of the condition. This study investigated the sagittal movement of the arch in subjects with and without plantar fasciitis during gait. Methods: Digital fluoroscopy was used to acquire dynamic lateral radiographs from 10 subjects with unilateral plantar fasciitis and 10 matched control subjects. The arch angle and the first metatarsophalangeal joint angle were digitized and their respective maxima recorded. Sagittal movement of the arch was defined as the angular change between heel strike and the maximum arch angle observed during the stance phase of gait. The-thickness of the proximal plantar fascia was determined from sagittal sonograms of both feet. ANOVA models were used to identify differences between limbs with respect to each dependent variable. Relationships between arch movement and fascial thickness were investigated using correlations. Results: There was no significant difference in either the movement or maximum arch angle between limbs. However, subjects with plantar fasciitis were found to have a larger metatarsophalangeal joint angle than controls (P < 0.05). Whereas the symptomatic and asymptomatic plantar fascia were thicker than those of control feet (P < 0.05), significant correlations were noted between fascial thickness and peak arch and metatarsophalangeal joint angles (P < 0.05) in the symptomatic limb only. Conclusions: Neither abnormal shape nor movement of the arch are associated with chronic plantar fasciitis. However, arch mechanics may influence the severity of plantar fasciitis once the condition is present. Digital flexion, in contrast, has a protective role in what might be a bilateral disease process.

Comparison of the pharmacokinetics of oxycodone and noroxycodone in male dark agouti and Sprague-Dawley rats: Influence of streptozotocin-induced diabetes

Purpose. The aims of this study are to evaluate whether cytochrome P450 (CYP)2D1/2D2-deficient dark agouti (DA) rats and/or CYP2D1/2D2-replete Sprague-Dawley (SD) rats are suitable preclinical models of the human, with respect to mirroring the very low plasma concentrations of metabolically derived oxymorphone seen in humans following oxycodone administration, and to examine the effects of streptozotocin-induced diabetes on the pharmacokinetics of oxycodone and its metabolites, noroxycodone and oxymorphone, in both rodent strains. Methods. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to quantify the serum concentrations of oxycodone, noroxycodone, and oxymorphone following subcutaneous administration of bolus doses of oxycodone (2 mg/kg) to groups of nondiabetic and diabetic rats. Results. The mean (+/- SEM) areas under the serum concentration vs. time curves for oxycodone and noroxycodone were significantly higher in DA relative to SD rats (diabetic, p < 0.05; nondiabetic, p < 0.005). Serum concentrations of oxymorphone were very low (< 6.9 nM). Conclusions. Both DA and SD rats are suitable rodent models to study oxycodone's pharmacology, as their systemic exposure to metabolically derived oxymorphone (potent mu-opioid agonist) is very low, mirroring that seen in humans following oxycodone administration. Systemic exposure to oxycodone and noroxycodone was consistently higher for DA than for SD rats showing that strain differences predominated over diabetes status.

Voltage-dependent inhibition of recombinant NMDA receptor-mediated currents by 5-hydroxytryptamine

1 The effect of 5-HT and related indolealkylamines on heteromeric recombinant NMDA receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp recording technique. 2 In the absence of external Mg2+ ions, 5-HT inhibited NMDA receptor-mediated currents in a concentration-dependent manner. The inhibitory effect of 5-HT was independent of the NR1a and NR2 subunit combination. 3 The inhibition of glutamate-evoked currents by 5-HT was use- and voltage-dependent. The voltage sensitivity of inhibition for NR1a+NR2 subunit combinations by 5-HT was similar, exhibiting an e-fold change per similar to20 mV, indicating that 5-HT binds to a site deep within the membrane electric field. 4 The inhibition of the open NMDA receptor by external Mg2+ and 5-HT was not additive, suggesting competition between Mg2+ and 5-HT for a binding site in the NMDA receptor channel. The concentration-dependence curves for 5-HT and 5-methoxytryptamine (5-MeOT) inhibition of NMDA receptor-mediated currents are shifted to the right in the presence of external Mg2+. 5 The related indolealkylamines inhibited glutamate-evoked currents with the following order of inhibitory potency: 5-MeOT = 5-methyltryptamine > tryptamine > 7-methyltryptamine > 5-HTmuch greater than tryptophan melatonin. 6 Taken together, these data suggest that 5-HT and related compounds can attenuate glutamate-mediated excitatory synaptic responses and may provide a basis for drug treatment of excitoxic neurodegeneration.

Integrating technology in the workplace for people with spinal cord injury

Computer technology can overcome mobility and functional limitations resulting from spinal cord injury (SCI) and enable re-employment. This study aimed to identify barriers and supports to effective technology use at work from the unique perspectives of technology users themselves. A qualitative research design was used to explore the perspectives of 11 technology users with SCI. In-depth, open-ended interviews and observations were conducted at each person’s workplace. Five major themes emerged: identifying the best or right technology; acquiring the technology; customizing and learning to use the technology; supporting the technology; and empowerment. Understanding these consumer perspectives enables professionals to empower people with SCI to optimize their work potential.

Patterns of neuronal activation in the rat brain and spinal cord in response to increasing durations of restraint stress

By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint- induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation ( as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint ( e. g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For example, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.

Characteristics of speech following cervical spinal cord injury

The present study examined 24 individuals with either complete or incomplete injuries to the cervical spinal cord through the use of standardized assessments of dysarthria and a perceptual rating scale. Perceptual assessment revealed predominantly prosodic and phonatory disturbances, while physical impairments were common in the respiratory and laryngeal subsystems of speech production. A reduction in intelligibility and speaking rate resulted in a diminished communicative effectiveness ratio for most participants. Individuals showed a high degree of variation, with no clear relationship between lesion type and impairments present. Further investigation is required to verify the physiological nature of the respiratory and laryngeal impairments found in the present investigation and to determine the relative contributions of these to the overall presentation of speech and voice post cervical spinal cord injury (CSI).

National audit of post-operative management in spinal surgery

Background: There is some evidence from a Cochrane review that rehabilitation following spinal surgery may be beneficial. Methods: We conducted a survey of current post-operative practice amongst spinal surgeons in the United Kingdom in 2002 to determine whether such interventions are being included routinely in the post-operative management of spinal patients. The survey included all surgeons who were members of either the British Association of Spinal Surgeons ( BASS) or the Society for Back Pain Research. Data on the characteristics of each surgeon and his or her current pattern of practice and post-operative care were collected via a reply-paid postal questionnaire. Results: Usable responses were provided by 57% of the 89 surgeons included in the survey. Most surgeons (79%) had a routine post-operative management regime, but only 35% had a written set of instructions that they gave to their patients concerning this. Over half (55%) of surgeons do not send their patients for any physiotherapy after discharge, with an average of less than two sessions of treatment organised by those that refer for physiotherapy at all. Restrictions on lifting, sitting and driving showed considerable inconsistency both between surgeons and also within the recommendations given by individual surgeons. Conclusion: Demonstrable inconsistencies within and between spinal surgeons in their approaches to post-operative management can be interpreted as evidence of continuing and significant uncertainty across the sub-speciality as to what does constitute best care in these areas of practice. Conducting further large, rigorous, randomised controlled trials would be the best method for obtaining definitive answers to these questions.

Species accumulation curves and their applications in parasite ecology

Species accumulation curves (SACs) chart the increase in recovery of new species as a function of some measure of sampling effort. Studies of parasite diversity can benefit from the application of SACs, both as empirical tools to guide sampling efforts and predict richness, and because their properties are informative about community patterns and the structure of parasite diversity. SACs can be used to infer interactivity in parasite infra-communities, to partition species richness into contributions from different spatial scales and different levels of the host hierarchy (individuals, populations and communities) or to identify modes of community assembly (niche versus dispersal). A historical tendency to treat individual hosts as statistically equivalent replicates (quadrats) seemingly satisfies the sample-based subgroup of SACs but care is required in this because of the inequality of hosts as sampling units. Knowledge of the true distribution of parasite richness over multiple host-derived and spatial scales is far from complete but SACs can improve the understanding of diversity patterns in parasite assemblages.