No description available.

A number of investigators have suggested that the early and late phases of the formalin test are mediated by separate neural systems. Evidence is presented which suggests that in addition to a dissociation between the two phases based on nociceptor stimulation and inflammation, the late phase of the formalin test is also dependent upon plasticity in the central nervous system which occurs during the transient early phase. Selectively blocking neural activity during the early phase with local anesthetics given peripherally, or in the cingulum bundle or fornix, prevents the development of these changes. Locally anesthetizing the cingulum bundle, fornix or medial bulboreticular formation prior to testing in the late phase produces analgesia which exceeds the duration of the anesthetic. It was also demonstrated that a thermal injury to the hindpaw or electrical stimulation of the sciatic nerve prior to neurectomy produces changes in the pattern and severity of self-mutilation following peripheral neurectomy, suggesting that the injury is encoded and maintained in central structures.

The four studies in this thesis deal with peripheral and central factors in phantom limb phenomena. Study 1 documents sensations referred to the phantom limb during transcutaneous electrical nerve stimulation (TENS) applied at the outer ears, face, and torso. The results suggest that some phantom sensations are maintained by activity of sympathetic fibers in the stump. Other sensations appear not to involve a peripheral mechanism. Studies 2 and 3 focus on sympathetic nervous system correlates of phantom sensations reported during TENS applied at the outer ears and contralateral leg. The results indicate that TENS significantly reduces the intensity of phantom limb paresthesias whereas a placebo control has no effect. Significant relationships between (a) phantom limb intensity and (b) stump skin conductance and temperature suggest that a cycle of sympathetic-efferent-somatic-afferent activity explains phantom limb paresthesias. Skin temperature was significantly lower at the stump than the intact limb in amputees with phantom limb pain (PLP), but not in those with a painless phantom, or no phantom limb at all, indicating that PLP is associated with reduced blood flow to the stump. Study 4 examines PLP that resembles pain experienced in the limb before amputation. These somatosensory memories constitute compelling evidence of a purely central component of PLP. Finally, amputees with and without PLP could not be differentiated by scores on personality, depression, or anxiety inventories. The results of the four studies indicate that the experience of phantom limb paresthesias involves a central mechanism that acts on peripheral structures whereas others qualities of experience depend exclusively on activation of central neural structures. Implications for treatment, research, and clinical practice are discussed.

The present study used phenomenology to inquire about the quality of life experiences of six adults who had undergone an amputation. This study also explored how the adults perceive their lives. All participants resided in Western Canada and had undergone an upper limb amputation several years prior to the study. Each participant was interviewed twice. Some of the interview questions were from Roberts and Cairns’ (1999) adaptation of Keith and Schalock’s (1994) QOL model. Interviews were conducted, transcribed, and thematically analyzed. Results indicated that some participants experienced a change whereas others reported stability in quality of life. The data analysis revealed specific categories, clusters, and themes of participants’ quality of life experiences. Quality of life categories related to empowerment, satisfaction and well-being, and the social realm. Participants described their lives as being significantly changed as a result of an amputation. The data analysis also revealed specific categories, clusters, and themes of participants’ perceptions of their lives. Psychological attributes and health care were two categories. The present study offers implications for several groups of people. / Graduate

The Hedgehog (Hh) signalling pathway is essential for embryogenesis and regulating cellular homeostasis in the adult, however much remains unknown about the molecular mechanisms that control ligand expression. In 2002, Lee et al. demonstrated that conditional mutation of the Drosophila hyperplastic discs gene (hyd) resulted in increased hh levels, suggesting that Hyd can act as a negative regulator of hh gene expression. Based on this evidence, the aim of this project was to investigate the hypothesis that UBR5, the murine homologue of Hyd, acts as a novel regulator of Hh gene expression in mammals. To investigate this hypothesis in vivo, I utilized the developing mouse limb as a model system that is highly sensitive to abnormal Hh expression. Morphological analysis of Ubr5 limb mutant embryos did not reveal an obvious phenotype, however quantitative analysis of Ihh gene expression and its downstream targets at E13.5 demonstrated a significant decrease in levels. In addition, changes in the expression of Runx2 and Msx2 were detected. Therefore, these data indicate that UBR5 can act as a positive regulator of Ihh expression, in addition to regulating other factors involved in chondrogenesis. The role for UBR5 as a positive regulator of Hh expression was also supported by in vitro investigations, demonstrating that UBR5 is required for Shh expression in mouse embryonic stem cells. Morphological analysis of adult Ubr5 limb mutant mice revealed the presence of significantly shorter long bones. These observations support previous reports that interference with IHH during early chondrogenesis can negatively affect long bone growth in the adult. Interestingly, adult Ubr5 limb mutant mice also possess osteophytes, a feature typically observed in osteoarthritis (OA), in addition to sites of ectopic mineralization (EM) near tendons of the knee and ankle. Based on these observations and evidence from the literature, I hypothesize that in addition to the role for UBR5 as a positive regulator of Ihh expression in the bone, UBR5 also plays a role in ligament/tendon development and/or maintenance, whereby its loss results in defective ligaments/tendons that are incapable of stabilizing the joints of the limb, culminating in joint deterioration, as observed in OA, in addition to EM. However, further investigation is required to determine whether this is also related to deregulated Ihh. These experiments suggest that Ubr5 limb mutant mice could provide a novel mouse model in the study of OA and prompt the investigation of the potential role for EDD, the human homologue of UBR5, in OA initiation and progression.

No description available.

Four cases of extremity cancers received effective management with cisplatin and etoposide via isolated limb perfusion. They demonstrated minimal, if any, soft tissue damage. This result counters the theory that a caustic response is a prerequisite for successful therapy. This characteristic allows for simultaneous surgical resection with regional, isolated limb perfusion of potent cytotoxic agents without increased morbidity from tissue necrosis, a common consequence of previously used drugs. There is no apparent affect on wound healing, even in cases involving extensive, radical operative procedures.

The intent of this study was to describe the effects of long term paraplegia and wheelchair use on upper limb function. Bilateral upper extremity isokinetic and grip strength, pain, and active range of motion were compared in 52 men with paraplegia (mean age 44 years: mean duration of spinal cord injury (SCI) 17 years) and 52 age and activity-level matched able-bodied men. The impact of upper limb pain on activities of daily living (ADL) performance was examined in the paraplegic sample. Strength was not significantly different between the two samples except for bilateral shoulder flexion (able-bodied stronger) and bilateral elbow extension (paraplegia stronger). Strength changed similarly with age in the two groups. The effect of duration of SCI on strength, excluding age, was significant for grip strength only. Duration of paraplegia and activity-level were better predictors of strength than age in 9 of 14 muscle groups, whereas in the able-bodied, age was the best strength predictor. Limited bilateral shoulder internal rotation and non-dominant external rotation were associated with paraplegia. Upper limb pain in the past week was associated with paraplegia (shoulder p<.001; elbow p<.00l; wrist/hand p<.00l). Reported pain prevalences for the paraplegic sample were: shoulder 39%, elbow 31%, wrist/hand 40%. The paraplegic subjects' pain intensity ratings revealed them to be experiencing mild to moderate levels of upper limb pain. Shoulder pain was associated with duration of injury, exclusive of age (p<.05). Measurement of the impact of upper limb pain On 18 activities of daily living (ADL) tasks revealed pain to be experienced by the majority of subjects with paraplegia (mobility tasks 60%; self-care tasks 5 8 % ; general activities tasks 60%). However, only 23-35% had made changes in their routines, and 6-16% had sought assistance with ADL due to upper limb pain. ++ / When age was excluded, it appeared that duration of SCI was more associated with pain during ADL, but this was significant only for pain during self-care tasks. The tasks most reported to cause upper limb pain were work/school, sleep, wheelchair transfers, outdoor wheeling, and driving. These results suggest that preventative and management steps are required to ensure continued independence and quality of life in this group over time. The effect of duration of SCI suggests that limitations in upper limb function may be seen in this population at relatively young ages.

Maternal administration of a single dose of retinoic acid (vitamin A acid, 100 mg/kg) on either the 11 th, 11 1/2, 12th, 12 1/2, 13th or 13 1/2 day of gestation produced phocomelia or partial phocomelia in ICR/DUB fetuses. The results depended upon the time of treatment and two gradients of effect were produced: 1) cranio-caudal gradient, since forelimb defects resulted from treatment between days 11 and 13, while similar hindlimb abnormalities were produced by administration of retinoic acid 12 to 24 hours later: 2) proximo-distal gradient, due to the heterogenous sensitivity among individual bones of the limb. In the forelimb, early treatment (11th day) produced humero-ulnar defects and later treatment (12th day) ulnoradial defects. A similar proximo-distal gradient was observed in the hindlimb. The use of teratological studies as a tool to assist morphogenetic investigation is discussed.

No description available.