Proefschrift--Utrecht. / Vita. Includes bibliographical references.

Thesis (M.Nurs.)--University of Hong Kong, 2004. / Also available in print.

Proefschrift--Utrecht. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Houston, 1967. / Degree granted by Dept. of Psychology. Bibliography: leaves 132-136.

Inaug.-diss.--Halle. / Vita.

Inaug.-Diss.--Breslau. / Vita. Bibliography: p. 2.

Thesis (M.S.)--Ohio State University. / Includes bibliographical references (leaves 20-27). Available online via OhioLINK's ETD Center.

Application of the molluscan neuropeptide FMRFamide to two identified neurones in the cerebral ganglia of Helix aspersa induces quite different effects. In the Cl neurone, FMRFamide produces a slow hyperpolarizing current carried by K+ while with the C2 neurone it causes a fast depolarizing current carried by Na+. Possible mechanisms underlying the slow K+ response were examined and the fast response was characterized using voltage clamp techniques. Some patch clamp experiments were also used for the slow response. The slow response was shown to depend on a G protein, which was sensitive to inhibition by pertussis toxin, indicating that it was mediated by a Gi or Go protein. Second messengers such as cyclic AMP, cyclic GMP, IP3, arachidonic acid and Ca2+ along with the activation of protein kinase C were all found not to be directly involved in producing the FMRFamide response. These negative results with the second messengers gave rise to the view that the FMRFamide receptors and K+ ion channels may be linked directly through the activation of G proteins. 5-HT, probably acting through raised cyclic AMP levels, reduced the amplitude of the FMRFamide response which suggests that the channel opened by FMRFamide may be an "S" K+ type channel. Activation of protein kinase C by phorbol ester also reduced the FMRFamide response. A role for protein phosphorylation was indicated by the use of okadaic acid which inhibits protein phosphatases 1 and 2A. Its application reduced the amplitude of the FMRFamide response which suggested that increased protein phosphorylation levels lead to smaller responses. Thus, it seemed possible that protein phosphorylation levels controlled by cyclic AMP, protein kinase C activation and protein phosphatases 1 and 2A might modulate the activity of the receptor/ G protein/ ion channel complex. Alternatively, FMRFamide may operate through the activation of protein phosphatase(s) which reduce protein phosphorylation levels. Patch clamp studies in cell attached mode on the Cl neurone failed to reveal any channel openings induced by FMRFamide. This result also tends to rule out the direct involvement of a second messenger. The fast depolarizing FMRFamide response of the C2 neurone, which is due to the opening of a ligand gated channel, was found to be carried by Na+ and not Ca2+. Amiloride produced a reversible block of the current. Tetrodotoxin and lignocaine had no effect on the FMRFamide response while raised cyclic AMP levels potentiated the response. In the presence of okadaic acid and increased levels of cyclic AMP, the FMRFamide response is potentiated. This potentiation was not maintained in the presence of okadaic acid alone. The raised protein phosphorylation levels therefore did not cause potentiation, which suggested that cyclic AMP may have a direct effect on the receptor/channel complex.

Spinal cord injuries can cause the catastrophic loss of motor and sensory function. The neurological deficits that result are the consequence of not only the primary injury to the spinal cord, but also a complex milieu of secondary pathological processes that are now beginning to be understood. The major mechanisms that underlie this secondary pathology include vascular disruption, ischemia, oxidative stress, excitotoxicity, and inflammation. In light of this, the fact that this secondary pathology occurs after the initial impact makes it potentially amenable to therapeutic intervention. Pharmacotherapies may attenuate some of these processes and minimize secondary damage. Some of the promising treatments that are emerging for acute spinal cord injury are drugs that are already used by physicians for the treatment of unrelated diseases. These drugs, which have already been established to be safe for humans, offer the unique advantage over other novel therapeutic interventions that have yet to be tested in humans. This would save a tremendous amount of time and money needed for human safety studies, if considered as a treatment for spinal cord injury. Examples of such drugs include minocycline (an antibiotic), erythropoietin (a recombinant hormone used to treat anemia), and statins (a popular class of blood cholesterol reducers), all of which have demonstrated the ability to attenuate the various pathophysiological processes initiated after trauma to the central nervous system. In a series of studies, erythropoietin, darbepoetin, atorvastatin, simvastatin, and minocycline were all evaluated for their ability to improve neurologic recovery in a clinically relevant model of spinal cord injury. My experiments revealed that erythropoietin, darbepoetin, atorvastatin and minocycline did not significantly improve neurological recovery. These negative results were in stark contrast to the positive findings which had been published in the literature suggesting that differences in experimental models and methodology influence the neuroprotective efficacy of these drugs. Simvastatin, on the other hand, demonstrated significant improvements in locomotor and histological outcomes. Although this is indeed exciting, the results were modest at best. My results highlight the need for further preclinical work on the above treatments to refine and optimize them prior to proposing them for human testing. / Science, Faculty of / Zoology, Department of / Graduate

This exploratory study was designed to gather information about the needs and concerns of significant others of patients with recent spinal cord injuries. The respondents were asked about the impact of the patients' injuries on their own lives and about their feelings in relation to the treatment they and their patients were receiving from health care personnel. The study was conducted with a convenience sample of seven respondents, five women and two men, designated as significant others by seven patients with recent spinal cord injuries. Using a semi-structured interview guide each significant other was interviewed in depth from one to three times over a period of three to six weeks following their patient's injury. The interview guide covered eight selected themes relating to the significant other's': - need to feel that he or she is getting adequate information - need to feel that he or she is being helpful to the patient - need to feel able to cope with home and family responsibilities - need to have someone from whom he or she can obtain emotional support - need to express feelings, both positive and negative - need to feel that his or her patient is getting good care - past experiences and methods of coping with crisis situations - needs and concerns that may arise because of the likely major effects the patient's injury will have on the significant other's life in the future. All respondents reported needing initial access to physicians who would give a true report of their patients' medical conditions and progresses. Thereafter five respondents reported receiving adequate information from their patients or the nurses. The six respondents who were given a negative prognosis for their patients' recovery of function expressed less apparent emotional conflict than the one who was told there was some possibility of recovery. After the first interview three respondents stressed the need for practical information about how to help with their patients' physical care, although during the first interview all respondents expressed fear that any physical assistance they attempted might harm their patients. All respondents felt their greatest value to their patients was as a source of emotional support. Two respondents reported being able to defer all home and family responsibilities; the other five stated their home and family responsibilities were not directly increased by their patients' injuries. However these five reported stress caused by the necessity of coping with the patients' needs as well as home and family responsibilities. All seven significant others reported using some sources of external support, the most common being family members and close friends. All respondents voiced positive feelings about their patients and the health care they were receiving. Only three respondents expressed strong negative feelings which were directed at the cause of their patients' injuries or what they perceived as incorrect or inappropriate information given to them by health care personnel. All respondents stressed their need to know their patients were receiving good care. All significant others reported their patients' injuries were the severest crises they or their patients had ever undergone, but all also stated they believed they would be able to cope with the crisis. The respondents reported their patients' gravest concerns for the future related to finances, work and sexual functioning. The respondents themselves voiced less concern about finances and sexual functioning. Other concerns for the future expressed by the respondents related to housing, transportation, family activities, social relationships and coping with the inevitable "ups and downs" of the patients. There were some differences in concerns expressed by male and female respondents. The findings of the study demonstrated the presence of selected needs and concerns in a small convenience sample of significant others of spinal cord injured patients. Further research would be necessary to determine whether the findings are representative and whether there is a relationship between expressed needs and concerns and the sex of patients and/or significant others. The study offers suggestions to practicing nurses who wish to improve their care of spinal cord injured patients and their significant others. / Applied Science, Faculty of / Nursing, School of / Graduate