Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.

Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery.

Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative--hollow nerve guidance conduits (NGCs)--have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell-material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic.

Do Greek healthcare users and healthcare providers share cancer care priorities? Analysing the results from two Delphi studies.

Traditionally healthcare providers have determined how healthcare resources should be allocated. However, in recent years, healthcare users have increasingly been invited to identify those priorities important to them. Yet, healthcare users' priorities do not always match the priorities set by healthcare providers. In Greece, there has not been any research to measure the extent of agreement between healthcare providers and users on cancer care priorities. This project aimed to identify the priorities of healthcare users and providers with regards to the areas of cancer care that needed to be developed or improved in Greece and to examine the extent of agreement between the two groups. Two parallel Delphi surveys were conducted to identify the priorities and arrive at a consensus. Thirty participants formed the panel of healthcare providers and 30 participants the panel of healthcare users. The participants identified 18 key cancer care areas that require development or improvement; however, there were significant differences on the prioritisation between the two panels. It is encouraging that 18 key areas were shared by both panels. These areas can form an agenda for further exploration. Healthcare users can participate in developing priorities for cancer care; however, education is required so that they are better able to make informed choices.

IS EXERCISE CORTISOL RESPONSE OF ENDURANCE ATHLETES SIMILAR TO LEVELS OF CUSHING'S SYNDROME?

Several theories exist as to the mechanism causing the development of the Overtraining Syndrome in athletes. One theory proposes hypercortisolemic states (e.g., "pseudo" Cushing's Syndrome type-condition) brought on by intensive exercise training and the stress of sporting competitions results in neuroendocrine dysfunctions and subsequent physiological compromise. We wondered whether stressful exercise could provoke changes in cortisol to the magnitude of that seen in Cushing's Syndrome patients. Therefore we conducted a study to determine if the cortisol levels in highly trained endurance athletes in response to a stressful exercise bout compared to that found in Cushing Syndrome patients. Cortisol levels were examined in physically active men at rest, and after intensive, prolonged exercise (~85 min at 75% VO2max) and compared to that of Cushing's patients at rest. Results showed exercise does significantly (p<0.001) and substantially elevate cortisol to near Cushing's Syndrome levels. However, the cortisol response to exercise in athletes is highly transient and abates rapidly. The present findings support that cortisol responses to exercise such as what endurance athletes might encounter in their sporting competition (or during an intensive exercise training session) can elevate cortisol to the levels seen in Cushing Syndrome patients (i.e., for only a short period of time).

Relationship between stress hormones and testosterone with prolonged endurance exercise.

Previous pharmacological and pathological studies have reported negative relationships between circulating testosterone and certain stress hormones (i.e., cortisol and prolactin) in humans. These relationships have subsequently been used in hypotheses explaining the subclinical resting testosterone levels often found in some endurance-trained males, but as of yet no one has specifically examined these relationships as they relate to exercise. Thus, we examined the relationship between total and free testosterone levels and cortisol, and between total and free testosterone and prolactin following prolonged endurance exercise in trained males. Twenty-two endurance-trained males volunteered to run at 100% of their ventilatory threshold (VT) on a treadmill until volitional fatigue. Blood samples were taken at pre-exercise baseline (B0); volitional fatigue (F0); 30 min (F30), 60 min (F60), and 90 min (F90) into recovery; and at 24 h post-baseline (P24 h). At F0 [mean running time = 84.8 (3.8) min], exercise induced significant changes (P<0.05) from B0 in total testosterone, cortisol and prolactin. All three of these hormones were still significantly elevated at F30; but at F60 only cortisol and prolactin were greater than their respective B0 values. Free testosterone displayed no significant changes from B0 at F0, F30, or the F60 time point. At F90, neither cortisol nor prolactin was significantly different from their B0 values, but total and free testosterone were reduced significantly from B0. Cortisol, total testosterone and free testosterone at P24 h were significantly lower than their respective B0 levels. Negative relationships existed between peak cortisol response (at time F30) versus total testosterone (at F90, r=-0.53, P<0.05; and at P24 h, r=-0.60, P<0.01). There were no significant relationships between prolactin and total or free testosterone. In conclusion, the present findings give credence to the hypothesis suggesting a linkage between the low resting testosterone found in endurance-trained runners and stress hormones, with respect to cortisol.

PEAK CORTISOL RESPONSE TO EXHAUSTING EXERCISE: EFFECT OF BLOOD SAMPLING SCHEDULE.

INTRODUCTION: Strenuous exercise provokes increases in circulating cortisol levels. When the peak cortisol response to exercise occurs is a point of contention, as some research suggests the peak response coincides with the end of exercise while other indicate it is delayed and occurs during recovery. AIM OF THE STUDY: This study examined when peak cortisol levels occur in response to intensive, exhausting exercise of a prolonged nature. METHODS: Thirty-four healthy male subjects ran on a treadmill until volitional exhaustion. Blood specimens were analyzed for cortisol levels immediately at the end of exercise and at 30, 60, and 90 minutes into recovery. RESULTS: A significantly greater number (25/34; i.e., 73.5%) of the peak cortisol responses occurred during the recovery period (at 30 - 90 minutes) after the subjects reached volitional exhaustion and had stopped exercising. CONCLUSION: The findings suggest that if researchers are interested in assessing the peak cortisol response to exhausting exercise they should continue blood sampling for approximately 1 hour into the recovery period.

The Eye Book of Master Peter of Spain--a glimpse of diagnosis and treatment of eye disease in the Middle Ages.

Peter Hispanus, who became Pope John XXI, wrote a book about eye diseases and their treatment in the 13th century. De Oculis was not a scholarly treatise about eye diseases, but a manual intended for general physicians. Nevertheless, Latin copies were made into the 16th century, indicating its influence and importance. We present the first published English translation of De Oculis, based on a synthesis of the medieval Latin manuscripts and a German translation from the 19th century. The sources of Peter's understanding of the causes and treatment of eye diseases were the more scholarly and complete treatises by Greek and Arab writers. Many of the diseases described then cannot be correlated precisely with ophthalmic disorders known to us today because of the limited understanding of anatomy, function and pathophysiology that existed. However, De Oculis provides us with a glimpse of the practice of medicine in the Middle Ages.

The development of an alternative method in the assessment of critical thinking as an outcome of nursing education.

RATIONALE: Critical thinking is currently a highly valued educational outcome throughout the educational spectrum, but particularly so in relation to higher and professional education. Nursing education worldwide is also embracing the construct critical thinking as a desirable educational outcome, to the extent that some commentators refer to the importance of critical thinking in nursing as a given. The body of evidence relating to the impact that nursing education has upon the development of critical thinking is currently inconclusive. Many commentators claim that this may be because the instruments used in many studies are not sufficiently domain-specific. STUDY AIMS: The primary purpose of this descriptive-illuminative study was to explore and develop an alternative domain-specific method for identifying critical thinking in student nurses' reasoning processes. DESIGN: A longitudinal multimethod design incorporating across-method triangulation has been utilized for this purpose. Data collection from a group of student nurses involved the combination of the Watson and Glaser (1991) critical thinking appraisal test and a researcher developed think aloud technique incorporating a videotaped client simulation, a cognitive task and stimulated recall strategy. FINDINGS: Findings indicate no significant differences in pre and postprogramme Watson-Glaser mean scores. With regard to the think aloud evidence the sample consistently displayed evidence of reasoning that reflected an absolutist epistemology portraying limited evidence of critical thinking. In instances where more complex reasoning was demonstrated there was evidence to suggest that metacognitive strategies may contribute to this phenomenon. CONCLUSIONS: The findings make a further contribution to the assessment of critical thinking and raise interesting challenges to future curriculum development in nursing education, assessment of learning and nursing practice.

Strategies for the construction of a critical review of the literature.

This paper describes the process by which a literature review is conducted. It begins by identifying the purpose of a literature review, and then explores how key words can be used to define the scope of the review, how the review can be organized into t hemes and how conclusions can be drawn from the literature to inform further studies. Examples from nursing and health care are provided to illustrate the processes described.

Synthesis of paucidisperse poly(gamma-benzyl-alpha,L-glutamate) oligomers and star polymers with rigid arms.

The synthesis of highly uniform gamma-benzyl-alpha,L-glutamate (BLG) oligomers via a convergent solution phase approach is reported. BLG oligomers were produced with designed lengths of 4, 8, 12, and 16 as a first step to production of BLG-4-mer and BLG-8-mer rod stars. The star oligomers were purified by size-exclusion chromatography and reversed phase HPLC, and characterized by MALDI-TOF mass spectrometry and reversed phase HPLC. These star-shaped BLG oligomers could be used as initiators for growing larger stars.

Upper extremity socket design options.

A careful evaluation of the amputee's physical situation is necessary to determine the best available prosthetic options. Evaluation of the psychologic and vocational needs are needed to determine the most appropriate designs. Other factors, such as hobby and sport activities, need to be determined to complete the prescription. Because the function of a prosthesis cannot restore all of the lost capability of the missing limb, every effort should be taken to provide the best available substitute by careful prescription, design, and construction.

The use of portfolios in the assessment of learning and competence.

BACKGROUND: Portfolios have been used to incorporate accreditation of prior learning into nursing and midwifery assessment. This article aims to review the available literature on the use of portfolios. CONCLUSION: There needs to be a thorough evaluation of portfolios to determine their effectiveness as assessment tools in relation to the curriculum.

Biomechanical evaluation of a crimp clamp system for loop fixation of monofilament nylon leader material used for stabilization of the canine stifle joint.

OBJECTIVE: To test a crimp clamp system designed to secure monofilament nylon leader (MNL) material commonly used as lateral fabellotibial sutures (LFS) in extra-articular stabilization of the canine stifle joint. STUDY DESIGN: In vitro biomechanical tests of MNL loops secured with either the crimp clamp system or knots were performed. Suture loops (n = 94) were created from 27.3 kg tensile strength MNL and fastened with knots or crimp clamps. Tests were conducted on steam-sterilized, ethylene-oxide-sterilized, and nonsterilized MNL sutures. Loops were evaluated in single load tests and cycled tests. Values for load to failure, initial loop tension, loop elongation, mode of failure, and point of failure were determined. RESULTS: Crimp-clamped loops were superior to knotted loops in all parameters tested in both cycled and noncycled tests. Loop failure generally occurred by breaking within 3 mm of the fixation in both clamped and knotted tests. Loop elongation after cycling was greater in the knotted loops compared with clamped loops (P < .001). Load to failure was greater in clamped tests than in knotted tests (P < .001), regardless of sterilization technique used. Significantly higher initial loop tension could be achieved with the clamp system compared with knot fixation (P < .001). CONCLUSIONS: The crimp clamp system provides superior in vitro loop fixation characteristics compared with knot fixation in 27.3 kg test MNL. CLINICAL RELEVANCE: Based on the results of biomechanical testing and the known biocompatibility of the system's implant components, clinical trials using the crimp clamp system are warranted.

Critical thinking as an outcome of nursing education. What is it? Why is it important to nursing practice?

Critical thinking is currently a highly valued educational outcome throughout the educational spectrum, but particularly so in relation to higher and professional education. International concerns have focused upon citizen's thinking abilities and thus the nations' abilities to function and compete in complex societies and economies. Educationalists are questioning the wisdom of teaching content as opposed to teaching how to think as a means of dealing with relentless information development and change. Nursing education is also embracing the construct critical thinking as a desirable educational outcome. Some commentators refer to the importance of critical thinking in nursing practice as a central component or in some cases a given. This paper intends to examine the background to the construct and address in detail some of the important questions surrounding critical thinking, and its association with competent nursing practice.

The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer.

OBJECTIVE: To analyze the effects of 5-fluorouracil (5-FU) chemotherapy combined with preoperative irradiation and the role of intraoperative electron beam irradiation (IOERT) on the outcome of patients with primary locally advanced rectal or rectosigmoid cancer. METHODS: From 1978 to 1996, 145 patients with locally advanced rectal cancer underwent moderate- to high-dose preoperative irradiation followed by surgical resection. Ninety-three patients received 5-FU as a bolus for 3 days during the first and last weeks of radiation therapy (84 patients) or as a continuous infusion throughout irradiation (9 patients). At surgery, IOERT was administered to the surgical bed of 73 patients with persistent tumor adherence or residual disease in the pelvis. RESULTS: No differences in sphincter preservation, pathologic downstaging, or resectability rates were observed by 5-FU use. However, there were statistically significant improvements in 5-year actuarial local control and disease-specific survival in patients receiving 5-FU during irradiation compared with patients undergoing irradiation without 5-FU. For the 73 patients selected to receive IOERT, local control and disease-specific survival correlated with resection extent. For the 45 patients undergoing complete resection and IOERT, the 5-year actuarial local control and disease-specific survival were 89% and 63%, respectively. These figures were 65% and 32%, respectively, for the 28 patients undergoing IOERT for residual disease. The overall 5-year actuarial complication rate was 11%. CONCLUSIONS: Treatment strategies using 5-FU during irradiation and IOERT for patients with locally advanced rectal cancer are beneficial and well tolerated.

Time-dose considerations in the treatment of anal cancer.

PURPOSE: To analyze the impact of patient and treatment parameters in concurrent chemoradiation treatment for anal carcinoma. METHODS AND MATERIALS: Retrospective review of 50 MO anal cancer patients treated from 1984-1994. Most patients received concurrent 5-FU, mitomycin, and radiation. Local control and disease-free/overall survival were determined and analyzed according to patient and treatment parameters. RESULTS: With 43 month median follow-up, projected overall survival is 66% at 5 and 8 years. Disease-free survival is 67% at 5 years and 59% at 8 years. Local control is 70% at 5 and 8 years. Doses of > or =54 Gy are associated with improved 5-year survival (84 vs. 47%, p = 0.02), disease-free survival (74 v. 56%, p = 0.09), and local control (77 vs. 61%, p = 0.04). Although local control, disease-free survival, and overall survival were improved in patients whose overall treatment time was <40 days, this was not statistically significant. Outcome in the four patients with pretreatment hemoglobin (Hgb) <10 appeared worse with 3-year overall survival 50 vs. 68% (p = 0.07), disease-free survival 0 vs. 67% (p = 0.11), and local control 0 vs. 74% (p = 0.05). Projected 5-year overall survival, relapse-free survival, and local control in 4 HIV(+) patients is 0, 75, and 75%. Multivariate analysis reveals that dose (p = 0.02) and Hgb (p = 0.05) independently affect local control, dose (p = 0.02) affects disease-free survival, and dose (p = 0.01), Hgb (p = 0.03), T-stage (p = 0.03), and HIV-status (0.07) independently influence overall survival. CONCLUSION: Radiation doses of > or =54 Gy are associated with significantly improved survival and local control in anal cancer patients treated with chemoradiation. Overall treatment times of less than 40 days are associated with a trend towards improved outcome, but this is not significant. Pretreatment hemoglobin <10 is associated with worse treatment outcome. Survival of HIV (+) patient is poor, but the majority of such patients in this series died of intercurrent disease with their anal carcinomas controlled by chemoradiation.