Safety studies of l-alanyl-l-glutamine (l-AG).

The safety of l-alanyl-l-glutamine (l-AG) derived by fermentation using a recombinant Escherichia coli strain containing the l-amino acid alpha-ligase gene from Bacillus subtilis, was assessed in acute and subchronic toxicity studies in the rat. l-AG was tested in vitro in a bacterial reverse mutation assay and in a chromosome aberration assay. l-AG was not acutely toxic when administered to Sprague-Dawley rats by gavage at 2000mg/kg bw. In a 14-day range-finding study, l-AG at up to 5% in the diet was without effect. In the 13-week dietary study, there were no toxicologically significant differences between the treated groups (1.0, 3.0 and 5.0% l-AG) and the controls (0% and 5% l-AG produced via a different method) with respect to body weight gain, feed consumption, feed efficiency, or the results of ophthalmological, haematological, clinical chemistry, and urinalysis evaluations. Three of 10 high-dose males had mild testicular changes, however, these were of exactly the same nature and severity as those that occur spontaneously, and were considered unlikely to be treatment-related. The NOAEL in both males and females was established as the highest dose tested at 3129 and 3601mg/kg bw/day, respectively (5.0% in the diet). There was no evidence of genotoxicity of l-AG in the Ames assay or in the in vitro CHL cell chromosome aberration study.

A comparative study of transformational leadership in nursing development units and conventional clinical settings.

AIMS: This is a comparative study of the leadership provided by nurse managers and leaders in Nursing Development Units and conventional clinical settings in England. BACKGROUND: Nursing development units (NDUs) were originally conceived as centres of nursing excellence, innovation and leadership development. This article describes the first published use of a leadership practices inventory (LPI) explicitly based upon a model of transformational leadership. This style of leadership has been commended as highly effective and suitable for nursing. METHODS: The use of the LPI was piloted as a postal questionnaire and as a schedule for telephone interviewing, these pilots supported the use of telephone interviewing in the main study. Two matched samples of 70 nurses in total were recruited from across England, comprising 14 nurse leaders and 56 of their day to day colleagues. Data was collected by telephone interviewing over a 6-week period between February and April 1998. Six null hypotheses were developed to identify significant inter-group differences in leadership behaviour. Descriptive and inferential data analysis techniques were employed using SPSS for Windows. FINDINGS: The leadership provided by NDU leaders was evaluated more highly than non-NDU leaders. A higher level of congruence between self and observer evaluations was shown by NDU leaders. Statistically significant inter-group differences were apparent in three of the five practices of exemplary leadership and in the overall leadership behaviour. NDU leaders show greater self awareness and are more transformational than their non-NDU counterparts. The limitations of the study design are discussed. CONCLUSIONS: NDU leaders provide leadership of a more transformational nature than their counterparts working in conventional settings. This finding suggests that NDU leaders have enhanced leadership potential and that formalizing nursing development within NDUs may promote the emergence of transformational leadership and provide a microculture in which it might flourish. The LPI is regarded as a useful, adaptable tool suitable for use in UK nursing applications including research, leadership development and education.

Selenium causes growth inhibition and apoptosis in human brain tumor cell lines.

We examined the effect of the trace element selenium on human glioma cell lines: T98G, U373MG, and U87MG, in addition to dermal fibroblast cells. Cultures were incubated with sodium selenite, and the following parameters were studied: cell growth, mitochondrial function, and ultrastructure. Cell growth was assayed by counting the number of viable cells after treatment with selenium. Mitochondrial function was analyzed using the MTT (tetrazolium salt reduction) assay. Apoptosis was determined by evaluating nuclear chromatin condensation by electron microscopy. The results indicated that selenium had a significant inhibitory effect on the growth of the tumor cells but had little effect upon dermal fibroblasts which had been passaged numerous times. Selenium also induced mitochondrial damage as shown by MTT assay in two brain tumor cell lines and in minimally passaged fibroblasts, but it had little effect upon the high-passage fibroblasts. Ultrastructurally, mitochondria had electron-dense inclusions resulting from selenium treatment. High rates of apoptosis were induced by selenium in the tumor cell lines and in the minimally passaged fibroblasts, whereas the fibroblasts with a high number of passages had some resistance to selenium treatment. This study correlates the adverse effects of selenium on mitochondrial function, inhibition of cell growth, and apoptosis and shows that selenium similarly affects three different brain tumor cell lines and minimally passaged fibroblasts. Further, the results with fibroblasts show that some types of cells after repeated passages can develop resistance to selenium damage.

Reconstruction of the temporalis muscle for pterional and cranio-orbital craniotomies.

BACKGROUND: Atrophy of the temporalis muscle can result after dissection and reattachment with pterional and cranio-orbital craniotomies. To prevent this sequel, a number of surgical modifications have been used to preserve the deep temporal nerve and artery, and also to allow for reconstruction of the temporalis muscle with minimal damage. In this report another surgical modification for reconstruction of the temporalis muscle is described that can be used in both pterional and cranio-orbital craniotomies. METHODS: The subperiosteum of the temporalis muscle is dissected sharply away from the temporal fossa preserving the deep temporal arteries and nerves. After the intracranial procedure, the bone flap is resecured and attached to the bone, and then several small holes are made along the superior temporal line, to which the temporalis muscle is directly reattached with sutures. RESULTS: We have used the technique described in over 100 cases without related cosmetic or temporalis atrophy. With this technique, muscle tension has been maintained with good stabilization and cosmetic appearance. CONCLUSION: In our technique, the temporalis muscle is anatomically reconstructed to the bone with easy attachment to the superior temporal line. The muscle tension is maintained with good stabilization and cosmetic appearance.

Sequential imaging and volumetric analysis of an intracerebral C6 glioma by means of a clinical MRI system.

In this study, using high resolution coils; implanted growing rat brain tumors were imaged sequentially with 3-D volume measurements generated by means of a clinical magnetic resonance imaging system (CMRI) and commercially available wrist coil. Ten female Sprague-Dawley rats were used, eight were implanted with C6 rat glioma cells and two served as controls. The images that were used for the three-dimensional (3-D) measurements were obtained from T1 weighted post contrast sequences. A commercially available computer work station with 3-D image analysis software was used to generate the tumor volumes. In addition to the rat studies a mouse was included to see if the resolution would be adequate for imaging very small brains. Six rats had brain tumor growth after transplantation and two rats did not have any tumor growth, however, their images were similar to the controls animals. Tumor volumes varied widely among the implanted rats. The number of implanted tumor cells had no direct relationship to developing tumor volumes. This study demonstrates that high resolution images of a rat brain tumor can be obtained from a CMRI system using a commercially available wrist coil which is capable of imaging two rats at the same time or even a mouse brain. A commercially available computer work station was able to generate the tumor volumes. The ability to image brain tumor and generate volume measurements over time has potential for animal research.

Long-term remission of malignant brain tumors after intracranial infection: a report of four cases.

OBJECTIVE: This report describes four patients with malignant brain tumors in whom regression or cure seems to be related to infection with bacteria. METHODS: An analysis of the four clinical cases reported and a review of the literature produced a comprehensive body of both experimental and clinical data concerning the antineoplastic properties of bacteria. RESULTS: Although direct oncolytic effects from bacteria have been suggested, immune adjuvant responses to tumor suppression are emphasized. In one of our patients, infiltration of numerous granulocytes and lymphocytes into the tumor at the time of initial surgery was observed, suggesting that a spontaneous immune reaction had begun. Also, in two other patients, tumor aggression occurred in association with a bacterial process that was not in direct contact with the tumor. In three of the cases described, Enterobacter aerogenes was recovered from the microbial cultures. Whether the presence of this organism was coincidental or whether this organism plays an important role in tumor defense is not known; however, a specific cross-reactive immunological attack to the tumor is suggested. CONCLUSION: The case histories presented in conjunction with the relevant literature reviewed support the concept that microbial infections may influence immune responses in brain tumor defense.

Head, neck, and mandible dynamics generated by 'whiplash'.

That injuries to the temporomandibular joint (TMJ) can be imposed by short-acting forces generated during rear-end collisions of motor vehicles was first proposed more than 50 years ago. Since that time, numerous anecdotal and clinical reports relating the onset of TMJ symptoms to low-velocity rear-end collisions have appeared in the literature. Various mechanisms of injury to the TMJ occurring during extension and flexion phases of 'whiplash' have been proposed. However, transient forces developed at the TMJ in impact velocity changes on the order of 8.0 kilometers per hour (km/h) have been shown to be well within typical physiologic ranges. This study applies current head/neck extension-flexion dynamic data to develop linear and angular force-time histories experienced at the TMJ. Fourteen test collisions of motor vehicles utilizing seven live test subjects were conducted in July 1993. Linear and angular accelerometers and high-speed photographic cameras recorded the vehicle and human-subject responses. Head accelerations and forces generated at the TMJ bore a generally linear relationship to the impact velocity changes in the range tested (3.9-10.9 km/h). Mandibular opening responses were measured on three test subjects. Neither neck hyperflexion nor hyperextension occurred for any subject on any trial. At some point in the series, all test subjects experienced neck muscle strain symptoms lasting 1-3 days. No TMJ symptoms were experienced. The head, neck, and mandible motions occurring in the 'whiplash' maneuver are more complex than previously described. The cervical muscle injury threshold appears to be reached in the 8.0 km/h range. Linear and rotational forces generated at the TMJ in rear-end impacts below the 11.0 km/h velocity-change level do not appear to be injurious.

Should endolymphatic sac tumors be considered part of the von Hippel-Lindau complex? Pathology case report.

OBJECTIVE: Von Hippel-Lindau (vHL) disease is an inherited disorder characterized by numerous cystic and solid neoplasms. Because of the recent identification of the vHL gene, other investigators have demonstrated genetic mutations in this gene in several of the neoplasms associated with the disease. We describe a patient with an endolymphatic sac (ELS) tumor and vHL disease. The purpose of this study was to identify a similar genetic mutation within the vHL gene of the ELS tumor. METHODS: Using the patient's archival pathological slides, neoplastic cells were microdissected to yield a purely neoplastic cell population. The deoxyribonucleic acid of these cells was then extracted and amplified via polymerase chain reaction. After sufficient amplification, the specimen was analyzed on a single-strand conformation polymorphism gel system to detect putative changes in the base sequence. RESULTS: Single-strand conformation polymorphism gel system analysis yielded two bands representing the two single strands of deoxyribonucleic acid that were amplified. The upper band of the specimen was shifted down (compared with controls), representing a conformational change as a result of genetic mutation. CONCLUSION: ELS tumors are uncommon, and, to our knowledge, only seven cases associated with vHL disease have been reported in the literature. Although this association has been previously mentioned, no definitive studies have linked the two together. We report the eighth case of ELS tumor and vHL disease. We have demonstrated through molecular biological techniques, that, in our patient's tumor, a genetic mutation occurred, and that this mutation is similar to mutations previously reported in other neoplasms associated with vHL. We therefore suggest that ELS tumors be considered among the neoplasms associated with vHL.

Maffucci's Syndrome and Intracranial Chondrosarcoma.

Maffucci's syndrome is a rare, congenital mesenchymal dysplasia characterized by multiple enchondromata and hemangimata, both of which may undergo malignant degeneration. Intracranial involvement is uncommon. A literature review yielded only six cases of Maffucci's syndrome with intracranial chondrosarcoma and two cases of Ollier's disease (enchondromata alone) with intracranial chondrosarcoma. We report the seventh case of Maffucci's syndrome in a patient with a very large and extensive skull base chondrosarcoma requiring staged operations for removal.

Skull base approaches for posterior circulation aneurysms.

With the emergence of skull base surgery, surgical approaches have been developed and redefined, providing surgeons with accessible avenues to difficult lesions of the cranial base. Although the majority of lesions to which these techniques have been applied have been for tumors, we find that these skull base approaches can equally provide access to difficult vascular lesions, especially complex aneurysms of the posterior circulation. In this report three different skull base approaches were used in four patients for the treatment of posterior circulation aneurysms. A cranio-orbital-zygomatic approach was used for the acute stage of a ruptured basilar tip artery anenrysm and for a giant posterior cerebral artery aneurysm. A petrosal approach was used for a ruptured basilar trunk aneurysm, and the transcondylar approach was used for a vertebral artery aneurysm. Each approach provides a wide field and excellent exposure of vital structures with minimal brain retraction. Neck clipping of the aneurysms was successfully achieved in all cases. We believe that our skull base approaches facilitate the surgical treatment of posterior circulation aneurysms.

Relative abundance and behavior of marine mammals exposed to transmissions from the Heard Island Feasibility Test.

The Heard Island Feasibility Test source transmitted a hum at 209-220 dB re: 1 microPa at 175-m depth, centered on 57 Hz with a maximum bandwidth of 30 Hz for 1 h of every 3. Experienced marine mammal observers conducted line-transect surveys and monitored marine mammal behavior visually and acoustically in a 70 x 70 km square centered on the transmission site. Thirty-nine groups of cetaceans and 19 of pinnipeds were sighted from both vessels before the start of transmissions. Thirty-nine groups of cetaceans and 23 of pinnipeds were sighted during transmissions. Blue (Balaenoptera musculus), fin (B. physalus), and sperm (Physeter macrocephalus) whales were sighted during the base line period; blue, sperm, and possibly sei (B. borealis) whales were sighted during the transmission period. More schools of hourglass dolphins (Lagenorhynchus cruciger) were sighted during transmissions, but fewer groups of pilot whales (Globicephala melas), southern bottlenose whales (Hyperoodon planifrons), and minke whales (B. acutorostrata). The density of all cetaceans was 0.0157 groups/km2 before the transmissions and 0.0166 groups/km2 during. Antarctic fur seals (Arctocephalus gazella) and southern elephant seals (Mirounga leonina) were seen, but not in sufficient numbers to estimate abundance. One blue whale tracked before, during and after a transmission changed respiration and reorientation rates, but did not avoid the source detectably. Sperm whales and pilot whales were heard in 23% of 1181 min of baseline acoustic surveys; but in none of 1939 min during the transmission period. Both species were heard within 48 h after the end of the test.

Neuromuscular causes of prolonged ventilator dependency.

We prospectively evaluated 21 patients with prolonged ventilator dependency, to determine the frequency of unsuspected neuromuscular disease as a cause of this condition, and to determine the types of such diseases. Assessment was performed with routine and specialized electrophysiologic procedures. None of the patients had known prior neuromuscular disease, and none had ongoing medical problems that could account for their continued ventilator dependency. Sixty-two percent were found to have a neuromuscular disease severe enough to account for the ventilator dependency. Most of the remaining cases had a contributory neuromuscular disease. In addition to critical illness polyneuropathy, several other significant categories were identified. Myopathic EMG changes were found in 50% of the subgroup assessed by quantitative EMG. We conclude that neuromuscular disease is the most important factor in prolonged ventilator dependency, and that diseases other than critical illness polyneuropathy represent an important cause of this syndrome.