An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.     

New stand magnifiers do not meet rated levels of performance

A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'_v) rather than equivalent dioptric power (F_m) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use.     

Scholarly productivity: are nurse academics catching up?

The aim of this study was to document the amount of recent change in Australian nurse academics' scholarly productivity and to investigate the influence of demographic factors such as gender, academic rank, qualifications, increase in qualifications, state of residence, university and university size. Scholarly productivity was calculated from an audit of journal articles. The findings of this study indicate that, while there has been a slight increase in scholarly productivity in the last five years, nursing still lags behind other disciplines. Scholarly productivity was found to be positively associated with highest academic qualification, academic rank and promotion. The study indicates the continuing need for senior nurse academics to provide mentoring to colleagues and foster the development of skills associated with scholarly productivity.     

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.     

Protection of CGS 10078B against ouabain-induced arrhythmia in the cat

CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4-(2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.     

Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.     

The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.     

Training Synergies Between Medical Informatics and Health Services Research: Successes and Challenges

Stanford''s two decades of success in linking medical informatics and health services research in both training and investigational activities reflects advantageous geography and history as well as natural synergies in the two areas. Health services research and medical informatics at Stanford have long shared a quantitative, analytic orientation, along with linked administration, curriculum, and clinical activities. Both the medical informatics and the health services research curricula draw on diverse course offerings throughout the university, and both the training and research overlap in such areas as outcomes research, large database analysis, and decision analysis/decision support. The Stanford experience suggests that successful integration of programs in medical informatics and health services research requires areas of overlapping or synergistic interest and activity among the involved faculty and, hence, in time, among the students. This is enhanced by a mixture of casual and structured contact among students from both disciplines, including social interactions. The challenges to integration are how to overcome any geographic separation that may exist in a given institution; the proper management of relationships with those sub-areas of medical informatics that have less overlap with health services research; and the need to determine how best to exploit opportunities for collaboration that naturally occur.Training in medical informatics and health services research has been closely linked at Stanford University for almost two decades. Although the close linkage was deliberate, it was facilitated by historical circumstances, in particular the common academic structures in which both programs arose. In this paper, we describe some of that rationale and history, identifying the areas of overlap that we have pursued in coordinating the training opportunities for graduate students and fellows in both areas of study. As we shall note, the synergies have been great, and in some cases trainees have collaborated closely on research while also taking some of the same courses. We believe that these interactions can be a model for the design of training programs that encourage scholarly interactions between medical informatics and health services research. Although our initial charge was to describe both the successes and failures in integrating the programs, we found that we could not identify any outright failures and that it would be better to delineate the complexities and challenges that we have faced in bringing together these two disciplines.