Increased brain edema in aqp4-null mice in an experimental model of subarachnoid hemorrhage.

We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid hemorrhage in which 30 microl of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of the glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4 null mice had comparable baseline brain water content, intracranial pressure and neurological score. At 6 h after blood injection, aquaporin-4 null mice developed more brain swelling than wildtype mice. Brain water content increased by 1.5+/-0.1% vs. 0.5+/-0.2% (Mean+/-Standard Error, P<0.0005) and intracranial pressure by 36+/-5 vs. 21+/-3 mm Hg (P<0.05) above pre-injection baseline, and neurological score was worse at 18.0 vs. 24.5 (median, P<0.05), respectively. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice had a twofold reduction in glia limitans osmotic permeability. We conclude that aquaporin-4 null mice manifest increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water.

Improved outcome after lumbar microdiscectomy in patients shown their excised disc fragments: a prospective, double blind, randomised, controlled trial.

BACKGROUND: Lumbar microdiscectomy (LMD) is a commonly performed neurosurgical procedure. We set up a prospective, double blind, randomised, controlled trial to test the hypothesis that presenting the removed disc material to patients after LMD improves patient outcome. METHODS: Adult patients undergoing LMD for radiculopathy caused by a prolapsed intervertebral disc were randomised into one of two groups, termed experimental and control. Patients in the experimental group were given their removed disc fragments whereas patients in the control group were not. Patients were unaware of the trial hypothesis and investigators were blinded to patient group allocation. Outcome was assessed between 3 and 6 months after LMD. Primary outcome measures were the degree of improvement in sciatica and back pain reported by the patients. Secondary outcome measures were the degree of improvement in leg weakness, paraesthesia, numbness, walking distance and use of analgesia reported by the patients. RESULTS: Data from 38 patients in the experimental group and 36 patients in the control group were analysed. The two groups were matched for age, sex and preoperative symptoms. More patients in the experimental compared with the control group reported improvements in leg pain (91.5 vs 80.4%; p<0.05), back pain (86.1 vs 75.0%; p<0.05), limb weakness (90.5 vs 56.3%; p<0.02), paraesthesia (88 vs 61.9%; p<0.05) and reduced analgesic use (92.1 vs 69.4%; p<0.02) than preoperatively. CONCLUSION: Presentation of excised disc fragments is a cheap and effective way to improve outcome after LMD.

AQP4 gene deletion in mice does not alter blood-brain barrier integrity or brain morphology.

The glial cell water channel aquaporin-4 (AQP4) plays an important role in brain edema, astrocyte migration, and neuronal excitability. Zhou et al. [Zhou J, Kong H, Hua X, Xiao M, Ding J, Hu G (2008) Altered blood-brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19:1-5] recently reported that AQP4 deletion significantly altered blood-brain barrier integrity and glial fibrillary acidic protein (GFAP) immunoreactivity in their AQP4 null mice. Here we describe a detailed characterization of baseline brain properties in our AQP4 null mice, including gross appearance, neuronal, astrocyte and oligodendrocyte characteristics, and blood-brain barrier integrity. Gross anatomical measurements included estimates of brain and ventricle size. Neurons, astrocytes and oligodendrocytes were assessed using the neuronal nuclear marker NeuN, the astrocyte marker GFAP, and the myelin stain Luxol Fast Blue. The blood-brain barrier was studied by electron microscopy and the horseradish peroxidase extravasation technique. There were no differences in brain and ventricle sizes between wild type and AQP4 null mice, nor were there differences in the cerebral cortical density of NeuN positive nuclei, perimicrovessel and glia limitans GFAP immunoreactivity, or the thickness and myelination of the corpus callosum. The ultrastructure of microvessels in the frontal cortex and caudate nucleus of wild type vs. AQP4 null mice was indistinguishable, with features including intact endothelial tight junctions, absence of perimicrovessel astrocyte foot process edema, and absence of horseradish peroxidase extravasation. In contrast to the report by Zhou et al. (2008), our data show that AQP4 deletion in mice does not produce major structural abnormalities in the brain.

Current neurosurgical trainees' perception of the European Working Time Directive and shift work.

The introduction of the shift system in response to the European Working Time Directive has had an enormous impact on the running of neurosurgical units in the UK. This study seeks to establish what provisions are currently in place for out of hours cover and what has been the effect of the introduction of shifts in three main areas: patient safety, training and 'work/life balance'. The on-call registrar at each UK neurosurgical unit was contacted by telephone. Data regarding current emergency provision were sought. Registrars who had worked both on-calls and the shift system during their career as a neurosurgical registrar were asked to make a comparison. Data were collected from all 33 UK units. Twenty-two still use a traditional 24-h on-call system. Twenty-one on-call rotas were classed as non-resident although 12/21 of those officially on non-resident rotas were in fact resident whilst on call. Twenty-two registrars had worked both systems as a neurosurgical registrar. Twenty-one (95.45%) felt that traditional on-calls gave better clinical exposure. Twenty-one (95.45%) felt that on-calls allowed the provision of better patient care. Nineteen (86.36%) felt that on-calls were safer. Thirteen (59.09%) reported that they were more tired when doing shift work than on-calls. Fourteen (63.63%) found that the on-call system gives more useful spare time and more time to deal with family commitments. Current neurosurgery registrars feel the shift system is less safe, harmful to training and worse in terms of work/life balance. More than one-third of units are claiming to have non-resident on-call systems in order to appear compliant with EWTD when registrars are in fact resident.

Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases.

Glioblastoma is the most common primary brain tumour. The aim of this study was to determine trends in survival over a 12-year period. Survival data were collected retrospectively for 625 patients who had surgery for histologically-confirmed glioblastoma between 1993 and 2004 in a single centre. Data including age, sex, preoperative Karnofsky performance score, tumour site, date of surgery, and type of surgical and adjuvant treatment were collected. Overall median survival was 189 days; there was no significant change in survival over 12 years. Multivariate analysis identified the following independent positive prognostic factors: age <60 years (p < 0.0005), Karnofsky score > or = 70 (p < 0.0001), tumour debulking, rather than biopsy (p < 0.001), right-sided lesion (p < 0.05), unilateral tumour (p < 0.05) and radiotherapy (p < 0.0001). Despite neurosurgical advances, the survival of patients with glioblastoma has not changed for more than a decade. Although, overall, glioblastoma has a short survival, our data show that individual patient survival is heterogeneous.

How much can be concluded from the International Subarachnoid Aneurysm Trial (ISAT)?

Recently published data from the International Subarachnoid Aneurysm Trial (ISAT) shows that for patients enrolled in the trial there is a 7.4% reduction in the incidence of death or dependency at 1 year if they undergo coiling, rather than clipping. Furthermore, extrapolation of longer-term follow-up data for patient mortality appears to suggest that this advantage will be maintained in the longer term. Based on a reassessment of the published data, the authors note: (1) the incidence of rebleeding following treatment is approximately three times higher in the coiled group (p<0.001); (2) the need for aneurysm retreatment is likely to be higher in the coiled group; (3) trends in longer-term mortality data are not a reliable basis for predicting future outcomes of the trial; (4) trends in longer-term morbidity data are more reliable and suggest that the advantage of coiling diminishes with time; (5) The absence of up-to-date published rates of aneurysm retreatment and of longer-term rates of death or dependence makes ISAT extremely hard to interpret. It is far from clear that the early advantage of coiling will be maintained in the future and, hence, longer follow-up is required. Treatment of aneurysms is a continually evolving field and there is currently no other major source of information concerning management of aneurysms. For these reasons the authors recommend the instigation of a national aneurysm registry to prospectively collect data.

Susceptibility of Pseudomonas and Staphylococcus wound isolates to topical antimicrobial agents: a 10-year review and clinical evaluation.

A 10-year review of Ps. aeruginosa and Staph. aureus susceptibility to various topical agents is presented. Susceptibility testing was performed using the agar well diffusion (AWD) method. A reduction in microbial growth to numbers less than 10(5) per gram of tissue in the wound, measured by quantitative biopsy, was compared with predicted susceptibility test results. In this measurement of clinical efficacy, silver sulphadiazine and mafenide acetate compared most favourably with AWD results, 83 per cent and 82 per cent respectively. However, nitrofurazone only reduced bacterial counts to less than 10(5) per gram 42 per cent of the time when an inhibition zone was present. Hydrogen peroxide solution (1 per cent) was 100 per cent effective by the AWD test, but no relationship to clinical efficacy could be shown. Minimal inhibitory concentration (MIC) data for gentamicin sulphate was compared to AWD and showed a positive relationship of greater than 80 per cent for both organisms. The AWD test has been a useful aid in the decision-making process for the choice of topical agent by providing data which eliminates agents inappropriate for use.

Rapid quantification of bacterial and fungal growth in burn wounds: biopsy homogenate Gram stain versus microbial culture results.

A prospective analysis of 370 burn wound biopsies was done to correlate Gram-stain results from biopsy homogenates with quantitative culture results. The number of bacteria seen in a total of 10 oil immersion microscope fields of Gram-stained homogenates was correlated with significant microbial growth (1 x 10(5) organisms/gram of tissue) of the same biopsy homogenate plated on trypticase soy agar. Of the biopsies examined, Gram-negative rods were present in 36.8 per cent, Gram-positive cocci in 49.7 per cent and yeast in 15.9 per cent. Mixtures of organisms were present in 24.3 per cent. When Gram stains showed one or more organisms per oil immersion microscope field, the correlation with significant microbial growth was 94.5 per cent or more. When five or more organisms were seen per field, the correlation with significant growth became 97 per cent or greater. When no organism was seen on Gram stain, the cultures grew significant numbers of organisms 19.1 per cent of the time or less. This false-negative rate was considered to be high. It is believed, however, that this method of early detection of significant burn wound microbial growth may prove to be valuable in the management of severely burned patients.