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Object: Cerebrospinal fluid shunts in patients with posthemorrhagic hydrocephalus are prone to failure, with some patients at risk for multiple failures. The objective of this study was to identify factors leading to multiple failures., Methods: The authors performed a retrospective analysis of cases of posthemorrhagic hydrocephalus requiring neurosurgical intervention between 1982 and 2010., Results: In the 109 cases analyzed, 54% of the patients were male, their mean birth weight was 1223 g, and their mean head circumference 25.75 cm. The mean duration of follow-up was 6 years, and 9 patients died. Grade III intraventricular hemorrhage was seen in 47.7% and Grade IV in 43.1%. Initial use of a ventricular access device was needed in 65 patients (59.6%), but permanent CSF shunting was needed in 104 (95.4%). A total of 454 surgical procedures were performed, including 304 shunt revisions in 78 patients (71.6%). Detailed surgical notes were available for 261 of these procedures, and of these, 51% were proximal revisions, 13% distal revisions, and 17% total shunt revisions. Revision rates were not affected by catheter type, patient sex, presence of congenital anomalies, or type of hydrocephalus. Age of less than 30 days at the initial procedure was associated with decreased survival of the first shunt. Regression analysis revealed that lower estimated gestational age (EGA) and obstructive hydrocephalus were significant predictors of multiple shunt revisions., Conclusions: We found a high rate of need for permanent CSF shunts (95.4%) in patients with posthemorrhagic hydrocephalus. Shunt revision was required in 71.6% of patients, with those with lower birth weight and EGA at a higher risk for revisions.

Ketoconazole is recognized as the prototypical CYP3A inhibitor and is often used to determine the metabolic CYP3A liabilities of new chemical entities in preclinical and clinical studies. Ketoconazole has been commercially available for approximately 30 years and was marketed before drug-metabolizing enzymes were well characterized; consequently, little is known about its metabolic profile. Semagacestat, a γ-secretase inhibitor investigated as a potential therapy for Alzheimer's disease, was determined to be a potent CYP3A autoinducer in human hepatocytes. Two human studies were conducted to assess the induction potential of semagacestat. In the first study (study 1, n = 20), semagacestat increased the mean apparent clearance (CL/F) of oral midazolam (76-324 l/h) and nifedipine (63-229 l/h) as predicted from hepatocytes. In a second (steady-state) study (study 2, n = 20), semagacestat CL/F increased from 22 after a single dose to 31 l/h. Ketoconazole decreased semagacestat CL/F by 32% after a single dose of semagacestat [geometric means ratio estimate, 0.68; 90% confidence interval (CI). 0.64, 0.73] and 46% at steady state (geometric means ratio estimate. 0.54; 90% CI, 0.51, 0.58). Ketoconazole area under the concentration-time curve over 8 h decreased 49% from first to last day of semagacestat dosing. Semagacestat significantly increases the oral clearance of CYP3A substrates, confirming its inducer designation. More importantly, when administered with a potent CYP3A inducer at steady state, ketoconazole's plasma exposure decreased, indicating that it may also be cleared by CYP3A, other inducible enzymes or transporters, or both.

Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first study (n = 14) compared tablet to capsules. For all formulations, the median time to maximum plasma concentration (t(max)) was generally 1.0 hour. Plasma elimination was rapid, with a half-life of approximately 2.5 hours. Tablet form II bioavailability (F) relative to capsule was approximately 100% (F = 1.03 [90% confidence interval (CI), 0.96-1.10]). In the second study, participants (n = 27) received semagacestat either fed or fasting in the morning or fasting in the evening. No significant change in exposure (AUC(0-∞) [area under the concentration-time curve from 0 to infinity] ratio = 1.02, [90% CI, 0.990-1.05]) occurred with food, whereas maximum plasma concentration (C(max)) declined approximately 15%, and median t(max) was delayed to 1.5 hours. Time of dosing made no significant difference in AUC(0-∞), C(max), or t(max) (AUC(0-∞) ratio 1.01, [90% CI, 0.975-1.04]). No clinically significant safety concerns occurred in either study. Accordingly, semagacestat may be dosed without regard to formulation, food, or time of administration.

Objective: This thorough QT/ QT interval corrected for heart rate (QTc) study was designed to assess the potential of semagacestat, a functional gamma-secretase inhibitor, to delay cardiac repolarization., Methods: In this Phase I, single-dose, randomized, 4-period crossover study, semagacestat was compared with placebo in 54 healthy male and female subjects between the ages of 19 and 63 years, inclusive. Each study period included single oral-dose administrations of semagacestat 140 mg, semagacestat 280 mg, moxifloxacin 400 mg, or placebo. Study subjects and the investigator were blinded to the identity of semagacestat and placebo; however, moxifloxacin was administered as open-label. Moxifloxacin was compared with placebo for assay sensitivity analysis. Pharmacokinetic parameters were also assessed., Results: For each QTc, the upper bound of the 2-sided 90% confidence interval (CI) for the least squares mean difference between semagacestat (at both the 140- and 280-mg dose levels) and placebo was < 10 msec at all time points, and thus, within the limits set for clinical relevance in regulatory guidelines., Conclusions: The results of this study indicate that single doses of 140 and 280 mg semagacestat did not prolong QTc to a clinically significant degree.

Background: Implementation of consensus guidelines for esophageal variceal hemorrhage yields improved outcomes. We evaluated guideline adherence and outcomes after variceal hemorrhage at a university hospital (UH) and a staff-model health maintenance organization (HMO)., Study: Factors associated with short-term bleeding, infection, and death were retrospectively identified in UH (n=160) and HMO (n=123) patients with esophageal variceal hemorrhage from January 2000 to December 2006. A second analysis of factors associated with long-term rebleeding was conducted in patients who survived ≥14 days without rebleeding., Results: UH patients were younger, with more severe liver disease and overall illness (P<0.01). UH patients more often received vasoactive agents and prophylactic antibiotics (P<0.01), however the rate of endoscopic therapy did not differ. Infections at 14-days were similar (18.2% vs. 13.0%, P=0.25), but UH patients had greater in-hospital rebleeding (16.4% vs. 5.7%, P<0.01) and mortality (15.2% vs. 4.1%, P<0.01). Poor liver function and overall illness predicted infection, rebleeding, and death (adjusted odds ratio 2.75 to 13.39). Long-term rebleeding occurred in 36.1% of UH patients and 25.9% of HMO patients. Secondary prophylaxis reduced late rebleeding (hazard ratio 0.37 to 0.41). Poor liver function did not predict late rebleeding. Adherence to secondary prophylaxis was greater at the HMO (P<0.05), but late rebleeding did not differ (36% vs. 26%, P=0.13)., Conclusions: Irrespective of practice setting, poor liver function and critical illness predicted short-term bleeding, infection, and death after esophageal variceal hemorrhage, and secondary prophylaxis prevented long-term rebleeding. Differing guideline adherence did not influence outcomes between tertiary care and non-tertiary care centers.

Objective: To investigate the effects that prevalence has on the diagnostic performance of junior doctors in interpreting x-rays., Design: Two-armed cross-sectional design using systematic sampling., Setting: Emergency department in the UK., Participants: From a sample of 2593 patients (1434 men and 1159 women) taken from an unselected attending cohort between January and April 2002, 967 x-rays were analysed. The sex distribution was 558 men and 409 women, and the mean age of those receiving an x-ray was 34.6., Interventions: The interpretation of x-rays by junior doctors after their triage into high- and low-prevalence populations by radiographers., Main Outcome Measures: Sensitivity, specificity, likelihood ratios, diagnostic odds ratios and receiver operator characteristic curve., Results: There were statistically significant differences in the performance characteristics of junior doctors when interpreting high-probability and low-probability x-rays. For the high- and low-probability populations, respectively, the sensitivities were 95.8% (95% CI 91.1% to 98.1%) and 78.3% (95% CI 65.7% to 87.2%) and the specificities were 56.0% (95% CI 41.9% to 69.2%) and 92.3% (95% CI 90.0% to 94.2%). Hierarchical logistic regression showed that the sensitivity did depend on the type of x-ray being interpreted but the diagnostic odds ratios did not vary significantly with prevalence, suggesting that doctors were changing their implicit threshold between the two populations along a common receiver operator characteristic curve., Conclusions: This study provides evidence on how the prevalence may affect the performance of diagnostic tests with an implicit threshold and potentially includes the clinical history and examination. This has implications both for clinicians applying research findings to their practice and the design of future studies.

Pt was deposited onto tungsten carbide powders using atomic layer deposition to produce core-shell catalysts for the hydrogen evolution reaction (HER). The Pt loading on these catalysts was reduced nearly ten-fold compared to a bulk Pt catalyst while equivalent HER activities were observed., (This journal is © The Royal Society of Chemistry 2012)

Objectives: Solanezumab is a humanized anti-amyloid β monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). Pharmacokinetics (PK), pharmacodynamics, safety, and tolerability after a single dose of solanezumab were compared between Japanese and white patients with AD., Methods: Japanese and white patients with mild to moderate AD were enrolled in 2 separate studies. In each study, single doses of solanezumab at 0.5, 1.5, 4.0, and 10.0 mg/kg were administered by intravenous infusion. Plasma concentrations of solanezumab and amyloid β (Aβ) were measured. A safety assessment was conducted up to 112 days after a single-dose administration of solanezumab., Results: The PK profile was similar between the Japanese and the white patients with AD. In both the Japanese and the white patients, clearance and volume of distribution appeared similar across doses, suggesting that solanezumab exhibited dose-proportional PK within the studied dose range. A marked increase in plasma total Aβ was observed; both the magnitude and time to reach maximum concentration tended to increase with increasing doses of solanezumab. Administration of solanezumab was generally well-tolerated in both Japanese and white patients with AD., Conclusions: When administered as a per-kilogram single dose of solanezumab, PK and pharmacodynamics (plasma total Aβ1-40 concentration) in the Japanese patients with AD were comparable with those in the white patients with AD. In addition, solanezumab was generally well tolerated in both Japanese and white patients at all dose levels.

Background: Over the last decade there have been a number of guidelines published, aimed at improving the quality of reporting in published studies and reviews. In systematic reviews this may be measured by their compliance with the PRISMA statement. This review aims to evaluate the quality of reporting in published meta-analyses of diagnostic tests, using the PRISMA statement and establish whether there has been a measurable improvement over time., Methods: Eight databases were searched for reviews published prior to 31(st) December 2008. Studies were selected if they evaluated a diagnostic test, measured performance, searched two or more databases, stated the search terms and inclusion criteria, and used a statistical method to summarise a test's performance. Data were extracted on the review characteristics and items of the PRISMA statement. To measure the change in the quality of reporting over time, PRISMA items for two periods of equal duration were compared., Results: Compliance with the PRISMA statement was generally poor: none of the reviews completely adhered to all 27 checklist items. Of the 236 meta-analyses included following selection: only 2(1%) reported the study protocol; 59(25%) reported the searches used; 76(32%) reported the results of a risk of bias assessment; and 82(35%) reported the abstract as a structured summary. Only 11 studies were published before 2000. Thus, the impact of QUOROM on the quality of reporting was not evaluated. However, the periods 2001-2004 and 2005-2008 (covering 93% of studies) were compared using relative risks (RR). There was an increase in the proportion of reviews reporting on five PRISMA items: eligibility criteria (RR 1.13, 95% CI 1.00 - 1.27); risk of bias across studies (methods) (RR 1.81, 95% CI 1.34 - 2.44); study selection results (RR 1.48, 95% CI 1.05 - 2.09); results of individual studies (RR 1.37, 95% CI 1.09 - 1.72); risk of bias across studies (results) (RR 1.65, 95% CI 1.20 - 2.25)., Conclusion: Although there has been an improvement in the quality of meta-analyses in diagnostic research, there are still many deficiencies in the reporting which future reviewers need to address if readers are to trust the validity of the reported findings.

We analysed retrospectively the effect of missile trajectory on outcomes from civilian gunshot injury to the spine (GSIS) between 1994 and 2008. Most of the 98 patients were male (88.8%). A minority (8%) of patients had multiple column injuries and a bone or bullet fragment in the spinal canal (14%). Neurologic injury was seen in 33%; and external bracing was applied to 30% of patients. The odds of bracing among patients with multiple levels of damage were 3.4 times than for patients with a single vertebral level of damage. The odds of paralysis among black patients were 6.33 times the odds among non-black patients. The odds of paralysis among patients with a fragment in the spinal canal were 12.99 times those without. We conclude that the supero-inferior trajectory affects the number of vertebral levels involved and consequently the need for bracing. The lateral trajectory affects neurological outcomes., (Published by Elsevier Ltd.)

Background: The last decade has seen a number of methodological developments in meta-analysis of diagnostic test studies. However, it is unclear whether such developments have permeated the wider research community and on which applications they are being deployed. The objective was to assess the uptake and deployment of the main methodological developments in the meta-analysis of diagnostic tests, and identify the tests and target disorders most commonly evaluated by meta-analysis., Methods: Design--systematic review. Data Sources--Medline, EMBASE, CINAHL, Cochrane, PsychInfo, Global health, HMIC, and AMED were searched for studies published before 31st December 2008. Selection criteria--studies were included if they satisfied all of the following: evaluated a diagnostic test; measured test performance; searched two or more databases; stated search terms and inclusion criteria; used a statistical method to summarise performance. Data extraction--included the following data items: year; test; reference standard; target disorder; setting; statistical and quality methods., Results: 236 studies were included. Over the last 5 years the number of meta-analyses published has increased, but the uptake of new statistical methods lags behind. Pooling the sensitivity and specificity and using the SROC remain the preferred methods for analysis in 70% of studies, with the bivariate random effects and HSROC model being used in only 22% and 5% of studies respectively. In contrast, between 2006 and 2008 the QUADAS tool was used in 40% of studies. Broadly, radiological imaging was the most frequent category of tests analysed (36%), with cancer (22%) and infection (21%) being the most common categories of target disorder. Nearly 80% of tests analysed were those normally used in specialist settings., Conclusion: Although quality assessment in meta-analyses has improved with the introduction of QUADAS, uptake of the newer statistical methods is still lagging behind. Furthermore, the focus of secondary research seems to be in evaluating specialist tests in specialist settings, in contrast to the more routine tests and settings encountered in the majority of clinical practice.

Aim: To determine the potential of cortisol secretion, in response to a physiological stressor, as a biomarker for centrally active compounds targeting the hypothalamic-pituitary-adrenocortical (HPA) axis., Methods: Cortisol response to hypoglycaemia was measured in 26 healthy males in two stages: firstly to derive an algorithm for individualized, graded insulin infusion rates to achieve defined hypoglycaemic targets over 3 h and secondly to determine the inter- and intra-subject variability of cortisol response to hypoglycaemia over two identical periods by measuring the maximum (t(max) ), time to maximum (C(max) ) response and cortisol area under the response curve (AUC)., Results: Hypoglycaemia induced a consistent cortisol response starting at approximately 1 h, corresponding to blood glucose concentrations of approximately 3.3 mmol l⁻¹, and peaking approximately 3 h after the start of infusion. The inter- and intra-subject coefficients of variation (CVs) of cortisol response were approximately 19 and 19% (AUC), 15 and 19 % (C(max) ) and 10 and 14% (t(max) ), respectively. The intra-subject CVs for the ratio of maximum cortisol response to baseline concentration and rate of initial cortisol response between study days were more variable (32.8% and 59.0%, respectively). The blood glucose-cortisol response model derived from the study was predictive of the individual observed cortisol responses, and estimated a blood glucose EC(50) associated with onset of the cortisol response of 3.3 mmol l⁻¹., Conclusions: Gradual hypoglycaemia is an effective, reproducible and well-tolerated method of stimulating a cortisol response and may therefore be useful in assessing the neuroendocrine response to HPA axis inhibitors, such as corticotropin-releasing hormone-1 (CRH-1) antagonists., (© 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.)

Lhermitte-Duclos disease is a rare cerebellar lesion that poses many diagnostic, pathophysiologic and therapeutic conundrums. Here we present a case that highlights the most important imaging characteristics for diagnosis, the pathophysiology of the disease, and the current management recommendations.

Object: Hydrocephalus is a notorious neurosurgical disease that carries the adage "once a shunt always a shunt." This study was conducted to review the treatment results of pediatric hydrocephalus., Methods: Pediatric patients who underwent ventriculoperitoneal shunt surgery over the past 14 years were reviewed for shunt revisions. Variables studied included age at shunt placement, revision, or replacement; programmable shunts; infection; obstruction; and diagnosis (congenital, posthemorrhagic, craniospinal dysraphism, and others including trauma, tumors, and infection). Multiple regression analysis methods were used to determine independent risk factors for shunt failure and the number of shunt revisions. The Kaplan-Meier method of survival analysis was used to compare etiologies on the 5-year survival (revision-free) rate and the median 5-year survival time., Results: A total of 253 patients were studied with an almost equal sex distribution. There were 92 patients with congenital hydrocephalus, 69 with posthemorrhagic hydrocephalus, 48 with craniospinal dysraphism, and 44 with other causes. Programmable shunts were used in 73 patients (other types of shunts were used in 180 patients). A total of 197 patients (78%) underwent revision surgeries due to shunt failures. The mortality rate was 1.6%. Age at first revision, the 5-year survival rate, and the median 5-year survival time were significantly less for both posthemorrhagic and craniospinal dysraphism than for either the congenital or "other" group (p < 0.05). The failure rate and number of revisions were not significantly reduced with programmable shunts compared with either pressure-controlled or no-valve shunts (p > 0.5)., Conclusions: Posthemorrhagic hydrocephalus and craniospinal dysraphism hydrocephalus had significantly earlier revisions than congenital and other etiologies. Programmable systems did not reduce the failure rate or the average number of shunts revisions.

Object: The aim of the study was to analyze the outcome of surgical treatment for posthemorrhagic hydrocephalus in premature infants., Methods: From 1990 to 2006, 32 premature infants underwent surgical treatment for posthemorrhagic hydrocephalus, and their charts were retrospectively reviewed to analyze the complications and outcome with respect to shunt revisions. Multivariate analysis and time series were used to identify factors that influence the outcome in terms of shunt revisions., Results: The mean gestational age was 27+/-3.3 weeks, and mean birth weight was 1192+/-660 g. Temporary reservoir placement was performed in 15 patients, while 17 underwent permanent CSF diversion with a ventriculoperitoneal (VP) shunt. In 2 patients, reservoir tapping alone was sufficient to halt the progression of hydrocephalus; 29 patients received VP shunts. The mean follow-up period was 37.3 months. The neonates who received VP shunts first were significantly older (p=0.02) and heavier (p=0.04) than those who initially underwent reservoir placement. Shunts were revised in 14 patients; 42% of patients in the reservoir group had their shunts revised, while 53% of infants who had initially received a VP shunt required a revision. The revision rate per patient in the reservoir group was half that in the direct VP shunt group (p=0.027). No patient in the reservoir group had >2 revisions. Shunt infections developed in 3 patients (10.3%), and 2 patients in the reservoir group died of nonneurological issues related to prematurity., Conclusions: Birth weight and age are useful parameters in decision making. Preterm neonates with low birth weights benefit from initial CSF drainage procedures followed by permanent CSF diversion with respect to the number of shunt revisions.

When applying study results to their practice, the clinician is constrained by a number of factors, perhaps none more important than spectrum bias, which describes the effect a change in patient case mix may have on the performance of a test. Although the literature contains notable examples of spectrum bias, the emphasis has been to demonstrate its existence and its implications on study design rather than how it affects the clinician. Here a definition is proposed before considering it from a GP's perspective. As a patient's probability of disease is in part determined by the test's result, having reliable estimates of a test's performance is imperative to making good decisions on patient management. Knowing how the test performs on a patient usually means knowing its performance within a particular subgroup. Unfortunately, studies tend to report weighted average estimates of performance across broad populations. Such estimates may be inaccurate at an individual level and at a population level with the overall performance of the test in practice varying significantly from the average estimate reported, owing to differing case mixes. To avert such problems, investigators should design studies to evaluate tests over all relevant subgroups, and where this is not possible, to be explicit about the case mix in the study sample. Furthermore, GPs should endeavour to know both individual patients and practice populations as a whole in terms of demographics and co-morbidities before applying study results to their patients.

Object: The purpose of this study was to determine whether cocaine use is a significant prognostic factor for outcome measures such as Hunt and Hess grade and Glasgow Outcome Scale (GOS) score among patients presenting with ruptured intracranial aneurysms (IAs)., Methods: The authors performed a MEDLINE/PubMed search for cases of ruptured IAs associated with cocaine use. Fourteen cases from the authors' experience were combined with 50 from a literature review, for a total of 64 cases associated with cocaine use. These 64 cases were compared with 65 cases without cocaine use (controls), which had been obtained from an aneurysm database. Logistic regression analysis was performed to determine significant prognostic factors for a poor Hunt and Hess grade and a poor GOS score, and a general linear model was applied to identify significant factors for these measures among cocaine users., Results: There were 40 women in each group. The mean age was 32.3 +/- 8.1 years in the cocaine group and 49.7 +/- 10.6 years in the control group; thus, patients in the cocaine group were significantly younger (p < 0.01). Cocaine was snorted in 21% of cases, smoked in 55%, and intravenously injected or taken in through a combination of routes in 24%. Fifty-one percent of cocaine users and 7.7% of nonusers presented with a poor GOS score (p < 0.01). Fifty-six percent had ictus during cocaine abuse. At the end of a 30-day follow-up, 51% of the patients in the cocaine group had a good GOS score compared with 92% in the control group (p < 0.01). Controlling for the effects of other significant factors, cocaine use had a significant effect on Hunt and Hess grade (p < 0.03) and GOS score (p < 0.01). The odds of having a poor Hunt and Hess grade among cocaine users were 4.2 times greater than those in nonusers, and the odds of having a poor GOS score among cocaine users were 38.8 times greater., Conclusions: Aneurysms were significantly smaller and ruptured at a younger age among cocaine users compared with nonusers. Although the poor clinical grade was not significantly different between the 2 groups, outcome was significantly worse in cocaine users.

Objective: To assess the accuracy of Senior House Officers at interpreting plain X-rays following their triage by radiographers in an emergency department., Method: We collected 2593 patients' records by systematic sampling of all those seen by emergency physicians between January 2002 and April 2002 (ca 10 000 patients) in a UK emergency department. The variables recorded included evidence of X-ray investigations and, when present, the Senior House Officer's diagnosis, the presence (abnormal) or absence of a radiographers red dot and the reference standard diagnosis. A separate category of uncertain (inconclusive) was applied to the Senior House Officer and reference standard diagnosis where appropriate. Diagnostic performance was measured by likelihood ratios with associated pre-test and post-test probabilities., Results: Including the uncertain category as abnormal gave the following results: there were 967 X-rays and those with a red dot had a probability of an abnormality of 80%. Although a further opinion of abnormal by a Senior House Officer increased this probability to 89% when they overrode the red dot opinion of the radiographer, it was incorrect in 26% of cases., Conclusion: Currently, the Senior House Officer contributes to the red dot system by improving on the radiographer in rates of diagnosis of both abnormal and normal X-rays. Further reductions in error rates, however, are unlikely to be achieved until there is a change to the existing system. This may ultimately involve removing some of the responsibility of X-ray interpretation from the Senior House Officer. Any future research should consider the methodological issues highlighted by this study.

Object: A dural tear resulting in a cerebrospinal fluid (CSF) leak is a well-known risk of lumbar spinal procedures. The authors hypothesized that the incidence of CSF leakage is higher in cases involving repeated operations and those in which the surgeon performing the surgery is less experienced; however, they postulated that the overall outcome of the patient would not be adversely affected by a dural tear., Methods: An institutional review board-approved protocol at Louisiana State University Health Sciences Center, Shreveport, was initiated in August 2003 to allow prospective comparison of data obtained in patients in whom a CSF leak occurred (Group A) and those in whom no CSF leak occurred (Group B) during lumbar surgery. Basic demographic information, descriptive findings regarding the tear, history of other surgeries, hospital length of stay (LOS), and immediate disposition at the time of discharge were compared between the two groups. Seventy-seven patients were eligible for this study. One patient refused to participate. In 12 (15.8%) of 76 patients CSF leakage developed. In three patients the presence of a tear was questioned, and the patients were clinically treated as if a tear were present. The patients in Group A were older than those in Group B (59.8 +/- 16.9 and 49.4 +/- 13.6 years of age, respectively; p = 0.02, Fisher exact test). In terms of those with a history of surgery, there was no significant difference between patients with and patients without a CSF leak (three [25%] of 12 patients [Group A] compared with 28 [43.8%] of 64 patients [Group B]; p = 0.34, two-sample t-test). In the 12 patients with dural tears, nine (75%) were caused by a resident-in-training, and the Kerrison punch was the instrument most often being used at the time (55%). This is significantly greater than 50% at the 5% level (p = 0.044, binomial test). The authors were able to repair the tear primarily with suture in all but one patient, whose tear was along the nerve root sleeve. In all cases fibrin glue and a muscle/fat graft were used to cover the tear, and all patients were assigned to bed rest from 24 to 48 hours after the operation. In Group A one patient required rehabilitation at discharge. The LOS in Group A was greater than that in Group B (median 5 days compared with 3 days), but no additional complication was noted., Conclusions: The incidence of CSF leakage was 16% in 76 patients, and there were no other complications. Older patient age and higher level of the surgeon's training were factors contributing to the incidence, but the history of surgery was not.

Objective: The early management of posthemorrhagic hydrocephalus in premature infants is challenging and controversial. These infants need a temporary cerebrospinal fluid (CSF) diversion procedure until they gain adequate weight, and the blood and protein levels in CSF are reasonably low before permanent shunt can be placed. Various options are available with their associated advantages and disadvantages. Ventriculosubgaleal shunts have been recommended as a more physiologic and less invasive means of achieving this goal. We have performed this procedure in 6 premature infants to evaluate their effectiveness and complications., Methods: Six consecutive premature infants with posthemorrhagic hydrocephalus underwent placement of ventriculosubgaleal shunts over a 1-year period of time. We reviewed their clinical and imaging progress to assess the ability of the shunt to control hydrocephalus and the complication rates., Results: In all 6 patients, the ventriculosubgaleal shunt controlled the progression of hydrocephalus as assessed by clinical and imaging parameters. A permanent shunt was avoided in 1 patient (16.6%). However, 4 patients developed shunt infections, 1 involving the ventriculosubgaleal shunt itself, and 3 immediately after conversion to ventriculoperitoneal shunt. The total infection rate of the series was 66.6%. All infections were caused by staphylococcus species. There was only a 1% shunt infection rate in our institution for all nonventriculosubgaleal shunts during the same period of time., Conclusion: Placement of ventriculosubgaleal shunts for interim CSF diversion in neonates with posthemorrhagic hydrocephalus is effective as a temporary method of CSF diversion. However, our experience has shown that it is associated with a unacceptably high CSF infection rate. A potential cause for infection is CSF stasis just beneath the extremely thin skin of the premature infants, promoting colonization by skin flora. CSF sampling before conversion to a permanent shunt and replacement of the proximal hardware, which has been in situ for a prolonged period, may decrease the infection rates. At present, the procedure is no longer performed at our institution.

Object: There are various surgical treatment alternatives for trigeminal neuralgia (TN), but there is no single scale that can be used uniformly to assess and compare one type of intervention with the others. In this study the objectives were to determine factors associated with pain control, pain-free survival, residual pain, and recurrence after gamma knife surgery (GKS) treatment for TN, and to correlate the patients' self-reported quality of life (QOL) and satisfaction with the aforementioned factors., Methods: Between the years 2000 and 2004, the authors treated 81 patients with medically refractory TN by using GKS. Fifty-two patients responded to a questionnaire regarding pain control, activities of daily living, QOL, and patient satisfaction. The median follow-up duration was 16.5 months. Twenty-two patients (42.3%) had complete pain relief, 14 (26.9%) had partial but satisfactory pain relief, and in 16 patients (30.8%) the treatment failed. Seven patients (13.5%) reported a recurrence during the follow-up period, and 25 (48.1%) reported a significant (> 50%) decrease in their pain within the 1st month posttreatment. The mean decrease in the total dose of pain medication was 75%. Patients' self-reported QOL scores improved 90% and the overall patient satisfaction score was 80%., Conclusions: The authors found that GKS is a minimally invasive and effective procedure that yields a favorable outcome for patients with recurrent or refractory TN. It may also be offered as a first-line surgical modality for any patients with TN who are unsuited or unwilling to undergo microvascular decompression.

Tethered cord syndrome (TCS) is a rare entity in adults, with only about 100 cases being reported in the literature. It is a syndrome in which patients have neurologic, urologic, and orthopedic signs and symptoms. We present a case of a 40-year-old man with back pain and urinary incontinence who was diagnosed with tethered cord syndrome. After the cord de-tethering in the operating room, his pain improved. TCS is an important condition to consider in the differential diagnosis of an adult who presents with back pain and urological symptoms. Imaging studies should be done, and operative treatment may be required to alleviate the symptoms. TCS should be in the differential diagnosis of any patient who presents with back and lower extremity complaints with superimposed urological problems. If TCS is confirmed radiologically by MRI, surgery can be performed with reasonable results provided that the disease process has not progressed.

Background: Glioblastoma multiforme (GBM) is a high-grade primary brain tumor that is refractory to current forms of treatment. In cell studies, the growth rate of GBM cells correlates with the level of Cyclooxygenase-2 (COX-2) enzyme expression. COX-2 has been implicated in carcinogenesis of systemic cancers. Recently, COX-2 inhibition has been shown to increase the radiosensitivity of various tumors. We wished to assess whether the expression of COX-2 is greater in radioresistant versus radiosensitive forms of GBM., Materials and Methods: The radiosensitive (A172) and radioresistant (T98G) Glioblastoma multiforme cell lines were assayed for COX-2 expression using standard immunofluorescence histochemistry. Fluorescence readings were recorded per field. Western blot analysis was performed on both A172 and T98G GBM cell lines. The radioresistant cells were exposed to incremental doses of radiation in the presence and absence of a COX-2-selective inhibitor. Radioresistant cells were then exposed to incremental doses of COX-2-selective inhibitor at a constant dose of radiation., Results: The radioresistant cell line T98G had an approximate 1. 7-fold greater expression of COX-2 than did the radiosensitive cell line A172, as per immunofluorescence histochemistry. Western blot analysis confirmed this finding. Statistical analysis (Bonferroni/Dunn) showed the results to be significant (p<0.0001). The wells containing radioresistant cells exposed to incremental doses of radiation and COX-2 inhibitors appeared to have higher cell kill when compared to radiation alone. Furthermore, increasing the COX-2 inhibitor concentration yielded higher cell kill., Conclusion: The results presented here show that the radioresistant GBM cell line, T98G, has a greater expression of COX-2 than does the radiosensitive GBM cell line, A172. These results suggest that: (i) COX-2 expression may serve as a marker for assessing radioresistance in GBM, (ii) COX-2 inhibition may lower the required doses of postoperative radiation, (iii) COX-2 inhibitors may have a role in radiosensitizing otherwise radioresistant forms of GBM.

Object: The objective of this retrospective study was to analyze the results of stereotactic radiosurgery performed using a gamma knife in the treatment of 44 consecutive patients with brain metastases from lung carcinoma., Methods: Forty-four patients with lung carcinoma were treated for metastatic brain tumors by performing radiosurgery with a Leksell Gamma Knife. Twenty-one patients (47.7%) were women and 23 were men. The mean age of the patients was 56 years (range 35-77 years). Twenty-two patients (50%) had solitary tumors and the rest had multiple tumors (two-six lesions). Eighteen patients (40.9%) presented with a recurrent and/or progressive brain disease that previously had been treated with other modalities (surgery, external-beam radiotherapy, or both). Fifteen patients had controlled lung disease and 19 patients had systemic metastases (in lymph nodes, liver, and/or bones) at the time of radiosurgery. The median follow-up period was 18.25 months. All patients were followed up for three different end points: 1) death caused by the disease; 2) clinical and/or radiological evidence of progression of the tumor that had been treated with radiosurgery; and 3) appearance of new lesions. At the last follow-up review, 17 patients (38.6%) were alive and 27 (61.4%) had died. Ten patients (22.7%) died as a result of brain disease (failure of local control or new metastases). Controlled primary disease at the time of detection of metastases and the ability to achieve local tumor control after radiosurgery significantly improved the patient survival (p < 0.01). Control of the treated tumor(s) was achieved in 32 of 44 patients (72 tumors) and 10 patients experienced treatment failure. In addition to the 44 patients comprising the study population, two other patients were treated, but died of lung disease too early in the follow-up period to have been assessed. As of the last follow-up review, no new brain metastasis had occurred in 36 patients (81.8% [includes surviving and nonsurviving patients]). The median duration of overall survival was 7 months, the median period of controlled brain disease was 21 months, and the median period of freedom from new brain metastases was 17 months (95% confidence interval 13-19 months)., Conclusions: Gamma knife surgery has significantly reduced the incidence of mortality from brain disease by effectively accomplishing local tumor control in patients with metastatic lung cancer. Local control and freedom from new brain metastases is not influenced by prior external-beam radiotherapy.

Pharmacological therapy for essential tremor (ET), the most common movement disorder, remains largely unsatisfactory. Surgical options such as radiofrequency or thermocoagulation are only suitable for a select group of patients, the young and those free of pre-existing medical conditions. Radiosurgery using the Leksell Gamma Knife has recently gained acceptance as a viable treatment option for tremor control in ET patients. We describe our experience with the first reported ET patient treated with radiosurgery in Louisiana.

Purpose: Multiple studies have demonstrated that catheter-related bloodstream infections (CRBI) can be successfully treated without catheter removal (in situ therapy), but there is insufficient information available to determine if catheter design can influence the eradication of bacteremia or recurrence., Patients and Methods: Bacteremic episodes in patients at St Jude Children's Research Hospital between January 1996 and May 2001 were identified and patient records were reviewed., Results: A total of 172 unique episodes of CRBI were identified. In situ therapy resulted in successful eradication of bacteremia in 87% of the episodes. Bacteremia recurred in 10% of the episodes. Although catheter design (Hickman and Broviac versus totally implantable central venous catheter) did not influence short-term eradication of bacteremia, totally implantable central venous catheters were significantly associated with recurrence of bacteremia (odds ratio, 10; 95% confidence interval, 3.1 to 33.3). In a multivariable analysis, this association between catheter design and recurrence remained statistically significant after adjustment for other factors that influenced recurrence in this study (isolation of coagulase-negative staphylococci and inadequate duration of initial antibiotic therapy)., Conclusion: This study demonstrates that patients with CRBI with a totally implantable central venous catheter in place are more likely to develop recurrent bacteremia. Management strategies to prevent recurrence in this setting should be explored.

Objective: Secondary prostate cancer affection of the cauda equina (SPCCE) can be an ultimate cause of morbidity and mortality. Since the results of management of this particular disease condition remain largely unknown, a retrospective case review was undertaken to determine the effects of treatment by radiation in SPCCE patients., Methods: The records of 12 patients with SPCCE treated at the Division of Therapeutic Radiology during the period 1984 to 1998 were reviewed. The administered total radiation dosage ranged from 6 Gy to 32 Gy (average, 26.6 +/- 2.0 Gy). Two individuals underwent decompressive laminectomy and bilateral orchiectomy at the time of SPCCE and prostate cancer diagnoses. Ten patients had prior hormonal manipulative treatment (orchiectomy, estrogen, or Flutamide therapy)., Results: Pain was relieved in three of four symptomatic patients (75%). Five of nine patients unable to walk before therapy could walk after treatment. One of two individuals with anal or bladder sphincter dysfunction improved following irradiation. The overall mean duration of survival was five months. With treatment, survival was approximately three times as long for ambulatory versus non-ambulatory patients., Conclusion: We conclude that radiation treatment is efficacious in promoting palliation of SPCCE, although it may not prolong life.

Background: The objective of this study was to assess the role of selective intraoperative angiography and to analyze the factors associated with faulty clip application., Methods: Two hundred thirty-eight patients undergoing surgery for intracranial aneurysms were studied consecutively for intraoperative angiography (IOA)-related events. The procedure was performed in 155 operations. Demographic details, clinical grade of the patient, location and size of the aneurysm, intraoperative rupture, application of the temporary clip, IOA findings, and final outcome were analyzed., Results: In the 155 patients in the series, there were 125 anterior circulation aneurysms and 30 on the vertebrobasilar system. Aneurysms were smaller than 10 mm in 63% of the patients, and 19 were giant aneurysms. Thirty-eight percent were unruptured, 36% were Hunt and Hess Grades I and II, 21% were Grade III, and 5% were Grades IV and V. An intraoperative rupture occurred in 18 operations. Intraoperative angiography was normal in 88%; in 11 cases (7%) there was a residual neck, and in 8 (5%), occlusion of the artery was observed. An incomplete clipping was significantly related to intraoperative rupture of the aneurysm (p < 0.008) and anterior location of the aneurysm (p = 0.05), whereas vessel occlusion had a significant association with posterior location of the aneurysm (p < 0.0005). An eventful IOA had significant association with poor outcome (p < 0.003)., Conclusion: Intraoperative rupture and a posterior location of the aneurysm had a significant correlation with residual aneurysm and vessel occlusion, respectively. The use of IOA is justified in aneurysms associated with these factors.

Louisiana's first ever Leksell Gamma Knife was commissioned at Louisiana State University Health Sciences Center (LSUHSC) in Shreveport in January 2000. Between January 2000 and January 2001,113 patients with various indications were treated using the 201-source Co-60 Leksell model "B" Gamma Knife (Elekta Instruments, Atlanta, Georgia) at LSUHSC-Shreveport. Sixty-three patients were female and 50 were male. The patient age ranged between 13 and 87 years (mean age = 57 years). Fifty-eight (51.3%) patients received radiosurgery as the first line of treatment for their disease, while 55 (48.7%) had previous operations or radiation therapy. The median Karnofsky Performance Score of the patients was 80 (range = 70 to 100). Cerebral metastases were the main indication for radiosurgery at our center accounting for 35% of the patients, while meningioma, arteriovenous malformation, trigeminal neuralgia, and primary central nervous system malignant tumors were the other indications.

Objective: To analyze 18 months of results of gamma knife stereotactic radiosurgery in the treatment of brain metastases and determine factors affecting outcome by examining the effectiveness of additional external-beam radiotherapy (XRT)., Materials and Methods: Between January 2000 and September 2001, 61 patients with 103 tumors diagnosed as cerebral metastases were treated with gamma knife. Mean patient age was 57 years (range = 36-81). Lung carcinoma (55.7%) was the most common primary cancer, followed by melanoma (14.8%) and breast carcinoma (11.5%). Mean KPS of the patients was 70 (range = 50-90). Twenty-seven patients had solitary metastases while 34 had multiple tumors. Forty-three patients (59 tumors in total) received only radiosurgery, while 18 patients (44 tumors in total) had prior XRT. Tumor volume ranged from 0.5 to 33 cm(3) (mean = 9.74 cm(3)). Mean marginal dose prescription to the tumor was 15 Gy (range = 11-21 Gy)., Results: Median follow-up was 11 months. Twenty-one patients (34.4%) were alive at last follow-up and 40 (65.6%) had died. Seventeen deaths (42.5%) were reported to be due to progressive brain disease, while 23 deaths (57.5%) were due to uncontrolled primary. Control of the treated lesions was achieved in 45 patients (73.8%) and 84 tumors (81.6%). Mean overall survival of the patients is 8 months (range = 1-19 months). The actuarial 12-month tumor control rate using the Kaplan-Meier method for this series is 68.2 +/- 0.06%. Results of the log-rank test revealed that younger age (<55 years), small tumor volume (<10 cm(3)), and increasing tumor dose (>15 Gy) correlated with improved brain disease-free survival (p < 0.05). Overall survival, local tumor control rate and the freedom from brain disease period (based on the appearance of new brain tumors after radiosurgery) were analyzed separately for the groups receiving radiosurgery alone and those with prior XRT to detect any additional benefit of XRT. No statistically significant difference was found between the two groups for any of the considered outcomes., Conclusion: Gamma knife stereotactic radiosurgery is a safe and effective treatment option for patients with cerebral metastases. It provides survival benefits and improves quality of life by achieving excellent control of the brain disease, irrespective of patients' age or number of brain tumors. The addition of XRT in younger patients with small brain metastases does not improve survival and/or control of the brain disease., (Copyright 2002 S. Karger AG, Basel)