Cerebrospinal fluid shunt failure, predominantly from shunt obstruction and infection, remains a persistent problem in pediatric hydrocephalus. Two new valve designs did not significantly affect shunt failure rates.

This open pilot study of vagus nerve stimulation (VNS ™ ) in 60 patients with treatment-resistant major depressive episodes (MDEs)

Background: A previously reported multicenter randomized trial assessed whether 2 new shunt valve designs would reduce shunt failure rates compared to differential pressure valves. The study did not show a significant difference in the time to first shunt failure. Patients entered the trial between October 1, 1993, and October 31, 1995. The primary results were based on the patients’ status as of October 31, 1996 (a minimum follow-up of 1 year). This report describes the late complications based on the patients’ most recent follow-up. Methods: Three hundred and forty-four hydrocephalic children at 12 North American and European centers were randomized to 1 of 3 valves: a standard differential pressure valve; a Delta valve (PS Medical-Medtronic) or a Sigma valve (NMT Cordis). Patients were followed until their first shunt failure. Shunt failure was defined as shunt surgery for obstruction, overdrainage, loculation or infection. If the shunt did not fail, follow-up was continued until August 31, 1999. Results: One hundred and seventy-seven patients had shunt failure. Shunt obstruction occurred in 131, overdrainage in 13, loculated ventricles in 2 and infection in 29. The overall shunt survival was 62% at 1 year, 52% at 2 years, 46% at 3 years, 41% at 4 years. The survival curves for the 3 valves were similar to those from the original trial and did not show a survival advantage for any particular valve. Conclusions: Prolonged follow-up to date does not alter the primary conclusions of the trial: there does not appear to be one valve that is clearly the best for the initial treatment of pediatric hydrocephalus.

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Cranioplasty is almost as ancient as trephination, yet its fascinating history has been neglected. There is strong evidence that Incan surgeons were performing cranioplasty using precious metals and gourds. Interestingly, early surgical authors, such as Hippocrates and Galen, do not discuss cranioplasty and it was not until the 16th century that cranioplasty in the form of a gold plate was mentioned by Fallopius. The first bone graft was recorded by Meekeren, who in 1668 noted that canine bone was used to repair a cranial defect in a Russian man. The next advance in cranioplasty was the experimental groundwork in bone grafting, performed in the late 19th century. The use of autografts for cranioplasty became popular in the early 20th century. The destructive nature of 20th century warfare provided an impetus to search for alternative metals and plastics to cover large cranial defects. The metallic bone substitutes have largely been replaced by modern plastics. Methyl methacrylate was introduced in 1940 and is currently the most common material used. Research in cranioplasty is now directed at improving the ability of the host to regenerate bone. As modern day trephiners, neurosurgeons should be cognizant of how the technique of repairing a hole in the head has evolved.

Background and Purpose Patients with intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) have a reported mortality of 50–80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events and for its effect on the rate of intraventricular clot lysis. Methods 48 Patients were enrolled at 14 centers and randomized to treatment with 3mg recombinant tissue plasminogen activator (rt-PA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the two groups. Results Severity factors, including admission GCS, ICH volume, IVH volume and blood pressure, were evenly distributed, as were adverse events except for an increased frequency of respiratory system events in the placebo-treated group. Neither ICP nor Cerebral Perfusion pressure (CPP) differed substantially between treatment groups on presentation, with EVD closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the pre-specified threshold: mortality (18%, rt-PA; 23%, placebo); ventriculitis (8%, rt-PA; 9%, placebo); symptomatic bleeding (23%, rt-PA; 5% placebo, which approached statistical significance (p=0.1)). The median duration of dosing was 7.5 days for rt-PA and 12 days for placebo. There was a significant beneficial effect of rt-PA on rate of clot resolution Conclusions Low-dose rt-PA for the treatment of ICH with IVH has an acceptable safety profile compared to placebo and prior historical controls. Data from a well-designed Phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration Information Participant enrollment began prior to July 1, 2005.

The proto-oncogenes c-, L-, and N-myc can all be translated by the alternative method of internal ribosome entry whereby the ribosome is recruited to a complex structural element (an internal ribosome entry segment [IRES]). Ribosome recruitment is dependent upon the presence of IRES-trans-acting factors (ITAFs) that act as RNA chaperones and allow the mRNA to attain the correct conformation for the interaction of the 40S subunit. One of the major challenges for researchers in this area is to determine whether there are groups of ITAFs that regulate the IRES-mediated translation of subsets of mRNAs. We have identified four proteins, termed GRSF-1 (G-rich RNA sequence binding factor 1), YB-1 (Y-box binding protein 1), PSF (polypyrimidine tract binding protein-associated splicing factor), and its binding partner, p54nrb, that bind to the myc family of IRESs. We show that these proteins positively regulate the translation of the Myc family of oncoproteins (c-, L-, and N-Myc) in vivo and in vitro. Interestingly, synthesis from the unrelated IRESs, BAG-1 and Apaf-1, was not affected by YB-1, GRSF-1, or PSF levels in vivo, suggesting that these three ITAFs are specific to the myc IRESs. Myc proteins play a role in cell proliferation; therefore, these results have important implications regarding the control of tumorigenesis.The proteins encoded by the myc gene family function as sequence-specific transcription factors that regulate target genes integral to the processes of cell proliferation, differentiation, and cell death (2, 9). Although many of the functions of the three major myc genes are overlapping, unique properties have been ascribed to individual Myc proteins. For example, each of the Myc proteins can restore the growth and proliferative defects of c-myc null fibroblasts and can promote apoptosis following growth factor deprivation (23,30). In addition, all three proteins can regulate known myc target genes (23). Unique roles for these proteins are supported by the following observations: during embryogenesis and in adult tissues, the expression patterns of c-, L-, and N-Myc are distinct (52); homozygous null c-or N-myc mice die early in development, whereas targeted disruption of both L-myc alleles is not lethal; and in some instances, L-myc displays distinct cell transformation and transcriptional properties (1, 38, 39).It is not surprising, given the role of the Myc family of proteins in proliferation and apoptosis, that the expression of these proteins is highly regulated at the levels of both transcription and translation. Indeed, deregulated Myc expression, through either of these mechanisms, has been associated with tumorigenesis (12,35,36,49,50).Previous studies have shown that the 5Ј untranslated regions (UTRs) of c-, L-, and N-myc encoded by exon 1 each contain a complex RNA structural element known as an internal ribosome entry segment (IRES). Consequently, synthesis of the Myc family proteins can occur by the process of internal ribosome entry (18,19,28,45). In this mechanism of translation initi...

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