Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, clinical study.

OBJECTIVE: To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Neurosurgical intensive care unit of a University hospital. INTERVENTIONS: One hundred ten patients were randomized to receive intravenous magnesium sulfate or to serve as controls. Magnesium treatment was started with a bolus of 16 mmol, followed by continuous infusion of 8 mmol/hr. Serum concentrations were measured every 8 hrs, and infusion rates were adjusted to maintain target levels of 2.0-2.5 mmol/L. Intravenous administration was continued for 10 days or until signs of vasospasm had resolved. Thereafter, magnesium was administered orally and tapered over 12 days. MEASUREMENTS AND MAIN RESULTS: Delayed ischemic infarction (primary end point) was assessed by analyzing serial computed tomography scans. Transcranial Doppler sonography and digital subtraction angiography were used to detect vasospasm. Delayed ischemic neurologic deficit was determined by continuous detailed neurologic examinations; clinical outcome after 6 months was assessed using the Glasgow outcome scale. Good outcome was defined as Glasgow outcome scale score 4 and 5.The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209). Delayed ischemic neurologic deficit was nonsignificantly reduced (9 of 54 vs. 15 of 53 patients; p = .149) and transcranial Doppler-detected/angiographic vasospasm was significantly reduced in the magnesium group (36 of 54 vs. 45 of 53 patients; p = .028). Fewer patients with signs of vasospasm had delayed cerebral infarction. CONCLUSION: These data indicate that high-dose intravenous magnesium can reduce cerebral ischemic events after aneurysmal subarachnoid hemorrhage by attenuating vasospasm and increasing the ischemic tolerance during critical hypoperfusion.

An anatomical assessment of the supracerebellar midline and paramedian approaches to the inferior colliculus for auditory midbrain implants using a neuronavigation model on cadaveric specimens.

The inferior colliculus (IC) is an alternative site for electrode placement in neural deafness due to its surgical accessibility and its well-known tonotopic stratification. In patients where tumor surgery has already occurred and the cerebellopontine angle contains scar tissue or tumor-remnants, midline and paramedian supracerebellar approaches are alternative routes. They are often avoided due to concerns regarding the venous drainage of the cerebellum, the electrode trajectory and the course of the electrode cable. We studied these surgical routes in five neuronavigated fixed cadaveric specimens. For paramedian and midline approaches, the transverse sinus was exposed 5.8mm on average. A mean of 1.6 cerebellar veins, with an average diameter of 2.0mm, draining to the tentorium were transected to reach the tentorial notch. Only 0.4 arterial branches were met. We conclude that the supracerebellar midline and paramedian approaches provide a good exposure of the IC and offer safe and viable alternative routes to the IC. Additionally, they provide a wider angle of action for optimal electrode placement.

Alteration of the MDM2-p73-P14ARF pathway related to tumour progression during urinary bladder carcinogenesis.

Transitional cell carcinomas (TCC) of the urinary bladder develop by a multistep process characterized by various stages of transformation differing in their grade of malignancy and biological behaviour. Since the prospective clinical outcome cannot be reliably predicted on histopathological grounds, we analysed the mRNA expression of the MDM2-p73-P14ARF tumour surveillance pathway in an attempt to detect alterations of gene activity, allowing a better understanding of the mechanisms responsible for conversion of low to high malignant TCC. Expression of the mRNA was determined in 71 TCC of various grades and stages using the real-time quantitative reverse transcription-polymerase chain reaction. The MDM2-p73-P14ARF pathway was dominated by the MDM2 gene, the mRNA expression of which proved to be significantly (5-fold) lower in advanced high-grade, high-stage than in superficial low-grade, low-stage TCC. Conversely, the expression of p73 mRNA increased with increasing tumour grades and stages, while the activity of the P14ARF gene was not substantially altered during early and late phases of urothelial carcinogenesis. Analysing the expression of spliced variants of MDM2 mRNA, we found a heterogeneous pattern including a novel splicing transcript coding for an abnormal protein. Promoter hypermethylation of P14ARF occurred in 10% of the TCC with an under-expression of mRNA. An analysis of the effects of lifestyle and occupational bladder cancer risk factors revealed that TCC of smokers showed a 2-fold elevated expression of MDM2 mRNA and an approximately 2-fold lower expression of P14ARF mRNA, whereas the activity of the p73 gene was unchanged. Heavy coffee consumption was associated with a 2-fold decreased expression level of P14ARF mRNA. Exposure to certain occupational hazards (plastic products, paints and lacquer, polycyclic hydrocarbons, chemical solvents) was observed to modulate the activity of the genes analysed. Our findings suggest that an alteration in the MDM2-p73-P14ARF pathway is involved in the progression of bladder cancer to a more malignant and aggressive form.