XTERNAL ventricular drain catheters are of major importance in the treatment of patients with head trauma, subarachnoid hemorrhage, and other causes of increased ICP. These catheters provide a reliable means of monitoring ICP and controlling elevated pressure by draining CSF. The benefits derived from the placment of an EVD catheter, however, can be offset by catheter-related complications, such as an infection of the CSF.Infection occurs when microorganisms colonize along the catheter surface. Coating catheters with antibiotics decreases bacterial colonization and catheter-related infection. 3,8,14 Catheters impregnated with the antibiotic combination of minocycline and rifampin have been shown to significantly reduce the risk of catheter-related infections associated with the percutaneous placement of central venous lines. Given the clinical results with central line catheters, we conducted a randomized, prospective clinical trial to compare the safety and efficacy of EVD catheters impregnated with minocycline and rifampin with those of standard (no coating or surface treatment) control catheters for the prevention of catheter-related infections.Object. Catheter-related infection of the cerebrospinal fluid (CSF) pathways is a potentially life-threatening complication of external ventricular drainage. A major source of infection is bacterial contamination along the external ventricular drain (EVD) catheter track. The authors examined the efficacy of EVD catheters impregnated with minocycline and rifampin in preventing these catheter-related infections.Methods. The authors conducted a prospective, randomized clinical trial at six academic medical centers. All hospitalized patients 18 years or older who required placement of an EVD catheter were eligible for inclusion in the study. Patients were randomly assigned to undergo placement of an EVD with a catheter impregnated with minocycline and rifampin or a standard untreated catheter (control group). To assess primary outcome, CSF samples were collected using a sterile technique at the time of catheter insertion, at least every 72 hours while the catheter remained in place, and at the time of catheter removal. At the time of removal, CSF cultures were obtained from the tip and tunneled segments of each catheter by performing semiquantitative roll-plate and quantitative sonication techniques.Of the 306 patients enrolled in the study, data from 288 were included in the final analysis. Eighteen patients were excluded from analysis: 14 because the ventricular catheter was in place less than 24 hours, and four because CSF cultures obtained at the time of catheter insertion were positive for infection. Of these 288 patients, 139 were assigned to the control group and 149 to the treatment group. The two groups were well matched with respect to all clinical characteristics, including patient sex and mean age, indication for catheter placement, and length of time the catheter remained in place. The antibiotic-impregnated catheters were one half as likely to become colonized...

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.

A prototype device called an extracranial stereotactic radiosurgery frame was used to deliver stereotactic radiosurgery, with a modified linear accelerator, to metastatic neoplasms in the cervical, thoracic, and lumbar regions in five patients. In all patients, the neoplasms had failed to respond to spinal cord tolerance doses delivered by standard external fractionated radiation therapy to a median dose of 45 Gy (range, 33-65 Gy/11-30 fractions). The tumors were treated with single-fraction stereotactic radiosurgery with the spinal stereotactic frame for immobilization, localization, and treatment. The median number of isocenters was one (range, one to five) with a median single fraction dose of 10 Gy (range, 8-10 Gy) with median normalization to 80% isodose contour (range, 80-160%). There has been a single complication of esophagitis to date from radiosurgery of a tumor involving the C6-T1 segments; the esophagitis resolved with medical therapy. Median follow-up in this group of patients has been 6 months (range, 1-12 mo). To date, there has been no radiographic or clinical progression of the treated tumor in any patient. Two patients have died from systemic metastatic disease. In the three surviving patients, there has been computed tomographic- or magnetic resonance-documented regression of the treated tumor with a decrease of thecal sac compression with a median follow-up of 6 months (range, 3-14 mo). These five patients represent the first clinical application of stereotactic radiosurgery in the spine. The results suggest that extracranial radiosurgery may be suitable for the treatment of paraspinal neoplasms after external fractionated radiation therapy, even in the face of spinal cord compression.

Interferon-beta (IFN-beta) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-beta by providing local, sustained delivery of IFN-beta to gliomas, the safety and biological activity of a human IFN-beta (hIFN-beta)-expressing adenovirus vector (Ad.hIFN-beta) was evaluated in patients with malignant glioma by stereotactic injection, followed 4-8 days later by surgical removal of tumor with additional injections of Ad.hIFN-beta into the tumor bed. Eleven patients received Ad.hIFN-beta in cohorts of 2 x 10(10), 6 x 10(10), or 2 x 10(11) vector particles (vp). The most common adverse events were considered by the investigator as being unrelated to treatment. One patient, who was enrolled in the cohort with the highest dose levels, experienced dose-limiting, treatment-related Grade 4 confusion following the post-operative injection. Ad.hIFN-beta DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-beta protein was detectable within the tumor. At the highest doses tested, a reproducible increase in tumor cell apoptosis in post-treatment versus pre-treatment biopsies with associated tumor necrosis was observed. Direct Ad.hIFN-beta injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction.