Slow degeneration of zebrafish Rohon-Beard neurons during programmed cell death.

Rohon-Beard cells are large, mechanosensory neurons located in the dorsal spinal cord of anamniote vertebrates. In most species studied to date, these cells die during development. We followed labeled Rohon-Beard cells in living zebrafish embryos and found that they degenerate slowly, over many days. During degeneration, the soma shrinks and finally disappears, and the processes become beady in appearance and finally break apart, but they do not retract. Zebrafish Rohon-Beard cells apparently fragment their DNA, as revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) labeling, before undergoing degenerative morphologic changes. We also followed the development of labeled dorsal root ganglion neurons, as they are developing at the same stages that Rohon-Beard cells are degenerating. We found that, although axons of both cell types extend into similar regions, Rohon-Beard cells degenerate normally in mutants lacking dorsal root ganglia, providing evidence that interactions between the two cell types are not responsible for Rohon-Beard cell degeneration. Developmental Dynamics 229:30-41,2004.     

CLOTBUST: Design of a Randomized Trial of Ultrasound-Enhanced Thrombolysis for Acute Ischemic Stroke

BACKGROUND: Intravenous tissue plasminogen activator (TPA) therapy can be monitored with 2 MHz transcranial Doppler (TCD). This article describes the design of CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA), the first prospective international multicenter randomized clinical trial of noninvasive externally applied ultrasound to enhance systemic thrombolysis in human stroke. SUBJECTS: Patients with acute ischemic stroke eligible for intravenous TPA therapy within 3 hours of symptom onset who have detectable middle cerebral artery occlusion on a prebolus TCD are included in this trial. All patients receive standard 0.9 mg/kg TPA therapy. Patients are randomized (1:1) to either 2 hours of continuous monitoring with TCD or placebo monitoring. FDA-approved portable diagnostic TCD equipment and standard headframes (Marc series, Spencer Technologies, Seattle, WA) are used. Output of TCD units is set at 100% power achievable at depths of insonation that display the worst TIBI flow grade signals. METHODS AND END-POINTS: Acute MCA occlusion on prebolus TCD is defined as thrombolysis in brain ischemia (TIBI) flow grades 0-3. Treating physicians are blinded to randomization assignment, and certified scorers measure stroke severity using the National Institute of Health Stroke Scale (NIHSS). Safety of continuous TCD monitoring is determined by rates of symptomatic (NIHSS score increase by 4+ points) intracerebral hemorrhage within 72 hours after initial symptom onset. Potential enhancement of TPA therapy will be determined using combined primary end-point of early complete recanalization on TCD (TIBI flow grades 4-5), dramatic recovery (NIHSS < or = 3 points), or decline in the NIHSS > or = 10 points repeatedly measured every 30 minutes within 2 hours after TPA bolus. Other end-points include recovery at 24 hours and 3 months, modified Rankin scores (mRS) are obtained at 90 days, and favorable outcome is determined as NIHSS or mRS scores 0-1. CONCLUSIONS: The aim of phase II CLOTBUST trial is to determine the rates of early complete recanalization and dramatic/early clinical recovery in TPA + TCD and TPA groups. The sample size is set at 126 patients since a medium effect size (.50) is anticipated for TPA + TCD group vs TPA alone to achieve combined primary end-point.     

Iodine-125 Brachytherapy of Brain Stem Tumors

PURPOSE: To report on iodine-125 ((125)I) interstitial irradiation in the treatment of brain stem tumors. PATIENTS AND METHODS: Two patients with brain stem tumors were treated with CT- and image fusion-guided (125)I stereotactic brachytherapy. RESULTS: By March 2003, the patients had been followed up for 47 and 13 months, respectively. In case 1, the tumor volume was 1.98 cm(3) on the control CT, indicating a 65.5% shrinkage as compared to a target volume of 5.73 cm3 at the time of brachytherapy. In case 2, shrinkage was more distinct. After irradiation, the cyst volume was 0.16 cm(3) on the control MRI, indicating a 97.4% shrinkage as compared to a target volume of 6.05 cm(3) at the time of brachytherapy, i. e., the metastasis had virtually disappeared. CONCLUSION: CT- and image fusion-guided (125)I stereotactic brachytherapy can be performed during the biopsy session. The procedure can be well planned dosimetrically and is surgically precise.     

Total extrusion of the talus: A case report

Total extrusion of the talus without recovery of the bone is a very unusual injury. The authors present a case of a 25-year-old man who sustained an open total enucleation of the talus in a motorcycle accident. The talus was not recovered at the scene of the accident. An immediate tibiocalcaneal stabilization was performed by using an external fixator. In the postoperative period, a polymicrobic infection was observed and treated with parenteral antibiotics. Nine months after injury, the patient developed an infection of both the empty space and the distal third of the tibia. A wound debridement with tibial sequestrectomy and insertion of gentamicin-impregnated polymethylmethacrylate beads was performed. Three months later, after multiple negative bacteriologic examinations, a tibiocalcaneal arthrodesis with staples and autogenous bone graft was performed. Because of a pseudoarthrosis, the patient underwent a revision of the arthrodesis by retrograde tibiocalcaneal nailing, achieving clinical and radiographic success. The definitive treatment of total enucleation of the talus is still controversial because of its rarity and the high rate of complications, such as avascular necrosis, osteomyelitis, and ankle stiffness. In this case, without recovery of the talus, retrograde nailing afforded good stability by bypassing the bone defects.