Peri-Balloon Leak Flow Velocity Assessed by Intra-Cardiac Echography Predicts Pulmonary Vein Electrical Gap　- Intra-Cardiac Echography-Guided Contrast-Free Cryoballoon Ablation.

BACKGROUND: The use of iodine contrast agents is one possible limitation in cryoballoon ablation (CBA) for atrial fibrillation (AF). This study investigated intracardiac echography (ICE)-guided contrast-free CBA.Methods and Results:The study was divided into 2 phases. First, 25 paroxysmal AF patients (Group 1) underwent CBA, and peri-balloon leak flow velocity (PLFV) was assessed using ICE and electrical pulmonary vein (PV) lesion gaps were assessed by high-density electroanatomical mapping. Then, 24 patients (Group 2) underwent ICE-guided CBA and were compared with 25 patients who underwent conventional CBA (historical controls). In Group 1, there was a significant correlation between PLFV and electrical PV gap diameter (r=-0.715, P<0.001). PLFV was higher without than with an electrical gap (mean [±SD] 127.0±28.6 vs. 66.6±21.0 cm/s; P<0.001) and the cut-off value of PLFV to predict electrical isolation was 105.7 cm/s (sensitivity 0.700, specificity 0.929). In Group 2, ICE-guided CBA was successfully performed with acute electrical isolation of all PVs and without the need for "rescue" contrast injection. Atrial tachyarrhythmia recurrence at 6 months did not differ between ICE-guided and conventional CBA (3/24 [12.5%] vs. 5/25 [20.0%], respectively; P=0.973, log-rank test). CONCLUSIONS: PLFV predicted the presence of an electrical PV gap after CBA. ICE-guided CBA was feasible and safe, and could potentially be performed completely contrast-free without a decrease in ablation efficacy.

The Sustained Release of Tafluprost with a Drug Delivery System Prevents the Axonal Injury-induced Loss of Retinal Ganglion Cells in Rats.

PURPOSE: To investigated whether a new drug delivery system (DDS) could enable the controlled release of tafluprost and suppress retinal ganglion cell (RGC) death in rats after optic nerve transection (ONT). METHODS: A DDS containing 0.04%, 0.20% or 1.00% tafluprost, or vehicle, was injected intravitreally in 8-12-week-old male Sprague-Dawley rats 7 days before ONT, and the retinas were extracted 7 days after ONT. For comparison, eye drops containing 0.0015% tafluprost or vehicle were used once a day. The extracted retinas were analyzed with liquid chromatography-tandem mass spectrometry, immunohistochemistry and western blotting. RESULTS: The level of tafluprost acid in the groups that received the 0.20% and 1.00% tafluprost DDSs was stable, and higher than the maximum concentration in the eye drop group, even after 14 days. In the retinas treated with the 1.00% tafluprost DDS, the active form of the drug had a high concentration (~50 times higher than eye drops), but no significant IOP difference compared with its vehicle in this study. The 1.00% tafluprost DDS group also had less cleaved α-fodrin and fewer c-Jun-positive cells than the vehicle DDS group. CONCLUSIONS: This study found that a newly developed DDS allowed the controlled release of tafluprost and prevented the loss of RGCs after ONT IOP independently. The duration of drug action on the target site was longer with a tafluprost DDS than with topical instillation and should therefore reduce problems related to lack of patient compliance. This system may also enable new treatments to prevent RGC degeneration in diseases such as glaucoma.

Dose selection for optimal treatment results and avoidance of complications.

What is the optimal treatment for metastatic brain tumors (MBTs)? We present our experience with gamma knife (GK) treatments for patients with five or more MBTs. Our new formula for predicting patient survival time (ST), which was derived by combining tumor control probability (TCP) calculated by Colombo's formula and normal tissue complication probability (NTCP) estimated by Flickinger's integrated logistic formula, was also evaluated. ST=a*[(C-NTCP)*TCP]+b; a, b, C: const. Forty-one patients (23 male, 18 female) with more than five MBTs were treated between March 1992 and February 2000. The tumors originated in the lung in 15 cases, in the breast in 8. Four patients had previously undergone whole brain irradiation (WBI). Ten patients were given concomitant WBI. Thirteen patients had additional extracranial metastatic lesions. TCP and NTCP were calculated using Excel add-in software. Cox's proportional hazards model was used to evaluate correlations between certain variables and ST. The independent variables evaluated were patient factors (age in years and performance status), tumor factors (total volume and number of tumors in each patient), treatment factors (TCP, NTCP and marginal dose) and the values of (C-NTCP)*TCP. Total tumor number was 403 (median 7, range 5-56). The median total tumor volume was 9.8 cm3 (range 0.8-111.8 cm3). The marginal dose ranged from 8 to 22 Gy (median 16.0Gy), TCP from 0.0% to 83% (median 15%) and NTCP from 0.0% to 31% (median 6.0%). (0.39-NTCP)*TCP ranged from 0.0 to 0.21 (median 0.055). Follow-up was 0.2 to 26.2 months, with a median of 5.4 months. Multiple-sample tests revealed no differences in STs among patients with MBTs of different origins (p=0.50). The 50% STs of patients with MBTs originating from the breast, lung and other sites were 5.9, 7.8 and 3.5 months, respectively. Only TCP and (0.39-NTCP)*TCP were statistically significant covariates (p=0.014, 0.001, respectively), and the latter was a more important predictor of ST than the former (Beta= -2.2, -14.1, respectively). The relationship between (0.39-NTCP)*TCP and ST was significant. Linear regression analysis showed this value to predict ST (p=0.002, R2=0.22). The slope of the regression line for patients with MBTs originating from the breast was steeper (a=218.2, p=0.08, R2=0.41) than the slopes of regression lines for patients with tumors of other origins (lung; a=56.8, p=0.004, R2=0.49, others; a=50.4, p=0.03, R2=0.25). In treating multiple lesions, the maximum doses and dose distribution for individual lesions were often different. The formula described by Colombo is used to calculate the residual clonogenic cell number of every sub-volume of the tumor, with different doses. NTCP must also integrate every complication probability for each sub-volume of normal brain tissue in the relatively high dose area in proximity to the tumor. Herein, we present a method for determining the irradiation dose necessary for cases with multiple brain metastases. A personal computer-aided calculation is employed.

[A case of solitary neurocysticercosis of unknown transmission route].

We report a case of solitary neurocysticercosis of unknown transmission route. A 26-year-old male was taken to our hospital with a history of general convulsions. On admission, physical and neurological findings were normal. On the basis of neuroimaging (computed tomography scan and magnetic resonance imaging), initial diagnosis was brain abscess and the patient was treated with antibiotics. Two months later, the patient, at times, presented a loss of consciousness. The follow-up MRI revealed that the enhanced lesion became enlarged and perifocal edema became evident, so the patient was surgically treated. By histopathological examination, the lesion was diagnosed as a cysticercus. The immunoserologic assay gave a positive result for the disease. Postoperatively, the symptoms improved. Cerebral cysticercosis is the most common parasitic disease of the central nervous system, but rare in Japan. Therefore its diagnosis remains difficult, especially in the case of solitary cerebral cysticercosis, which has been reported only 7 times in Japan. The pathological examination or the immunoserologic assay should be taken into consideration to obtain definitive diagnosis of cerebral cysticercosis.