Competitive repopulation assay of two gene-marked cord blood units in NOD/SCID/gammac(null) mice.

In multiunit cord blood transplantation, hematopoietic stem cells from each unrelated cord blood (UCB) unit competitively reconstitute the hematopoietic system in a recipient. To evaluate the fate of the progeny of each UCB unit and to determine the effects of graft-versus-graft reaction, we established a novel competitive repopulation assay using NOD/SCID/gammac(null) mice in which human T lymphocytes develop from CD34+ cells. CD34+ cells from each UCB unit were labeled with recombinant lentivirus vectors carrying genes encoding either enhanced green fluorescent protein (EGFP) or enhanced yellow fluorescent protein (EYFP). Hematopoietic chimerism composed of both EGFP+ and EYFP+ cells was stably maintained up to 6 months after transplantation with purified CD34+ cells; the ratio of EGFP+ to EYFP+ cells in peripheral blood and bone marrow posttransplantation was equivalent to the ratio of these cells at transplantation. However, when mononuclear cells from two UCB units were cotransplanted with CD34+ cells, engraftment was highly competitive, with cells from only one or the other of the two UCB units surviving. Further subfractionations of mononuclear cells indicate that the skewed chimerism that is often observed in clinical multiunit cord blood transplantation may be mediated by the cooperation of both CD4+ and CD8+ T cells. The assay established here will be a useful tool for analyzing hematopoietic reconstitution in clinical multiunit cord blood transplantation.     

Beneficial effect of a prone position for patients with hypoxemia after transthoracic esophagectomy

OBJECTIVE: Although the prone position has been reported to improve arterial oxygenation in patients with acute respiratory distress syndrome, there have been no reports on its efficacy in patients with hypoxemia after transthoracic esophagectomy with three-field lymphadenectomy. This study was undertaken to assess the efficacy of the prone position on hypoxemia after three-field lymphadenectomy for thoracic esophageal carcinoma. DESIGN: Prospective randomized clinical study. SETTING: General intensive care unit at a university hospital. INTERVENTIONS AND MEASUREMENTS: Sixteen patients who underwent three-field lymphadenectomy and showed hypoxemia (PaO2/FiO2 ratios of <200 under positive end-expiratory pressure of >5 cm H2O) on the fifth postoperative day were randomly assigned to prone (eight patients) and nonprone (eight patients) groups. Prone position for 6 hrs was carried out for four consecutive days. The PaO2/FiO2 ratio, the duration of ventilatory support, and length of stay, were measured. RESULTS: Oxygenation: The PaO2/FiO2 ratio markedly increased by 32% +/- 22% in seven of eight patients (p <.05) when the patients were moved from the supine to the prone position. The PaO2/FiO2 ratio after the fourth prone position (238 +/- 55, p <.05) was significantly higher than that before the first trial of prone position (166 +/- 25) in these seven patients. Duration of ventilatory support and intensive care unit length of stay: Both the ventilation period (11.6 +/- 2.2 vs. 14.0 +/- 1.6 days, p =.0029) and the length of stay in the intensive care unit (12.8 +/- 4.4 vs. 17.2 +/- 3.4 days, p =.0032) were significantly shorter in the prone group compared with the nonprone group. The PaO2/FiO2 ratio at the time of cessation of prone positioning was significantly higher than the corresponding value in the nonprone group. CONCLUSION: In hypoxemic patients after three-field lymphadenectomy, the prone position improved arterial oxygenation without any deleterious effects. The beneficial effect of the prone position is possibly attributable to opening of the bronchi obstructed by secretions.     

Whole-body distribution and radiation dosimetry of [11C]telmisartan as a biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3

IntroductionTelmisartan, a nonpeptide angiotensin II AT1 receptor antagonist used as an antihypertensive drug, is specifically taken up by the liver through the OATP1B3. PET imaging with [¹¹C]telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as its transport property by OATP1B3. The purpose of the study was to determine the biodistribution and radiation dosimetry of [¹¹C]telmisartan in humans.MethodsBiodistribution of [¹¹C]telmisartan was measured in three rats and six healthy male human volunteers. In the rat study, a dynamic emission scan was performed for 90 min. In the human study, dynamic whole-body PET images were acquired after intravenous injection of [¹¹C]telmisartan. ROIs were defined for source organs on the PET images to measure time-course of [¹¹C]telmisartan uptake as percentage injected dose and the number of disintegration for each organ. Radiation dosimetry was calculated with OLINDA/EXM.ResultsIn the rat study, most radioactivity was rapidly taken up by the liver and part of it was excreted into the biliary tract and intestine. Extrapolating from the rat data, the effective dose for the adult human being was estimated to be 3.65±0.01 microSv/MBq (n=3). In the human study, most of the tracer was taken up by the liver as well, although not as rapidly as in the rat. The activity in the gall bladder and intestine increased gradually. The effective dose for the adult human being was 4.24±0.09 microSv/MBq (n=6).Conclusions[¹¹C]Telmisartan is a safe PET tracer with a dosimetry profile comparable to other common ¹¹C PET tracers.     

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.     

Definitive radiotherapy for primary vaginal cancer: correlation between treatment patterns and recurrence rate

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1–169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III–IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge.