The histone deacetylase inhibitor vorinostat selectively sensitizes fibrosarcoma cells to chemotherapy

Soft tissue sarcoma (STS) is a rare malignancy that is generally resistant to chemotherapy. We investigated the ability of the histone deacetylase inhibitor vorinostat to sensitize STS cells versus normal fibroblasts to chemotherapy. Fibrosarcoma, leiomyosarcoma, and liposarcoma cells and normal fibroblasts were treated with vorinostat to determine effects on proliferation and basal apoptosis as measured by total cell number and cleaved caspase 3 staining. Effects on histone deacetylases (HDAC) activity were confirmed by Western blotting for acetylated histone H3. A clinically relevant dose of vorinostat that had no effect on basal apoptosis was selected to examine altered sensitivity to doxorubicin. The effects of vorinostat, doxorubicin, or the combination on fibrosarcoma growth in vivo were determined in a xenograft model. Tumor volume was measured biweekly and HDAC activity and cell death were assessed by immunohistochemical analysis of acetylated histone H3, cleaved caspase 3, and TUNEL staining. Vorinostat inhibited proliferation and induced histone acetylation without affecting basal apoptosis levels. Combined treatment with vorinostat and doxorubicin synergistically induced apoptosis in vitro in fibrosarcoma but not leiomyosarcoma, liposarcoma, or normal fibroblasts. In nude mice, the combination of vorinostat and doxorubicin inhibited fibrosarcoma xenograft growth further than either agent alone. Cell death, as measured by cleaved caspase 3 and TUNEL staining, was greatest in xenografts from mice treated with vorinostat and doxorubicin. Vorinostat inhibits growth and induces chemosensitivity in fibrosarcoma cells in vitro and in vivo, suggesting that the combination of vorinostat and chemotherapy may represent a novel treatment option for this STS subtype. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:623–632, 2011     

Gossypiboma mimicking posterior urethral stricture

INTRODUCTIONForeign bodies in the urogenital tract are not uncommon. Hairpins, glass rods, umbilical tapes, ball point pen are described in lower urogenital tract. Retained gauze piece (gossypiboma) in posterior urethra may cause diagnostic dilemma. Symptoms and investigations may mimic stricture of posterior urethra.PRESENTATION OF CASETwo cases of retained gauze pieces in the urethra are described here. The micturating cystourethrogram was suggestive of posterior urethral stricture.DISCUSSIONTwo cases described here had retained gauze piece as a cause of filling defect and abnormal appearance in the micturating cystourethrogram. Gossypiboma may be a possibility where posterior urethral stricture are seen after previous surgery in paediatric age group.CONCLUSIONIn the setting of previous urogenital surgery gossypiboma should be kept in the differential diagnosis where posterior urethral stricture are seen in the paediatric age group.     

Perioperative steroids in tonsillectomy using electrocautery and sharp dissection techniques

OBJECTIVE: To determine the effect of preoperative dexamethasone sodium phosphate administration on posttonsillectomy morbidity for electrocautery ("hot") and sharp ("cold") dissection techniques. DESIGN: Prospective, randomized, double-blind study. SETTING: University pediatric hospital and county teaching hospital.Subjects A total of 219 children, aged 9 months to 12 years, undergoing tonsillectomy.Intervention Participants who underwent tonsillectomy were randomly assigned to receive either intravenous dexamethasone sodium phosphate (1 mg/kg) or placebo. OUTCOME MEASURES: Pain scores, oral intake, and emesis on postoperative day (POD) 1. RESULTS: A total of 106 subjects (62 undergoing hot and 44 cold tonsillectomies) received preoperative steroids, and 113 (56 hot and 57 cold tonsillectomies) received placebo. On POD 1, pain scores reported by patients (P =.02), parents (P =.002), and physicians (P<.001) were significantly lower in subjects receiving steroids than in those receiving placebo. Emesis was reduced from a mean of 2.1 (placebo group) to 1.2 episodes (steroid group) (P =.02). Oral intake improved from 24.5% of normal diet (placebo) to 31.7% (steroid group) (P =.004). When all 4 groups were compared (cold placebo, cold steroid, hot placebo, and hot steroid), pain scores reported by physicians and parents were significantly lower in the cold steroid group than in the other groups. CONCLUSIONS: Perioperative dexamethasone use reduces posttonsillectomy morbidity in pediatric patients in the early postoperative period after hot or cold tonsillectomy. The combination of steroid and cold dissection technique provided the greatest advantage in reducing posttonsillectomy subjective pain levels.     

Initial experience of the High-Density Grid catheter in patients undergoing catheter ablation for atrial fibrillation

Purpose

A significant proportion of patients undergoing catheter ablation for atrial fibrillation (AF) experience arrhythmia recurrence. This is mostly due to pulmonary vein reconnection (PVR). Whether mapping using High-Density Wave (HDW) technology is superior to standard bipolar (SB) configuration at detecting PVR is unknown. We aimed to evaluate the efficacy of HDW technology compared to SB mapping in identifying PVR.

Methods

High-Density (HD) multipolar Grid catheters were used to create left atrial geometries and voltage maps in 36 patients undergoing catheter ablation for AF (either due to recurrence of an atrial arrhythmia from previous AF ablation or de novo AF ablation). Nineteen SB maps were also created and compared. Ablation was performed until pulmonary vein isolation was achieved.

Results

Median time of mapping with HDW was 22.3 [IQR: 8.2] min. The number of points collected with HDW (13299.6±1362.8 vs 6952.8±841.9, p<0.001) and used (2337.3±158.0 vs 1727.5±163.8, p<0.001) was significantly higher compared to SB. Moreover, HDW was able to identify more sleeves (16 for right and 8 for left veins), where these were confirmed electrically silent by SB, with significantly increased PVR sleeve size as identified by HDW (p<0.001 for both right and left veins). Importantly, with the use of HDW, the ablation strategy changed in 23 patients (64% of targeted veins) with a significantly increased number of lesions required as compared to SB for right (p=0.005) and left veins (p=0.003).

Conclusion

HDW technology is superior to SB in detecting pulmonary vein reconnections. This could potentially result into a significant change in ablation strategy and possibly to increased success rate following pulmonary vein isolation.