Medial (intra-cisternal) acoustic neuromas

The clinical characteristics of "medial" or "intra-cisternal" acoustic neuroma (AN) treated in our institute were reviewed. Among 466 patients with ANs in our series during the last 20 years, 6 patients (1.3%) were considered to fill the criteria of medial AN definition. Compared with those with non-medial ANs, the patients with medial ANs show a tendency to have cerebellar and/or cranial nerve dysfunction (especially trigeminal and/or facial nerves) in addition to hearing loss at the time of initial presentation. On magnetic resonance imaging, medial AN is visualized as a multi-cystic mass lesion in the cerebello-pontine cistern without extension into the internal auditory canal in most cases. Although total removal of tumor was achieved in all cases, the results of preservation of facial nerve function were not satisfactory. Medial AN can be considered as a clinical, but not pathological, subtype in terms of the functional outcomes of the facial nerve and hearing.     

As originally published in 1996. Usefulness of pulsatile bidirectional cavopulmonary shunt in high-risk Fontan patients. Updated in 2002

BACKGROUND: A bidirectional cavopulmonary shunt has been performed for the high-risk Fontan patient. It is well known that in the presence of the bidirectional cavopulmonary shunt alone to secure pulmonary blood flow, the central pulmonary artery size decreases over time. We have performed pulsatile bidirectional cavopulmonary shunt (PBCPS), keeping pulmonary blood flow from the ventricle through the stenotic pulmonary valve, or a Blalock-Taussig shunt in patients who do not meet the criteria for the Fontan operation. METHODS: Eleven patients who underwent PBCPS between 1989 and 1993 were reviewed. We compared the results of cardiac catheterization immediately before PBCPS and during the postoperative observation period (310 +/- 257 days). RESULTS: Pulmonary blood flow and arterial oxygen saturation increased significantly after PBCPS (p = 0.01). Pumonary artery area index showed a tendency to increase (p = 0.11). The mean number of risk factors for the Fontan procedure decreased significantly from 1.8 +/- 1.1 to 0.7 +/- 0.8 after PBCPS (p < 0.05). Overall, 5 of the 11 patients (45.5%) met the criteria for the Fontan procedure, and a fenestrated Fontan procedure was carried out in 4 of them. CONCLUSIONS: The PBCPS is useful for high-risk Fontan patients not only in the staged Fontan operation, but also as definitive palliation.     

Right heart bypass for left circumflex coronary artery bypass grafting

Displacement of the heart to expose the left circumflex artery (LCX) causes hemodynamic disturbance during off-pump coronary artery bypass grafting (CABG). We applied right heart bypass (RHB) using a heparin-coated centrifugal pump without an oxygenator in an attempt to stabilize the hemodynamics. Five mongrel dogs (15.5–20 kg) were used. Hemodynamic parameters were continuously monitored at a fixed rate of 80 beats/min. The LCX was exposed with the use of an Octopus Tissue Stabilizer. After baseline data were obtained, each dog was placed in the Trendelenburg position. Finally, RHB was established with different pump flows. LCX exposure caused a significant decrease in aortic flow (to 33.1% ± 13.1% of the baseline value) and arterial mean pressure (to 68.3% ± 8.5%) (P < 0.001). Trendelenburg positioning caused these values to recover to 57.1% ± 6.7% and 72.5% ± 7.7%, respectively. RHB with 50% flow significantly improved the hemodynamic values, although 100% flow significantly increased LAP by 134.8% ± 19.7% (P < 0.01). Tilting of the canine heart to expose the LCX caused significant deterioration of the hemodynamic values. Trendelenburg positioning was moderately effective, and RHB very effective, in improving the hemodynamics. In a limited number of cases, an appropriate flow of RHB may provide safe hemodynamic assistance during off-pump CABG of the LCX. Received: March 10, 2000 / Accepted: May 27, 2000     

Developmental disorders and altered gene expression in the tropical clawed frog (Silurana tropicalis) exposed to 17α‐ethinylestradiol

Several endocrine‐disrupting chemicals with estrogenic activity can affect sexual development and reproduction in aquatic wildlife. The occurrence of oocytes in the testis (testis‐ova) is one reproductive disorder and can be used as a valid endpoint when studying disruptive effects of estrogenic chemicals. To elucidate the molecular basis of testis‐ova induction, we conducted gene expression analysis in the gonads of Silurana tropicalis exposed to 0, 3, 10 and 30 ng l^?1 17α‐ethinylestradiol (EE2) from 2 days after fertilization to the juvenile stage (14 weeks after fertilization). The frequencies of testis‐ova induction or male to female sex‐reversal of the gonads increased in an EE2 dose‐dependent manner. Microarray analysis showed that expressions of a large number of genes were significantly changed by EE2 exposure. Genes including egg envelope composition (zp4, zpax, zpc, zp3.2 and egg cortical granule lectin), 42S particle genes (42Sp50, 42Sp43 and 42Sp48) and regulation of female germ cells (figla) are associated with the testis‐ova and sex‐reversal situation in the gonads. Of those, expression of zpc and 42Sp50 genes is associated with testis‐ova. Thus, we propose that these genes are useful biomarkers for toxicological research in amphibians developmentally exposed to estrogenic chemicals. Copyright © 2012 John Wiley & Sons, Ltd.     

Impaired social behavior in chicks exposed to sodium valproate during the last week of embryogenesis

Rationale and objectives

To evaluate direct exposure to sodium valproate (VPA) during embryogenesis, we administered VPA to chick embryos and examined their social behaviors after hatching.

Methods and results

Embryos treated with VPA (35 μmol/egg) on day 14 were similar to controls for hatching date (day 21) and hatchlings' abilities, such as motor, imprinting, and surface righting. However, these VPA chicks on posthatching day 3 scored significantly low in the chick's social separation stress (SSS) test as follows. Aggregation test evaluated the speed of four chicks, individually isolated by a cardboard in a box, to aggregate upon removal of the cardboards. Belongingness test evaluated the speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner. Vocalization test for each chick was performed in an isolated corner by using a sound level meter. The results demonstrated that compared with controls, VPA chicks were significantly slow in aggregation (12.7?±?2.5 s vs. 2.9?±?0.9 s, p?=?0.006) and belongingness (3.6?±?0.28 s/40 cm vs. 2.6?±?0.14 s/40 cm, P?=?0.003) and weak in vocalization (13.4?±?2.8 dB/30 s vs. 26.7?±?1.3 dB/30 s, P?=?0.001), respectively. Weight of cerebellum of VAP chick was 15 % lighter than controls (P?=?0.004).

Conclusions

Chick embryos exposed to VPA during the last week of embryogenesis had impaired social behaviors in spite of normal mortar and imprinting ability. The present method will be a useful animal model for assessing the effects of environment during embryogenesis on social behaviors in later life.     

Propranolol is more effective than pulsed dye laser and cryosurgery for infantile hemangiomas

Propranolol hydrochloride is a nonselective β-blocker that is used for the treatment of hypertension, arrhythmia, and angina pectoris. In Japan, it was recently approved for the treatment of childhood arrhythmia. It has been observed to produce drastic involution of infantile hemangiomas. The aim of this prospective study was to examine propranolol’s superiority to classical therapy with pulsed dye laser and/or cryosurgery in treating proliferating infantile hemangiomas. Fifteen patients between the ages of 1 and 4 months with proliferating infantile hemangiomas received grinded propranolol tablets 2 mg/kg per day divided in three doses. Twelve patients with proliferating infantile hemangiomas receiving pulsed dye laser and/or cryosurgery were enrolled as controls. Baseline electrocardiogram, echocardiogram, and chest x-ray were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed every 2 weeks. Efficacy was assessed by performing blinded volume measurements and taking photographs at every visit. Propranolol induced significantly earlier involution and redness reduction of infantile hemangiomas, compared to pulsed dye laser and cryosurgery. Adverse effects such as hypoglycemia, hypotension, or bradycardia did not occur. Conclusion: The dramatic response of infantile hemangiomas to propranolol and few side effects suggest that early treatment of infantile hemangiomas could result in decreased disfigurement. Propranolol should be considered as a first-line treatment of infantile hemangiomas.     

LaSOM 335, active against bladder cancer cells,interferes with Let-60 (hRas) and reduces CD73 expression/activity

Bladder cancer is the fourth most common malignancy in men. It can present along the entire continuum of severity, from mild to well-differentiated disease to extremely malignant tumors with low survival rates. Human RAS genes are the most frequently mutated oncogenes in human cancers, and the critical role of aberrant Ras protein function in carcinogenesis is well established. Therefore, considerable efforts have been devoted to the development of anti-Ras inhibitors for cancer treatment. This study presents the biphenyl dihydropyrimidinone LaSOM 335 with high activity against T24 bladder cancer cells (IC₅₀ = 10.73 ± 0.53 μM) and selectivity of cytotoxicity for this cancer cell line compared to two non-cancer cell lines investigated. Furthermore, we also show that this compound reduced vulvar development in the mutant let-60 gene of Caenorhabditis elegans. Let-60 is a homolog of the mammalian Ras gene. In addition, we observed that LaSOM 335 inhibits the enzymatic activity of CD73 and decreases CD73 expression. Possibly, this expression decrease is due to downstream EGFR signaling via the Ras–Raf–ERK pathway, that directly regulates CD73 expression via ERK1/2. Evidence suggests that non-immunomodulating functions of CD73 play an equally important role for cancer cell survival, progression, and migration. Regarding we also notice that LaSOM 335 was safe in the in vivo model of C. elegans. The set of these findings makes this biphenyl dihydropyrimidinone a promising candidate for further investigations in the bladder cancer field.     

Effective bone engineering with periosteum-derived cells

Bone augmentation via tissue engineering has generated significant interest. We hypothesized that periosteum-derived cells could be used in place of bone marrow stromal cells (which are widely used) in bone engineering, but the differences in osteogenic potential between these 2 cell types are unclear. Here, we compared the osteogenic potential of these cells, and investigated the optimal osteoinductive conditions for periosteum-derived cells. Both cell types were induced, via bFGF and BMP-2, to differentiate into osteoblasts. Periosteal cells proliferated faster than marrow stromal cells, and osteogenic markers indicated that bone marrow stromal cells were more osteogenic than periosteal cells. However, pre-treatment with bFGF made periosteal cells more sensitive to BMP-2 and more osteogenic. Transplants of periosteal cells treated with BMP-2 after pre-treatment with bFGF formed more new bone than did marrow stromal cells. Analysis of these data suggests that combined treatment with bFGF and BMP-2 can make periosteum a highly useful source of bone regeneration.     

Effect of the Neutrophil Elastase Inhibitor Sivelestat on Perioperative Inflammatory Response After Pediatric Heart Surgery With Cardiopulmonary Bypass: A Prospective Randomized Study

Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. The neutrophil elastase inhibitor sivelestat is known to suppress this systemic inflammatory response, which can eventually result in acute organ failure. The prophylactic effect of sivelestat on acute lung injury, especially in pediatric cardiac surgery, remains unclear. This prospective double‐blind, randomized study evaluated the perioperative prophylactic effect of sivelestat in patients undergoing elective pediatric open heart surgery with CPB. Thirty consecutive patients, weighing 5–10 kg and undergoing open heart surgery with CPB, were assigned to sivelestat (n = 15) or control (n = 15) groups. From CPB initiation to 24 h after surgery, patients in the sivelestat group received a continuous intravenous infusion of 0.2 mg/kg/h sivelestat, whereas patients in the control group received the same volume of 0.9% saline. Blood samples were collected, and levels of interleukin (IL)‐6, IL‐8, tumor necrosis factor alpha, polymorphonuclear elastase (PMN‐E), C‐reactive protein (CRP), as well as the white blood cell (WBC) count, platelet count, and neutrophil count (NC) were measured. PMN‐E levels, IL‐8 levels, WBC count, NC, and CRP levels were significantly lower, and platelet count was significantly higher in the sivelestat group, according to repeated two‐way analysis of variance. The activated coagulation time was significantly shorter in the sivelestat group, similarly, blood loss was significantly less in the sivelestat group. In conclusion, Sivelestat attenuates perioperative inflammatory response and clinical outcomes in patients undergoing pediatric heart surgery with CPB.