Bilateral cerebellar cysts and cerebral white matter lesions with cortical dysgenesis: Expanding the phenotype of LAMB1 gene mutations.

LAMB1 gene analysis should be considered for intellectually disabled patients with cerebellar cysts, white matter signal change, and cortical malformation. Muscular involvement is absent, in contrast to the α-dystroglycanopathy types of congenital muscular dystrophies.

Effectiveness of fibrin coating in the management of web formation after laryngomicrosurgery.

PURPOSE: To explore the effectiveness of fibrin coating in reducing web formation after endoscopic management of the anterior commissure of the larynx. MATERIALS AND METHODS: Using a spray device that is generally used for laparoscopic operations, we covered the wound with fibrin glue (Bolheal®) to avoid web formation. This technique was employed in cases wherein the anterior commissure was mainly managed by laser operation; the glue was sprayed after vaporization. Fibrinogen was first sprayed and the wound was properly soaked with a swab, which was followed by application of thrombin. We used this method in 17 cases and evaluated voice function by acoustic analysis - pitch perturbation quotient (PPQ) and amplitude perturbation quotient (APQ) - and maximum phonation time (MPT) before and after the operation. RESULTS: No severe web formation was observed at three months after the operation. PPQ values improved from 3.048±2.801% to 0.653±0.463% (p<0.05, paired t-test). APQ values improved from 7.996±5.003% to 3.042±1.872% (p<0.05, paired t-test). Voice quality did not worsen in any of the cases. MPT values improved from 17.2±10.8s to 26.7±14.2s (p<0.05, paired t-test) Voice function improved 3months after the operation in all cases. CONCLUSION: The fibrin coating method is an easy and effective approach to avoid web formation without creating cervical wounds in cases that require handling of the anterior commissure under laryngomicrosurgery.

Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update.

The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non-pathogenic adeno-associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild-type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non-hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off-target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.

Clinical outcomes of tracheoesophageal diversion for intractable aspiration.

OBJECTIVES: The purpose of the present study was to examine the clinical outcomes of using tracheoesophageal diversion for preventing intractable aspiration. METHOD: We retrospectively reviewed 25 patients who underwent tracheoesophageal diversion from 2003 to 2009 at our hospital (median age, 25 years; range, 0-78 years). End-to-side anastomosis was used in 16 cases and side-to-side anastomosis was used in 9. RESULTS: The average operative time was 141 minutes for end-to-side anastomosis and 191 minutes for side-to-side anastomosis. Peri-operative complications were observed in only two (8 per cent) cases: one with infection and one with haematoma. No fistulas were observed. Aspiration was prevented in all cases, but the nutritional route depended on the swallowing function of the patient. Oral feeding was the main nutritional route after surgery in only four patients (16 per cent). CONCLUSION: This procedure is well suited to patients who lack speech communication and are at high risk of aspiration.

New technique for laryngomicrosurgery: narrow band imaging-assisted video-laryngomicrosurgery for laryngeal papillomatosis.

OBJECTIVE: In the present report, we describe the use of narrow band imaging during video-laryngomicrosurgery for laryngeal papillomatosis. CASE REPORT: It is difficult to peri-operatively locate all the superficial papillomatous lesions when the disease is widespread, which then results in tumor recurrence. Therefore, we have constructed a narrow band imaging video-laryngomicrosurgery system, which we have used for two cases of laryngeal papillomatosis. CONCLUSION: Our narrow band imaging-assisted video-laryngomicrosurgery system to visualise superficial laryngeal papillomatosis more clearly.

Detection of pulsation in unruptured cerebral aneurysms by ECG-gated 3D-CT angiography (4D-CTA) with 320-row area detector CT (ADCT) and follow-up evaluation results: assessment based on heart rate at the time of scanning.

PURPOSE: Many epidemiological studies on unruptured cerebral aneurysms have reported that the larger the aneurysm, the higher the risk of rupture. However, many ruptured aneurysms are not large. Electrocardiography (ECG)-gated 3D-computed tomography angiography (4D-CTA) was used to detect pulsation in unruptured cerebral aneurysms. The differences in the clinical course of patients in whom pulsation was or was not detected were then evaluated. METHODS: Forty-two patients with 62 unruptured cystiform cerebral aneurysms who underwent 4D-CTA and follow-up 3D-CTA more than 120 days later were studied. The tube voltage, tube current, and rotation speed were 120 kV, 270 mA, and 0.35 s/rot., respectively. ECG-gated reconstruction was performed, with the cardiac cycle divided into 20 phases. Patients with heart rates higher than 80 bpm were excluded, so 37 patients with 56 aneurysms were analyzed. RESULTS: Pulsation was detected in 20 of the 56 unruptured aneurysms. Of these 20 aneurysms, 6 showed a change in shape at the time of follow-up. Of the 36 aneurysms in which pulsation was not detected, 2 showed a change in shape at follow-up. There was no significant difference in the follow-up interval between the two groups. The aneurysms in which pulsation was detected were significantly more likely to show a change in shape (P = 0.04), with a higher odds ratio of 7.286. CONCLUSION: Unruptured aneurysms in which pulsation was detected by 4D-CTA were more likely to show a change in shape at follow-up, suggesting that 4D-CTA may be useful for identifying aneurysms with a higher risk of rupture.

A transfection method for short interfering RNA with the lipid-like self-assembling nanotube, A6K.

The aim of the present study was to develop a novel transfection method for short interfering RNA (siRNA). A nanotube with surfactant activity, A6K, consisting of six alanine residues and a hydrophilic head, lysine, was compared to the conventional cationic transfectant reagents siFECTOR and Lipofectamine 2000. Cytotoxicity for the human glioblastoma cell lines U87MG, A172, and T98G was examined with the MTS assay. Transfection efficiency was analyzed with FITC-labeled siRNA targeting matrix metalloproteinase (MMP)-2 mRNA by fluorescent activity on microscopy. The ultrastructure of A6K was evaluated by electron microscopy. The level of cytotoxicity associated with A6K in the U87MG cells was significantly lower than with siFECTOR and Lipofectamine 2000. Transfection efficiency for siRNA was increased in a dose- and time-dependent fashion. The relative expression of MMP-2 mRNA to ß-actin was reduced in a dose-dependent manner by real-time RT-PCR analysis. The ultrastructure of the A6K was transformed to micelle formation when mixed with the siRNA. The lipid-like self-assembling peptide, A6K, has genes in the micelle associated with the hydrophilic tail. This transfection method is a novel and stable technique with lower cytotoxicity than the current standard methods.

Relationship between the acid-inhibitory effects of two proton pump inhibitors and CYP2C19 genotype in Japanese subjects: a randomized two-way crossover study.

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Axillary apocrine carcinoma with Paget's disease and apocrine naevus.

Apocrine carcinoma is a rare malignant sweat-gland neoplasm with apocrine differentiation. There have been some reported cases of apocrine carcinoma with apocrine naevus. We report a case of a 78-year-old man with a painless tumour of the left axilla. Positron emission tomography (PET) showed slight fluorodeoxyglucose (FDG) uptake in both axillae. The patient underwent radical excision of the left axilla with left axillary lymph-node resection. The resected specimen showed apocrine adenocarcinoma with extramammary Paget's disease and apocrine naevus. Two years later, the patient noted enlargement of the right axilla, and PET showed increased FDG uptake. On resection of this enlarging right axilla, an apocrine naevus was found. FDG-PET is a useful method for detecting precancerous lesions, allowing monitoring of abnormal foci that are not suspicious for cancer and have no clinically apparent cause for concern.

[Bentall operation in left sinus of valsalva aneurysm with anomalous origin of left coronary artery and severe aortic regurgitation].

We report a successful Bentall operation in a 74-year-old man with an unruptured left sinus of Valsalva aneurysm and aortic regurgitation. The coronary angiogram showed an absent left main trunk (split origination of left coronary arteries from the same left sinus of Valsalva). We implanted a stented bovine pericardial valve and a Valsalva tube graft as a composite graft. To reconstruct the coronary arteries, we made one left coronary button including both ostia of the left anterior descending coronary artery and circumflex artery, and reimplanted the coronary button with interposition of a short small synthetic graft. Excessive tension of the coronary ostia can be avoided and a new left main trunk can also be created in this manner. Postoperative course was uneventful.

[Surgical cryoablation and left ventriculoplasty for electrical storm after acute myocardial infarction].

A 65-year-old man was referred to our hospital to treat recent anterior myocardial infarction. Coronary artery angiography showed acute occlusion of left anterior descending coronary artery (LAD) and chronic occlusion of right coronary artery. After emergent percutaneous coronary intervention for LAD, drug-refractory electrical storm necessitating frequent electrical defibrillating cardioversion occurred. This patient successfully underwent surgical cryoablation, left ventriculoplasty and coronary revascularization. At 2 years and 10th month after the operation, he is well without limitation of daily activities and any evidence of myocardial ischemia and ventricular tachycardia.

[Esophago-bronchial fistula confirmed with bronchoscopy utilized an indocyanine green].

The patient was a 54-year-old female with both headache and vomit presented to the emergency room. Endoscopic examination revealed an advanced esophageal cancer located on the middle thoracic esophagus. Histological analysis revealed squamous cell carcinoma. The clinical stage was diagnosed as T4N2M0 and this case was treated by the chemoradiation. She presented progressive moist cough after chemoradiotherapy. Esophagography demonstrated esophago-bronchial fistula (EBF). EBF was not detected by routine broncoscopy. To confirm fistula, we were performed the bronchoscopy which utilized an indocyanine green. Contrast media colored green were over from the superior segmental bronchus in a bronchoscope. The bronchoscope which utilized an indocyanine green is effective for EBF.

[Coronary artery bypass grafting in patients with dialysis-dependent renal failure].

From January 1995 to May 2003, 36 patients with dialysis-dependent renal failure underwent coronary artery bypass grafting. We performed the operation with cardiopulmonary bypass (group On) in 17 cases and without cardiopulmonary bypass (group Off) in 19 patients [off-pump coronary artery bypass grafting (OPCAB) 15, minimally invasive direct coronary artery bypass (MIDCAB) 4]. There were no statistical differences regarding mean age, sex, duration of dialysis, preoperative hypertension, diabetes and peripheral and cerebral vascular diseases. Mean operation time and the number of bypass grafts were 315 +/- 53 minutes, 2.8 +/- 0.8 grafts in group On and 284 +/- 78 minutes, 2.4 +/- 1.1 grafts in group Off, respectively (not significant). Seventeen patients (100%) of group On and 12 patients (63%) needed blood transfusion. Hospital stay after operation was significantly longer in group On (40 days) of group Off than that in group Off (26 days). After the operation, continuous hemodiafiltration (CHDF) was used in 10 cases (59%) in group On and 3 cases (16%) in group Off. In coronary artery bypass grafting (CABG) on dialysis patient, it is very effective to have various operation techniques, such as off-pump bypass and on-pump beating bypass. Also control of water-electrolyte balance using early postoperative CHDF is useful. However, off-pump cases could be controlled by conventional hemodialysis.

Olfactory schwannoma.

We report a case of olfactory schwannoma with calcification. Intraoperative findings indicated that the tumour originated from the olfactory groove. Intraoperative findings of previous studies have not indicated a clear relationship between subfrontal schwannoma and the olfactory nerve, which seems strange, given the association between tumours and cranial nerves at other sites. We suggest this observation has not been reported because the growing olfactory schwannoma changes the local morphology, affecting the appearance of the olfactory nerve.

[Ascending aorta to biaxillar and left femoral artery bypass].

A 68-year-old man was admitted to our hospital because of ischemia in the upper and lower extremities with rest pain. Aortography revealed complete bilateral subclavian artery occlusion and left femoral artery occlusion. We planned simultaneous revascularization of upper and lower extremities. Ascending aorta to biaxillar and left femoral artery bypass was performed. The postoperative course was uneventful and he was discharged on the 18th day after operation. This procedure was useful for patient with upper and lower limb ischemia.

Exogenous expression of Fas-ligand or CrmA prolongs the survival in rat liver transplantation.

Modulation of donor organs by transfection of a gene encoding immmunosuppresive molecules has been recognized as a less toxic approach to prevent allograft rejection. Fas-ligand (FasL) plays a critical role in activation-induced cell death of activated cytotoxic lymphocytes. This may provide a potential for induction of "immune privileged sites" to escape the host immune surveillance system. Cytokine response modifier A (CrmA), a gene product of cowpox virus, blocks caspase as well as perforin/granzyme-mediated apoptotic pathways. Therefore, it may suppress intragraft apoptosis. The aim of the present study was to investigate whether transfection of FasL or CrmA genes prolonged the survival of rat liver allografts. Using the high responder rat combination of DA (RT-1(a)) donor to LEW (RT-1(1)) recipient, we performed orthotopic liver transplantation with subsequent delivery of adenoviral vectors containing FasL, CrmA, or LacZ, at a dose of 1 x 10(9) pfu via a recipient tail vein using a Cre-mediated gene expression system. Recipient survival was assessed as well as immunohistochemical examination of the grafts for anti-CD2, TUNEL, and H&E staining. Statistical analysis was performed with the Mann-Whitney U test. The therapeutic groups showed significantly prolonged recipient survival compared with the LacZ-treated control group. Histologic analysis revealed reduced hepatocyte apoptosis in the CrmA-treated group and increased apoptosis of infiltrating mononuclear cells in the FasL-treated group. These data suggested that FasL and CrmA may be potent genes to prolong rat liver allograft survival.

Interobserver agreement on classifying endoscopic diagnoses of nonerosive esophagitis.

BACKGROUND AND STUDY AIMS: The majority of patients with gastroesophageal reflux disease in Japan have low-grade esophagitis, including minimal changes. A modified Los Angeles classification of esophagitis, consisting of erosive esophagitis (grades A - D) and nonerosive esophagitis (grades M and N) has been proposed and is in clinical use in Japan. However, it is unclear whether nonerosive esophagitis with only undemarcated mucosal discoloration (grade M) is clinically significant, since interobserver variations in classification have not been investigated. The aim of the present study was therefore to evaluate interobserver variance and diagnostic agreement in the diagnosis of nonerosive esophagitis (grades M and N). MATERIALS AND METHODS: A total of 84 endoscopists were enrolled to assess the grade of esophagitis in 30 patients by viewing endoscopic images of the gastroesophageal junction. The images were projected onto a screen, and all of the endoscopists reviewed them concurrently. The diagnosis was selected from the following three categories in the modified Los Angeles classification: grades N, M, or A. The endoscopists were grouped according to their experience, whether they had a board license, and whether they had received specialist training in esophagitis. The kappa coefficient of reliability was calculated. RESULTS: The kappa coefficient of reliability for all the endoscopists in the diagnosis of cases of grade M and N nonerosive esophagitis was unacceptably low at 0.22 (95 % CI, 0.21 - 0.24). Endoscopists with a board license and those who had completed a special esophagitis diagnostic course had slightly higher kappa values (0.26; 95 % CI, 0.23 - 0.30 and 0.29; 95 % CI, 0.26 - 0.32), respectively. CONCLUSIONS: Interobserver agreement on the endoscopic diagnosis of nonerosive esophagitis (grades M and N) is too low to be of clinical value.