Pharmaceuticals and Medical Device Agency approval summary: Amenamevir for the treatment of herpes zoster

In July 2017, Japan’s Ministry of Health, Labor and Welfare issued a marketing authorization valid throughout Japan for N-(2,6-dimethylphenyl)-N-(2-{[4-(1,2,4-oxadiazol-3-yl)phenyl]amino}-2-oxoethyl)-1,1-dioxothiane-4-carboxamide (amenamevir) for the first time worldwide. The decision was based on the favorable opinion of the Pharmaceuticals and Medical Device Agency (PMDA) recommending a marketing authorization of amenamevir for treatment of herpes zoster (HZ). Amenamevir has a different action mechanism from previously approved synthetic nucleoside compounds for the treatment of HZ including acyclovir, valacyclovir and famciclovir. The usual adult dose is 400 mg amenamevir p.o. once daily for 7 days. The benefit is its ability to cure HZ as well as preventing postherpetic neuralgia. The most common side-effects are increase of urine N-acetyl-β-D-glucosaminidase and α1-microglobulin levels. However, based on the detailed evaluation of the submitted clinical studies, there seems to be no serious safety concerns about amenamevir regarding the kidney of both renally normal and impaired patients. The objective of this article is to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the PMDA website ( www.pmda.go.jp/PmdaSearch/iyakuSearch/ ).     

The Use of a Circular Side Stapling Technique in Laparoscopic Low Anterior Resection for Rectal Cancer: Experience of 30 Serial Cases

The double-stapling technique using a circular stapler (CS) to create an end-to-end anastomosis is currently used widely in laparoscopic-assisted rectal surgery. However, a high rate of anastomotic failure has been reported. We report new side-to-side anastomosis creation using a CS, the so-called circular side stapling technique (CST). After excising the rectum at the oral and anal sides of the tumor with a linear stapler, a side-to-side colorectal anastomosis was made on the anterior wall of the rectosigmoid colon and the anterior or posterior wall of the rectum with a CS. Between 2012 and 2013, we recorded 30 serial cases of rectal-sigmoid or rectal cancer that were treated with laparoscopic-assisted surgeries using this method. In the 30 cases, the mean age was 68 ± 12 years, operating time was 288 ± 80 minutes, and blood loss was 66 ± 67 mL. None of the patients suffered from anastomosis leakage or postoperative anastomotic bleeding, and none complained of their stool habits. Three months after the last surgery in this cohort, no anastomosis strictures were reported. Based on these results, we propose an alternative method of side-to-side anastomosis for low anterior resection by using a CS to prevent staple overlap. Our experience indicates that the CST is easy and safe. Therefore, this method is a useful alternative to the current method used in laparoscopic surgery.Key words: Laparoscopy, Circular stapler, Colorectal cancer, Low anterior resectionLaparoscopic surgery for the treatment of colorectal disease has proven to be a safe and effective method compared with an open procedure.^1–3 Laparoscopy has the advantages of reduced blood loss, hospital stay, and use of anesthetics as well as a better cosmetic outcome. Although many clinical studies have demonstrated the advantages and low complication rates of laparoscopic colectomy and low anterior resection,^1–5 a high rate of anastomotic leakage has been reported in laparoscopic rectal surgeries. The reported incidence of leakage after laparoscopic surgery for the treatment of rectum varies from 6% to 17%.^1–3 Additionally, anastomotic leakage might raise concerns about local recurrence and may limit the patients prognosis.^6–8 Therefore, despite great advances in laparoscopic surgery, the risks of anastomotic complications persist to a greater extent than those for other colonic resections.^6,7Recent reports have included proposed methods for reducing anastomotic leakage, and recently a transanal drainage tube has been recommended, because the high pressure experienced in the rectum could cause anastomotic failure.⁹ Another group reported the use of anti-traction sutures supporting the anastomosis to reduce anastomotic leakage.¹⁰ Despite these proposals, anastomotic failure has not been completely resolved.In typical laparoscopic rectal surgery, a double-stapling technique (DST) with a circular stapler is used to create the anastomosis. This method is thought to be the only method available to complete an intracorporeal anastomosis of the rectum. However, the DST requires the excision of the stump of the staple line created by the linear stapler. Our previous endoscopic experience with anastomotic leakage shows that leakage occurs frequently at the point where the staples overlap in the DST.¹¹ In this study we demonstrate a new circular side stapling technique (CST), which does not require the excision of the linear staple line in a laparoscopic low anterior resection.     

Generation and characterization of a novel shoulder contracture mouse model

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self‐limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1732–1738, 2015.     

Enhanced heat shock protein 25 immunoreactivity in cranial nerve motoneurons and their related fiber tracts in rats prenatally‐exposed to X‐irradiation

Alterations in histoarchitecture of the brainstem were examined immunohistochemically in 4‐week‐old rats with a single whole body X‐irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 using anti‐heat shock protein 25 (HSP25). HSP25 immunostaining was seen in the neuronal perikarya of cranial nerve motoneurons, that is, the motor and mesencephalic nuclei of the trigeminal nerve, facial nucleus, abducens nucleus and accessory facial nucleus in the pons, and the ambiguous nucleus, dorsal nucleus of vagus nerve and hypoglossus nucleus in the medulla oblongata of intact controls. In 0.5 to 1.5 Gy‐irradiated rats, HSP25 immunostaining in those neurons was more intense than in controls, while the most intense immunostaining was marked in 1.5 Gy‐irradiated rats. HSP25 immunostaining was also apparent in the spinal tract of the trigeminal nerve and facial nerve tracts in 0.5 to 1.5 Gy‐irradiated rats, but was faint in controls. Interestingly, HSP25 immunostaining was aberrantly enhanced in dendritic arbors in the magnocellular region of medial vestibular nucleus of 0.5–1.5 Gy‐irradiated rats. Those arbors were identified as excitatory secondary vestibulo‐ocular neurons by double immunofluorescence for HSP25 and SMI‐32. The results suggest an increase of HSP25 expression in cranial nerve motoneurons and their related fiber tracts from prenatal exposure to ionizing irradiation. This may be an adaptive response to chronic hypoxia due to malformed brain arteries caused by prenatal ionizing irradiation.     

The effect of duration and force of mechanical toothbrushing stimulation on proliferative activity of the junctional epithelium

BACKGROUND: Gingival bleeding is frequently accompanied by an ulcerated epithelium, with repair depending on the proliferative activity of the epithelial cells. The present study examined the proliferative activity of the junctional epithelium (JE) under several different methods of toothbrushing stimulation. METHODS: Twelve dogs were used in this 3-week experiment. Prior to the experiment, all teeth underwent daily removal of plaque and calculus using a scaler. Teeth were then divided into quadrants: 9 teeth in 3 quadrants (test, 3 per quadrant) were mechanically stimulated by toothbrushing for various time intervals (10, 20, or 40 seconds) and at various forces (100, 200, or 250 gf). The 3 teeth in the fourth quadrant served as controls. The proliferative activity of the basal cells of the junctional epithelium was evaluated for expression of proliferating cell nuclear antigen (PCNA). The numbers of PCNA-positive basal cells and total basal cells were counted, and the width of the junctional epithelium was measured. RESULTS: Toothbrushing force significantly affected the PCNA-positive basal cell ratio (P < 0.05). The 200 g toothbrushing force produced the highest PCNA-positive basal cell ratio, which was significantly higher than that using the 100 g force (P < 0.05). CONCLUSION: In junctional epithelium stimulated with a toothbrush, the PCNA-positive basal cell ratio is more sensitive to toothbrushing force than to duration.     

Comparison of stability of mandibular segments following the sagittal split ramus osteotomy with poly-l-lactic acid (PLLA) screws and titanium screws fixation

The purpose of this study was to retrospectively compare the stability of the mandible following the surgical orthodontic treatment by sagittal split ramus osteotomy (SSRO) and orthodontic multi-bracket treatment using fixation methods with poly-l-lactic acid (PLLA) or titanium screws. The sample examined was 23 subjects with PLLA screws (PLLA group) and 22 subjects with titanium screws (Titan group). Lateral cephalometric radiographs were reviewed before surgery (T0), 2–3 days after surgery (T1), 1 month after surgery (T2), and after postoperative orthodontic treatment (T3) and changes in the position of bony segments were examined by cephalometric linear and angular measurements. A similar movement of the mandible following setback surgery was indicated, and statistical analysis showed no significant differences in skeletal changes between the two groups during whole postoperative periods. However, a relapse following surgical counterclockwise rotation of the distal segment in PLLA group tended to be slightly greater during T1–T2 compared with Titan group. These results suggest that a use of the PLLA screw fixation may not influence on the stability of bony segments after mandibular setback surgery by SSRO during the postoperative period, although a slight tendency for clockwise rotation of the distal segment was indicated in patients with PLLA screws. It is suggested that fixation of bony segments with PLLA screws after SSRO may be effective in properly selected cases.     

Oral rehabilitation of an orthodontic patient with cleft lip and palate and hypodontia using secondary bone grafting, osseo-integrated implants, and prosthetic treatment.

OBJECTIVE: Complete skeletal and dental reconstruction of the anterior maxilla is of great importance to patients with cleft lip and palate. Accordingly, osseo-integrated implants have been utilized for dental reconstruction after secondary bone grafting. In this report, the orthodontic management of a patient with unilateral cleft lip and plate with associated hypodontia is described. The patient was treated with comprehensive orthodontic treatment in addition to secondary bone grafting, and dental reconstruction was achieved with a combination of osseo-integrated implants and fixed prosthodontic treatment.