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 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.     

Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.

Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 +/- 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, delta(CS-Ao)BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [delta(AIV-Ao)BNP] was comparable to delta(CS-Ao)BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.     

Usefulness of laparoscopic subtotal cholecystectomy with operative cholangiography for severe cholecystitis

Purpose

Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot’s triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery.

Methods

Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed.

Results

LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43–82 years). The median operative time was 125 min (range 60–215 min) and the median postoperative inpatient stay was 6 days (range 3–21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study.

Conclusions

LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis.     

Gender differences in prognosis after esophagectomy for esophageal cancer

Purpose

The purpose of this study was to clarify the gender differences in the prognosis, as well as mortality and morbidity, of patients who have undergone esophagectomy for esophageal cancer.

Methods

The clinical results of esophagectomy were compared between 975 male and 156 female patients with esophageal cancer.

Results

The male to female ratios of cervical and thoracic esophageal cancer were 1.87 and 7.38, respectively (P < 0.01). The incidence of preoperative comorbidities was 32.4 and 17.4 %, respectively, and the rates of both tobacco and alcohol abuse were significantly lower in the females than in the males. The mortality rate was lower in the females (3.8 %) than in the males (5.7 %), although the differences were not significant. The overall survival was significantly better in the female than in the male patients (P = 0.039). The 5- and 10-year overall survival rates were 32.6 and 20.5 % in the males and 39.5 and 32.5 % in the females, respectively. A multivariate analysis revealed gender to be an independent prognostic factor. However, no significant differences were recognized in disease-specific survival.

Conclusions

These results suggest that the prognosis of females with esophageal cancer is better than that of males after esophagectomy, most likely due to multiple clinical factors, such as a more favorable lifestyle and general status.