Yumiko Maruyama

Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma

Matrix metalloproteinase 2 (MMP‐2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1‐MMP (MT1‐MMP) was originally identified as an activator of MMP‐2. Tissue inhibitor of MMP‐2 (TIMP‐2) was identified as an inhibitor of MMP‐2 and MT1‐MMP. However, TIMP‐2 was reported to be essential for cell‐mediated activation of MMP‐2 and thus, the contribution of TIMP‐2 to tumor invasion has remained controversial. This study was designed to analyze the role of TIMP‐2 for activation of MMP‐2 and its prognostic value in tongue squamous cell carcinoma (SCC). Expression of MMP‐2, MT1‐MMP and TIMP‐2 protein was analyzed by immunohistochemistry, and their association with clinical factors was evaluated in 51 patients treated surgically for tongue SCC. Expression of MMP‐2, MT1‐MMP and TIMP‐2 was significantly correlated with local and distant metastatic tumor recurrence and poor prognosis (MMP‐2 and MT1‐MMP, p < 0.0001; TIMP‐2, p = 0.0002). Activation of MMP‐2, analyzed by gelatin zymography in 17 fresh specimens, was remarkably associated with expression of MMP‐2 (r = 0.779, p < 0.0001), MT1‐MMP (r = 0.674, p < 0.0022) and TIMP‐2 (r = 0.858, p < 0.0001). Increased expression of TIMP‐2, as well as MMP‐2 and MT1‐MMP, was an important prognostic factor in patients with tongue SCC.

Clonal spread of β-lactamase-producing amoxicillin–clavulanate-resistant (BLPACR) strains of non-typeable Haemophilus influenzae among young children attending a day care in Japan

OBJECTIVE Resistant strains of non-typeable Haemophilus influenzae (NTHi) are one of the principal causes of recurrent acute otitis media (otitis prone), rhinosinusitis, and pneumonia in young children. Beta-lactamase-nonproducing ampicillin-resistant (BLNAR) strains are particularly common in Japan, and beta-lactamase-producing amoxicillin-clavulanate resistant (BLPACR) strains are now emerging. We investigated the nasopharyngeal carriage status of these resistant strains among children attending a same day care center during a 10-year period. METHODS From 1999 to 2008, we obtained nasopharyngeal swab specimens from young children attending a same day care center and examined the incidence of resistant strains of NTHi. Antimicrobial resistance of NTHi was identified based on PCR analysis of mutation of the penicillin binding protein (PBP) genes. Pulsed-field gel electrophoresis (PFGE) was performed to examine the clonal relationship of each resistant strain. RESULTS The prevalence of resistant strains of NTHi among the children attending this day care has significantly increased during the past 10 years and most of this day care children recently have resistant strains with PBP gene mutations in their nasopharynx. Genetically BLPACR (gBLPACR) strains have rapidly increased since 2007 and PFGE analysis demonstrated that all gBLPACR were clonally identical. This is the first report of apparent clonal dissemination of gBLPACR strains of NTHi occurring in a certain environment such as day care. CONCLUSIONS The rapidly increasing prevalence of resistant strains, in particular gBLPACR, in this day care center may predict a high incidence of these resistant bacteria from clinical isolates in the near future and potential serious medical problems worldwide.

Effects of Japanese herbal medicine, Juzen-taiho-to, in otitis-prone children – a preliminary study

Conclusion: Juzen-taiho-to (JTT, TJ-48), a Japanese herbal medicine that improves immune function, was found to be effective in otitis-prone in children. Objective: To evaluate the efficacy of JTT against intractable and recurrent infections in immature immune systems, we administered JTT to otitis-prone infants and investigated clinical changes before and during JTT administration. Subjects and methods: Twenty-four otitis-prone infants were administered JTT at 0.10–0.14 g/kg/day twice a day for 3 months. We compared clinical course, such as frequency of acute otitis media (AOM), duration of fever and antibiotics administration, and hospital visits for the periods before and during JTT administration. Results: Medication compliance rate was 87.5%, and administration of JTT led to remission in 95.2% patients. No apparent side effects were observed. The frequency of AOM decreased significantly (Wilcoxon signed rank test, p=0.000) with JTT. The duration of fever (p=0.000) and administration of antibiotics (p=0.001), as well as the number of hospital visits (p=0.001) and emergent hospital visits (p=0.000) showed significant decreases after JTT administration. After the end of the JTT period, 14 of 21 (66.7%) patients started to take it again, as they experienced purulent otitis media and/or other infections after discontinuation. The frequency of AOM increased significantly after stopping JTT (p=0.004) and decreased again with JTT resumption (p=0.005).

Case of three delayed complications of radiotherapy: Bilateral vocal cord immobility, esophageal obstruction and ruptured pseudoaneurysm of carotid artery

We report the first case of three delayed complications following irradiation for laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed.

A case of chronic otitis media caused by Mycobacterium abscessus

Although it appears very uncommon in adult COM, Mycobacterium abscessus should be considered as a possible cause of a chronically draining ear. Multi-antibiotic chemotherapy including high-dose clarithromycin can effectively treat adult COM cased by M. abscessus. The first case report of adult chronic otitis media (COM) caused by M. abscessus is described here. A 61-year-old woman presented persistent otorrhea for 2 months, despite treatment with standard antimicrobial drugs. Physical examination revealed a small perforation of the tympanic membrane and edematous middle ear mucosa. Mycobacterial cultures and PCR yielded non-tuberculous mycobacteria (NTM); M. abscessus. Intravenous panipenem/betamipron and amikacin and oral clarithromycin were administered for 36 days. Computed tomography of the temporal bone showed improved aeration in the tympanic cavity, but soft tissue shadow remained unchanged in the mastoid 31 days after starting medication. She therefore underwent tympano-mastoidectomy at 36 days. At surgery, inflammation remained in the middle ear, and edematous pale mucosal tissue was noted around the stapes and ossicular chain. Histopathologic examination showed inflammation and granulation tissue, but no caseating necrosis or acid-fast bacilli. After surgery the symptoms resolved and remained well without evidence of infection recurrence 12 months after the operation.

Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media

OBJECTIVE Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children. METHODS Children prone to recurrent AOM aged 6-48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10-0.25g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention. RESULTS At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61±0.54 vs. 1.07±0.72 AOM instances/month; P=0.005) and also significantly decreased number of coryza episodes (P=0.015) and total antibiotic administration (P=0.024). CONCLUSIONS This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections.

Efficacy and safety of garenoxacin in the treatment of upper respiratory tract infections

OBJECTIVE To determine the efficacy and safety of garenoxacin, a new generation of quinolone antimicrobial agent, in the treatment of adult upper respiratory tract infections. METHODS A total of 113 subjects were enrolled in this study. Garenoxacin (400mg/day) was administered to patients with pharyngolaryngitis, tonsillitis, and otitis media for 5-7 days and to those with sinusitis for 7-10 days. Clinical symptoms and findings were examined and quantitatively evaluated using a scoring system. RESULTS We found 80 to 100% improvement rate in symptoms and findings for each infection. In addition, we found significant improvement in subjective evaluations from patient questionnaires even in the early stage of the treatment. X-ray examination for acute sinusitis demonstrated that the clinical efficacy was 84% (27/32) and 76% (19/25) patients were already improved within seven days. Among the detected 84 bacteria, 75 (89%) were identified as the major pathogenic bacteria of respiratory tract infections such as Streptococcus pneumoniae (27 strains) and Haemophillus influenzae (14 strains). Garenoxacin administration completely eradicated bacteria in 53 out of 54 cases (98%). There were 8 adverse events (8.3%) including 3 diarrhea cases (3.1%). CONCLUSION These results suggest that garenoxacin is a highly effective and safe antimicrobial agent in the treatment of community-acquired upper respiratory infections. Additionally, garenoxacin did not induce the growth of resistant bacteria because of its strong antimicrobial activity.

Effects of the Herbal Medicine "Juzen-taiho-to" on Otitis-Prone Children

Juzen-taiho-to (JTT) is known as a herbal medicine that improves immune function. We evaluated whether JTT has a beneficial effect in otitis-prone children. Twenty otitis-prone infants took JTT at 0.1-0.14mg/kg/day twice a day for three months. The medication compliance rate was 85%. The frequency of otitis media purulenta significantly decreased (t-test, p=.000, Wilcoxon signed rank test, p=.000) by the oral administration of JTT. The number of days of fever (t, p=.000, Wilcoxon, p=.000), antibiotic administration (t, p=.002, Wilcoxon, p=.001), hospital visits (t, p=.014, Wilcoxon, p=.005), and emergency hospital visits (t, p=.000, Wilcoxon, p=.000) also showed significant decreases after taking JTT as compared with before.The onset and progression of infection depends on the balance between the reproductive power of microbes and host defense. The effects of JTT on otitis-prone individuals have not been investigated before. JTT is thought to be one of the effective treatments for otitis-prone cases, and avoiding the overuse of antibiotics would prevent the increase of drug-resistant bacteria both in terms of their number and level of resistance.

Seven Cases of Laryngospasms in Everyday Life.

We report 7 cases of acute and recurrent inspiratory dyspnea in which no organic cause could be identified. Patients were from 12 to 68 years old (43.6 in average), consisting of five males and two females. In three of the seven cases, fiberoptic laryngoscopy during an attack of dyspnea revealed laryngospasms following symmetric adduction of the vocal cords. Each patient experienced loud, stridorous noise during inspiration at the beginning of an attack as well as the subsequent inability to inspire. The attacks ranged from several tenths of a second to a few minutes in duration and occurred frequently, several times a day in some cases. Results of physical examinations, lung function tests, roentgenograms of the chest and larynx, and CTs of the lungs and the neck were unremarkable. Laboratory findings including blood gas analysis between attacks were within normal limits. No atopic stigmata were found.Drinking water or swallowing could sometimes relieve the grade of the attack, and the patient could completely prevent attacks once they understood the condition of the dyspnea and mastered a breathing maneuver during the attack. Previous upper respiratory infection, cough, and sleep apnea were suggested to correlate with the episodes. Our patients did not require drastic maneuvers such as tracheostomy or intubation. Administration of Eperisone hydrochloride and Etizolam proved effective in some cases.Laryngospasm as a cause of recurrent inspiratory dyspnea is functional, and we suspect that it is not such a rare occurrence. An awareness of this entity could prevent unnecessary tracheotomies.