Kazuhiro Yamakawa

Valacyclovir and prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-controlled study.

Objective: To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bells palsy, excluding zoster sine herpete. Study Design: Prospective, multicenter, randomized placebo-controlled study. Setting: Six academic tertiary referral centers. Patients: Ultimately, 221 patients with Bells palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bells palsy from zoster sine herpete. Intervention: The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally. Main Outcome Measure: Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis. Results: The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p < 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p < 0.05). Conclusion: The valacyclovir and prednisolone therapy was more effective in treating Bells palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bells palsy cases based on an etiologic background.

Bumetanide-induced enlargement of the intercellular space in the stria vascularis critically depends on Na+ transport

The intercellular space in the stria vascularis (intrastrial space) is a closed space and isolated from both the endolymph and the perilymph in normal tissue. Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space in association with a decline in the endocochlear potential. It is known that bumetanide inhibits the Na+-K+-2Cl- cotransporter, which is expressed abundantly in the basolateral membrane of marginal cells. We studied ionic mechanisms underlying the bumetanide-induced enlargement of the intrastrial space using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with artificial perilymph containing 100 microM bumetanide caused marked enlargement of the intrastrial space, as reported previously. Removal of K+ from the perilymph did not affect the bumetanide-induced enlargement, whereas removal of Na+ from the perilymph inhibited it almost completely. Perilymph containing 1 mM amiloride also inhibited the enlargement of the intrastrial space almost completely. These results indicate that perilymphatic Na+, but not K+, and amiloride-sensitive pathways are essential to the bumetanide-induced enlargement of the intrastrial space. Two possible pathways could yield these results. Na+ in the perilymph could enter the endolymph via Reissners membrane or the basilar membrane; Na+ in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na+-K+-ATPase in the basolateral membrane of them. Another, less likely possibility is that Na+ in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na+-K+-ATPase of intermediate cells.

Bumetanide-induced Enlargement of the Intercellular Space in the Stria Vascularis Requires an Active Na + -K + -ATPase

OBJECTIVE Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space of the stria vascularis, with an associated decline in the endocochlear DC potential (EP). The aim of this study was to determine the role played by the Na+-K+-ATPase in the bumetanide-induced enlargement of the intrastrial space, and to examine the importance of the balance between the activities of the Na+-K+-2Cl- cotransporter and the Na+-K+-ATPase to the physiological function of the stria vascularis. MATERIAL AND METHODS Albino guinea pigs were used in experiments involving perilymphatic perfusion, EP measurement and electron microscopy. The effects of bumetanide on the stria vascularis were examined following inhibition of the Na+-K+-ATPase by ouabain. Ouabain was administered to the perfusate and, when the EP reached 0 mV, both ouabain and bumetanide were administered. RESULTS Although there was no enlargement of the intrastrial space, vacuoles were apparent in marginal cells. The vacuolar change in marginal cells was similar to that caused by ouabain alone. CONCLUSION This study indicates that the enlargement of the intrastrial space requires not only the blockade of the Na+-K+-2Cl- cotransporter but also normal activity of the Na+-K+-ATPase, and suggests that the bumetanide-induced enlargement of the intrastrial space resulted from the imbalance between the activities of the Na+-K+-2Cl- cotransporter and the Na+-K+-ATPase.

Time course of dehydrating effects of isosorbide on experimentally induced endolymphatic hydrops in guinea pigs.

Osmotic diuretics are therapeutic agents used to reduce endolymphatic hydrops. However, glycerol-induced change in endolymph volume is followed by a rebound phenomenon. In this study, we investigated the rebound phenomenon occurring with isosorbide, an osmotic diuretic used as a therapeutic agent for Ménière’s disease in Japan. Forty guinea pigs underwent surgical obliteration of the endolymphatic sac. Thirty received isosorbide orally 1 month after surgery. These animals were sacrificed 3, 6, or 12 h after isosorbide intake. The remaining 10 animals served as controls. Quantitative assessment of changes in the endolymphatic space was performed light-microscopically. Isosorbide reduced cochlear endolymph volume, with a peak reduction 6 h after intake. Thereafter, no prominent rebound phenomenon was noted. Clinically, since isosorbide is orally administered every 8 h, rebound phenomenon need not be considered in the treatment with isosorbide.

Initial Lesions in Bell’s Palsy and Ramsay-Hunt Syndrome

Conclusion: The antidromic facial nerve response (AFNR) revealed that the initial lesion in both Bell’s palsy and Hunt syndrome was mainly located around the geniculate ganglion within 1 week after onset of paralysis. The preoperative AFNR reflected the response near the initial lesion. Objectives: To review the initial lesion in Bell’s palsy and Ramsay-Hunt syndrome using intraoperative monitoring of the AFNR. Methods: 15 patients, including 8 with Bell’s palsy and 7 with Ramsay-Hunt syndrome, were checked for the AFNR before and during transmastoid decompression surgery within 1 week after onset of paralysis. The AFNR monitoring was performed at the posterosuperior part of the anulus tympanicus preoperatively and at 4 points of the facial nerve during surgery. The nerve conduction block sites were diagnosed by the AFNR waveform. Results: The monophasic wave revealing the block site was mainly observed at the geniculate ganglion in both diseases. The latencies of the preoperative responses corresponded to those recorded intraoperatively around the pyramidal segment of the facial nerve.

What are the Most Responsible Pathogenic Bacteria in the Adenoid for Intractable Acute Otitis Media in Japanese Children

Introduction: Although Streptococcus pneumoniae (SP), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) are major pathogenic bacteria of acute otitis media (AOM) in children, responsibility of their resistance to antimicrobial agents for intractable AOM has not been cleared. In this study, cultured bacteria from the adenoid of otitis-prone children were compared with those of children who had no apparent episodes of AOM to know the most responsible pathogens for intractable AOM. Methods: Sixty-eight children who had episodes of recurrent or persistent AOM were subjected to this study and 19 children without apparent episodes of AOM but with obstructive sleep apnea were taken as controls. Nasopharyngeal swab specimens were obtained from the adenoid transorally during the adenoidectomy, instead of conventional transnasal harvesting, to avoid contamination. Prevalence of SP, HI, and MC in each group was compared using the chi-squared or Fischers exact test, and p-values <0.05 were considered significant. Results: SP was identified in 60.3% of otitis-prone children and in 52.6% of control children, and this difference indicated no statistically significance (p=0.54). HI was isolated from 77.9% of subjects and from 47.4% of controls, and the difference revealed significant (p=0.009). Above all, beta-lactamase negative HI (BLNAR) was caught in 39.7% of the study group, but in none of the control group (p=0.002). MC was identified in 32.4% and in 5.3%, individually, with significant difference (p=0.04). Conclusion: HI was more frequently isolated from otitis-prone children, and was considered to make AOM more intractable. The pathogenic role of MC for AOM may be evident.

Early Assessment of Nerve Degeneration Using the Antidromic Facial Nerve Response

Conclusion: The antidromic facial nerve response (AFNR) is recommended as a monitoring method to detect cases resulting in facial nerve degeneration within 1 week after onset in patients with Bell’s palsy and Hunt syndrome. Objectives: The purpose of this study was to establish criteria for the AFNR to predict the prognosis of Bell’s palsy and Hunt syndrome in the early stages, not exceeding 1 week after onset. Materials and Methods: 54 patients, including 40 with Bell’s palsy and 14 with Hunt syndrome, were examined in this study. All patients were tested for the AFNR within 1 week after onset of paralysis and AFNR waveforms were analyzed. Four AFNR parameters, the total (peak-to-peak) amplitude (T-amp), the amplitudes of the positive wave (P-amp) and the negative wave (N-amp), and the N-amp/T-amp (N/T) ratio, were compared with the outcomes of facial paralysis. Results:In most patients with poor outcomes, T-amp was <4 µV and N-amp was <2 µV. The mean value of the N/T ratio in patients with a poor outcome fell to <0.4 after the 3rd day from onset, while that in patients with a good outcome was stable between 0.4 and 0.6 during the first week.

A Totally Implanted Intra-Arterial Chemotherapy System for Advanced Maxillary Sinus Carcinoma

Conclusion: Both reservoir systems for intra-arterial cisplatin and intravenous sodium thiosulfate infusions are low- invasive, safe and effective procedures for treatment of advanced maxillary sinus carcinoma. Objectives: To use our reservoir system for intra-arterial high-dose cisplatin infusion therapy in patients with advanced maxillary sinus carcinoma. Materials and Methods: Eight patients with advanced maxillary sinus carcinomas underwent treatment utilizing intra-arterial cisplatin (CDDP) infusion and radiation therapy followed by planned surgical resection. For intra-arterial infusion of high-dose cisplatin, both intra-arterial and intravenous reservoir systems were used. Results: CDDP was infused 4–6 times (mean 5.1) and the total dose of CDDP was between 690 and 910 mg (mean 771 mg). The response rate was 100 with 50% CR and 50% PR and all patients underwent medial maxillectomy. Only 1 T4 patient had local recurrence and 1 other patient had bilateral neck metastasis.

A Case of Ramsay Hunt Syndrome Followed by Cerebellar Encephalitis

We report a case of Ramsay Hunt syndrome followed by cerebellar encephalitis. A 69-year-old man with concomitant presentation of right severe facial palsy, ipsilateral auricular vesicle and vertigo was referred to our hospital under a diagnosis of Ramsay Hunt syndrome. A high dose of steroid and a conventional dose of acyclovir were administered from the second day of the disease onset. He quickly recovered from the vertigo, but the facial palsy persisted. He also exhibited an ataxic gait several days after the primary treatment. An increase in cell count, protein and VZV Ig-G in the cerebrospinal fluid led to a diagnosis of VZV-associated cerebellitis, even though VZV DNA was negative on PCR. Twice the previous doses of steroid and acyclovir each was administered and thereafter his walking ability improved. Care for central nerve complication should be taken in cases with VZV reactivation.

Rapid diagnosis of VZV DNA reactivation using real-time PCR in patients with facial palsy

Objectives: Since the early administration of anti-viral agents is thought to be effective for the treatment of facial palsy caused by varicella-zoster virus (VZV) reactivation, a method for the early diagnosis of possible reactivation needs to be established regardless of whether aural eruption coexists or not. To achieve this goal, a rapid detection of VZV DNA using real-time PCR was attempted in various samples from patients with facial paralysis. Methods: The subjects consisted of 13 patients with typical Ramsay Hunt syndrome (RHS), 7 patients with no concomitant aural eruptions and final diagnosis of VZV reactivation, and 74 patients with Bell’s palsy. Auricular skin cells and saliva were collected from all these 94 patients. DNA of these samples was extracted using a DNA extraction kit (QIAamp DNA blood mini kit, Qiagen), and DNA was examined using real-time PCR (LightCycler, Roche Molecular Biochemicals). Results: VZV DNA was detected in auricular skin cells from all 13 patients with typical RHS and also in saliva from 2 out of 13. VZV DNA, however, was proved neither in auricular skin cells nor saliva from the remaining 81 patients. The LightCycler system required approximately 45 minutes to complete PCR examination. Conclusion: The detection of VZV DNA using LightCycler PCR may be an applicable test for early diagnosis of VZV infection, though sensitivity, timing, and sampling method should be further investigated.