Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.     

Callysponginol sulfate A,an MT1-MMP inhibitor isolated from the marine sponge Callyspongia truncata

Callysponginol sulfate A (1) was isolated from the marine sponge Callyspongia truncata as a membrane type 1 matrix metalloproteinase (MT1-MMP) inhibitor. Its structure was elucidated by a combination of spectroscopic and chemical methods and found to be a new sulfated C(24) acetylenic fatty acid. Compound 1 inhibited MT1-MMP with an IC(50) of 15.0 microg/mL.     

Intrahepatic biloma formation (bile duct necrosis) after transcatheter arterial chemoembolization

OBJECTIVE: The purpose of our study was to discuss the incidence, predisposing factors, and clinical course of intrahepatic biloma after transcatheter arterial chemoembolization for hepatic tumors including hepatocellular carcinoma and metastatic liver tumor. MATERIALS AND METHODS: Nine hundred seventy-two patients with hepatocellular carcinoma (n = 920) or metastatic liver tumor (n = 52) underwent chemoembolization during a 12-year period beginning in January 1989. We retrospectively reviewed the medical records and follow-up radiographs of chemoembolization and analyzed the risk factors associated with the development of intrahepatic biloma. RESULTS: Intrahepatic biloma developed after chemoembolization in 35 patients (3.6%, 35/972) in our series. The incidence of intrahepatic biloma formation in patients with metastatic liver tumor (9.6%, 5/52) was higher than that in patients with hepatocellular carcinoma (3.3%, 30/920) (p < 0.05, Fisher's exact test). The incidence of intrahepatic biloma formation in patients with hepatocellular carcinoma was statistically higher in patients with main tumor size of less than 5 cm and in those with the presence of intrahepatic bile duct dilatation. Technique-related risk factors such as injection site of drugs, repeated chemoembolization with frequency of less than 3 months, and regimen of chemoembolization significantly influenced the incidence of biloma formation in patients with hepatocellular carcinoma. No patient died of infected biloma or septicemia, but one patient died of hepatic failure 2 months after chemoembolization. CONCLUSION: Biloma formation was significantly more prevalent in the metastatic lesion group than in the hepatocellular carcinoma group. Significant prognostic factors for biloma formation in patients with hepatocellular carcinoma were tumor size of less than 5 cm, bile duct dilatation, proximal injection site, repeated injection with frequency of less than 3 months, and injection of a suspension of anticancer drugs.     

Optimal application time of lidocaine adhesive tape examined using current perception threshold measurement

BACKGROUND: We often use lidocaine adhesive tape (Penles, Wyeth Lederle Japan, Ltd., Tokyo, Japan) as a topical anesthetic prior to puncturing a vein with a needle. Since the tape is usually in place for a long time, we often experience problems with creasing and flaring when inserting the needle. We attempted to determine the optimal time for application of the tape as well as for vein puncture after its removal by measuring pain sensation in human subjects. METHODS: Lidocaine tape was applied to the dorsum of volunteer hands for 2, 4, 6, and 12 hours, and we evaluated changes after removal by determining current perception threshold (CPT), pain score, touch sensation score, diameter of the vein, pruritus, and flare. RESULTS: CPT levels were found to increase within 1 hour after removal of the lidocaine tape with all 3 electrical stimulus rates used (2000 Hz, 250 Hz, 5 Hz). Further, pain and touch sensation scores were low within 2 hours of removal regardless of application time. Notably, with 4 and 6 hours of application, scores were stable 4 and 6 hours after removal. However, vein diameter and pruritis results did not change regardless of application time, while crease and flare were only observed within 30 minutes after removal. CONCLUSIONS: We concluded that lidocaine tape provided maximum pain relief when applied 4 to 6 hours prior to vein puncture and up to 1 hour after removal.     

Deafness due to A1555G mitochondrial mutation without use of aminoglycoside

OBJECTIVES/HYPOTHESIS: The objective was to clarify the characteristics of deafness associated with the A1555G mutation within mitochondrial 12S ribosomal RNA gene in the absence of aminoglycoside exposure. STUDY DESIGN: Clinical and genetic studies in family members with the A1555G mitochondrial mutation were performed. METHODS: The subjects were 123 maternally related members of a large Japanese family with the A1555G mutation. All subjects had no previous history of exposure to aminoglycosides. Hearing disability and handicap, tinnitus, and medical histories were analyzed by interviews in all of the subjects, genetic testing was performed in 41 subjects, and pure-tone audiometry was conducted in 26 subjects with hearing disability and handicap. RESULTS: The A1555G mutation was detected in a homoplasmic form (meaning that all the mitochondrial DNA carries the mutation) in all 41 subjects who were screened. The risk for developing postlingual hearing loss was likely to be much higher in the present subjects than in the general population. Both the severity and age at onset of the phenotype were similar in affected subjects within the same sibling group. Pure-tone averages were significantly worse in subjects who developed hearing loss before age 10 years than in those who developed hearing loss later. CONCLUSION: The present study demonstrated that the prevalence of deafness in individuals with the A1555G mitochondrial mutation was likely to be high even in the absence of aminoglycoside exposure and clearly showed the association of severe to profound hearing loss with the onset of hearing loss before age 10 years.     

Switch to Latanoprost Monotherapy from Combined Treatment with β-Antagonist and Other Antiglaucoma Agents in Patients with Glaucoma or Ocular Hypertension

Purpose To investigate the effects on intraocular pressure (IOP) and the occurrence of adverse events upon switching directly to latanoprost monotherapy from multiple drug therapy, including a -antagonist, for glaucomatous eyes.Methods Patients with primary open-angle glaucoma or ocular hypertension and receiving long-term therapy with two or three topical ocular hypotensive drugs (including one topical -antagonist) were switched to latanoprost monotherapy for 12 weeks without any intervening washout period. Observations were performed before switching (baseline) and at weeks 4, 8, and 12 after switching to latanoprost monotherapy.Results Of the 29 enrolled patients, 26 (90%) completed this protocol. Three patients had excessive IOP elevation, and these patients were withdrawn. The switch to latanoprost monotherapy was followed by a significant (P < 0.0001) mean reduction of 3.9mmHg at week 12 in per-protocol cases (n = 26) and a significant (P = 0.0016) mean reduction of 2.8mmHg at last postswitch visit in patients in the intent-to-treat analysis group (n = 29). Adverse ocular events other than IOP elevation were mild.Conclusions The switch to latanoprost monotherapy in glaucoma patients receiving multiple drug therapy resulted in an additional, significant IOP reduction. Jpn J Ophthalmol 2004;48:276–280 © Japanese Ophthalmological Society 2004     

Video-Assisted Thoracic Surgery Lobectomy for Extralobar Pulmonary Sequestration in a Child: Report of a Case

Pulmonary sequestration in infants and children is conventionally treated by resecting the sequestered lung parenchyma (sequestrectomy) or by performing lobectomy through a standard thoracotomy. We performed lobectomy by video-assisted thoracic surgery, using an original tracheal tube that we designed, in a 6-year-old boy with extralobar pulmonary sequestration and bronchiectasis in the left lower lobe.     

Urinary acidification in extremely low birth weight infants

Premature infants often present metabolic acidosis without protein load in the early neonatal period, around days 4–6. In order to elucidate the cause of acidosis, we investigated urinary acidification of infants in the early neonatal period.

Urine pH, fractional excretion of HCO₃⁻ (FEHCO₃), excretion of HCO₃⁻ and NH₄⁺ of the appropriate-for-date infants were measured on days 0–2 and on days 4–6 of life.

Extremely low birth weight (ELBW) infants showed higher urine pH than more than 1500 g birth weight infants. FEHCO₃ and HCO₃⁻ excretion were of high values in ELBW infants on days 0–2, but decreased on days 4–6. Urine NH₄⁺ excretion rate was lower in ELBW infants than in birth weight more than 1000 g on days 0–2 of life and still remained at a low rate on days 4–6.

These data indicated that insufficiency of NH₄⁺ excretion is the main cause for metabolic acidosis of ELBW infants in the early neonatal period.