A recovery from enhancement of activation in auditory cortex of patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: We previously reported enhanced activation of auditory cortex in patients with bilateral chronic inner-ear hearing loss. To determine whether this enhancement can exhibit a short-term alteration, we measured auditory evoked magnetic fields (AEFs) in patients with idiopathic sudden sensorineural hearing loss (ISSHL) in the acute phase (AP) and recovery phases (RPs). METHODS: We recorded AEFs in two unilateral ISSHL patients at three time points (AP, RP1, and RP2) using a whole-head neuromagnetometer. Tone bursts of 1 kHz were presented monaurally to the affected and healthy ear at four different intensities (40-70 dB HL). RESULTS: Both patients showed the enhancement of N100 m moment at AP and not at RPs in response to the affected ear stimulation, and stronger N100 m moment in ipsilateral than contralateral hemisphere in response to the healthy ear stimulation at AP. CONCLUSIONS: Enhancement of N100 m amplitude occurs in ISSHL patients and disappears on the scale of days. Enhancement of activity in the auditory cortex derived from inner-ear hearing loss can thus exhibit short-term change. SIGNIFICANCE: The results of this study provide first evidence for a recovery from enhancement of activation in the auditory cortex following injury of peripheral hearing organ.

Enhanced activation of the auditory cortex in patients with inner-ear hearing impairment: a magnetoencephalographic study.

OBJECTIVE: Injury of peripheral auditory organ often induces abnormality of loudness sensation such as loudness recruitment. However, objective evaluation of this phenomenon has rarely been performed. To elucidate this abnormal loudness sensation, cortical mechanisms were investigated by recording auditory evoked magnetic fields (AEFs). METHODS: We recorded AEFs in 8 patients suffering from inner-ear hearing impairment with loudness recruitment and in 14 healthy hearing controls using a 122-channel whole-head neuromagnetometer. Tone bursts of 1 kHz were presented monaurally at 4 different intensities (40, 50, 60, 70 dB HL) with a constant interstimulus interval of 1 s. RESULTS: In both groups, the 100 ms response (N100m) increased in amplitude and decreased in latency as a function of stimulus intensity in both hemispheres. Concerning the source strength, increment of dipole moment of N100m was more rapid according to the stimulus intensity in patients compared with that in healthy subjects. Source strength of N100m was enhanced at high stimulus intensity in patients, and its ratio to healthy subjects was 1.08 at 50 dB, 1.69 at 60 dB and 2.04 at 70 dB. CONCLUSIONS: In patients with inner-ear hearing impairment, enhanced activation of the auditory cortex was observed, and may help explain loudness recruitment.

Maturational change of parallel auditory processing in school-aged children revealed by simultaneous recording of magnetic and electric cortical responses.

OBJECTIVES: To elucidate the maturational change of cortical auditory processing, we analyzed simultaneously recorded auditory evoked potentials (AEPs) and magnetic fields (AEFs) in school-aged children. METHODS: Simultaneous recording of AEP and AEF were performed in 32 healthy children of age ranging from 6 to 14 years and 10 adults. Tone bursts of 1 kHz were presented to the left and right ears alternately with 3 different within-ear stimulus onset asynchronies (SOAs) (1.6, 3.0 and 5.0 s for each ear) under attention-distracted condition. RESULTS: All subjects showed clear N100 and N100m peaks under the longest SOA condition (5.0 s). Under the shortest SOA condition (1.6 s), 4 out of 19 subjects under 12 years (21%) failed to show the N100m component. By contrast, N250 and N250m were observed in the majority of children (29/32: 91%) while those were detected in only 4 out of 10 adults (40%). The spatial distribution of N100 in children under 9 years differed from that in older subjects, whereas the dipole orientation of N100m was constant among age groups, suggesting that radially oriented sources might make additional contribution to the generation of N100 in early childhood. N250 was significantly larger in children than in adults. The strength of N250 was suppressed with longer SOAs, whereas that of N100 was enhanced. The dipole of N250m was located around Heschl's gyrus on the superior temporal plane which was significantly medial, anterior and inferior to that of N100m. CONCLUSIONS: Dissociation of maturational change between the tangential and radial components of N100 suggests that auditory processing at around 100 ms consists of multiple parallel pathways which mature independently. Furthermore, a negative peak at around 250 ms specifically seen in children has different generators from N100 and might represent a special auditory processing which takes an active part until acquisition of the efficient cortical networks of the adult brain.

Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine.

To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.

Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines.

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 microg) was intranasally (i.n.) inoculated with influenza vaccine (10 microg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3-14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 microg) was i.n. inoculated with the vaccine (10 microg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27-50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 microg) and influenza HA vaccine (1 microg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 microg) each and diphtheria-pertussis-tetanus (DPT) vaccine (10 microg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 microg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.

Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C.

We evaluated the synergistic effect of zinc supplementation on the response to interferon (IFN) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc. No clinical differences were observed between patients treated with IFN alone (n=40) and IFN with polaprezinc (IFN + Zn, n=35). All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum. Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course. No additional side-effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects. Complete response (CR) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy. Incomplete response (IR) was normal liver enzyme and positive serum HCV RNA. Both of them were evaluated at the 6 months after the completion of the treatment. Patients with higher levels of serum HCV (more than 5 x 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 x 105/mL) showed high response rates in combination group (CR: 11/27, 40.7%; CR + IR 15/27, 64.3%), better than IFN alone (CR: 2/15, 18.2%; CR + IR: 2/15, 18.2%). Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group. Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis C.

Iron enhances hepatitis C virus replication in cultured human hepatocytes.

BACKGROUND: Iron overload in the presence of increasing concentrations of iron is one of the indicators of poor response to interferon therapy in chronic hepatitis C. In order to analyze the effect of iron on hepatitis C virus (HCV) replication, we measured replication in an HCV-infected cell line. METHODS AND RESULTS: Cells from a non-neoplastic HCV-infected human hepatocyte line (PH5CH8) susceptible to HCV infection and supportive of HCV replication were used in this study. The replication of HCV RNA was measured by reverse transcription-nested polymerase chain reaction (RT-nested PCR). PH5CH8 cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. PH5CH8 cells were incubated with 0, 1, 10, 50, and 100 microM of FeSO4 at 37 degrees C with 5% CO2. Forty-eight hours after iron supplementation, the quantity of HCV RNA in the cells incubated in 50 and 100 microM of FeSO4 was approximately ten times that of the cells with no iron supplementation. Similar changes were observed beginning at 12 h from supplementation with FeSO4 and continued for at least 72 h after supplementation. MTT assay indicated that iron did not have cytotoxic effects on the PH5CH8 cells. CONCLUSION: Iron enhances HCV replication in a hepatocyte cell line. The results suggest that iron deposition in hepatocytes could facilitate HCV infection in the liver.

Nausea and vomiting induced by arterial chemo-embolization in patients with hepatocellular carcinoma and the antiemetic effect of ondansetron hydrochloride.

To determine the incidence of nausea and vomiting and the antiemetic effect of ondansetron hydrochloride (OND) in patients with hepatocellular carcinoma treated with arterial chemo-embolization, we studied 59 patients with hepatocellular carcinoma who were treated with transcatheter arterial embolization (TAE) or lipiodolized transcatheter arterial infusion (L-TAI). We investigated the incidence of nausea and vomiting and the amount of food intake when TAE or L-TAI was performed. All patients who experienced nausea and vomiting received OND administered prophylactically at the time of the next TAE or L-TAI to evaluate the antiemetic effect of the drug. Cumulative rates of nausea and vomiting during the week following arterial chemo-embolization were 44.8% and 27.6%, respectively. There was a tendency for the incidence to be higher in patients treated with the anticancer agent zinostatin stimalamer (SMANCS) than in those treated with epirubicin hydrochloride (EPI). Regarding food intake, 53.1% of the patients stated that they ate "half or more than half" of the food provided on the day of arterial chemo-embolization. The rate improved as time went on. In 5 patients who experienced nausea and vomiting at the time of arterial chemo-embolization, nausea and vomiting were inhibited satisfactorily by OND. When arterial chemo-embolization was performed, antiemetic treatment for approximately 3 days was necessary to improve patients' quality of life (QOL) to an acceptable level, and OND was found to be effective for the purpose in our 5 patients who had experienced nausea and/or vomiting at the previous treatment.

Modality-specific subregions in human inferior parietal lobule: a magnetoencephalographic study during cognitive tasks.

The inferior parietal lobule (IPL) has been considered to be a multimodal sensory association area. Both event-related potentials and magnetic responses have examined the relationships between IPL and cognitive processing. However, there have been no studies clarifying the functional subregions in IPL. We studied the event-related magnetic response during conventional auditory and visual oddball paradigms. We were able to distinguish non-invasively modality-specific subregions in IPL. The subregion in IPL activated by auditory target stimuli was located more anterior and superior than that responding to visual target stimuli on each hemisphere. The data suggests that modality-specific subregions in the IPL are differentially activated by auditory or visual stimuli.

Transcatheter arterial embolization-induced bilious pleuritis in a patient with hepatocellular carcinoma.

A 52-year-old man with hepatocellular carcinoma (HCC) was admitted with cough and fever. He had undergone four series of treatments, including transcatheter embolization and chemoembolization with lipiodol and anticancer drugs, over the previous 2 years. Computed tomography demonstrated dilated hepatic ducts, localized necrosis in the right hepatic lobe, and subphrenic abscess. He died of respiratory failure, because of increased effusion of the right pleura, about 3 weeks after admission. Autopsy revealed adhesions in the lower lobes of the right lung, diaphragm, and liver, with granulomas with bile pigment. A fistula was observed from the necrotic regions of the right hepatic lobe to the pleura through the diaphragm. A tumor thrombus in the portal trunk was histologically confirmed as well and moderately differentiated HCC with trabecular arrangement. Direct invasion of HCC with necrotic tissue to the pleura through the diaphragm appeared to have caused the respiratory failure. Although bilious pleuritis is a rare complication of transcatheter arterial embolization (TAE), it should be considered as an adverse effect of TAE in patients with a dilated hepatic duct.

Automatic detection method of P300 waveform in the single sweep records by using a neural network.

Event-related potentials (ERPs) are responses related to the recognition of certain stimuli. P300 is the most important positive component in the ERP and appears around 300 ms after the target stimulus in the oddball paradigm. In our previous work, we proposed a method for the automatic detection of the P300 waveform in single-sweep records by using a correlation technique. However, determination of the threshold values of the P300 waveform for the correlation study was not an easy task. In skirting this problem, we developed an automatic method of detecting a single-sweep P300 waveform by using an artificial neural network. We selected appropriate characteristic parameters of positive peaks as input signals for the input layer units, and the weights between the layers were determined by using the back-propagation algorithm. The neural network for P300 detection was obtained automatically, based on the data of ERPs obtained from 11 healthy males, and gave substantial accuracy for P300 detection. Furthermore, by using this neural network we clarified the way in which the P300 waveform is judged visually by each inspector.

Biotinidase activity in patients with liver disease.

To investigate whether biotinidase deficiency may occur in liver disease, we determined biotinidase activity, biotin levels, and organic acids in patients with liver disease. Serum biotinidase activity in patients with liver disease (2.63 +/- 1.40 nmol/min/ml) was significantly lower than in the control group (5.43 +/- 1.06 nmol/min/ml). Serum biotinidase activity in decompensated liver cirrhosis (LC) and hepatoma was significantly lower than in acute viral hepatitis (AVH), chronic viral hepatitis (CVH), and compensated LC. The mean serum level of biotin in decompensated LC (1.8 +/- 0.6 microgram/ml) and hepatoma (1.7 +/- 0.8 microgram/ml) was significantly lower than in the control group (2.5 +/- 1.0 microgram/ml), and urinary excretion of biotin was increased in patients with liver disease, particularly in decompensated LC. Biotinidase activity correlated positively with serum biotin level and correlated negatively with urinary biotin level. Moreover, in four of five patients with severe liver disease the excretion of propionate, lactate, and 3-hydroxybutyrate decreased after biotin supplementation. The data for patients with severe liver disease so resembled those for late-onset multiple carboxylase deficiency that biotinidase deficiency is likely in patients with severe liver disease.

[The effects of biotin on the metabolism of ammonia and amino acids in urease-induced hyperammonemic rats].

The effects of oral and intraperitoneal administration of biotin in urease-induced hyperammonemic rats, as well as the influence of biotin deficiency, have been studied. Biotin deficiency was produced by feeding standard diet MF (Oriental Yeast Co.) supplemented with dry egg-white (egg-white group). Egg-white + biotin group had free access to 0.0014% of biotin solution at all time. Following an intraperitoneal injection of urease, 25 U/kg (B.W.), plasma ammonia levels in egg-white + biotin group were lower than in egg-white group, especially there was significance (p less than 0.05) at 8 hours after the urease injection. Similarly, plasma ammonia levels in biotin-injected rats, in which 1 mg of biotin had been injected intraperitoneally prior to the experiment, were significantly low compared with saline-injected controls at 4 and 6 hours after urease administration. Results of plasma amino acid analysis, 9 hours after the urease injection indicated that Fischer's molar ratio (Leu + Ileu + Val/Tyr + Phe) was significantly higher in the biotin-injected rats than the saline-injected control. It suggests that biotin might decrease blood ammonia by facilitating the detoxification mechanism as follow: L-glutamate + NH3----L-glutamine.

[Effect of combination therapy with an adriamycin-lipiodol emulsion and a mitomycin C microcapsule in hepatocellular carcinoma complicated by portal thrombosis].

An intra-arterial injection of an Adriamycin-Lipiodol emulsion and a Mitomycin C microcapsule has been given to two patients of hepatocellular carcinoma (HCC) complicated with a tumor thrombosis of the portal trunk. One patient showed a partial response, while the other evidenced no change, alpha-Fetoprotein decreasing from 4510 to 419 ng/ml in the partial response case, and from 328 to 283 ng/ml in the no change case. In each instance the hepatic injury treated by this combination therapy was mild and reversible. Bone marrow suppression by this therapy was not demonstrated. Thus, this therapy is thought to be applicable to cases of hepatocellular carcinoma complicated with a tumor thrombosis of the portal trunk who should not be indicated for transcatheter arterial embolization.

Secondary reconstruction of the mandible with an aluminum oxide prosthesis.

A case is presented where secondary mandibular reconstruction with an aluminum oxide ceramic prosthesis was performed for a patient who had had an earlier hemimandibulectomy and primary bone graft for management of an ameloblastoma. Various factors that were considered in the construction of the prosthesis and problems encountered during operation are discussed. Although the prosthesis was found to be quite useful for the restoration of facial contour, the results of a long-term follow-up are needed to obtain a final evaluation of the reconstruction.