Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.

[Nonspecific IgE potential in nasal discharge for diagnosing allergic rhinitis].

Given that the nasal discharge of subjects with allergic rhinitis contains IgE, we studied nonspecific IgE potential in nasal discharge as a diagnostic marker for allergic rhinitis. We divided 38 adults into 2 groups, one with 22 with Japanese cedar pollinosis and one with 16 with watery rhinorrhea negative to MAST33. The pollinosis group was exposed to Japanese cedar pollen in an environmental exposure unit, and eosinophils in nasal discharge, serum total IgE, pollen-specific IgE, and local IgE in nasal discharge were examined for the 2 groups to determine IgE levels in nasal discharge using the Allerwatch rapid test. In the pollinosis group, nasal discharge IgE correlated significantly with the number of eosinophils. The nasal discharge IgE had higher specificity than the eosinophil examination, whereas nasal discharge eosinophils had higher sensitivity than the IgE examination. We thus found that measuring IgE and eosinophils in nasal discharge is useful for clinically diagnosing allergic rhinitis.

Nonfunctional parathyroid carcinoma.

A 65-year-old female patient was admitted to our hospital presenting with a superior mediastinal big mass that was elastic, hard, and painless. Laboratory data including serum calcium level and thyroid and parathyroid hormonal functions revealed no abnormalities. Further examination consisting of computed tomography, magnetic resonance imaging, and ultrasonography demonstrated that it was a solid tumor extending into the superior mediastinum. Technetium (Tc-99) sestamibi scan revealed a hypofunctioning focus in that area. The preoperative diagnosis was a thyroid tumor or a metastatic lymph node. Parathyroid carcinoma was suspected on intraoperative frozen pathological examination. The tumor was successfully removed with left thyroid lobectomy, and neck node dissection was performed. Macroscopically, it appeared as a dark reddish solid tumor, and the cut surface presented opalescence. Immunohistology confirmed that there was proliferation of tumor cells with positive chromogranin A staining. Thus, the tumor was diagnosed as parathyroid carcinoma histopathologically despite a lack of clinical evidence for hyperparathyroidism. This patient has been followed with no evidence of recurrence, a normal serum calcium 4 years after surgery, and postoperative radiotherapy. This report describes a case of nonfunctional parathyroid carcinoma with a massive mass that technetium (Tc-99) sestamibi scan failed to detect, and we showed negative immunostaining for parathyroid hormone (PTH) (N).

[Chemotherapy with MTX, 5-FU and CDGP for treatment of newly diagnosed head and neck cancer].

Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP) with methotrexate (MTX) and leucovorin(LV)as biochemical modulators was performed on patients with newly diagnosed head and neck cancer. We treated 45 patients with MTX, 5-FU and CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg and infusion of CDGP at 100 mg/m2. Forty-three patients were concurrently treated with radiotherapy. Seven of the 45 had distant metastasis. In spite of the metastasis, 6 of the 7 underwent radiation therapy only on the primary or cervical metastatic mass because their primary tumor was bulky. Treatment-associated toxicities, e. g., mucositis and myelosuppression were significant but acceptable. The overall response rate was 97.6% with 61.9% of CR.

[Docetaxel (TXT) and irinotecan (CPT-11) as a second-line chemotherapy for platinum-pretreated squamous cell carcinoma of the head and neck].

Cisplatin(CDDP), combined with 5-fluorouracil, is considered one of the most active chemotherapeutic combinations in the treatment of patients with squamous cell carcinoma of the head and neck(SCCHN)and is accepted today as a standard regimen. But second-line chemotherapy for platinum-pretreated patients has not yet been established. Eighteen patients with recurrent SCCHN were treated using docetaxel (TXT) and irinotecan (CPT-11). All of them had been pretreated with platinum included regimen. In principle, our regimen consisted of TXT(50-60 mg/m(2), day 1) and CPT-11(60-90 mg/m(2), day 1, 8, 15). The adverse events were significant, including 13(72.2%)of grade 3 and 4 neutropenia, but acceptable. Seventeen patients were eligible for evaluation of response. Two complete responses (CR; 11.8%)and 6 partial responses (PR; 35.3%)were observed with an overall response rate of 47.1%. Patients pretreated with TXT had a 25.0% response rate (1 PR and 3 progressive disease). We conclude that the combination of TXT and CPT-11 is a worthwhile treatment for platinum-pretreated SCCHN as a 2nd-line-chemotherapy.

Clinical efficacy of probiotic Bifidobacterium longum for the treatment of symptoms of Japanese cedar pollen allergy in subjects evaluated in an environmental exposure unit.

BACKGROUND: Japanese cedar pollinosis (JCPsis) affects nearly one in six Japanese. Oral administration of Bifidobacterium longum BB536 has been shown to be effective in relieving JCPsis symptoms during the pollen season. METHODS: This double- two-way crossover study was designed to evaluate the efficacy of BB536 on reducing symptoms in JCPsis patients exposed to Japanese cedar pollen (JCP) in an environmental exposure unit (EEU) outside of the normal JCP season. After a 1-week run-in period, subjects (n=24) were randomly allocated to receive BB536 powder (approximately 5x1010) or placebo twice a day for 4 weeks. After a 2-week washout period, subjects were crossed over to another 4 weeks of intake. At the end of each intake period, subjects received controlled JCP exposure for 4 hours in the EEU. Symptoms were self-rated 30 minutes before and every 30 minutes during the exposures. From the first day of exposure through the next 5 successive days, participants self-rated their delayed symptoms and medication uses. Blood samples were taken before the exposures. The mean JCP levels for exposures were 6500 to 7000 grains/m3 air. RESULTS: In comparison with placebo, BB536 intake significantly reduced the ocular symptom scores during JCP exposures. Evaluating delayed symptoms after exposures indicated that scores for disruption of normal activities were significantly lower in the BB536 group compared with the placebo group. Prevalence of medication use was markedly reduced by BB536 intake. CONCLUSIONS: These results suggest the potential beneficial effect of BB536 in relieving symptoms of JCP allergy.

[Epidemiological survey of allergic diseases in first-year junior high school students in Wakayama Prefecture in 2003].

Allergic diseases have been increasing in prevalence in developed countries, including Japan. The aim of the present report was to determine the prevalence of allergies in Wakayama prefecture using an epidemiological study. In total, 759 first-year students attending junior high school in Hidaka country, Wakayama prefecture, were surveyed. The results for 699 cases were then analyzed. A questionnaire regarding allergic diseases, specific IgE measurements performed using a MAST26 system (Hitachi Co., Ltd.), and total serum IgE levels measured using RIST (Pharmacia Co., Ltd.) were performed. The prevalence (present + past) of various allergic diseases was 37.9%. The prevalence of rhinitis, including pollinosis, was 31.0%, while that of atopic dermatitis was 26.2% and bronchial asthma was 11.3%. The positive rates for specific IgE antibodies against Japanese cedar pollen was 48.6%. The positive rate for Dermatophagoides farinae, timothy and housedust II were 44.2%, 29.6%, and 28.9%, respectively. Statistically significant differences were recognized between the students with allergic rhinitis, atopic dermatitis, allergic conjunctivitis or bronchial asthma and positive results for D. farinae, housedust II, cedar pollen, Penicillium, Cladosporium, or Aspergillus-specific antibodies. Regarding family history (two generations), a statistical significant difference between family history and positivity for specific IgE antibodies like D. farinae, housedust II, ragweed, cedar pollen or Cladosporium was observed. The total IgE titer was correlated with the number of positive allergen items. The increasing prevalence of various allergic diseases in developed countries remains a mystery, but the hygienehypothesis has attracted some attention. The findings of this epidemiologic study will contribute to basic data on the increasing prevalence of various allergic diseases.

Uvulopalatopharyngoplasty decreases levels of C-reactive protein in patients with obstructive sleep apnea syndrome.

BACKGROUND: C-reactive protein is a crucial risk factor for cardiovascular diseases. Previous studies demonstrated that in patients with obstructive sleep apnea syndrome (OSAS), levels of this protein elevate dependently on the degree of upper airway obstruction. However, it has not been determined whether the surgery for OSAS reduces the levels of C-reactive protein by restoring the airway opening. Therefore, we evaluated the effect of uvulopalatopharyngoplasty (UPPP) on levels of serum C-reactive protein in patients with this syndrome. METHODS: Fifteen adult patients with mild to severe OSAS were enrolled in this study. Levels of serum C-reactive protein and sleep parameters including apnea-hypopnea index a month before and 3 months after UPPP were evaluated using peripheral venous blood and polysomnography, respectively. RESULTS: Uvulopalatopharyngoplasty significantly restored sleep parameters, accompanying with decreased levels of C-reactive protein (from 0.21 +/- 0.17 to 0.10 +/- 0.16 mg/dL, P < .05). CONCLUSIONS: In patients with OSAS, UPPP appears to decrease levels of serum C-reactive protein. Surgical therapy may reduce inflammatory response in these patients.

Transient evoked otoacoustic emissions in newborn infants: Effects of ear asymmetry, gender, and age.

Our aim was to examine the effects of gender, ear asymmetry, and age of infants on various parameters of transient evoked otoacoustic emissions (TEOAEs). Three hundred thirty-two infants (181 males, 151 females) were tested using the ILO292 Otodynamics Analyzer (Otodynamics Ltd, England) as a screening procedure. The subjects were divided into two age groups: group 1, newborn infants prior to hospital discharge (mean age of 4 days), and group 2, infants at the 1-month-old health checkup (mean age of 35 days). Responses to TEOAE stimuli were recorded at 1.0, 1.5, 2.0, 3.0, and 4.0 kHz. There were significant effects of gender and ear (left/right) on the signal-to-noise ratio, response level, and whole-wave and band reproducibility values in TEOAEs. The right ear had higher values of whole-wave reproducibility, response level, signal-to-noise ratio, and band reproducibility than the left ear. Females displayed higher whole-wave reproducibility, response level, band reproducibility, and signal-to-noise ratio values than males. There was no significant difference in response level, signal-to-noise ratio, and band reproducibility between the two age groups. The findings of the present investigation may contribute toward future improvements in neonatal hearing screening based on the community.

[Problems in the evaluation of hearing of infants].

Infant hearing loss should be identified early to prevent delays in the development of speech and language. However, evaluation of hearing of infants is not so easy, because training is required to estimate auidiometric thresholds from behavioral testing such as conditioned orientation response audiometry (COR). Most ENT physicians who are not capable of behavioral testing tend to evaluate hearing of infants only from testing auditory brainstem response (ABR). Information about the infant's auditory response to the environmental sounds could be obtained easily and might be a substitute for a behavioral testing. We administered a questionnaire to the parents to obtain accurate information about the infant's auditory response. Tanaka-Shindo's developmental battery test of auditory function is an established questionnaire with various questions about auditory response and development of speech according to the age of infants from 0-15 month. We administered Tanaka-Shindo's questionnaire to the parents of infants before 8 months, and administered the following questionnaire to the parents of infants over 8 months. (1) If you call out the child's name from behind, does the child turn his/her head? (2) Does the child turn his/her head to any sounds on television, to any small sounds (for example: listened when someone opens the door or opens wrapping paper), or to beeping sounds from electric devices? To investigate the clinical usefulness of the questionnaire to estimate hearing in infants, 79 children (under 4 y.o.) evaluated their hearing at the Tottori University Hospital were studied. Forty-three out of 45 (95.6%) who had normal hearing had yes in the questionnaire, but the 18 who had moderate to severe (60 dB) hearing loss did not have yes in the questionnaire. For the mentally retarded 33 children, 27 out of 29 (93%) who had normal hearing had yes in the questionnaire, but the 4 who had moderate to severe hearing loss did not have yes in the questionnaire. Questionnaire about the infant's auditory response is useful to differentiate between normal hearing and moderate to severe hearing loss. We recommend our questionnaire as screening procedure to most ENT physicians to identify hearing loss in infants. It is important refer patients not evaluated as normal to an ENT physician who is capable of diagnosing the hearing of infants by behavioral testing.

[Managing small pulmonary nodules in head and neck malignant tumors].

The recent increase in the use of helical CT has produced a higher detection rate of small pulmonary nodules than in conventional CT application, and has presented a serious problem in their treatment. We carried out a retrospective study to identify a clinical standard in the management of those nodules in head and neck malignant tumors. The subjects were 108 in-and out patients (87 men and 21 women) with head and neck malignant tumors who received radiation therapy in our university hospital between 2003 and 2004 (ages ranging from 25 to 93 years; mean, 66 years). Helical CT of the chest was applied to 92 patients of the 108 (85%). We determined small pulmonary nodules as round nodules 5 mm or more and less than 1 cm in diameter, and observed them in 14 of the 92 (15%). Firstly, we compared nodule growth by dividing the patients into 2 groups. The nodules grew in 2 of 7 patients of Group I, where chemotherapy was not done or where chemotherapy was not effective on the primary tumor, and in 3 of 7 patients of Group II, where chemotherapy was effective on the primary tumor. Secondly, disregarding the effects of chemotherapy, we analyzed nodule growth: the nodules grew in 5 of the 14 patients (36%). Those small pulmonary nodules were all pulmonary metastases. When small pulmonary nodules are detected by helical CT, accompanying malignant tumors of the head and neck, and bearing in mind the probability of their growth of at least 36%, we should therefore follow them up carefully.

[Hearing outcome of canal wall reconstruction tympanoplasties for the treatment of cholesteatoma].

While the hearing outcome of patients undergoing a tympanoplasty with canal reconstruction is generally thought to be inferior to that of patients undergoing a canal-up tympanoplasty, a direct comparison of these two procedures, performed by the same operator, has not been reported. Consequently, we compared the hearing outcomes of these two techniques and discussed the postoperative complications that could accompany the procedures. Hearing was evaluated in 52 ears with middle ear cholesteatoma. Using the postsurgical hearing result assessment criteria published by the Japanese Society of Otology in 2000, hearing was then evaluated again at least 6 months after surgery. When the data was analyzed according to the type of operation, the success rates (as determined using the above assessment criteria) were 78.6% for type I, 88.5% for modified type III, and 50.0% for modified type IV. The success rate for the modified type III operations was superior to that of the modified type IV operations, and the incidence of a postoperative air-bone gap in the type IV tympanoplasties was significantly larger than that in other groups. Procedures involving external auditory canal surgery can be particularly problematic for the treatment of cholesteatoma. In this series, the same author (KH) performed all the canal-up tympanoplasty procedures that took place during 1990-1996, and all other tympanoplasties, mainly canal reconstruction procedures, that took place during 1998-2001. The success rate was 68.4% (13/19) for the canal-up tympanoplasties, 100% (8/8) for the atticotomies and 76% (19/25) for the canal wall reconstructions. The postoperative success rate in the atticotomy group was significantly higher than the rates of the other groups. Among the canal reconstructive tympanoplasty procedures, a second exploratory surgery was performed in 15/24 cases, and residual cholesteatoma was observed in 3 cases. The major postoperative complications were epitympanic pocket formation (12/24) and taste disturbances, caused by chordal damage (2/24). These findings indicate that tympanoplasties with canal reconstruction improve the hearing outcome, compared with the outcome of canal-up tympanoplasties. However, epitympanic retraction pocket formation, resulting in recurrent cholesteatoma, is a possible complication of both surgical procedures, and new approaches or techniques should be sought to minimize such postoperative changes.

Presence and connections of auditory neurons in the rostrodorsal and rostrolateral parts of the thalamic reticular nucleus.

OBJECTIVE: Auditory neurons have been identified in the caudoventral part of the thalamic reticular nucleus (TRN). We examined the acoustic input to single cells in the rostrodorsal part of the TRN. MATERIAL AND METHODS: In alpha-chloralose-anesthetized cats, we extracellularly recorded the responses of single neurons in the rostral TRN to acoustic and light stimuli. Next, to examine efferent projections of auditory neurons in the rostral TRN, we injected wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into other thalamic nuclei where auditory neurons were detected, including the lateral posterior nucleus (LP), the lateral medial and suprageniculate nuclei and the centromedian nucleus. Finally, intracortical microstimulation of the LP was performed to demonstrate antidromic activation of the auditory neurons in the rostral TRN. RESULTS: In the rostral TRN, 2 types of response to auditory stimuli were observed: brief, short-latency bursts (13-20 ms; mean 16.5 ms) and longer bursts with a long latency (38.8-50 ms; mean 44.8 ms). Injection of WGA-HRP into the medial LP labeled cells only in the rostrodorsal TRN, while extending the injection to the other nuclei labeled cells in the rostrodorsal and rostrolateral parts of the nucleus. Auditory neurons in the rostral TRN were activated antidromically by microstimulation of auditory neurons in the LP, with a latency of 1.2 ms. CONCLUSIONS: These results strongly suggest that auditory neurons in the rostrodorsal TRN project to auditory neurons in the LP. The rostral auditory TRN may be involved in transmission of auditory information via the non-specific association system of the thalamus.

[Combined MTX.5-FU.CDGP for the treatment of head and neck cancer].

Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP) with methotrexate (MTX) and leucovorin (LV) was administered for modulation in patients with head and neck cancer. We treated 19 patients with MTX.5-FU.CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg and infusion of CDGP at 100 mg/m2. Six patients had recurrent head and neck cancer, and 13 had newly diagnosed disease. Eleven of the new patients were concurrently treated with radiation therapy. Treatment-associated toxicity was significant, including mucositis and myelosuppression, but acceptable. Sixteen patients were eligible for evaluation of response. The overall complete response rate was 75.0% (12/16). Patients treated with radiotherapy had a 90.0% (9/10) overall complete response rate.

[2001 survey of pollen in Wakayama City with a real-time pollen counter].

Self-care is gradually being recognized as important in the treatment of pollinosis, based up to now on data on airborne pollen. To determine the real-time numbers of airborne pollen would be more useful in self-care, however, so we studied the usefulness of the real-time pollen counter. Between Feb. 2, 2001, and Apr. 26, 2001, 4 types of airborne pollen i.e., Japanese cedar, Japanese cypress, black alder, and beech observed in Wakayama City were counted with a Durham pollen counter and a real-time pollen counter (Yamato Manufacturing Co. Ltd.). Correlation between the 2 pollen counters was r = 0.69 for Japanese cedar in March and r = 0.89 for Japanese cypress in April. A high correlation was observed between outcomes of the 2 pollen counters. The amount of pollen from black alder and beech was less than that from Japanese cedar and cypress. Unexpected peaks were observed not related to the pollen number is apparently due to snow. We have taken measure against snow, so we concluded that the real-time pollen counter was useful in counting the amount of airborne pollen over time.

[Outcome of neonatal screening for hearing loss in neonatal intensive care unit and well-born nursery infants].

A newborn hearing screening was conducted on 319 neonatal intensive care unit (NICU) and 1200 well-born nursery (WBN) infants. Mean NICU birth weight was 1997 g and mean gestational age 34 weeks. Auditory brainstem response was studied in screening in NICU infants. Otoacoustic emission (OAE) or automated auditory brainstem response (AABR) was used in primary WBN screening. All infants not bilaterally passing hearing screening before discharge were recalled for outpatient retesting. If the outcome was still failure, ABR screening was conducted. The prevalence of infants diagnosed with hearing loss was 1.1% (16 of 1519). Of these 16, 75% were from the NICU and 75% were at risk for hearing loss. Mean age at hearing loss identification was 12.9 weeks in the WBN and mean age at hearing aid fitting was 16.1 weeks. Mean age at hearing aid fitting was lower for WBN than for NICU infants. Hearing loss identification and hearing aid fitting are thus feasible in NICU and WBN infants in universal newborn hearing screening.