Calcium Channel-Dependent Induction of Long-Term Synaptic Plasticity at Excitatory Golgi Cell Synapses of Cerebellum.

Golgi cells, together with granule cells and mossy fibers, form a neuronal microcircuit regulating information transfer at the cerebellum input stage. Despite theoretical predictions, little was known about long-term synaptic plasticity at Golgi cell synapses. Here, we have used whole-cell patch-clamp recordings and calcium imaging to investigate long-term synaptic plasticity at excitatory synapses impinging on Golgi cells. In acute mouse cerebellar slices, mossy fiber theta-burst stimulation (TBS) could induce either long-term potentiation (LTP) or long-term depression (LTD) at mossy fiber-Golgi cell and granule cell-Golgi cell synapses. This synaptic plasticity showed a peculiar voltage dependence, with LTD or LTP being favored when TBS induction occurred at depolarized or hyperpolarized potentials, respectively. LTP required, in addition to NMDA channels, activation of T-type Ca2+ channels, while LTD required uniquely activation of L-type Ca2+ channels. Notably, the voltage dependence of plasticity at the mossy fiber-Golgi cell synapses was inverted with respect to pure NMDA receptor-dependent plasticity at the neighboring mossy fiber-granule cell synapse, implying that the mossy fiber presynaptic terminal can activate different induction mechanisms depending on the target cell. In aggregate, this result shows that Golgi cells show cell-specific forms of long-term plasticity at their excitatory synapses, that could play a crucial role in sculpting the response patterns of the cerebellar granular layer.SIGNIFICANCE STATEMENT This article shows for the first time a novel form of Ca2+ channel-dependent synaptic plasticity at the excitatory synapses impinging on cerebellar Golgi cells. This plasticity is bidirectional and inverted with respect to NMDA receptor-dependent paradigms, with long-term depression (LTD) and long-term potentiation (LTP) being favored at depolarized and hyperpolarized potentials, respectively. Furthermore, LTP and LTD induction requires differential involvement of T-type and L-type voltage-gated Ca2+ channels rather than the NMDA receptors alone. These results, along with recent computational predictions, support the idea that Golgi cell plasticity could play a crucial role in controlling information flow through the granular layer along with cerebellar learning and memory.

Systematic characterization of human testis-specific actin capping protein ß3 as a possible biomarker for male infertility.

STUDY QUESTION: Is actin capping protein (CP) ß3 involved in human spermatogenesis and male infertility? SUMMARY ANSWER: Human CPß3 (hCPß3) is expressed in testis, changes its localization dynamically during spermatogenesis, and has some association with male infertility. WHAT IS KNOWN ALREADY: The testis-specific α subunit of CP (CPα3) was previously identified in human, and mutations in the cpα3 gene in mouse were shown to induce malformation of the sperm head and male infertility. However, CPß3, which is considered to be a heterodimeric counterpart of CPα3, has been neither characterized in human nor reported in association with male infertility. STUDY DESIGN, SIZE, DURATION: To confirm the existence of CPß3 in human testis, fresh semen samples from proven fertile men were analyzed. To investigate protein expression during spermatogenesis, cryopreserved testis obtained from men with obstructive azoospermia were examined by immunofluorescent analysis. To assess the association of CP with male infertility, we compared protein expression of human CPα3 (hCPα3) and hCPß3 using immunofluorescent analysis of cryopreserved sperm between men with normozoospermia (volunteers: Normo group, n = 20) and infertile men with oligozoospermia and/or asthenozoospermia (O + A group, n = 21). PARTICIPANTS/MATERIALS, SETTING, METHODS: The tissue-specific expression of hCPß3 was investigated by RT-PCR and Western blot analysis. To investigate whether hCPα3 and hCPß3 form a heterodimer, a tandem expression vector containing hcpα3 tagged with monomeric red fluorescent protein 1 and hcpß3 tagged with enhanced green fluorescent protein in a single plasmid was constructed and analyzed by co-immunoprecipitation (Co-IP) assay. The protein expression profiles of hCPα3 and hCPß3 during spermatogenesis were examined by immunohistochemical analysis using human spermatogenic cells. The protein expressions of hCPα3 and hCPß3 in sperm were compared between the Normo and O + A groups by immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: RT-PCR showed that mRNA of hcpß3 was expressed exclusively in testis. Western blot analysis detected hCPß3 with anti-bovine CPß3 antibody. Co-IP assay with recombinant protein showed that hCPα3 and hCPß3 form a protein complex. At each step during spermatogenesis, the cellular localization of hCPß3 changed dynamically. In spermatogonia, hCPß3 showed a slight signal in cytoplasm. hCPß3 expression was conspicuous mainly from spermatocytes, and hCPß3 localization dynamically migrated from cytoplasm to the acrosomal cap and acrosome. In mature spermatozoa, hCPß3 accumulated in the postacrosomal region and less so at the midpiece of the tail. Double-staining analysis revealed that hCPα3 localization was identical to hCPß3 at every step in the spermatogenic cells. Most spermatozoa from the Normo group were stained homogenously by both hCPα3 and hCPß3. In contrast, significantly more spermatozoa in the O + A versus Normo group showed heterogeneous or lack of staining for either hCPα3 or hCPß3 (abnormal staining) (P < 0.001). The percentage of abnormal staining was higher in the O + A group (52.4 ± 3.0%) than in the Normo group (31.2 ± 2.5%). Even by confining the observations to morphologically normal spermatozoa selected in accordance with David's criteria, the percentage of abnormal staining was still higher in the O + A group (39.9 ± 2.9%) versus the Normo group (22.5 ± 2.1%) (P < 0.001). hCPß3 in conjunction with hCPα3 seemed to play an important role in spermatogenesis and may be associated with male infertility. LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: Owing to the difficulty of collecting fresh samples of human testis, we used cryopreserved samples from testicular sperm extraction. To examine the interaction of spermatogenic cells or localization in seminiferous tubules, fresh testis sample of healthy males are ideal. WIDER IMPLICATIONS OF THE FINDINGS: The altered expression of hCPα3 and hCPß3 may not only be a cause of male infertility but also a prognostic factor for the results of ART. They may be useful biomarkers to determine the fertilization ability of human sperm in ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JP16K20133). The authors declare no competing interests.

DISC1-ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1.

Disrupted-In-Schizophrenia 1 (DISC1), a risk factor for major mental illnesses, has been studied extensively in the context of neurodevelopment. However, the role of DISC1 in neuronal signaling, particularly in conjunction with intracellular cascades that occur in response to dopamine, a neurotransmitter implicated in numerous psychiatric disorders, remains elusive. Previous data suggest that DISC1 interacts with numerous proteins that impact neuronal function, including activating transcription factor 4 (ATF4). In this study, we identify a novel DISC1 and ATF4 binding region in the genomic locus of phosphodiesterase 4D (PDE4D), a gene implicated in psychiatric disorders. We found that the loss of function of either DISC1 or ATF4 increases PDE4D9 transcription, and that the association of DISC1 with the PDE4D9 locus requires ATF4. We also show that PDE4D9 is increased by D1-type dopamine receptor dopaminergic stimulation. We demonstrate that the mechanism for this increase is due to DISC1 dissociation from the PDE4D locus in mouse brain. We further characterize the interaction of DISC1 with ATF4 to show that it is regulated via protein kinase A-mediated phosphorylation of DISC1 serine-58. Our results suggest that the release of DISC1-mediated transcriptional repression of PDE4D9 acts as feedback inhibition to regulate dopaminergic signaling. Furthermore, as DISC1 loss-of-function leads to a specific increase in PDE4D9, PDE4D9 itself may represent an attractive target for therapeutic approaches in psychiatric disorders.

Evaluation of incidence, predictive factors and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy.

INTRODUCTION AND OBJECTIVES: Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. PATIENTS AND METHODS: A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. RESULTS: Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation. CONCLUSIONS: Genitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

Serum adiponectin and leptin levels are useful markers for prostate cancer screening after adjustments for age, obesity-related factors, and prostate volume.

AIM: Adiponectin and leptin, polypeptide hormones produced by adipocytes, have recently been reported to be associated with prostate cancer risk, though, the relationship remains poorly understood. We examined the association of adiponectin and leptin levels in serum with prostate cancer risk after adjustments for age, obesity-related factors, and prostate cancer risk. METHODS: Fifty-four prostate cancer patients and 70 control subjects provided blood sampled between 2008 and 2009. Using those, we determined serum adiponectin and leptin levels, and evaluated their relationships with prostate cancer risk after adjustments for age, obesity-related factors (body weight, body mass index, waist circumference), and prostate volume. Adipokine densities were calculated by dividing serum level with prostate volume. RESULTS: There were no differences for median serum adiponectin and leptin levels between the prostate cancer and benign control groups (P=0.22 and 0.78, respectively). Patients with levels of both adipokines in the highest quartile after adjustment for age had significantly higher risks of prostate cancer (adiponectin: odds ratio [OR] 2.79, P=0.014; leptin: OR 2.72, P=0.027). Patients with an adiponectin level greater than the median after adjustment for body weight also had a significantly elevated risk of prostate cancer (OR 2.22, P=0.031), whereas, those with a leptin level significantly greater than the median had a significantly lower risk (OR 0.46, P=0.027). Furthermore, median adiponectin density was significantly higher in the prostate cancer group than the benign group (P=0.0033). CONCLUSION: Serum adiponectin and leptin levels are useful markers for prostate cancer risk after adjustments for age, obesity-related factors, and prostate volume.

Middle ear cholesteatoma extending into the petrous apex: evaluation by CT and MR imaging.

CT and MR imaging findings were reviewed in four cases of acquired cholesteatoma of the middle ear that extended medially into the petrous apex and middle cranial fossa. In one case the lesion further extended anteromedially into the sphenoid sinus. CT demonstrated the lesions as nonenhancing hypodense masses with bone destruction, extending medially from the middle ear cavity to the petrous apex region. On MR imaging, the lesion was slightly hypointense relative to brain on T1-weighted images and hyperintense on T2-weighted images. MR imaging clearly delineated the extraaxial location of the lesion and associated brain displacement. The medial extension of the cholesteatomas seems to have proceeded via a detour around the bony labyrinth into the petrous apex region by following normal pathways of temporal bone pneumatization.

Coherence analysis of EEG changes during olfactory stimulation.

In a pilot study, EEG changes during odor stimulation were evaluated by coherence analysis. Ten normal adults were studied. Simultaneous recordings of 16 EEG channels with and without odor stimulation were stored on magnetic tape for further processing. EEG signals were analyzed using a signal analyzer. Coherence spectra were calculated between all possible channel pairs on the scalp. The amount of data was reduced by extracting broad band coherence values for five frequency bands: delta (2-3.9 Hz), theta (4-7.9 Hz), alpha 1 (8-9.9 Hz), alpha 2 (10-12.9 Hz), and beta 1 (13-17.9 Hz). Coherence values extracted from the control EEG recordings and those during odor stimulation were compared to evaluate the presence of any significant differences. The results demonstrated significant changes in the EEG coherence between the two control recordings (before and after) in the theta and beta 1 bands. These frequency bands were therefore excluded from the examination. During odorant stimulation with methyl-cyclopentenolone, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased in the bilateral temporal region. During odorant stimulation with scatol, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased in the frontal, temporal and occipital regions. It is suggested that EEG coherence mapping may provide the basis for the development of an objective test of olfactory function in humans.

Topography of binaural interaction in the auditory brainstem response.

The scalp topography of binaural interaction (BI) in the auditory brainstem response (ABR) was studied in fourteen normal individuals. BI was observed from all recording sites of the scalp, and the peak amplitude was noted mostly in the bilateral parietal and occipital regions. There was a significant difference in amplitude shown by significance probability mapping (SPM) when the waveform obtained by binaural stimulation was compared with the sum of the waves obtained by monaural stimulation. The topography of BI was different from that of the wave III and the wave IV/V complex. In contrast to previous reports by other workers, we found that BI mainly corresponded to the first half of the wave IV/V complex.

A device for controlling odorant stimulation and olfactory evoked responses in humans.

We developed a device for odorous stimuli control to record olfactory evoked responses from the human scalp. The characteristics of the apparatus are as follows. Translating the subject's respiration into electric signals with a sensor attached to the nose. The period and timing of odorous stimuli could be adjusted, so that stimuli could be synchronous with respiration. The interstimulus interval could be arbitrarily selected once every 1 to 9 respiration(s) so that adaptation could be prevented. We obtained evoked responses to odorous stimuli using this apparatus from the human scalp, whose positive peak latencies were approximately 350 and 700 msec. Such responses were not recorded if oxygen stimuli were used instead of odorous stimuli or with click sounds produced by the switching electromagnetic valve. Three types of odorant evoked scalp potentials were obtained in normal human subjects. The first type consisted mainly of two positive peaks with a peak latency of about 350 msec (P350) and about 700 msec (P700). The second type and the third type consisted of only one positive peak with a peak latency of about 350 msec and 700 msec, respectively. Such a P350 or P700 peak as that observed in the normal subjects was not detected in anosmic patients.

Analysis of auditory brainstem response waveforms derived ipsilaterally and contralaterally to monaural stimulation.

The auditory brainstem responses (ABRs) obtained from 28 normal healthy adults were studied using the ipsilateral and contralateral recordings from the positions of vertex and each mastoid to monaural stimulation. Each wave of ABRs recorded by ipsilateral and contralateral derivations to stimulation site showed slightly significantly differences. Comparing the ipsilateral and contralateral data, the latencies of waves II and V showed a slightly small reduction in the ipsilateral recording, while these of waves III and IV showed a small increase. Next, the distributions of potentials and latencies of waves II to V were investigated from ABRs situating different electrodes in mid-coronal array of the scalp and non-cephalic reference electrode on the seventh cervical vertebra (CVII). The results of latencies showed the reverse relation to the data obtained from the ipsilateral and contralateral recordings using the reference electrodes on each mastoid. These facts suggest that the comparable differences of latencies in the bilaterally recorded ABRs are explained by the pseudo-phenomena of differential recordings, which the phase delayed or advanced potential propagated to each mastoid being reference electrode position.

Coherence analysis of EEG changes during odour stimulation in humans.

In a pilot study, EEG changes during odour administration were evaluated by coherence analysis. Ten normal adults were studied. Simultaneous recordings of 16 EEG channels with, and without, odour administration were stored on magnetic tape for further processing. EEG signals were analysed using a signal analyser. Coherence spectra were calculated between all possible channel pairs on the scalp. The amount of data was reduced by extracting broad band coherence values for five frequency bands: delta (2-3.9 Hz), theta (4-7.9 Hz), alpha 1 (8-9.9 Hz), alpha 2 (10-12.9 Hz), and beta 1 (13-17.9 Hz). Coherence values extracted from the control EEG recordings and those during odour administration were compared to evaluate the presence of any significant differences. The results demonstrated significant changes in the EEG coherence between the two control recordings (control before and control after) in the theta and beta 1 bands. These frequency bands were therefore excluded from the examination. During odorant stimulation with methyl-cyclopentenolone, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased in the temporal region. During odorant stimulation with scatol, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased between the longitudinal electrode locations. It was suggested that EEG coherence mapping may provide the basis for the development of an objective test of olfactory function in humans.

[A case of Fournier's gangrene with healing accelerated by argatroban].

A 58-year-old man was admitted to our hospital complaining of pain and marked swelling of scrotum and perineum. Physical and radiological examinations revealed gas-producing gangrenous changes involving the scrotum. Debridement was urgently carried out. Following the debridement under control of diabetes mellitus, antimicrobial agents and argatroban, a newly synthesized antithrombin medicine, were administered. Argatroban was used for the purpose of improving vascular insufficiency. Healthy granulation tissue was present five weeks later. Then surgical closure was carried out. Computed tomography was useful to make early diagnosis, and argatroban was thought to accelerate healing of the gangrene.

[Laparoscopic nephropexy for symptomatic nephroptosis: a case report].

We present our clinical findings of laparoscopic nephropexy performed on a 32-year-old woman with symptomatic nephroptosis. Supine and erect excretory urography (DIP) revealed right renal descent of 2.5 vertebral bodies with hydronephrosis. Laparoscopic transperitoneal nephropexy was performed using nonabsorbable sutures, polyglactin net, hernial staplers and tissue adhesive. An upright DIP 1 month postoperatively revealed renal descent of only 1 vertebral body and no hydronephrosis. One year postoperatively, the patient is asymptomatic. A laparoscopic procedure, which is safe, effective and causes minimal morbidity, represents an excellent approach for repair of symptomatic nephroptosis.

[Bilateral breast metastases from prostatic carcinoma: a case report].

We report a case of bilateral breast metastases from prostatic carcinoma. A 49-year-old man with stage D2 prostate cancer, who had been treated by chemoendocrine therapy and radiotherapy for 2 years, complained of bilateral enlarged breasts. Oral administration of diethylstilbestrol diphosphate was started 2 months before the onset of this symptom. A firm mass that was not tender was palpable beneath the skin without fixation on each side. A needle biopsy of the masses showed poorly differentiated adenocarcinoma with positive immunohistopathological staining for prostate-specific antigen. The masses were diagnosed as metastatic adenocarcinoma of prostate gland origin. The patient died 3 months after the diagnosis of breast metastases. Autopsy revealed diffuse lymphogenous metastatic disease. Metastatic prostatic carcinoma to the breast is uncommon. Breast metastases in this patient might be associated with diffuse lymphogenous metastases as well as increased local blood and lymphatic supply caused by extrinsic estrogens.

[Evaluation of tissue concentrations of FT-207 and 5-FU in head and neck cancer].

FT-207 was administered to 30 patients with squamous cell carcinoma of the head and neck. After FT-207 administration tumor concentration of FT-207 and 5-FU was measured using a chemical assay method. Differences of FT-207 and 5-FU in total doses, administration routes (oral, intrarectal, and intravenous), tumor sites (larynx, maxillary sinus, tongue, neck and hypopharynx), and types of differentiation (well-differentiated, moderately-differentiated, and poorly-differentiated) were studied and the following results were obtained: 1. In FT-207 tumor concentration study, no significant difference was observed in any group. 2. 5-FU tumor concentration increased in higher total administration doses and in advanced differentiated type groups as well as in the non-irradiated group. 3. 5-FU tumor concentration was measured by T/N ratio; oral and intravenous administration methods showed 4.5 (P less than 0.05) and 2.4 (P less than 0.10) respectively. In larynx tumor the highest concentration of 3.9 (P less than 0.05) was obtained among various tumors. The value of 4.0 (P less than 0.05) was yielded in the well-differentiated type, which was significantly higher compared to that of other differentiation types. Overall T/N ratio (5-FU concentration in the tumor/5-FU concentration in the normal tissue) was 2.7 (P less than 0.025).

[Flow cytometric DNA analysis and chemosensitivity in squamous cell carcinoma of the head and neck].

Cellular DNA content and succinate dehydrogenase activity of 92 human head and neck (34 laryngeal, 24 pharyngeal, 21 oral cavity, 13 maxillary) squamous cell carcinomas were examined, and DNA ploidy status and chemosensitivity were analyzed and compared. DNA aneuploidy was observed in 54 tumors (58.7%). The aneuploid pattern was most common in tumors of the maxillary sinus (84%), and least common in tumors of the larynx (41.3%). Histologically, aneuploidy was detected in 71.4% of poorly-differentiated, 63.8% of moderately-differentiated and 37.5% of well-differentiated squamous cell carcinomas. There was a statistically significant difference between the survival rates of patients with diploid and aneuploid patterns. Chemosensitivity was determined by exposing fresh tumor material to five antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU) and mitomycin C (MMC). The average decrease in succinate dehydrogenase (SD) activity was 49.8% with ADM, 33.6% with CDDP, 39.9% with CQ, 68.4% with 5-FU and 45.5% with MMC. Histologically, poorly-differentiated squamous cell carcinomas were most sensitive to these five antitumor drugs. We also compared average SD activity in tumors from different organs and found that pharyngeal tumors tend to be most sensitive to these drugs, except for MMC. The chemosensitivity of a tumor with DNA diploidy tended to be higher among well- and moderately-differentiated squamous cell carcinomas. In contrast, tumors with DNA aneuploidy tended to have higher chemosensitivity in the poorly-differentiated type. The results of this study indicate that simultaneous analysis of DNA ploidy and chemosensitivity will be helpful in understanding the characteristics of tumors as well as in predicting the most effective chemotherapy agents for head and neck cancer patients.

[Negative potential auditory brainstem response with 3-msec latency in profoundly deaf patients: characteristics and relationship to vestibular evoked response].

A large negative deflection with a latency of 3 msec was observed in the auditory brainstem response (ABR) waveforms of 48 patients (6.5%), [59 ears (5.8%)] in 740 patients with profound peripheral deafness (1,009 ears) between 1978 and 1990 at our department. This negative deflection was termed the "N3 potential." We reviewed some of these patients and discuss some common characteristics found in abnormal ABR waveforms. We also inquired into the conditions and origins of these potentials. Although virtually all patients were less than 10 years of age, the N3 potential was also observed in the ABR waveform of adult patients. There were no sex differences. In the majority of patients audiograms showed no response to the maximum output of an andiometer in the high frequency range and a residual response in the low frequency range. The most common cause of deafness was "unknown" in children, and "sudden deafness" in adults. The N3 potentials were noted at intensities of 80 dBnHL or greater. A high repetition rate (83.3/sec) of the click stimulus influenced the latency and amplitude of the N3 potential. As the stimulus intensity increased, the amplitude of the potential increased, and the latency decreased. The potential was replicated on retesting within less than a month. The N3 potential had a consistent latency and amplitude over the scalp. We conclude that the N3 potential was a physiological "neural" response evoked by a loud sound rather than by an electrical artifact. The N3 potential was most likely not an auditory evoked response or a response from a semicircular canal, because of the 3-msec latency and sharpness of the waveform, with lack of vertigo. The results suggest that the N3 potential may be a saccular acoustic response.

[Multivariate analyses by quantitative method II of subjective pitch and tonality of tinnitus].

Factors affecting subjective tinnitus pitch and tinnitus tonality were analyzed with the use of the quantitative method II. Ninety-one patients with unilateral tinnitus of a single kind were studied. Major factors affecting subjective tinnitus pitch were pitch matched frequency, age, puerility and impurity of tinnitus tonality, and loudness of tinnitus. In addition, major factors affecting puerility and impurity of tinnitus tonality were pitch matched frequency, loudness of tinnitus, and nature of the test tone. Furthermore, subjective puerility of tinnitus was associated with middle-pitched frequency and high-pitched frequency, and a loudness level of tinnitus between 25 and 49 dB HL. Whereas impurity of tinnitus was related to low-pitched frequency and noise of the test tone. These results may contribute to the clinical evaluation of tinnitus.

[Multivariate analyses using quantitative method II of annoyance due to tinnitus].

Factors affecting annoyance due to tinnitus were analyzed using quantitative method II. Ninety-one patients with unilateral tinnitus of single kind were studied. Major factors affecting annoyance due to tinnitus were found to be subjective loudness of tinnitus, age, degree of hearing loss, tinnitus loudness level in dB HL, pitch matched frequency, puerility and impurity of tinnitus tonality, and subjective tinnitus pitch. Increased annoyance due to tinnitus was associated with an age of 30-49 years, a tinnitus loudness level between 25 and 49 dB HL, a tinnitus loudness level more than 15dB SL, impurity of tinnitus tonality, larger subjective loudness, and high-pitched tones above 4000Hz. Decreased annoyance due to tinnitus was related to the smaller subjective loudness, loudness level below 25dB HL, low-pitched tones below 250Hz, and purity of tinnitus tonality. Our results suggest that these factors are responsible for individual differences in annoyance caused by tinnitus.

Evaluación de la incidencia, factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin / Evaluation of incidence and predictive factors, and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy

Introducción y objetivos Aunque las complicaciones de la terapia intravesical con el bacilo de Calmette-Guérin (BCG) están bien descritas, pocas veces se ha comunicado la formación posterior de granulomas genitourinarios asintomáticos, y su estrategia de tratamiento sigue siendo controvertida. El objetivo de este estudio es evaluar la tasa de incidencia de la formación de granulomas genitourinarios asintomáticos que imitan la recurrencia del cáncer de vejiga tras el tratamiento intravesical con el BCG, así como identificar las estrategias de diagnóstico y tratamiento según las características de los pacientes. Pacientes y métodos Se realizó una revisión retrospectiva de 162 pacientes sometidos a terapia intravesical con BCG. En los pacientes que desarrollaron granulomas, se evaluó el intervalo de tiempo entre la instilación de BCG y el desarrollo del granuloma, la presencia de bacterias acidorresistentes en las muestras de patología, los resultados del cultivo/reacción en cadena de la polimerasa, las estrategias de tratamiento de las lesiones y los resultados clínicos. Resultados Se desarrollaron masas genitourinarias asintomáticas en 14 pacientes, de los cuales 5 se sometieron a evaluaciones histológicas confirmando en todos los casos una inflamación granulomatosa. Los órganos afectados fueron el riñón, la vejiga, la próstata y el pene. Aunque 5 de los 5 pacientes no recibieron tratamiento para los granulomas, a uno de ellos se le administró medicación antituberculosa para evitar el empeoramiento de la lesión durante el periodo perioperatorio de la cistoprostatectomía programada. Ninguno de los pacientes experimentó empeoramiento o recurrencia de las lesiones granulomatosas. Los pacientes que desarrollaron masas asintomáticas (n=14) eran significativamente más jóvenes que ...(AU)

Introduction and objectives Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.Patients and methods A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. Results Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n=14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation...(AU)