Cerebral phaeohyphomycosis: case report.

Cerebral phaeohyphomycosis is a rare and frequently fatal disease. This disease is often caused by hematogenous spread of pathogens that are inoculated in the skin of the extremities after slight or minor trauma, and its mortality rate is rather high despite aggressive treatment. Our patient presented with headache and pyrexia. She was diagnosed with fungal meningitis and treated by systemic administration of voriconazole (VRCZ). However, after initial improvement, meningitis recurred. MRI of the brain showed multiple small masses in the cerebral hemisphere and she was thus referred to our Department of Neurosurgery. On admission, an examination showed that the masses were deeply located in the brain and were too small to be excised; therefore, treatment with systemic VRCZ and intrathecal amphotericin B was initially selected. However, the intracerebral masses continued to grow; therefore, they were surgically excised. Histological examination of the surgical specimens at that time identified the masses as granuloma caused by infection with Aspergillus niger. After the surgery, her general condition improved; therefore treatment with systemic and intrathecal antifungal agents were continued. However, the intracerebral masses recurred, and despite further aggressive surgical treatment and systemic and intrathecal antifungal administration, she died 43 months after the initial diagnosis. Autopsy examination showed that the cerebral lesions were phaeohyphomycotic granulomas. This paper describes the clinical presentation, histopathological results and treatment for this rare disease.

Late spinal cord metastasis of fourth ventricle ependymoma appeared nineteen years after the initial treatment.

Spinal cord dissemination (metastasis) of a fourth ventricle ependymoma more than ten years after surgical resection is extremely rare. In this report, we present an unusual case of a fourth ventricle ependymoma with metastasis to the thoracic spinal cord 19 years after the initial therapy, but without local recurrence. A 37 year-old patient underwent gross total resection of a fourth ventricle ependymoma and postoperative radiation therapy to the posterior fossa. Computed tomography (CT) scanning and/or magnetic resonance (MR) imaging performed during follow up examinations, conducted annually for ten years after the therapy, revealed no evidence of local tumor recurrence. However, 19 years after the initial treatment, the patient complained of back pain and gait disturbances. MR imaging revealed an intradural extramedullary tumor at the Th2-5 levels. MR imaging of the brain revealed no local tumor recurrence or intracranial tumor dissemination. Cerebrospinal fluid cytology revealed no presence of tumor cells. Total resection of the spinal cord tumor was performed, and the tumor was diagnosed as an ependymoma. We describe the clinical features of this rare lesion and particularly emphasize the need for long-term follow up, for more than ten years after the initial treatment, in patients with fourth ventricle ependymoma.

Ossiculoplasty with a cartilage-connecting hydroxyapatite prosthesis for tympanosclerotic stapes fixation.

Many cases of tympanosclerotic stapes fixation are accompanied by fixation or erosion of malleus and/or incus. This status of the ossicular chain is one of the reasons that ossiculoplasty for tympanosclerotic stapes fixation is more difficult than that for otosclerosis. We conducted a retrospective review of seven patients who were operated on for tympanosclerotic stapes fixation between 2002 and 2006. All of the patients had abnormal conditions of the malleus and/or incus and underwent stapedectomy and total ossiculoplasty with hydroxyapatite prosthesis (Apaceram T-7 type), which has a planar-like head portion that contacts a piece of cartilage. Postoperative hearing results were assessed in all seven patients after at least 1 year. The postoperative air-bone gap (ABG) was closed within 10 dB in two of seven patients, and was less than 20 dB in six of seven patients. The mean postoperative ABG was closed within 10 dB at 1 and 2 kHz and less than 20 dB at low frequencies (0.25 and 0.5 Hz). There was almost no hearing improvement at high frequencies (4 and 8 kHz). There were no patients with postoperative sensorineural hearing loss. The present study shows that stapedectomy and total ossiculoplasty with cartilage-connecting hydroxyapatite prosthesis is effective and safe for stapes fixation accompanied by fixation or erosion of the malleus and/or incus.

Factors affecting outcome of intracerebral hemorrhage in patients undergoing chronic hemodialysis.

To date, despite a markedly high incidence of intracerebral hemorrhage (ICH) in patients with end-stage renal disease, only few studies have focused on factors that affect patient's prognosis. To elucidate these factors, we retrospectively investigated 22 consecutive patients who had chronic renal failure, were maintained by hemodialysis (HD), had suffered from ICH, and were hospitalized and treated in our institute from 2006 to 2008. Hematoma volume, blood pressure on admission, blood pressure 3 days after ICH onset, and neurological deterioration significantly affected patient mortality. Progression of neurological symptoms during HD was observed often in patients with hematoma of more than 60 mL or in patients with pontine hemorrhages. Age, gender, duration of HD, anti-platelet or anticoagulant therapies, or maximal dose of nicardipine did not affect patient's prognosis. Based on this study we conclude that controlling blood pressure on admission and within 3 days after onset of ICH may be the most important factor that would improve patient's prognosis. Further, special care might be required for patients with large hematomas (more than 60 mL) or those with brainstem hemorrhages, because progression of neurological symptoms occurs often in such patients.

Interlay Myringoplasty With Anterior Subannular Grafting Technique for Anterior and Subtotal Perforations.

OBJECTIVE: To describe the interlay myringoplasty with anterior subannular grafting technique and evaluate postoperative hearing and complications of this technique. STUDY DESIGN: Retrospective chart review. PATIENTS: We included 141 patients with anterior and subtotal tympanic membrane (TM) perforation. Patients who underwent concurrent ossicular chain reconstruction were included in graft success and complication rates evaluations, and were excluded from audiometric evaluation. INTERVENTIONS: Only squamous layer of the TM continuous with posterior meatal skin is elevated except one of anterioinferior annulus. The inner tympanic remnant is released from the anterioinferior annulus and then the subannular mucosa is separated from the annulus to fashion a subannular pocket. The anterior edge of the graft is inserted into the pocket, and the rest of the graft is sandwiched between the two divided layers of the TM. MAIN OUTCOME MEASURES: Graft success rate and hearing results were evaluated at 6 months postoperatively. Postoperative complications were also noted. RESULTS: The technique was successfully performed in 132 (93.6%) cases. Graft success rate was 98.3% (111/113) and the mean improvement of the air-bone gap was 9.5 dB, which was statistically significant (p < 0.001). There was no anterior blunting or TM lateralization. The pearl formations were found in six (5.3%) patients. All of them were easily removed at follow-up examination. CONCLUSIONS: The present study showed the interlay myringoplasty with anterior subannular grafting technique produces excellent results to repair anterior or subtotal TM perforations with few risk of anterior blunting and lateralization of the TM.

New potential therapy for orthotopic bladder carcinoma by combining HVJ envelope with doxorubicin.

PURPOSE: To establish a new therapeutic method to treat bladder carcinoma, we investigated the therapeutic potential of doxorubicin hydrochloride (DXR) combined with hemagglutinating virus of Japan-envelope vector (HVJ-E) in an orthotropic mouse bladder cancer model. METHODS: DXR and/or HVJ-E were instilled into the bladder after implantation of MB49 cells. Antitumor effects of combination therapy were evaluated by histological analysis of the bladder on day 14 after tumor implantation. The survival rate of MB49-disseminated mice was examined for 60 days after single or double administration of DXR alone or DXR/HVJ-E. The surviving mice were re-challenged with intravesical injection of MB49 cells, and the bladder was observed after 3 weeks. RESULTS: Combined intravesical instillation of HVJ-E and DXR resulted in a significantly higher rate of tumor-free mice (11/21) compared with mice treated using DXR alone (3/19, P<0.05). Median survival was >60 days for intravesical instillation of HVJ-E and DXR, compared with the 29 days for DXR instillation alone (P<0.05). After combination therapy, surviving mice formed no tumors in the bladder following intravesical re-instillation of MB49. CONCLUSIONS: HVJ-E increased antitumor effects in combination with chemotherapeutic agent (DXR). Antitumor immunity appeared to be enhanced using HVJ-E.

A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy.

BACKGROUND: Inactivated HVJ (hemagglutinating virus of Japan; Sendai virus) particles (HVJ envelope vector; HVJ-E can incorporate and deliver plasmid DNA, siRNA, antibody and peptide and anti-cancer drugs to cells both in vitro and in vivo. We attempted to eradicate tumors derived from mouse colon cancer cells, CT26, by combining bleomycin (BLM)-incorporated HVJ-E (HVJ-E/BLM) with cisplatin (CDDP) administration. METHODS: CT-26 tumor mass was intradermally established in Balb/c mice. HVJ-E/BLM was directly injected into the tumor mass with or without intraperitoneal administration of CDDP. The anti-tumor effect was evaluated by measuring tumor size and cytotoxic T cell activity against CT26. Re-challenge of tumor cells to treated mice was performed 10 days or 8 months after the initial tumor inoculation. RESULTS: We found that three intratumoral injections of HVJ-E/BLM along with a single intraperitoneal administration of CDDP eradicated CT26 tumors with more than 75% efficiency. When tumor cells were intradermally re-injected on day 10 after the initial tumor inoculation, tumors on both sides disappeared in most of the mice that received the combination therapy of HVJ-E/BLM and CDDP. Eight months after the initial tumor eradication, surviving mice were re-challenged with CT26 cells. The re-challenged tumors were rejected in all of the surviving mice treated with the combination therapy. Cytotoxic T lymphocytes specific for CT26 were generated in these surviving mice. CONCLUSION: Combination therapy consisting of HVJ-E and chemotherapy completely eradicated the tumor, and generated anti-tumor immunity. The combination therapy could therefore be a promising new strategy for cancer therapy.

[Value of diffusion-weighted MR imaging in the detection of middle ear cholesteatoma].

OBJECTIVE: This study, was conducted to determine the clinical value of diffusion-weighted MR imaging (DWI) in detecting the presence of cholesteatoma. SUBJECT AND METHODS: Fifty-six patients (21 female and 35 male patients; mean age, 43 years) who underwent middle ear surgery were referred to the radiology department for a preoperative DWI study. RESULTS: DWI depicted 41 out of 48 cholesteatomas involving the middle ear cavity (sensitivity, 85.4%). Seven patients with middle ear cholesteatoma who showed negative DWI findings (false-negative cases) had limited keratin accumulation due to simple atelectasis or meticulous evacuation of keratin debris before the MRI study. No falsepositive cases were found in this study (specificity, 100%). The positive predictive value and negative predictive value were 100% and 53.3%, respectively. The minimum size of middle ear cholesteatoma detected by the current MRI system was 5mm. CONCLUSION: Diffusion-weighted MR imaging was useful for the detection of middle ear cholesteatoma.

Preservation of the auditory nerve function after translabyrinthine removal of vestibular schwannoma.

OBJECTIVE: To evaluate the function of the postoperative auditory nerve preserved after translabyrinthine (TL) vestibular schwannoma (VS) removal. METHODS: Fifteen patients, who underwent unilateral VS resection via a TL approach, were preserved auditory nerve anatomically. The size and location of VS were measured on MRI preoperatively. After surgery, the electrical stimulation test (EST) or electrically evoked auditory brainstem response (EABR) was performed. RESULTS: Four cases (27%) out of fifteen patients were retained the functional integrity of the auditory nerve after surgery. The maximum tumor size in the group with a positive response to EST or EABR was significantly smaller than that in the group with a negative response to EST. It seems to be difficult to preserve auditory nerve function in cases where a tumor extends to the fundus of internal auditory canal. CONCLUSION: These results suggest that size of tumor and/or extension of tumor to the fundus might be important factors in preserving the auditory nerve function even if using a TL approach.

Direct percutaneous transluminal angioplasty for acute middle cerebral artery trunk occlusion: an alternative option to intra-arterial thrombolysis.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the safety and efficacy of direct percutaneous transluminal angioplasty (PTA) for patients with acute middle cerebral artery (MCA) trunk occlusion. METHODS: Over the past 9 years, a total of 70 patients with acute MCA trunk occlusion were treated with intra-arterial reperfusion therapy. In the last 5 years, 34 patients were treated with direct PTA, and subsequent thrombolytic therapy was added if necessary for distal embolization. The other 36 patients, mainly in the first 4 years, were treated with thrombolytic therapy alone and were used as controls. Pretherapeutic neurological status was evaluated with National Institutes of Health Stroke Scale scores. The modified Rankin Scale (mRS) was used to assess clinical outcome at 90 days. RESULTS: There were no significant differences in pretherapeutic National Institutes of Health Stroke Scale score and duration of ischemia between the 2 groups. The rate of partial or complete recanalization in the PTA group was 91.2%, whereas that in the thrombolysis-alone group was 63.9% (P<0.01). The incidence of large parenchymal hematoma with neurological deterioration in the PTA group was 2.9%, while that in the thrombolysis-alone group was 19.4% (P=0.03). Although direct PTA did not improve the rate of favorable outcome (mRS score 0 or 1; 41.7% for the thrombolysis-alone group versus 52.9% for the PTA group; P=0.48), outcome in terms of independence (mRS score 0, 1, 2) was significantly better in the PTA group (73.5%) than in the thrombolysis-alone group (50.0%; P=0.04). CONCLUSIONS: Although definitive conclusions on the comparative merits of these 2 therapies cannot be drawn because of an open trial, direct PTA may be an effective alternative option to intra-arterial thrombolysis for acute MCA trunk occlusion.

Expression of mucins in mucoid otitis media.

A hallmark of mucoid otitis media (MOM, i.e., chronic otitis media with mucoid effusion) is mucus accumulation in the middle ear cavity, a condition that impairs transduction of sounds in the ear and causes hearing loss. The mucin identities of mucus and the underlying mechanism for the production of mucins in MOM are poorly understood. In this study, we demonstrated that the MUC5B and MUC4 were major mucins in MOM that formed distinct treelike polymers (mucus strands). The MUC5B and MUC4 mRNAs in the middle ear mucosa with MOM were up regulated 5-fold and 6-fold, compared with the controls. This upregulation was accompanied by the extensive proliferation of the MUC5B- and MUC4-producing cells in the middle ear epithelium. Further study indicated that the mucin hyperproduction was significantly linked to CD4+ and CD8+ T cells and/or CD68+ monocyte macrophages. It suggests that MUC5B and MUC4 expression may be regulated by the products of these cells.

Combined direct percutaneous transluminal angioplasty and low-dose native tissue plasminogen activator therapy for acute embolic middle cerebral artery trunk occlusion.

BACKGROUND AND PURPOSE: In embolic middle cerebral artery (MCA) trunk occlusion, recanalization with direct percutaneous transluminal angioplasty (PTA) may be preferable to time-consuming thrombolysis. However, distal embolization with small crushed fragments is a complication of direct PTA. We prospectively evaluated combined direct PTA and low-dose native tissue plasminogen activator (t-PA) therapy for acute embolic MCA trunk occlusion. METHODS: Fifteen patients underwent direct PTA. The embolus was successfully crushed in 12, who received subsequent native t-PA infusion. Direct PTA was performed with a balloon catheter, which was advanced into the occlusion site and inflated several times until recanalization was established. After PTA, 7.2 mg of native t-PA in 100 mL of isotonic sodium chloride solution was infused for 30 minutes. Neurologic status was evaluated at admission and immediately and 1 month after treatment. In all patients, follow-up CT was performed within 24 hours and 3-7 days after onset, and follow-up MR imaging, 1 month after onset. RESULTS: Direct PTA failed to crush the embolus in three of 15 patients; these three had no clinical improvement. In 11 of 12 patients, combined therapy was successful, with no technical complication. Although no symptomatic intracerebral hemorrhage occurred, one patient had a small hematoma. All patients with successful recanalization had marked clinical improvement. Although angiograms showed distal embolizations in 10, cortical infarctions were confirmed in only three at follow-up. CONCLUSION: Combined direct PTA and IV low-dose native t-PA therapy may be a safe alternative to thrombolytic therapy in some patients with embolic MCA trunk occlusion.

Induction of mucous cell metaplasia by tumor necrosis factor alpha in rat middle ear: the pathological basis for mucin hyperproduction in mucoid otitis media.

Mucoid otitis media (MOM), one of the leading causes of acquired hearing loss in children, is characterized by mucous cell hyperplasia in the middle ear cleft associated with mucin accumulation in the middle ear cavity. The factors that stimulate mucous cell metaplasia-hyperplasia and mucin hyperproduction are poorly understood. Recent studies demonstrated that tumor necrosis factor alpha (TNF-alpha), present in human middle ear effusion, stimulated mucin production in vitro and up-regulated mucin gene expression in vivo. These findings suggest that TNF-alpha is important in the development of mucous cell metaplasia-hyperplasia. This study demonstrated that inoculation of TNF-alpha into the middle ear cavity followed by eustachian tube obstruction stimulated mucous cell metaplasia-hyperplasia in the middle ear cleft, accompanied by abundant mucin or mucin-like glycoproteins in the middle ear effusion--a phenotype of MOM in humans. This finding suggests that TNF-alpha plays a key role in the pathogenesis of MOM through induction of mucous cell metaplasia-hyperplasia and mucin production.

Neurotrophin-3 modifies potassium currents in isolated inner hair cells from guinea-pig cochlea.

OBJECTIVE: Neurotrophins elicited short-term glutamate release from the presynaptic locus. The aim of this study was to investigate short-term effects of neurotrophin-3 (NT-3) on the membrane current of inner hair cells (IHCs). METHODS: IHCs were isolated from the guinea-pig cochlea. Membrane currents were measured by conventional whole-cell voltage-clamp recordings. NT-3 was dissolved in a standard external solution and applied to the IHCs under pressure using pipettes. RESULTS: Six out of eight IHCs demonstrated a suppression of K currents by extracellular application of NT-3. At +60 mV, the amplitudes of the outward current in the control and NT-3 solutions were 5.6+/-1.3 and 4.2+/-1.0 nA, respectively. NT-3 suppression was voltage-independent. One cell showed an immediate suppression with NT-3 and the following potentiation during washing with standard saline. CONCLUSION: NT-3 suppressed the amplitude of K current on IHCs, suggesting that neurotrophins are capable of potentiating the hair cells' excitability. Neurotrophins may have a therapeutic value in the prevention and treatment of hearing impairment caused by inner ear damage.

[Effectiveness of intentional lateralization of the tympanic membrane to promote drainage of a large intracranial cholesterol cyst].

A 57-year-old male presented with headache and cerebellar symptoms. A magnetic resonance image demonstrated that the brain stem and the cerebellum were compressed by a large intracranial cholesterol cyst. Abundant drainage from the cyst into the tympanic cavity following the intentional lateralization of the tympanic membrane was very successful in aerating the cyst via the tympanic cavity, resulting in the eradication of the cyst. Our new method is recommended as a curative treatment for large intracranial cholesterol cysts because of its limited surgical stress and high radicality.

[Surgery for tympanosclerotic stapes fixation accompanied by malleus fixation at the anterior malleus: report of 2 cases].

Most tympanosclerotic stapes fixation involves fixation or erosion of the malleus and/or incus. This status of the ossicular chain is one reason that ossiculoplasty for tympanosclerotic stapes fixation is more difficult than that for otosclerosis. In some cases, the malleus is fixed only at the anterior, while the incus is intact. In such cases, anterior spinotomy can recover mobilization of the malleus, then a prosthesis can be used for the long process of the incus during ossiculoplasty. We conducted stapedectomy with anterior spinotomy on 3 ears in 2 patients. Over 15 dB of hearing was regained in all 3 ears 6 months after surgery. No significant sensorineural hearing loss was seen in any ear. To adapt this surgical procedure, it is necessary to evaluate preoperative CT findings and the status of the ossicular chain during surgery.

Hepatocyte growth factor stimulated angiogenesis without inflammation: differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor.

Based on the potent angiogenic effects of hepatocyte growth factor (HGF), therapeutic angiogenesis using human HGF plasmid DNA increased tissue perfusion and reduced symptoms in patients with critical limb ischemia (CLI) in randomized placebo-controlled clinical trials. To explore further the potent angiogenic activity of HGF, the present study compared the effects of HGF, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on angiogenesis and vascular inflammation. All of HGF, VEGF and bFGF significantly induced the formation of capillary blood vessel and granulation tissue in the rat paper disc model as an in vivo animal model of angiogenesis. However, although HGF, bFGF and VEGF significantly increased the growth of vascular endothelial cells, bFGF alone, but not HGF or VEGF, significantly increased the growth of vascular smooth muscle cells (VSMCs) in the in vitro proliferation assay. In addition, bFGF, but not HGF or VEGF, significantly activated an essential transcription factor for inflammation, NFκB, and gene expression of its downstream inflammation-related cytokines (IL-8 and MCP-1) in VSMCs, accompanied by an increase in the vascular permeability in the rat paper disc model. Thus, the present results indicated that HGF induced angiogenesis without vascular inflammation, different from bFGF and VEGF. These different properties between HGF, VEGF and bFGF might affect the efficiency of therapeutic angiogenesis.

Incidence of external auditory canal exostoses in competitive surfers in Japan.

OBJECTIVE: The objective of this study was to demonstrate the prevalence and severity of external auditory canal exostoses in a population of competitive surfers in Japan. The authors used a "surfing index," the product of the period (years) as an active surfer and the frequency (number of surfing days per week), to predict external auditory exostoses formation. STUDY DESIGN: Cross-sectional study. SETTING: A total of 5 surfing competitions that were held in Miyazaki, Japan. MATERIALS AND METHODS: The ear canals of 373 surfers with an average age of 33.1 years (range, 11-80 years) were examined with an otoscope. The severity of exostosis was classified into 4 groups, ranging from grade 0 to 3, according to otoscopic findings. Subjects also completed a questionnaire detailing their surfing habits. RESULTS: There was a 59.8% overall prevalence of exostoses in 373 surfers. The incidences of grade 1, 2, and 3 exostoses were 118 (31.6%), 71 (19.0%), and 34 (9.1%), respectively. The prevalences of grade 2 and 3 exostoses were higher in surfers with a surfing index of more than 20 (P < .0001). CONCLUSIONS: The authors determined that a positive association exists between the surfing index and the severity of exostoses. The findings suggest that it is possible to assume the likelihood of exostosis formation from the surfing index, and this may be of help to spread awareness of exostosis among surfers.

Primary diffuse large B-cell lymphomas of the temporoparietal dura mater and scalp without intervening skull bone invasion.

A 72-year-old man presented with an extremely rare case of primary diffuse large B-cell lymphomas (DLBCLs) of the dura and scalp existing independently without intervening cranial vault invasion. The patient presented with an indolent mass lesion at the left temporal parietal scalp. Magnetic resonance imaging and computed tomography revealed a solid homogeneously enhanced mass in the left temporoparietal scalp, and an extra-axial intracranial mass that existed just below the scalp without intervening skull invasion. The patient underwent gross total resection of these lesions via a left frontotemporoparietal craniotomy. Histological examination of the masses revealed DLBCLs. The patient received whole-brain radiation therapy, and subsequent chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone. He was discharged without neurological deficit. The present case of DLBCLs in the scalp and dura without intervening skull bone invasion indicates that malignant lymphoma should be considered in the differential diagnosis of scalp and dural tumors without intervening skull bone invasion.

Cervical (non-terminal) myelocystocele associated with rapidly progressive hydrocephalus and Chiari type II malformation--case report.

An infant presented with a rare cervical (non-terminal) myelocystocele as a congenital skin-covered mass located in the midline of the posterior aspect of her neck. Magnetic resonance (MR) imaging and computed tomography showed a cystic mass filled with cerebrospinal fluid in the midline of the posterior aspect of the neck, with a fibrous streak extending from the bottom of the sac to the dorsal surface of the cervical cord. Brain MR imaging also showed a dilated ventricular system and Chiari type II malformation. The patient underwent plastic repair of the lesion, which was diagnosed as myelocystocele. After the surgery, the patient experienced respiratory distress. Ultrasound tomography from the anterior fontanel revealed deterioration of hydrocephalus, so a ventriculoperitoneal shunt was inserted, and the respiratory distress improved. The present case illustrates the possibility of rapidly worsening of hydrocephalus and Chari type II malformation after surgical repair of cervical (non-terminal) myelocystocele.