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Conservative treatment is the principle approach used for olecranon stress fractures resulting from baseball pitching. Total rest from pitching is the core of this approach, as is the case for stress fractures in other parts of the body. Considering the risks of recurrence and the inconvenience of a prolonged ban on pitching, however, early surgical treatment is another possible option. Since 2002, we have been performing internal fixation with titanium cannulated cancellous screws and bone transplantation for professional baseball players who desire an early return to the game. We conducted a survey of our patients with regard to the types of fractures evident on X-ray, complications, the rate of bone union, the timing of a return to pitching, and the possibility of returning to the game. The survey included 11 players and 11 treated elbows, for which 6-month postoperative observation had been possible. The results indicated that a mean period of 10.4 weeks was necessary before the players could resume pitching after surgical treatment, and that 9 of the 11 players were able to return completely to the game. [ABSTRACT FROM AUTHOR]

Thirty-two cases of avulsion fractures of the anterior superior and anterior inferior iliac spine in sports were reviewed. From 1991 to 2002, 11 patients(10 male, 1 female) who suffered avulsion fractures of the anterior superior iliac spine were treated. The median age was 15.2 years (range, 14-17). Ten cases (90.9%) happened during sprinting. Three cases (27.3%) required surgical treatment. Two cases (18.2%) showed sensory disturbance of the lateral femoral cutaneous nerve palsy, but recovered spontaneously. On the other hand, 21 patients(19 male, 2 female) who suffered avulsion fractures of the anterior inferior iliac spine were treated. The median age was younger than that of anterior superior spine and 13.9 years(range, 12-16). Nineteen cases(90.5%) happened during kicking. Non-operative treatment resulted in excellent functional outcome in every case. [ABSTRACT FROM AUTHOR]

The treatment of choice for a resectable hilar cholangiocarcinoma is hepatectomy. Alternative treatment for unresectable cases includes liver transplantation;however, curative surgery is hindered by a distal cholangiocarcinoma extension into the intrapancreatic duct. Herein, we present a case of simultaneous living donor liver transplantation and pancreaticoduodenectomy for an extensive cholangiocarcinoma that is associated with primary sclerosing cholangitis, involving the perihilar and intrapancreatic duct. The treatment strategy involved neoadjuvant chemotherapy and radiation therapy, an exploratory laparoscopy and laparotomy for accurate staging, en-bloc whole bile duct and hepatoduodenal ligament resection, portal vein reconstruction with an interposition graft, and arterial reconstruction with the middle colic artery. The patient was discharged 122 days postoperatively although she suffered from postoperative ascites and delayed gastric emptying. Simultaneous living donor liver transplantation and pancreatoduodenectomy should be considered as treatment options for advanced cholangiocarcinoma.

The coronavirus disease 2019 (COVID-19) pandemic has had a major negative effect on the number of patients visiting pharmacies in Japan. The decrease in pharmacy visits during the pandemic compared with the pre-pandemic period may have increased the likelihood of adverse health outcomes; thus, it is important that pharmacy pharmacists take measures to prevent health disadvantages. In this study, we distributed a questionnaire survey to 104 pharmacy pharmacists (mainly in Kagoshima and Kumamoto Prefectures), and investigated changes in the extent of implementation and perceptions of measures considered necessary to protect patients' health between the pre-pandemic and pandemic period. The results showed that the proportions of respondents "sharing patient information between primary care doctors and pharmacy pharmacists" and conducting "follow-up after prescribing medications mainly via telephone" increased between the pre-pandemic period and September 2022. The perceived necessity of the above two measures, as well as "online medication instructions" and "a prescription refill system," increased during the same period. However, the proportion of respondents who perceived "0410 correspondence," which was introduced during the pandemic, as a necessity did not change. Moreover, many pharmacists indicated that, at their own discretion, they continued to correspond with patients in relation to the above, and to respond to specific requests during normal daily practice. Our results could help community-based pharmacists tackle serious public health problems, such as COVID-19.

This case was a 50-year-old healthy woman. After repeated transient amnesia, she developed tonic-clonic seizures and was admitted to our hospital. The brain MRI showed FLAIR hyperintensities in the left temporal lobe and EEG showed an epileptic discharge starting from the left temporal region. Based on these findings, we diagnosed temporal lobe epilepsy associated with acute limbic encephalitis. While she experienced recurrent transient amnesia, her cognitive functions were preserved except for her memory. These symptoms and EEG findings were consistent with transient epileptic amnesia (TEA). Acute limbic encephalitis that occurred in a healthy middle-aged woman may be antibody-mediated encephalitis, requiring immediate immunotherapies. In this case, GABA B receptor antibodies in cerebrospinal fluid were found positive. This is the first report showing that TEA was caused by GABA B receptor autoimmune encephalitis.

Although an important cause of vocal cord dysfunction (VCD) is psychogenic reaction, VCD may be associated with severe asthma and must be distinguished from the disease. A 30-years-old woman was admitted to our hospital with dyspnea despite treatment for asthma. Inspiratory stridor and expiratory wheezes were noted, and neck and chest computed tomography showed normal airways and lungs. Fractional exhaled nitric oxide levels were also normal. Pulmonary function test with a flow-volume loop curve showed normal expiratory loop with flattening of the inspiratory loop after methacholine inhalation. During the attack, bronchoscopy revealed the vocal cord closing with stridor during the inspiratory phase. Therefore, the patient was diagnosed with VCD. The dyspnea improved with respiratory rehabilitation and pursed-lip breathing. VCD should be considered in the differential diagnosis of intractable severe asthma. In this case, bronchoscopy and bronchial inhalation challenge with methacholine helped in the diagnosis.

A 63-year-old man was admitted to our hospital with a 2-month history of anxiety. He presented with cognitive impairment and muscle weakness. On MRI, T 2 -weighted images showed longitudinally extensive spinal cord lesion (LESCL) from C2 to T6 and gadolinium-enhanced T 1 -weighted images showed fan-shaped multiple linear enhancements converging to the lateral ventricles. He was diagnosed as primary central nervous system vasculitis (PCNSV) by brain biopsy. After using high dose corticosteroids, cognitive impairment and muscle weakness were dramatically improved. In patients with cognitive impairment, PCNSV should be included in the differential diagnosis of LESCL.

Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy caused by the human T-cell lymphotropic virus, type I and it has an extremely poor prognosis. A 66-year-old man with severe hepatic damage, massive pleural effusion and ATL cell infiltration-induced ascites was referred to our department. Reduced-intensity cytotoxic chemotherapy was attempted, but could not continue due to persistent hyperbilirubinemia. Laboratory results also showed elevated lactate dehydrogenase (LDH) and serum albumin levels were profoundly decreased. A humanized monoclonal antibody against chemokine receptor type 4 (CCR4), mogamulizumab (Moga), was thereby challenged and it successfully resolved the hepatic damage. Finally, a standard dose of chemotherapy could be administered, and it induced a complete remission. The patient is still in remission more than three years after the final dosage of standard chemotherapy. These results indicate that Moga, whose pharmacokinetics are not significantly influenced by hepatic function or serum albumin, could be a promising treatment option for patients with ATL complicated by severe hepatic damage due to infiltration of ATL cells.

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

We report a case of trigeminal neuralgia treated with microvascular decompression 10 years after We report a case of trigeminal neuralgia treated with microvascular decompression 10 years after Gamma Knife radiosurgery was performed. The patient was a 65-year-old female. The root entry zone of the trigeminal nerve received irradiation:a 4-mm shot, with a maximum dose of 80 Gy. The symptoms improved following treatment, however pain recurred five and a half years later. The pain gradually increased over time, to the point where the patient was unable to eat solid food. Carbamazepine was prescribed and the dosage increased. However, side effects such as dizziness and drowsiness manifested. Microvascular decompression was performed, revealing that the trigeminal nerve was markedly atrophied and being pressed upon by the superior cerebellar artery. The superior cerebellar artery was transpositioned with Teflon braided tape to the cerebellar tent. There were no abnormal findings such as arachnoid thickening, adhesions between vessels and nerves, or atherosclerotic plaque in the affected vessels. Pain completely abated following surgery, and side effects such as numbness of the face have not been observed at the time of writing this report.

We report on a 52-year-old woman with rheumatoid arthritis (RA) who developed methotrexate associated lymphoproliferative disorders (MTX-LPD) in the central nervous system (CNS) in the course of immunosuppressive therapy for RA. The patient was admitted because of monoplegia in her left hand. She had been receiving methotrexate (MTX) for her RA for several years and etanercept had also been introduced because of a worsening of the arthritis six months before admission. Brain MRI revealed multiple lesions with enhancement scattered throughout both hemispheres. 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography showed abnormal accumulation suggesting malignancy in the right frontal lobe where abnormal enhancement was observed on the MRI. A brain biopsy was performed at the identified site and it confirmed diffuse large B-cell lymphoma (DLBCL). We therefore diagnosed her as MTX-LPD. According to previous reports, most MTX-LPD cases tend to show regression after the cessation of MTX. However, our case showed no regression and even needed chemotherapy. The patient had a poorer prognosis than previous cases and died 17 months after the onset. Although it is an uncommon complication, particularly in the CNS, MTX-LPD should be considered as a critical differential diagnosis if a patient receiving MTX develops central nervous system lesions. Immediate medical intervention including brain biopsy is required.

We report the case of a 73-year-old right-handed female with a right parietal cerebral infarction and presented symptoms that were challenging to differentiate between alien hand sign (AHS) and sensory ataxia. She presented to our emergency department with chief complaints of abnormal involuntary movements and a feeling of foreignness on her left upper limb. The first neurological examination revealed left spatial neglect, left-side sensory impairment that included superficial and deep sensations, left limb-kinetic apraxia, and left limb ataxia. Furthermore, her symptoms and complaints had characteristics of AHS that includes a sensation that her left upper limb dose not belong to herself and an abnormal behavior of left hand that is contrary to her own intent. Brain MRI revealed an acute cerebral infarction confined to the right postcentral gyrus. This case highlights that sensory ataxia due to the disturbance of deep sensation might present symptoms similar to AHS. Previous studies suggested the involvement of the disturbance of somatosensory pathway in posterior-variant AHS. Therefore, a precise distinction between AHS and sensory ataxia, especially in posterior-variant AHS, is imperative to avoid confusion regarding the term "alien hand sign."

Background: We considered the factors of poor adherence to and dropout from sublingual immunotherapy (SLIT) by verifying patient backgrounds 1 year after start of treatment., Methods: We recruited 38 patients who began SLIT between November 2014 and September 2015. We analyzed their attributes and level of understanding of the treatment, and conducted a self-reported survey on factors behind dropout cases and poor adherence cases., Results: Four patients dropped out 1 year after start of treatment. Three left for reasons related to anxiety about side effects. There were five cases of poor adherence. There was no significant difference between good adherence, poor adherence, and dropout regarding level of understanding of the treatment (p=0.59). In the comparison between good and poor adherence groups, except four dropout patients, the adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients. Continuous rate of SLIT achieved about 90%, suggesting relatively high level of adherence., Conclusion: It appears possible that anxiety related to side effects could be a factor affecting dropout from SLIT. There was no significant difference regarding level of understanding of the treatment. The adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients.

A 72-year-old woman was admitted to our hospital because of muscle weakness and was diagnosed as having polymyositis. Whole-body evaluation revealed advanced transverse colon cancer, and we therefore considered it likely that the patient had paraneoplastic myositis. We performed a curative surgical resection for colon cancer, after which her serum creatine phosphokinase(CPK)level greatly decreased. Steroid therapy was administered postoperatively. However, her CPK levels remained persistently high, even after steroid pulse therapy, and we considered that this was due to steroid-resistance myositis. We administered chemotherapy for colon cancer using 5-fluorouracil plus Leucovorin(5-FU/LV), after which the CPK levels gradually decreased. There have been few previous reports of polymyositis associated with colon cancer and a standard treatment for paraneoplastic myositis has not been established. Most clinicians believe that treatment of the primary tumor may contribute to an improvement of myositis, and in our case, tumor resection and chemotherapy were effective.

A 62-year-old man, who underwent distal gastrectomy due to gastric cancer, was diagnosed with disseminated carcinomatosis of the bone marrow 8 years later. Chemotherapy was administered following treatment with recombinant human soluble thrombomodulin (rTM), and as a result, he successfully recovered from his disseminated intravascular coagulation (DIC) status and experienced improvement of his severe cancer-related pain. The use of rTM may enable the safe continuation of chemotherapy, and rTM may also be a useful treatment for DIC associated with solid cancer, such as gastric cancer.

We report a rare case of autonomic neuropathy associated with cytomegalovirus (CMV) infection. The patient, a 53-year-old male, was admitted to our hospital because of prolonged fever, headache and neck stiffness followed by urinary retention. Cerebrospinal fluid examination revealed pleocytosis (219/mm(3), predominantly lymphocytes) with a markedly increased protein level (217 mg/dl) and serum IgM anti-CMV antibody was detected. While his meningitic symptoms gradually improved after intravenous administration of ganciclovir, he complained of numbness in the extremities and difficulty in walking. Neurologically, marked orthostatic hypotension, glove and stocking type of paresthesia, severe muscle weakness in extremities, and neurogenic atonic bladder were noted. Nerve conduction studies showed normal except for F-waves, which were absent in the left tibial nerve. A sural nerve specimen appeared normal in both myelinated and unmyelinated fibers. He was given immunological therapies such as corticosteroid and intravenous high dose immunoglobulin therapies. After corticosteroid therapies, not only sensory and motor symptoms but also autonomic symptoms remarkably improved. Of the anti-ganglioside antibodies, IgM anti-GM1 antibody and IgM anti-GM2 antibody were detected. Although some cases with Guillain-Barré syndrome preceded by CMV infection have been reported, few cases with autonomic neuropathy have been described in association with successful corticosteroid therapies.

A 52-year-old man developed sudden occipital headache followed by vomiting and vertigo. On admission, he displayed right Horner syndrome with ipsilateral reduced facial sensation to pain and temperature that crossed in the body, affecting the left limbs. In addition, he had right hemiparesis. Diffusion weighted magnetic resonance images showed a high intensity lesion localized in the lower and right lateral medulla oblongata. Magnetic resonance angiography showed severe luminal stenosis in the right vertebral artery and T2-weighted sampling perfection with application optimized contrasts using different flip angle evolution (SPACE) showed arterial wall expansion. T1-weighted SPACE showed subacute intramural hematoma at that point, suggesting arterial dissection. First described in 1946, Opalski syndrome is considered a variant of Wallenberg syndrome with ipsilateral hemiparesis. This motor impairment is considered as a result of extension of the ischemia from the lateral medulla to the upper cervical cord involving corticospinal fibers caudal to pyramidal decussation. This case adds information regarding the anatomy of the pyramidal decussation.

We report a 4-year-old boy with severe congenital neutropenia (SCN), who was successfully treated with hematopoietic stem cell transplantation (HSCT). The patient had frequently developed bacterial infections since 6 months of age, and showed severe neutropenia below 100/μl at 1 year and 4 months of age. The patient harbored a heterozygous missense mutation in ELANE exon 3 (p.Q73P, g.2253 A>C). This was a novel de novo mutation, and he was thus diagnosed as having SCN. Because of failure to respond to granulocyte colony-stimulating factor treatment and repeated admissions due to bacterial infections, allogeneic HSCT was performed from a serologically matched unrelated donor following the conditioning regimen: fludarabine/melphalan/anti-thymocyte globulin and a low dose of total body irradiation. Tacrolimus and a short course of methotrexate were used for graft-versus-host disease prophylaxis. Engraftment was achieved at day 12, and the patient maintained normal hematopoiesis for over 15 months after HSCT. We concluded that HSCT is a useful treatment for SCN patients, especially those who are at high risk for leukemic transformation. However, a larger number of SCN patients and longer follow-up are necessary to identify appropriate conditioning regimens and long-term prognosis.

Patients who underwent hepatic resection of locally recurrent tumors after radiofrequency ablation(RFA)for colorectal liver metastases (CRLM) were retrospectively investigated. Among 12 patients who underwent RFA as first-line treatment for CRLM, 7 experienced local recurrence, 5 of whom (6 nodules) underwent hepatic resection. The mean diameter (range) of the tumors was 9.5(5-16) mm, and they were located at S2, S7 (adjacent to the right hepatic vein), S5/6 (between the root of the anterior and the posterior Glisson's pedicle), S1r (right paracaval portion), S6, and S3. No local recurrence was observed after hepatic resection. In conclusion, hepatic resection must be the initial therapeutic strategy for CRLM, and the indication for RFA must be considered carefully.

The aim of this study was to investigate distinctive change in the hearing impaired elderly listeners, especially about speech recognition. Subjects were 525 patients (235 males, 290 females), from 60 to 98 years of age who had visited the Hearing Aid Clinic of Otorhinolaryngology, National Center for Geriatrics and Gerontology Hospital, between June 2001 and December 2012. Pure-tone air conduction threshold determination was administered to each subject. The speech audiometry materials used to define speech discrimination ability were Japanese monosyllabic word lists, 67S word lists. Sex- and age-specific trends in maximum discrimination score (MDS) and rollover index (RI) were shown in this study. RI was computed by the formula (PBmax-PBmin)/PBmax. PBmax has almost the same meaning as MDS in Japan. PBmin represented the lowest PB score above the test intensity level of PBmax. Mean MDSs were 80.8% in their sixties, 75.3% in their seventies, 60.7% in their eighties, and 45.5% in their nineties. The rate of decrease in mean MDS per decade accelerated in the older generation. Mean RIs were 0.18 in patients in their sixties, 0.24 in their seventies, 0.30 in their eighties, and 0.30 in their nineties. It increased until the age of eighties. In the model 1, multiple logistic analyses were performed to examine the effect of age (in 10-year increments), sex and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (in 10 dB increments) on the MDS < 60%. Significant associations were observed between MDS < 60% and age (odds ratio, 3.03; 95% confidence interval, 2.38 to 3.85), and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (2.33; 2.03 to 2.68). Sex was not associated with MDS < 60%. In the model 2, multiple logistic analyses adjusted for age and sex were performed to examine the effect of hearing level at test frequencies of 125, 250, 500, 1000, 2000, 4000, and 8000 Hz (in 10 dB increments)on the MDS < 60%. Significant associations were observed between MDS < 60% and hearing level at 250 Hz (2.04; 1.44 to 2.89), and 2000 Hz (1.46; 1.16 to 1.83), and 4000 Hz(1.24; 1.02 to 1.50). These outcomes suggest that the important point in qualifying the fitting of hearing aid is to present the list words at an adequate sound pressure level for evaluation of speech understanding especially in the hearing impaired elderly listeners.

PL cream (combination of lidocaine and procaine) was launched on the market in April 2012 in Japan. We investigated differences in the anesthetic effect by employing two types of base: Carbopol and methylcellulose. Electron microscopy showed a distinct difference in appearance: densely-scattered, fine particles for Carbopol and sparse, large particles for methylcellulose. Accordingly, the extensibility of the cream was significantly greater at 4 and 25 degrees centigrade for methylcellulose, but was greater at 34 degrees centigrade for Carbopol. The steady flow viscosity (1 s(-1)) was greater for the Carbopol than methylcellulose base. The difference in the cutaneous permeability between the two bases increased over time: the methylcellulose base was removed at 90 min after application and, 30 min later, showed a significant difference. These results suggest that the methylcellulose base has a superior anesthetic effect in clinical settings.

Introduction: Allergic rhinitis and asthma are often comorbid, and allergic rhinitis has been shown to be a risk factor for asthma in adults and children. Recently, the prevalence of allergic rhinitis among bronchial asthma (BA) patients was reported to be 67.3% in Japan. However, seasonal variation in the prevalence of rhinitis in Japan remains unclear., Objectives and Methods: To investigate the seasonal differences in comorbid allergic rhinitis among asthmatic patients, a survey of BA outpatients aged six years and older was conducted at the Allergy Center, Saitama Medical University. In total, 150 patients (mean age, 43.8±21.8 years old) in summer 2012 and 181 patients (mean age, 48.7±18.3 years old) in spring 2013 completed the Self Assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire., Results: The prevalence of allergic rhinitis in BA patients was 50% in the summer of 2012 and 85.6% in the spring of 2013, indicating a significant seasonal variation. Control of asthma was significantly poorer in both seasons in patients with rhinitis compared to those without rhinitis. Furthermore, in patients with moderate/severe-persistent rhinitis, control of asthma was significantly worse than in patients with mild-intermittent rhinitis in spring 2013, but not in summer 2012., Conclusion: Although the comorbidity rate of rhinitis among BA patients was greater in the spring than in the summer, rhinitis is thought to be closely related with asthma control regardless of the season.

A 40-year-old woman, who was born in Thailand and moved to Japan 20 years previously, was admitted to our university hospital because of eosinophilia and abnormal chest radiography findings over a 6-month period. The chest CT showed multiple cavitary nodules in the subpleural area and a tubular structure that extended from each cavity to the pleura. Immunological examination revealed an elevation of antibody titers against Ancylostoma duodenale, Paragonimiasis miyazakii and Paragonimiasis westermanii based on an ELISA assay. In addition, hookworm eggs were found in the stool. We firstly administered pyrantel pamoates, following which the eggs become undetectable. Nevertheless, eosinophilia and abnormal chest CT findings persisted. We diagnosed the patient as having a superinfection with paragonimiasis and hookworm, then administered praziquantel. Subsequently, the number of eosinophils returned to a normal level and the abnormal shadow in the chest CT images diminished without scarring. The final diagnosis was a superinfection of paragonimiasis and hookworm.

Here we report the cases of eight patients who developed small bowel obstruction and/or gastric ulcers after ingesting rice cake, the traditional Asian food, and were managed conservatively. This report adds to the existing literature on gastrointestinal disorders induced by rice cake ingestion, which are characterized by gastrointestinal obstruction, perforation, and ulceration and are occasionally accompanied by peritonism. These conditions tend to occur in 50-60-year-old males who wear dentures or eat rapidly. Therapeutically, hard rice cake remnants in the upper gastrointestinal tract can be broken up by endoscopic snaring and can be detected by computed tomography as homogeneous high-density material at approximately 145 (range:120-206) Hounsfield units.

An 85-year-old woman was admitted to our hospital with the chief complaint of fever. Antibiotics were not effective and a chest computed tomography scan revealed a diffuse micronodular shadow and thoracic aortic aneurysm. Subsequently, a bronchoscopy sputum culture was positive for Mycobacterium tuberculosis. Two months after the initiation of chemotherapy, the thoracic aortic aneurysm enlarged despite the improvement in lung findings. Tuberculous aneurysms are quite rare, but can be critical and acute. Therefore, caution should be exercised when treating such patients.

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) possess a variety of carrier-mediated transport systems to support and protect brain function. Multidisciplinary research conducted on these transport systems has provided a foundation not only for understanding the pathophysiological role of the brain barriers better but also for the development of rational drug delivery and targeting strategies for the central nervous system (CNS). Drugs recognized by the blood-to-brain influx transport systems, e.g., an amino acid transporter LAT1/SLC7A5 and an unidentified organic cation transporter, are expected to have a great potential for CNS delivery. Nevertheless, drugs recognized by efflux transporters, including ATP-binding cassette transporters such as P-glycoprotein (MDR1/ABCB1), breast cancer resistance protein (BCRP/ABCG2) and multidrug-resistant protein 4 (MRP4/ABCC4), show low permeability across the brain barriers, resulting in low distribution to the brain. The brain-to-blood efflux transport systems also play an important role in the cerebral clearance of endogenous neurotoxic compounds such as prostaglandins and β-amyloid, the reduction of which is related to disorders of the CNS. Recently, we developed a method based on quantitative targeted absolute proteomics (QTAP) to determine the absolute expression levels of transporters of the human brain barriers. Data on absolute expression levels of transporters together with data on intrinsic transporter activity enables reconstruction of in vivo brain barrier transport function in humans. This review covers cutting-edge knowledge and methodologies related to transport systems at the BBB and BCSFB, which contribute to the knowledge regarding the management of endogenous and xenobiotic compounds by the brain, and the importance of these transport systems for CNS drug delivery and therapeutics.

Group B Streptococcus (GBS) infection in infants aged over 90 days, known as ultra-late onset disease (ULOD), is extremely rare. We present 2 cases of ULOD and investigate etiology from both the host and microbiological aspects. Case 1, 99-day-old girl born in the late preterm, had a history of 6-hour fever. Bacterial meningitis was diagnosed and the patient was treated with intravenous ampicillin for 14 days. The isolate was serotype III GBS. Case 2, a 7-month-old girl with no medically significant history had an intermittent fever for 2 weeks before admission. Serotype Ia GBS was isolated from urine and blood, leading to a diagnosis of urosepsis. Intravenous cefotaxime was administered for 7 days. Both patients were discharged without any sequelae. We examined the host risk factors for ULOD development. (i) One subject had underlying preterm birth and the other had bilateral vesicoureteral reflux. (ii) Both had extremely low serum anti-serotype specific immunoglobulin levels, an important measure of protective immunity. The anti-type Ia antibody concentration was 0.24 microg/mL and the anti-type III IgG antibody concentration was 0.25 microg/mL. We employed multilocus sequence typing (MLST) to determine the genetic background of bacterial isolates. Sequence types (STs) of isolates were ST-335 (one allele variant of ST-19) and ST-23. ST-335 is an epidemic invasive GBS disease strain in Japan and is dominantly correlated with serotype III. ST-23 is highly associated with serotype Ia and is also a common invasive type in Europe, the United States and Japan. Our findings suggest that ULOD likely develops combined with underlying host disease, immunological factors and highly virulent strains. Continuous investigation of large numbers of cases is needed to better understand ULOD etiology.

A83 -year-old man was admitted to our hospital for the treatment of advanced ascending colon cancer with liver metastases. He had initially undergone an ileocecal resection for ascending colon cancer. Subsequently, we started oral administration of UFT/LV(UFT 400mg/day, LV 75 mg/day, and 4 weeks of therapy followed by a week suspension of treatment). After 3 courses, his tumors responded well to treatment, and CT showed marked regression of liver metastases. After 10 courses, liver metastases had almost disappeared. Two years passed without any adverse events since UFT/LV therapy was started. These findings suggest that UFT/LV therapy is very safe and effective for elderly patients with unresectable colorectal cancer.

A 51-year-old man who underwent umbilical cord blood transplantation for acute lymphoblastic leukemia with a Philadelphia chromosome in April 2006 achieved complete remission. In June 2008, progressive renal dysfunction and melena emerged and the patient was diagnosed with B-cell-type malignant lymphoma. He presented with severe hypo-phosphate- mia(0. 1m g/dL)due to paraneoplastic syndrome, simultaneously. Because the development of tumor lysis syndrome followed by hyper-phophatemia was feared to occur after CHOP chemotherapy, we discontinued the adjustment of serum phosphorus. The serum phosphorus level was elevated to 11.6mg/dL after 3 days and decreased to 3. 8mg/dL after 5 days. We must be careful regarding hyper-phosphatemia and phosphorus adjustment even in patients with severe hypo-phosphatemia that is due to paraneoplastic syndrome.

To determine seasonal changes in the incidence of invasive pneumococcal disease (IPD) in children, we retrospectively analyzed 69 children with 72 episodes of IPD, admitted to a regional center in Kobe, Japan, between July 1994 and June 2011. IPD episodes involved occult bacteremia (n = 48), pneumonia (n = 10), meningitis (n = 10), periorbital cellulitis (n = 3), and mastoiditis (n = 1), including 3 cases of two IPD recurrences. We analyzed 5 IPD-associated factors previously documented in Europe and North Amrica with inconsistent results--1) age at onset, 2) sibling number, 3) preschool sibling number, 4) subjects' day care attendance, and 5) siblings' day care attendance. We collected information on these factors by reviewing medical charts or contacting subjects' parents or guardians by telephone. IPD peaked bimodally in April and May (n = 21) and in November and December (n = 20), decreasing prominently between July and September (n = 8). Subjects with IPD attending day care formed a significantly higher propotion during April and May than did those developing IPD during other months: 12/21 [57.1%] vs. 12/51 [23.5%], odds ratio 4.3, 95% confidence interval, 1.5-12.8; p = 0.006. Combined day care attendance among subjects with IPD and/or their siblings also differed significantly between these two groups: 17/21 [80.9%] vs. 27/51 [52.9%], odds ratio 3.8, 95% confidence interval, 1.1-12.8; p = 0.027. Not significant differences were seen in age at onset, sibling number, or preschool sibling number. In contrast, however children with IPD onset during November and December showed no significant difference in association with any of the 5 factors, compared to children with IPD onset in other months. Our findings showed a bimodal peak in IPD in children, the first and highest of which occurred in April and May and was significantly associated with day care attendance by those with IPD and/or their siblings. This first peak may, however, be related to circumstances in Japan, where preschool children usually enter day care center or kindergarten in April.

Aim: In this study we aimed to evaluate the frequency of cerumen impaction in Japanese elderly and clarify the associations between cerumen, cognitive function, and hearing impairment., Methods: The subjects enrolleded in this study were participants in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). The data of 792 community-dwelling participants aged 60 to 88 years old were collected. All had taken the Mini-Mental State Examination (MMSE) and had undergone pure tone audiometry (PTA) assessment and video recording of an otoscopic examination. We then analyzed associations between the incidence of the cerumen impaction of better-hearing ear, hearing level and MMSE scores using a general linear model., Results: Cerumen impaction of the better-hearing ear was observed in 10.7% of all participants. In participants with an MMSE score of less than 24, the frequency of cerumen impaction was 23.3%. Cerumen was significant associated with poorer hearing after adjustment for sex and age (p=0.0001). Cerumen impaction also showed a significant association with a low MMSE score after adjustment for sex, age, hearing level and education (p=0.02)., Conclusions: The frequency of cerumen impaction in Japanese elderly was estimated to be approximately 10%. The existence of cerumen impaction was associated with poorer hearing level and lower MMSE score.

Aim: The number of hearing-impaired elderly people in Japan remains to be clarified. In the present study, we analyzed the data from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) to ascertain the prevalence and 10-year incidence of hearing loss in Japanese elderly people., Methods: Hearing loss prevalence was calculated based on 2,194 subjects who had been included in the 6th survey of the NILS-LSA (2008-2010) and was represented as crude rates (calculation A) and as rates after the exclusion of occupational noise-exposure and ear disease history (calculation B). Estimates of hearing loss incidence were performed at a national level based on demographic statistics. Subsequently, we analyzed the 10-year incidence in 465 subjects showing no hearing loss at baseline (1997-2000 survey) all of whom also participated in the 6(th) survey of the NILS-LSA (2008-2010)., Results: The prevalence of hearing loss greatly increased after the age of 65 years. The prevalence observed in calculation A was 43.7%, 51.1%, 71.4%, and 84.3% in men aged 65-69, 70-74, 75-79, and over 80 years old, respectively. In women, the prevalence for the same age groups was 27.7%, 41.8%, 67.3%, and 73.3%, respectively. The size of the hearing-impaired population older than 65 years old was estimated to be 16,553,000. The 10-year incidence rates of hearing impairment in the 60-64- and 70-74-year-old age groups were 32.5% and 62.5% (age at baseline), respectively. These rates rapidly increased with age, although a number of elderly people with good hearing were also observed., Conclusions: Age-related hearing loss is an issue of national importance. These results also indicated that it is possible to preserve good hearing into later in life, and that hearing loss in the elderly may be preventable.

We report a patient with optic neuropathy and longitudinally extensive myelitis associated with anti-aquaporin 4 (AQP4) antibody and other autoantibodies. An 89-year-old woman presented with progressive numbness and weakness of the extremities which had acutely developed. She also complained of neck pain and gait disturbance. The results of a general physical examination were unremarkable. Neurologic examination disclosed right optic atrophy, an absence of touch sensation, pain, and muscular weakness in all her extremities. Her deep tendon reflexes were decreased, and the Babinski sign was bilaterally positive. Immunoserologic study yielded positive titers for anti-nuclear antibody (ANA), anti-double-stranded DNA, anti-Sjögren syndrome (SS)-A, anti-SS-B, and anti-ribonucleoprotein (RNP) antibodies. A lumbar cerebrospinal fluid examination showed a protein concentration of 54 mg/dL, a glucose concentration of 50 mg/dL (simultaneous blood concentration, 140 mg/dL), and a cell count of 2/mm(3). Chest radiography revealed interstitial pneumonia. Magnetic resonance imaging (MRI) of the cervical spine showed spondylotic cervical canal stenosis with cord impingement. T2-weighted MR images demonstrated increased signal intensity extending from C2 to C6, while contrast enhancement was noted in T1-weighted MR images upon gadolinium-DTPA administration. We suspected longitudinally extensive myelitis associated with the autoimmune disorders systemic lupus erythematosus and Sjögren syndrome. After intravenous methylprednisolone administration, her neurologic abnormalities gradually decreased, while MRI no longer showed increased signal or contrast enhancement. Anti-AQP4 antibody titers were positive. We consider that this patient had a neuromyelitis optica (NMO) spectrum disorder which was associated with systemic autoimmune disease. The possibility of NMO should be considered in similar patients with autoimmune disease, and anti-AQP4 antibody should be assessed.

A 77-year-old man underwent esophagectomy for esophageal cancer. Chest radiograph just after the operation showed opacification of the right lung. Although chest radiograph still showed a marked opacification of almost whole right lung in the ICU in spite of multiple bronchoscopy examination and suctioning of pulmonary secretions, he showed no dyspnea. On the second postoperative day, his respiratory symptoms deteriorated unexpectedly. Computed tomography showed torsion of the right upper and middle lobes, and urgent surgery was scheduled. Following double-lumen endotracheal intubation, thoracotomy was performed under one lung ventilation. The lung was found rotated. The surgeons tried to reduce the torsion to preserve the viable lung, but failed. Bleeding from infarcted lung was observed (approximately 150 ml). Accordingly, stapled lobectomy was performed. After the second surgery, he fortunately recovered without any complications. Although lung torsion is a rare complication, not only thoracic surgeons, but also we, anesthesiologists, should be aware of this disease.

A 65-year-old man who had suffered from traumatic spinal cord injury had chronic lumbar pain. He had exacerbation of lumbar pain and intermittent fever and consulted several doctors, but the cause of the lumbar pain was unknown. An orthopedic specialist took an MRI. Spinal MRI showed increased signal intensity at the level of T10-11 and a mass in his right lower lung field, so he was referred to our hospital. Two transbronchial lung biopsy procedures failed to obtain malignant cells. CT guided biopsy showed fibrous and hyalinizing tissue contained plasma cells and lyphocytes. Staphylococcus aureus was cultured from the second bronchial lavage fluids of brush and blood cultures, so we began administration of ampicillin-sulbactam. Avoiding threatened or actual cord compression due to collapse resulting from spinal instability, posterior fusion with instrumentation was done through the back of his chest wall. At once, bone biopsy was done, and showed no malignant cells. As soon as antibacterial treatment was stopped after the operation, he had bloody sputa and fever. The antibacterial agent was resumed and the symptoms improved. The mass decreased in size and lumbar pain improved gradually, so we concluded the diagnosis was pyogenic spondylitis caused by S. aureus. After about 5 months of antibacterial treatment, the tumor substantially diminished.

Using 49 clinical methicillin-susceptible Staphylococcus aureus isolates (MSSA) and 54 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, we examined the change of MIC using five different inocula (2.5-4 x 10(2) cfu/spot-2.5-4 x 10(6) cfu/spot). We found the big change of the MIC with the increase of the inoculum size in ampicillin against MSSA, and the change was small in cefazolin, meropenem, ciprofloxacin. For anti-MRSA antibiotics, we found the small change with the increase of the inoculums size in vancomycin and arbekacin, and the middle change in teicoplanin and linezolid against MSSA and MRSA. The data from this study suggest that in serious and high inocula infections caused by S. aureus, the presence of an inoculum effect should be considered in curing.

Following recent advance in medical technology, the increase of immunocompromised patients results in an increase of opportunistic infections such as nocardiosis. However, little is known about relationships between clinical features of nocardial infections and each Nocardia species, especially newly identified ones. Therefore, we identified clinical isolates of Nocardia species by genetic methods and analyzed clinical features of nocardiosis. Nine clinical isolates were obtained in Kyushu University Hospital from 2005 to 2008. Six different Nocardia species were identified by 16Sr RNA: Nocardiafarcinia (n=2), Nocardia brasiliensis (n=2), Nocardia cyriacigeorgica (n=2), Nocardia transvalensis (n=1), Nocardia araoensis (n=1) and Nocardia testacea (n=1). The underlying diseases of 9 patients were pulmonary diseases(n=5), malignant diseases(n=3), collagen diseases(n=1) or primary immunodeficiency diseases (n=l). According to antimicrobial susceptibility testing, none of them was resistant to minocycline or linezolid. Among seven isolates from respiratory specimens, one was resistant to imipenem, sulfamethoxazole/trimethoprim and amikacin, two were to ciprofloxacin. Three species identified recently (N cyriacigeorgica, N. araoensis and N. testacea) were involved in this study and most of them were considered as infectious pathogens to human. These data suggested the identification of Nocardia to the species level and susceptibility testing were important for diagnosis as infectious diseases and treatments.

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.

We report a patient with hairy cell leukemia Japanese variant (HCL-Jv) that developed after radiotherapy for orbital adnexal MALT lymphoma. A 78-year-old man was diagnosed as having MALT lymphoma in the left conjunctiva in December 2003. The patient was treated by local radiotherapy and the tumor disappeared. Thereafter, he gradually developed leukocytosis and mild splenomegaly. In May 2009, the leukocyte count was 34,300 with 80% lymphoid cells. A diagnosis of HCL-Jv was made since the lymphoid cells showed a hairy morphology with round nuclei and indistinct nucleoli. These cells expressed CD11c, CD19, CD20, CD103 and showed weak reaction for tartrate-resistant acid phosphatase (TRAP). Bone marrow was infiltrated by atypical cells with an intrasinusoidal pattern. No treatment was needed as the patient was asymptomatic without anemia, thrombocytopenia or lymphadenopathy. Results of the immunoglobulin light chain expression and the heavy chain rearrangement in the tumor cells indicated that the two mature B-lymphoid neoplasms, MALT lymphoma and HCL-Jv, in this patient were derived from independent clones. This appears to be the first reported case of HCL-Jv associated with other lymphoid tumor. Further analysis is needed to clarify the risk of secondary malignancy in HCL-Jv.

A 64-year-old woman was referred to our hospital because of disturbance of consciousness. She had undergone distal gastrectomy for gastric carcinoma 17 years previously. General physical examination was unremarkable, neurologic examination disclosed hyperactive deep tendon reflexes in the upper limbs. Laboratory abnormalities included elevations of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and findings suggesting disseminated intravascular coagulation (DIC). Lumbar cerebrospinal fluid showed a protein concentration of 408 mg/dl and a glucose concentration of 82 mg/dl (blood: 110 mg/dl), as well as a cell count of 16/mm3. Cranial computed tomography indicated brain edema. Magnetic resonance imaging (MRI) of the brain showed diffuse thickening of the dura mater, with contrast enhancement upon gadolinium-DTPA administration. These findings suggested hypertrophic pachymeningitis. Magnetic resonance venography (MRV) showed occlusion of the left transverse sinus and attenuation of the straight sinus. MRI of the spine as well as gallium scintigrams demonstrated multiple areas of increased uptake in areas near the skull and spine. We therefore suspected tumor metastasis. The patient was given heparin as well as pulse therapy with methylprednisolone, but she died 7 weeks after symptom onset. At postmortem examination, the dura was thickened. Histopathologically, numerous tumor cell emboli in the dura were confined to the lumens of veins. The tumor cells were thought to have metastasized to the dura through the vertebral venous plexus (Batson's plexus). Immunostaining demonstrated immunoreactivity of tumor cells to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The primary origin of the carcinoma was not precisely identified by these findings. Widespread dural vein tumor emboli should be taken into consideration as a cause in cases that develop rapid deterioration of consciousness associated dura mater thickening.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality among the immunocompromised, especially those undergoing hematopoietic stem cell transplantation. With spore inhalation the usual infection route, such subjects must be protected from environmental spore contamination, necessitating measures such as high-efficiency particulate air (HEPA) filtration. In April 2006, we implemented a new transplantation unit with HEPA filtration. We retrospectively evaluated its efficacy for hospitalized transplantation unit subjects whose sera were tested for aspergillus galactomannan antigen between April 2004 and March 2007. Subjects numbered 265 (973 samples) categorized as definite, probable, or possible. The earliest IA onset date was when symptoms, positive radiological findings, or positive galactomannan antigen tests occurred, based on revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions. We classified cases when IA occurred over 10 days after admission as hospital-acquired. No such cases were detected after November 2005 and IA incidence decreased significantly after the new unit began being used. Results suggest that the new unit and HEPA filtration helped eliminate nosocomial IA.

In this study, we investigated the level of gut absorption following oral beclomethasone dipropionate (BDP) administration by measuring the blood concentration of its metabolites measured by LC-MS/MS using the HPLC method. Five patients who were administered BDP orally for gut GVHD were included. The blood concentrations of beclomethasone-17-monopropionate (17BMP), which is one of the active metabolites of BDP, were 618 approximately 1, 749 pg/mL in 4 of the studied 5 patients, which was comparable to that after inhalation of BDP; however, it was relatively higher in one patient (2,439+/-161 pg/mL). As the blood concentration of 17BMP in this study patient was higher compared with healthy volunteers administered a single oral BDP 4 mg, GVHD patients might have a higher concentration than healthy volunteers. Given that a higher grade of gut GVHD was associated with a higher blood level of 17BMP, BDP absorption might be associated with gut mucosal injury. Thus, the systemic adverse effect following oral BDP administration might not be negligible especially in gut GVHD patients.

We report two cases of acute urinary retention secondary to benign inflammatory nervous disease. Case 1 is in a 48-year-old male who was diagnosed with aseptic meningitis. Case 2 is in a 67-year-old male who was diagnosed with acute disseminated encephalomyelitis. These two cases differred in specific mechanism of the disease, but both shared symptoms of temporal voiding disturbance due to sacral radiculopathy (Elsberg syndrome). This condition is extremely rare, but should be kept in mind because delayed treatment can lead to permanent impairment.

With Japan facing a rapidly aging society and health care for the latter-stage elderly only set up in April 2008, we analyzed the clinical features of elderly otolaryngology outpatients to clarify any differences between early and latter stage elderly. Subjects were 627 men and 702 women divided by age into below middle age (under 41-years-old), middle-aged (41- to 64-years-old), early-stage elderly (65- to 74-years-old), and latter-stage elderly (over 74-years-old). The most common symptom was sore throat in those below middle age, vertigo in those middle-aged on early-stage elderly, and hearing disorder in those latter-stage elderly. Older subjects took more medication, had more health problems, waited longer before going to an outpatient treatment facility, and visited such facilities less voluntarily. Central vertigo increased in the elderly, seen in 26% of the latterstage elderly. Those whose chief symptom involved hearing doubled among the latterstage elderly, 70% of whom had moderate to severe hearing problems. It is therefore imperative to understand the clinical background of elderly patients and to concentrate on learning about and treating vertigo and hearing problems.