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A 47-year-old female was admitted to our department because of a sensation of foreign body in the throat. After various medical examinations, partial resection of the lingual thyroid was initially planned. However, the tumor was extremely hard and impossible to resect, so total removal of the tumor was performed. The histological diagnosis was “thyroid tissue with hyalinized and calcified stroma without malignancy”. Even an extensive search of the literature failed to uncover a case similar to ours.

For the application of water-in-oil-in-water (w/o/w) emulsions to a nasal dosage form of secretin, permeation tests were conducted in vitro to assess the effects of hydrophilic surfactants in the internal aqueous compartment on the release rate of secretin. The amount of secretin that permeated through an artificial membrane from a donor cell to a receptor cell was affected by the addition of sodium chloride or sodium alkylsulfonate to the internal aqueous compartment of w/o/w emulsions in the donor cell. Sodium chloride decreased apparent permeation rate constants from the internal aqueous compartment to the external aqueous phase (K'1) as the difference in osmolartiy between the internal compartment and the external phase increased. While sodium alkylsulfonates increased K'1 in proportion to the values of (partition coefficient between the oil phase and the internal aqueous phase/partition coefficient between the oil phase and the external aqueous phase)/osmolarity ratio of the internal aqueous phase to the external aqueous phase. These results demonstrate that the release rate of secretion from w/o/w emulsions are affected by partition of the drug between aqueous and oil phases and by osmotic difference between the outer and internal phases.

Despite the decrease in Reye syndrome after the discontinuation of aspirin, acute encephalopathy (non-Reye syndrome type) has been continually reported in Japan. Recent studies suggested that the thermolabile phenotype of carnitine palmitoyltransferase II (CPT II) variation [F352C] was closely related to the pathomechanism of influenza-associated encephalopathy (IAE) in Japanese, causing mitochondrial ATP utilization failure during periods of high fever, resulting in brain edema. So, we analyzed CPT II polymorphism and peripheral blood ATP levels as a signal of “energy crisis” in 12 and 10 patients with acute encephalopathy, respectively. Out of the 12 patients with acute encephalopathy, six showed thermolabile CPT II variants [F352C], and of these six, two patients died in spite of intensive care. In contrast, the remaining six patients with no thermolabile CPT II variant [F352C] showed a relatively mild clinical course. Blood ATP levels of the 10 patients in the acute phase of encephalopathy were significantly lower than those during the convalescent phase and also those of patients with febrile seizure status. Our data suggest that the thermolabile F352C CPT II variant, found only in Japanese, might be one of the predisposing factors to trigger the pathomechanism of acute encephalopathy in the Japanese population, and that it is causally related to the severity of disease. The decreased blood ATP level seems to reflect systemic mitochondrial dysfunction including the blood brain barrier during the acute phase of encephalopathy.

Ubidecarenone, which has low photostability and is poorly absorbed in the intestine, was formulated into a novel powdered dosage form designated as a redispersible dry emulsion. In preparing the system, an oily solution containing the drug and a colorant emulsified in an aqueous solution of a surfactant (Pluronic F-68) were spray-dried with a suitable excipient. The resultant dry emulsion particles have good flow properties and readily release the oily droplets to form stable emulsions on rehydration. The redispersibility, i.e., the conversion to the original emulsion from the dry emulsion form, was found to be closely related to the viscosity of the oily carrier. The photostability of the drug dissolved in the oily carriers was much improved in the presence of colorants. The kinetics data for photolytic degradation of the drug in the dry emulsion particle were analyzed to clarify the effect of the amount of excipient and colorant on the photostability of the drug in the particle.

In order to improve the formation percentage of w/o/w emulsions, experiments were conducted in order to elucidate the influence of the addition of various kinds of surfactants in the internal aqueous phase of the emulsion, the formation percentage of w/o/w emulsion as compared with that without additives, and with sodium chloride or sorbitol. Several physico-chemical properties of intact w/o/w emulsion or each phase, such as the osmolarity, interfacial tension and viscosity, were investigated in order to determine the governing factor in improving the formation percentage of w/o/w emulsion. w/o/w emulsion was prepared via a two-step emulsification procedure. New coccine was employed as a marker to evaluate the formation percentage of w/o/w emulsion. Sodium alkylsulfonate, sodium alkylsulfate, sodium alkylcarbonate and polyoxyethylene (20) sorbitan monooleate were used as additives in the internal aqueous phase of w/o/w emulsion as well as sodium chloride and sorbitol. The formation percentage of w/o/w emulsion was improved by increasing the concentration of the additives, viz., various kinds of surfactants in the internal aqueous phase of the emulsion, as well as sodium chloride or sorbitol. This could be attributed to a decrease in interfacial tension between the internal aqueous phase of the w/o/w emulsion and the oily phase of the emulsion.

Solved mixtures of hydrogels (SMH), composed of hydroxypropylcellulose (HPC), a pseudo-hydrogel, and ethylcellulose, a water-insoluble polymer, were prepared by solvent evaporation. Phenylpropanolamine hydrochloride was used as a model drug. The amount of drug released from a matrix tablet containing SMH powder and the drug increased with decreasing weight fraction of HPC (WFH) in SMH. SMH showed improved properties compared to HPC alone, for example, flowability and hydroscopicity. These properties increased with decreasing WFH. The sorption apparatus described in this study is capable of an immediate, sensitive and accurate response to initial moisture sorption. The kinetics of moisture sorption measurement using this apparatus is useful for a preliminary study.

The dissolution behavior of two controlled-release matrix tablets, formualtions A and B, containing phenylpropanolamine HCl as a model drug was studied using a paddle method and a paddle-beads procedure. The paddle-beads method involves a system in which polystyrene beads are inserted into the dissolution medium to cause mechanical destruction or frictional force. These tablets have the advantages of pH- and agitation-independent release performance in vitro using the paddle method. These matrices and solution were orally administered to six beagle dogs, and the results were analyzed by deconvolution. In vitro dissolution curves using the paddle method did not coincide with the in vivo profiles in the fasted condition, while in vitro release using the paddle-beads method was similar to the in vivo profile in the fasted condition in dogs. The paddle-beads method may be useful for investigating in vivo/in vitro correlation of controlled-release dosage forms.

Needle-like crystals appeared on the surface of theophylline tablets containing anhydrous theophylline, hygroscopic materials such as potassium, and other formulation ingredients, when stored under conditions of high relative humidity. X-ray powder diffraction studies on these crystals showed that anhydrous theophylline was converted to the hydrate.Crystal growth was accelerated by increased moisture uptake in tablets containing the hygroscopic materials polyethylene glycol 6000 or sodium chloride. The appearance of needle-like crystals on the surface of tablets resulted in a decrease in the rate of release of theophylline.

The granulation of an organic powdered material in a tapered-fluidized bed has been studied experimentally and theoretically. The size and density of granules were measured under various conditions, and the effect of change in the fluidizing characteristics on these physical properties of granules were examined. As a result of this study, it was found that the factors dominating the physical properties of the granules were air velocity, the moisture content of the powdered material and the magnitude of the pressure fluctuation reflecting the size of the bubbles in the bed. From the theoretical consideration of the mechanism of granulation in the tapered bed, a granulation index consisting of these factors was newly proposed, and this index was found to be useful in expressing the physical properties of the granule in terms of a single factor.

The effect of a change in pressure drop in a distributor on the fluidizing characteristics in a tapered bed was investigated by measuring the pressure drop in the bed and the volume mean diameter of the bubbles. These measurements indicated that the volume mean diameter of the bubbles could be estimated with the magnitude of pressure fluctuation in the bed. In addition, a larger pressure drop in gas distributors was found to result in a smaller pressure fluctuation in the beds. Finally, the magnitude of the pressure fluctuation and the averaged pressure drop were found to be the important indices to characterize the fluidizing state of the powder beds.

An oily drug, dl-α-tocopherol nicotinate (VEN) was transformed to the newly developed powdered form, termed dry emulsion, by spray-drying the emulsified VEN or oily solutions of VEN with additives. The drug releasing property from the resultant particles was dependent on various factors such as the emulsifying method and the type and amount of the oily carrier and surfactant formulated. The desired releasing property was offered by use of medium chain triglyceride (MCT) as the oily carrier and polyoxyethylene-polyoxypropylene-blockcopolymer (Pluronic F-68) or polyoxyethylenesorbitan monolaulate (Tween 80) as the emulsifying agent. The difference in drug releasing property with various formulations was found to be mainly attributed to the difference in physical state of VEN surfactant in the dry emulsion particle, which was detected by differential scanning calorimetry.

Although the effect of the atmospheric pressure on Meniere's disease has been studied for over 15 years, and low pressure treatment seems to be effective, many questions are left unanswerd. The major reason is thought to be in the specifications of the pressure chamber.Most pressure chambers hitherto used are capable of generating either high or low pressure. Furthermore, since the chambers are not designed for otological examinations in most cases, ventilating with fresh air produces noise exceeding 60-70 dB in the chamber during the examination. Aiming at neurootological research, we built a new soud-proof pressure chamber in which pressure can be changed between±1, 000mmH2O at a maximum speed of 100mmH2O/sec. Noise in this chamber can be kept under 30-35 dB while pressure is maintain-ed at the same level.

Phospholipid nanosphere dispersions incorporating a lipophilic drug were prepared by the heating method. Prepared dispersions were powdered by depositing them on sugar nuclei in a fluidized-bed granulator in an aqueous system. Resultant free-flowing powders, which were agglomerates of sugar with phospholipid, reproduced phospholipid nanosphere dispersions when rehydrated with water. Incorporation of a lipophilic drug, e.g., tocopherol, into the nanospheres or increasing of phospholipid concentration in the formulation increased the sizes of rehydrated nanospheres compared to the original dispersion before powdering due to the fusion or aggregation of the nanospheres. Proper selection of sugar nuclei, decreasing the sizes of original phospholipid nanospheres for powdering and addition of polyhydric or sugar alcohols into the sprayed dispersion, however, significantly reduced the aggregation of rehydrated nanosphere. All procedures from the preparation of the original nanosphere dispersion to its powdering were performed in an aqueous system without use of any organic solvent. The procedures described here are recommended to produce stable powdered nanosphere which can be rehydrated to form phospholipid nanosphere dispersions when required.

Phospholipid nanosphere dispersion was prepared from phosphatidylcholine with or without vitamin E by the heating method. The dispersed particles had diameters of 8.6-150 nm. These nanosphere dispersions were powdered with sugars such as sucrose, lactose and mannitol by spray drying in an aqueous system. The resultant powders, except coformulation with mannitol, consisted of spherical, homogeneous and freely flowing particles, in which the sugar was amorphous. The powder yielded a nanosphere dispersion having almost the same particle size and optical density as the original dispersion, when rehydrated with water. The particle size of rehydrated nanospheres with vitamin E increased with the increasing amount of vitamin E coformulated. A water-soluble drug, 5-fluorouracil, could be entrapped in the nanospheres by rehydrating the powdered nanospheres with an aqueous solution of the drug. All the steps from the preparation of the original nanosphere dispersion to spray drying were performed in an aqueous system without using any organic solvent. The procedures described here should be suitable for the production of stable powdered nanosphere which can be rehydrated to form phospholipid nanosphere dispersions as required.

Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades heme to iron, carbon monoxide (CO), and biliverdin, the latter two of which are thought to mediate the anti-inflammatory and antioxidant actions of HO-1. Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1). Previous reports have demonstrated that the genetic ablation of Bach1 engenders an increased HO-1 expression and a marked reduction in the degree of oxidative tissue damage in vivo. However, the function of Bach1 in spinal cord injury is still not understood. In the present study, we examined whether Bach1 deficiency increases HO-1 expression and reduces neural tissue damage in a spinal cord injury model using Bach1 knock-out (KO) mice and wild-type (WT) mice. The expression of HO-1 protein in the spinal cord was significantly higher in the Bach1 KO mice than in the WT mice before and after injury. The KO mice also had significantly higher Basso mouse scale scores for locomotor function and larger areas of spared white matter than the WT mice at 6 weeks after injury. Neuronal loss and apoptotic cell death in the injured spinal cord was significantly reduced in the KO mice in comparison to the WT mice. These results suggest that Bach1 deficiency engenders a constitutively higher expression of HO-1 and a dramatic increase in cytoprotection against spinal cord injury.

An ovomucoid-conjugated polymer column was prepared for the liquid chromatographic resolution of racemic compounds. The column showed strong retention of acidic solutes, a characteristic attributed to the structure of the stationary phase support gel. Although the efficiency of the column was lower than that of an ovomucoid-conjugated silica gel column, enantiospecific chlorprenaline determination in plasma was achieved with solute amounts from 1.0 ng to 0.1 μg.

Pelizaeus–Merzbacher disease (PMD; MIM#312080) is a rare X-linked recessive neurodegenerative disorder. The main cause of PMD is alterations in the proteolipid protein 1 gene ( PLP1 ) on chromosome Xq22.2. Duplications and point mutations of PLP1 have been found in 70% and 10–25% of all patients with PMD, respectively, with a wide clinical spectrum. Since the underlining genomic abnormalities are heterogeneous in patients with PMD, clarification of the genotype-phenotype correlation is the object of this study. Comprehensive genetic analyses using microarray-based comparative genomic hybridization (aCGH) analysis and genomic sequencing were applied to fifteen unrelated male patients with a clinical diagnosis of PMD. Duplicated regions were further analyzed by fiber-fluorescence in situ hybridization (FISH) analysis. Four novel and one known nucleotide alterations were identified in five patients. Five microduplications including PLP1 were identified by aCGH analysis with the sizes ranging from 374 to 951-kb. The directions of five PLP1 duplications were further investigated by fiber-FISH analysis, and all showed tandem duplications. The common manifestations of the disease in patients with PLP1 mutations or duplications in this study were nystagmus in early infancy, dysmyelination revealed by magnetic resonance imaging (MRI), and auditory brain response abnormalities. Although the grades of dysmyelination estimated by MRI findings were well correlated to the clinical phenotypes of the patients, there is no correlation between the size of the duplications and the phenotypic severity.

Autophagy is a degradation of the cytoplasm and it induces autophagic cell death in several neurodegenerative conditions. Beclin 1, a Bcl-2-interacting protein, is known to be a promoter of autophagy. We investigated the alterations in the Beclin 1 protein expression and the involvement of autophagy and autophagic cell death after spinal cord injury using a spinal cord hemisection model in mice. In the present study, the Beclin 1 expression dramatically increased at the lesion site after hemisection. The increased expression of Beclin 1 started from 4 h, peaked at 3 d, and lasted for at least 21 d after hemisection. The Beclin 1 expression was observed in neurons, astrocytes, and oligodendrocytes. The nuclei in the Beclin 1 expressing cells were round, which should normally be observed in autophagic cell death, and they were not either shrunken or fragmented as is observed in apoptotic nuclei. The results of the present study suggested that autophagy is activated in the injured spinal cord. Furthermore, autophagic cell death is considered to clearly contribute to neural tissue damage after spinal cord injury.

This paper presents experimental results of TSTO (Two-Stage-To-Orbit) aerodynamic heating at hypersonic speed. TSTO is a promising space transportation system consisting of two stages, i.e., an orbiter and a booster, and is supposed to fly in a wide speed range from subsonic to hypersonic. However, when it flies at hypersonic speed, it undergoes severe aerodynamic heating under some conditions. Thus, in order to overcome this crucial problem, researchers are motivated to find how to reduce this heating load. Although there seems to be a lot of factors that could affect the heating, the present work focuses on the effects of TSTO configuration on the heating due to aerodynamic interaction. There are many parameters that influence the heating. In the present study two of these parameters are considered which are; i) the booster configurations and ii) the clearance between the two stages. The flight condition is fixed at a hypersonic speed of M∞=8.1. First, as a baseline TSTO configuration, a Hemisphere-Cylinder (HC) is employed as orbiter, and a Delta-Wing (DW) as booster. Then, we used a more practical configuration for the booster, i.e., a hypersonic-booster-model (HBM), which has a wider spanwise leading edge on the main wing in addition to a pair of fins. For these two models, their aerodynamic interaction flow fields as well as heating distributions have been examined with various clearance. As a result, the peak heat flux on the HC in the case of the HBM was reduced to half of that in the case of the DW. However, they showed a similar trend with regard to the interaction pattern change from shock/shock interaction to shock/boundary-layer interaction, which occurs when the clearance of the two bodies was increased.

§** This paper presents experimental results of TSTO (Two-Stage-To-Orbit) aerodynamic interactions at hypersonic speed. TSTO is a concept as space transportation system. The TSTO vehicle, where a booster is connected to an orbiter, has to fly in a wide range of speed from subsonic to hypersonic. However, a difficult problem of aerodynamic interaction arises between its two bodies, where high pressure and high heat flux occur. In the present study, a two-dimensional TSTO model is considered, where a flat plate is employed as the booster, and a hemi-circular cylinder as the orbiter; hence the flow field can be assumed to be nearly two-dimensional. Specifically the effects of the clearance between the two bodies on the flow field is examined at a hypersonic speed of M∞=8.1, where distributions of pressure and heat flux are measured. Especially, the main focus is on clarifying the mechanism of a feedback loop with regard to shock oscillations. The flow pattern can be classified, depending on the clearance between the two bodies as well as shock/shock interaction pattern in front of the orbiter. In the case of large clearance (h/D > 0.77; D is the diameter of the hemi-circular cylinder) as well as in no clearance case, the flow becomes steady, while in small clearance cases (0.00 < h/D < 0.77) highly unsteady interaction flow fields including Edney’s type IV shock interaction pattern are observed with a frequency of 1.5 kHz; at h/D=0.67, shock/shock interactions from type IV to VI are observed in a period. In addition, it is shown that this unsteadiness can be suppressed by installing a fence on some place of the booster.

Object The authors analyzed a series of 118 cases of spinal dumbbell tumors to elucidate the feature of the tumors. Methods Of 674 cases of spinal cord tumors, the incidence of dumbbell tumors was studied. The tumors were analyzed, and the authors focus on the distribution of age and sex, the pathological diagnoses, their locations, Eden classification, and the surgical methods used. Results The incidence of dumbbell tumors was 18%. The mean patient age was 43 years, which was younger than that for all spinal cord tumors (mean 50 years). There were 11 patients younger than 10 years of age. The rate of dumbbell tumors in the cervical spine was significantly higher than that of all spinal cord tumors. Fifteen (18%) of the 81 schwannomas were observed in the C-2 nerve root, thus having a higher incidence than those in the other nerve roots. In 99 cases (84%), the tumors were removed through a hemilaminectomy with or without a facetectomy and posterior fusion. Of 118 cases, 69% of the tumors were schwannomas, and malignant tumors were found in 10 cases (8.5%). Seven (64%) of 11 patients younger than 10 years of age had malignant tumors. Three patients older than 10 years of age had malignant tumors, thus accounting for 2.8% of the 107 older patients. Conclusions The incidence of dumbbell tumors was 18%, and they are not uncommon. Malignant dumbbell tumors were more common in children younger than 10 years of age than in older patients.

About 10 years have passed since a previous survey on the treatment of West syndrome in Japan. To elucidate current practice, a questionnaire was sent to 113 institutes. It included (1) the drugs used for the treatment, (2) their dosage, and (3) the dosage and the schedule of adrenocorticotropic hormone therapy. Response rate was 51.3%. Adrenocorticotropic hormone, valproic acid, vitamin B6, and zonisamide were frequently used. Vitamin B6was used most frequently as the first-choice drug followed by valproic acid, zonisamide, and adrenocorticotropic hormone. The most frequently used dose of synthetic adrenocorticotropic hormone-Z was 0.0125 mg/kg/d. Adrenocorticotropic hormone was administered every day for 2 weeks and then tapered off in more than 80% of the institutes. Although therapeutic strategy and drug usage have not changed largely during these 10 years, 2 alterations were observed: an increased use of zonisamide and a shortened duration of adrenocorticotropic hormone therapy.

We examined the present situation of children and adolescents with psycho-motor disabilities, and their parents by means of a questionnaire survey. The survey was conducted on the family members of outpatients, 116 males and 86 females. About half the patients were older than 15 years of age. The families of 128 patients did not use a home help service such as home nursing or a regional care service. Many family members had chronic ailments. The families of only 45 patients expressed that it would be better if their children would live in a care home in the future. We must develop a versatile system with social support and medical care for such cases.

A new configuration of TSTO (Two-Stage-To-Orbit) Booster model that can reduce the heat transfer rate produced by shock/shock and shock/boundary-layer interactions is proposed in this paper. Two types of the booster shape are examined; one is a delta wing as a baseline configuration, and the other is a caret wing, which is proposed here in this study. A detailed experimental study of hypersonic shock interactions around those TSTO models was made. Results show that the proposed configuration can reduce the heat transfer rate compared with the baseline one for all flow cases tested here. In the baseline case, the peak heat transfer rates on the orbiter and booster surfaces become about 4.1 times and 1.1 times as large as that at the stagnation value, respectively, while in the case of the caret wing that on the orbiter nose becomes about 3.1 times as large and that on the booster does not change. Thus, in the proposed caret wing booster, the heat transfer rate can be decreased by about 25% on the orbiter surface compared with the baseline case. Therefore, the caret wing is a promising configuration candidate as a booster.

Masashi Mizuguchi, Masayuki Itoh, Hiroshi Ozawa and Yukihiko Morikawa Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira and Departments of Pediatrics and Pathology, Tokyo Metropolitan Hachioji Children’s Hospital, Hachioji, Japan

The bullwhip effect is a problem of variation in customer demand that gets increasingly large as it propagates backward through the supply chain. A common assumption is that the company must learn to better respond to demand changes through better information systems leading to elaborate scheduling algorithms and 'visibility' of demand in real-time. The Toyota production system starts with the foundation of a levelled schedule and seeks to reduce the problem itself by smoothing demand, thus reducing variability in schedules, and at the same time reducing the lead time of response. This paper, for the first time, explains in detail how Toyota levels the schedule and still manages to satisfy customer demand. It requires cooperation between sales and production mediated by production control. Information displays are very simple using nothing more complicated then spreadsheets.

STUDY DESIGN A prospective observational study. OBJECTIVES To determine whether the pain in the neck or scapular regions in patients with cervical radiculopathy originates from the compressed root and whether the site of pain is useful for diagnosing the level. SUMMARY OF BACKGROUND DATA The pain has been thought to be caused not by root compression but by instability caused by disc degeneration or zygapophysial joint osteoarthritis because it usually precedes radicular symptoms in the arm/fingers. METHODS The subjects were 50 consecutive patients with pain as well as arm/finger symptoms, who underwent single-root decompression alone. The involved roots were C5 in 9 patients, C6 in 14, C7 in 14, and C8 in 13. RESULTS The pain preceded the arm/fingers symptoms in 35 patients (70%). Although the pain had lasted for more than 7 months on average before surgery, it was relieved early after surgery in 46 patients (92%). When the painful site was suprascapular, C5 or C6 radiculopathy was frequent (P < 0.01). When it was interscapular, C7 or C8 radiculopathy was frequent (P < 0.001). When it was scapular, C8 radiculopathy was frequent (P < 0.01). CONCLUSIONS Pain in the suprascapular, interscapular, or scapular regions can originate directly in the compressed root. The site of the pain is valuable for determining localization of the involved root.

This is a report of the setting up of a day group service system for severely disabled children, the "Koala Club". The "Koala Club" was started in 1993, and has been running outside of the hospital since 1997. A support group for the "Koala Club" was established in 1999. Currently 13 children attend the "Koala Club". The staff of the "Koala Club" consists of one coordinater, four nurses and eight care workers. The medical care is fulfilled by nurses. The "Koala Club" open two days a week. It has been supervised by a doctor and a case worker. There is an important role for physicians in the regional care of disabled children.

Cerebral mycotic aneurysms are one of the most serious complications of bacterial endocarditis but the mechanism underlying cerebral aneurysms is unclear. We reported the cytokine levels in a cerebral mycotic aneurysm in a child with Down's syndrome. The patient was a 12-year-old female. She was diagnosed as having Down's syndrome and congenital heart disease consisting of an endocardial cushion defect at birth. She underwent a radical operation at 9 years but mitral valve regurgitation remained. She was hospitalized with high fever, vomiting, loss of activity and gait disturbance. Neurological examination revealed facial palsy and hemiparesis on the left side. Cytokines such as IL-6, TNF-alpha, sTNFR1 and sE-selectin were elevated in blood, and IL-6, TNF-alpha and sTNFR1 in cerebrospinal fluid. T2-weighted MRI disclosed a low intensity area in the right Sylvian sulcus. MR angiography showed an aneurysm of the right middle cerebral artery. We think that cytokines and the formation abnormality of collagen fibers are related to the production of aneurysms.

Metabolites of collagen metabolism were analyzed in patients with Menkes' disease. The urinary deoxypyridinoline level was significantly low in the patients with Menkes' disease, indicating that it is a good marker of lysyl oxidase activity, which is related to the connective tissue abnormalities.

This study determined the concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1) and soluble E-selectin (sE-selectin) in cerebrospinal fluid (CSF) and serum from 15 children with influenza virus-associated encephalopathy to determine the role of cytokines in the pathogenesis. Cytokines and sTNFR1 were measured by enzyme-linked immunosorbent assay. The CSF IL-6, TNF-alpha and sTNFR1 concentrations were elevated in 9, 4 and 4 of 12 children, respectively. The serum concentrations of IL-6, TNF-alpha, sTNFR1 and sE-selectin were elevated in 10, 2, 5 and 7 of 13 children, respectively. Four children with elevated TNF-alpha and sTNFR1 levels in the CSF had neurological sequelae. The results suggested that cytokines not only in serum but also in CSF play a pivotal role in influenza virus-associated encephalopathy, and that the CSF TNF-alpha and sTNFR1 levels may be important for predicting neurological sequelae.

The application of pressure to the middle ear changes the normal inner ear pressure in animal experiments. In this study we tested the effect of exposure to under- or overpressure on hearing in a total of 78 normal ears (40 subjects) in a soundproof pressure chamber. [After exposure to underpressure, a 10 dB or more gain in 3 ears and loss in 2 ears for at least one of the test frequencies was observed in 38 ears. After exposure to overpressure, a 10 dB or more gain in 5 ears and loss in 1 ear for at least one of the test frequencies was observed in 40 ears.] The characteristics of transferred inner ear pressure during a series of exposures to underpressure seemed to be similar to those during exposures to overpressure.

Because the Eustachian tube controls middle ear pressure to maintain the best hearing level, we tested the equilibration capacity of the Eustachian tube by measuring hearing levels in a soundproof pressure chamber. The number of swallows to recover normal hearing after the chamber pressure reached -200 mm H2O (an index of equilibration capacity for the static pressure differences across the eardrum) was less than 9 in normal subjects. The worst level of hearing and the time required to recover normal hearing from the beginning of alteration in the chamber pressure to -700 mm H2O (indexes of equilibration capacity for dynamic pressure differences across the eardrum) were 0-17 dB and within 120 s in normal subjects. It was difficult to determine definitive normal ranges of the equilibrium capacity of the Eustachian tube when positive pressure was applied.

Apoptosis-modulating therapeutics using active-site mimetic peptide ketones (z-VAD-fluoromethylketone (fmk)) have been reported to be efficacious in delaying the apoptotic response in central nervous system lesions. The purpose of the present study was to examine whether the caspase inhibitor z-VAD fmk prevents apoptosis and improves neurological deficit and tissue damage. One-hundred twenty female Sprague-Dawley rats were randomized into groups that were administered 25 microg of z-VAD-fmk or vehicle 30 min and 24 h after moderate spinal cord contusion (NYU impactor, 12.5 mm at T10). Several routes of administration were tested: (1) via Gelfoam placed on the spinal cord, (2) into the cisterna magna via a subarachnoidal catheter, (3) intravenously via the external jugular vein, or (4) intraperitoneally. Another group was injected with 50 microg of zVAD-fmk or vehicle intraperitoneally 30 min, 24, 48, and 72 h after injury. Animals were evaluated for locomotor function (BBB score) at weekly intervals for 6 weeks after injury and treatment. Spinal cords were then processed for histological analysis to determine whether zVAD-fmk treatment decreased contusion volume. Other spinal cord samples were harvested 24 h after injury and examined for cleavage of XIAP by immunoblot analysis. There were no significant differences in the BBB scores, contusion volumes, and XIAP cleavage between animals receiving the broad specific caspase inhibitor by the various routes and animals receiving vehicle alone. These findings raise critical questions about the use of peptide ketone apoptotic inhibitors in improving functional and histopathological outcomes following spinal cord injury.

We report a case of Menkes disease with urinary bladder hemorrhage. Diverticulums were found at 1 year and 3 months of age. He had repetitive urinary tract infections at 2 years old and died of urinary hemorrhage at 2 years and 9 months. Large hematoma and diverticulum were found at necropsy. In patients with Menkes disease, attention should paid to urinary complications.

Early treatment reportedly prevents neurological disturbance in patients with Menkes disease. To promote early diagnosis, a questionnaire concerning symptoms during the neonatal period and at the age of 1 month was sent to the mothers of 14 patients with Menkes disease. The height, body weight and head circumference were almost normal in most of the Menkes patients. At the age of one month, all patients had abnormal hair. The mothers noticed it in 8 cases, and in the remaining 6 cases, the abnormalities were confirmed by the photos at the age of one month. At this age, the mothers noticed weak activity in 5, jaundice in 5, dyspnea in 4 cases, feeding disturbance in 3, hypothermia in 2 and eczema in 2. These results suggest that recognizing hair abnormalities at a one-month check-up may provide a clue to the early diagnosis of Menkes disease.

A 56-year-old male presented with a prolactin-secreting pituitary adenoma who suffered pituitary apoplexy associated with intracerebral hemorrhage of the caudate head and putamen. The centers of both the intratumoral hematoma and intracerebral hemorrhage appeared as hyperintense on T1-weighted and T2-weighted magnetic resonance imaging, indicating the subacute stage and probably similar timing of onset. The tumor was treated surgically 6 weeks after the onset. The causative factor for the apoplexy remains unclear.