[Eight Cases of Small Cell Neuroendocrine Carcinoma of the Head and Neck].

Small cell neuroendocrine carcinoma of the head and neck is a rarely occurring poorly differentiated and high-grade malignant neoplasm characterized by highly active proliferation of neuroendocrine tumor cells. There are no established therapies for this disease. To clarify the clinical course and develop effective treatment(s) for the carcinoma, we reviewed the data of 8 patients of small cell neuroendocrine carcinoma of the head and neck treated by us between 2006 and 2014 at the Department of Otolaryngology, Gifu University School of Medicine and our affiliated hospitals. The patients consisted of 3 men and 5 women, ranging in age from 38 to 84 years old (mean : 60.9 years). The tumor arose from the nasal cavity or the paranasal sinuses in 3 cases, from the parotid grand in 2 cases, from the oropharynx in 2 cases, and from the hypopharynx in 1 case. The tumor that arose from the hypopharynx was a combined small-cell carcinoma with squamous cell carcinomas, and the one that arose from the oropharynx had already metastasized to the brain. Most of the patients were treated by chemotherapy and radiotherapy based on the treatment employed for small cell carcinoma of the lung. Only the patient in whom the tumor arose from a paranasal sinus was treated by surgery despite the definitive diagnosis of small cell carcinoma. We selected CPT-11 and a platinum agent for 4 patients, and VP-16 and a platinum agent for 3 patients as the first-line chemotherapy. Although two patients showed carcinoma-free survival, one died of recurrence of the regional lymph node metastases and five died of distant metastases despite the absence of locoregional recurrence. The 5-year survival rate was a dismal 25%, suggesting that we need to establish effective treatment(s) for the control of distant metastases in cases of the small cell neuroendocrine carcinoma of the head and neck.

[A case of idiopathic neck bleeding from a parathyroid cyst].

Bleeding from parathyroid cysts is rare. The retropharyngeal space has a very soft structure and if bleeding spreads to this space, airway obstruction can easily occur. We report on a 50-year-old female case with idiopathic neck bleeding from a left parathyroid cyst without any episode of injury. The patient complained of neck swelling after exercise and went to a nearby hospital. At the hospital, the doctor thought this swelling was caused by retropharyngeal bleeding from a tumor behind the left thyroid gland. Embolization of the left thyroid artery was performed. However, the next day, airway obstruction.was occurred and she was brought to our hospital. An emergency operation was performed to open the left neck swelling region. The operation findings and pathological examination showed that the bleeding was caused by a parathyroid cyst and airway obstruction had occurred because of retropharyngeal edema. In this case, the bleeding may have been caused by torsion of the neck when the patient exercised. The retropharyngeal edema probably resulted from the delay of delivery of the lymphatic and venous return and the arterial embolization. 1 year after the operation, the patient is very well and there has been no recurrence.

Phosphazene-catalyzed intramolecular cyclization of nitrogen-tethered alkynyl esters.

Intramolecular cyclization of nitrogen-tethered alkynyl esters catalyzed by phosphazene organosuperbases P2-tBu and P4-tBu was investigated. Both acyclic and cyclic substrates underwent 5-exo-dig and 5-endo-dig cyclization. This reaction is a rare example of the intramolecular addition of enolates of simple esters to alkynes.

Features of pedestrian behavior in car-to-pedestrian contact situations in near-miss incidents in Japan.

OBJECTIVE: The objective of this study is to evaluate the severe conditions between car-to-pedestrian near-miss situations using pedestrian time-to-vehicle (pedestrian TTV) which is the time when the pedestrian would reach the forward moving car line. METHODS: Since the information available from the real-world accidents was limited, the authors focused on the near-miss situations captured by driving recorders installed in passenger cars. In their previous study, the authors found there were some similarities between accidents and near-miss incidents. It was made clear that the situations in pedestrians' accidents could be estimated from the near-miss incident data which included motion pictures capturing pedestrian behaviors. In their previous study, the vehicle time-to-collision (vehicle TTC) was investigated from the near-miss incident data. The authors analyzed data for 101 near-miss car-to-pedestrian incident events in which pedestrians were crossing the roads in front of a forward-moving car at an intersection or on a straight road. Using a video of near-miss car-to-pedestrian incidents captured by drive recorders and collected by the Society of Automotive Engineers of Japan (J-SAE) from 2005 to 2009, the pedestrian TTV was calculated. Based on the calculated pedestrian TTV, one of the severe conditions between car-to-pedestrian near-miss situations was evaluated for pedestrians who emerged from behind an obstruction such as a building, a parked vehicle and a moving vehicle. RESULTS: Focusing on the cases of the pedestrians who emerged from behind an obstruction, the averages of the vehicle TTC and pedestrian TTV were 1.31 and 1.05 seconds, respectively, and did not demonstrate a significant difference. Since the averages of the vehicle TTC and pedestrian TTV were similar, there would be a higher possibility of the contact between a car and pedestrian if the driver and pedestrian were not paying any attention. CONCLUSIONS: The authors propose that a moving speed of a pedestrian surrogate "dummy" should be determined considering the near-miss incident situations for the evaluation of a CDMBS for pedestrian detection. The authors also propose that the time-to-collision of the dummy to the tested car during the evaluation of the performance of the CDMBS for pedestrian detection should be determined considering the time such as the vehicle TTC in this study. Additionally or alternatively, the pedestrian TTV should be considered, in which the worst situation was assumed for a car that was moving toward a pedestrian without braking due to the car driver's inattentiveness and the pedestrian not slowing down their walking speed or stopping.

Risks of pedestrian serious injuries and fatalities associated with impact velocities of cars in car-versus-pedestrian accidents in Japan.

The first purpose of this study is to clarify the relation between the car impact velocity and pedestrian injury severity or mortality risk. We investigated the frequency of serious injuries and fatalities of pedestrians using vehicle-pedestrian accident data from the database of the Institute for Traffic Accident Research and Data Analysis (ITARDA) in Japan. The vehicle types considered are sedans, minivans, and box vans (ordinary automobiles) and light passenger cars and light cargo vans (light automobiles). The results revealed that a 10-km/h reduction in impact velocity could mitigate severe pedestrian injuries in cases involving impact velocities of 40 km/h or more for the five vehicle types analyzed. Specifically, if the impact velocity was 30 km/h or less, the frequency of serious injuries was less than 27% and the frequency of fatalities was less than 5% for the five vehicle types. Therefore, if the collision damage mitigation braking system (CDMBS) that uses a sensor to detect pedestrians can effectively reduce the impact velocity for various vehicle types, pedestrian injuries will be greatly mitigated. The second purpose of this study is to identify the factors that affect injury risk. Impact experiments were conducted in which a sedan impacted against a pedestrian full-scale dummy at 40 km/h and a pedestrian headform impactor was impacted against a road surface. The results indicated that the risk of pedestrian serious injury was significantly affected by multiple impact conditions, such as the pedestrian height, car impact velocity, car frontal shape, and car stiffness in cases where the car impacted the pedestrian's head, the degrees of influence of which were driven by the vehicle impact velocity.

Clinical outcomes of single or oligo-fractionated stereotactic radiotherapy for head and neck tumors using micromultileaf collimator-based dynamic conformal arcs.

PURPOSE: To assess the clinical outcomes of single or oligo-fractionated stereotactic radiotherapy (SRT) using dynamic conformal arcs (DCA) for head and neck tumors (HNTs). METHODS: Thirty-four consecutive patients with 35 lesions treated between 2005 and 2009 were retrospectively evaluated, of whom 85.7 % had recurrent or metastatic disease, and 45.7 and 34.3 % had previous radiotherapy and surgery, respectively. The median SRT dose was 22.3 Gy (11.2-32.8) in 2-4 fractions with a median interval of 7 days and 10.4 Gy (9.2-12.4) in one fraction. SRT was combined with upfront conventionally fractionated RT in 48.6 % of patients. RESULTS: The median follow-up periods were 18.4 months (2-84.1) for the entire cohort and 49.6 months for the survivors. The 1- and 2-year local control (LC) rates were 84.3 and 70.5 %, with the 1- and 2-year overall survival (OS) rates of 78.6 and 51.6 %. LC was significantly better for tumor volumes <25.6 cm(3) (p = 0.001). OS was significantly longer in patients without any disease outside the SRT site (p < 0.001), whereas LC after the SRT did not affect the OS. Late adverse events occurred in 9 patients, including cranial nerve (CN) injury (grade 3/4) in 2, brain radionecrosis in 5 (grade 1), and fatal bleeding in 2 patients harboring uncontrolled lesions abutting the carotid artery. CONCLUSIONS: DCA-based SRT can confer relatively long-term LC with acceptable toxicity in selected patients with HNTs. The patients with CN involvement or tumor volume ≥25.6 cm(3) were deemed unsuitable for this treatment regimen.

Kinetic study of proton-transfer reactions of phenylnitromethanes. Implication for the origin of nitroalkane anomaly.

Measurements of rate constants and substituent effects for three important elementary steps of proton-transfer reactions of phenylnitromethane were reported. The Hammett ρ values for the deprotonation of ArCH(2)NO(2) with OH(-), protonation of ArCH═NO(2)(-) with H(2)O, and protonation of ArCH═NO(2)(-) with HCl were determined in aqueous MeOH at 25 °C. Comparison of these experimentally observed ρ values with those calculated at B3LYP/6-31G* revealed that aci-nitro species (ArCH═NO(2)H), which is formed on the O-protonation of ArCH═NO(2)(-), does not lie on the main route of the proton-transfer reaction. Analysis of the Brønsted plot implies that the proton-transfer reaction of most XC(6)H(4)CH(2)NO(2) exhibits nitroalkane anomaly, but not for p-NO(2)C(6)H(4)CH(2)NO(2), and that the transition state charge imbalance is an origin of anomaly.

Osteoarthritis hip joints in Japan: involvement of acetabular dysplasia.

BACKGROUND: We conducted a nationwide epidemiologic study regarding hip osteoarthritis (OA) in Japan, and a previous report found these patients to be unique in comparison to Caucasians. This report focused on the data regarding each hip joint, and the involvement of acetabular dysplasia with hip OA was analyzed. METHODS: Seven hundred twenty OA hips were examined. Sixty-five joints with osteonecrosis of the femoral head and 215 non-OA contralateral joints of the unilateral patients were examined as controls. The revised system of stage classification for hip OA of the Japanese Orthopedic Association (JOA) was used according to the reproducibility in order to ensure reliable data from the multiple institutions. The acetabular dysplasia indexes were also chosen according to the reproducibility and measured in the radiograph of bilateral hip joints. The clinical score was assessed using the JOA scoring system. The relative risk of the grade of acetabular dysplasia indexes for hip OA was calculated as the odds ratio and the 95% confidence interval. RESULTS: The stage of the OA joints deteriorated with increasing age. The clinical scores also decreased. The grade of the acetabular dysplasia indexes of the OA joints was significantly higher than that of the control joints. Each index of acetabular dysplasia demonstrated significantly increased odds ratios for hip OA. Among the OA joints, the deterioration of the OA stage was found to be significantly associated with an increasing grade of acetabular dysplasia. The odds ratio for OA deterioration in the acetabular dysplasia index was also obtained. The joints of females tended to have a higher grade and prevalence of acetabular dysplasia than those of males. CONCLUSIONS: These findings confirmed a high prevalence of acetabular dysplasia in hip OA joints in Japan. Acetabular dysplasia was one of the most important factors associated with hip OA.

Enantioselective direct vinylogous Michael addition of functionalized furanones to nitroalkenes catalyzed by an axially chiral guanidine base.

The highly syn-diastereo- and enantioselective direct vinylogous Michael addition of α-thio substituted furanones with conjugate nitroalkenes was demonstrated using an axially chiral guanidine base catalyst. The method provides facile access to enantioenriched α,γ-functionalized butenolides that can be further manipulated, thereby rendering them useful synthetic intermediates.

Analysis of interobserver reliability for radiographic staging of coxarthrosis and indexes of acetabular dysplasia: a preliminary study.

BACKGROUND: We are planning a multicenter survey on coxarthrosis and acetabular dysplasia in Japan. To collect reliable data, we performed a preliminary study to elucidate the observer agreement on assessment items. METHODS: We collected radiographs of hip joints in eight patients with various findings of coxarthrosis. Twelve registered orthopedic specialists evaluated them regarding the roentgenographic stage of coxarthrosis and five indexes of acetabular dysplasia (acetabular angle, center-edge angle, acetabular roof obliquity, acetabular head quotient, approximate acetabular quotient). To assess observer agreement, we calculated the value of the kappa statistic for stages and the coefficient of variation for the indexes. The same 12 specialists then assessed the coxarthritis stage on the same radiographs 1 month after the first evaluation based on our own descriptions of the roentgenographic stages. RESULTS: For the first evaluation of the roentgenographic stage, the value of the kappa statistic was 0.448; and for the second evaluation it was 0.600. The results of the coefficient of variation for the indexes of acetabular dysplasia, ranked in ascending order, were as follows: acetabular angle, acetabular head quotient, acetabular roof obliquity, center-edge angle, approximate acetabular quotient. CONCLUSIONS: For the upcoming multicenter survey, clear descriptions of the stages of coxarthrosis and selection of appropriate indexes can be helpful for collecting dependable results.

Hydraulic tomography for detecting fracture zone connectivity.

Fracture zones and their connectivity in geologic media are of great importance to ground water resources management as well as ground water contamination prevention and remediation. In this paper, we applied a recently developed hydraulic tomography (HT) technique and an analysis algorithm (sequential successive linear estimator) to synthetic fractured media. The application aims to explore the potential utility of the technique and the algorithm for characterizing fracture zone distribution and their connectivity. Results of this investigation showed that using HT with a limited number of wells, the fracture zone distribution and its connectivity (general pattern) can be mapped satisfactorily although estimated hydraulic property fields are smooth. As the number of wells and monitoring ports increases, the fracture zone distribution and connectivity become vivid and the estimated hydraulic properties approach true values. We hope that the success of this application may promote the development and application of the new generations of technology (i.e., hydraulic, tracer, pneumatic tomographic surveys) for mapping fractures and other features in geologic media.

Insufficiency fracture in the medial wall of the acetabulum after total hip arthroplasty.

Insufficiency fracture following total hip arthroplasty (THA) frequently occurs in the superior and inferior pubic ramus, the puboischial rami, or the ischium around the obturator foramen, while it rarely occurs in the medial wall of the acetabulum. Here, we report three cases showing insufficiency fracture in the medial wall of the acetabulum following THA. In our three cases, two fractures resulted from the development of bone fragility due to osteolysis at the prosthesis site, and the convergence of mechanical stress on the acetabular load bearing point due to loosening of the cup. We consider it appropriate to describe these fractures as another entity of stress fracture, namely, osteolytic fracture, rather than either pathologic fracture or insufficiency fracture.

[Controversial points in cochlear implantation for patients with cochlear otosclerosis].

Most cases of otosclerosis show pathological changes only around the oval window. On the other hand, it is known that cavernous changes extending to the cochlea induce progressive sensorineural deafness. Three patients with severe bilateral deafness and severe cochlear otosclerosis as diagnosed by CT underwent cochlear implantation. The postoperative hearing abilities were satisfactory in two of the three patients at one year after the operation. However, one patient with advanced otosclerosis suffered from the complication of facial nerve stimulation two months later after the cochlear implantation. His available cochlear implant electrodes gradually decreased due to the facial nerve stimulation and at last the cochlear implant was no longer beneficial for reacquisition of his hearing ability. His CT densitometry revealed marked degradation of the CT value in the cochlear basal turn circumference in comparison with that in other patients showing good courses after the cochlear implantation. In conclusion, a cochlear implant operation is valuable in patients with severe sensorineural deafness with cochlear otosclerosis. However, we should cautious in performing cochlear implantation in patients with severe demineralization of the cochlear optic capsule.

Effects of risedronate on lumbar bone mineral density, bone resorption, and incidence of vertebral fracture in elderly male patients with leprosy.

There is no well-established treatment for osteoporosis in male patients with leprosy, because no clinical trials have examined the efficacy of treatment on bone mineral density (BMD) or fracture incidence in such patients. The purpose of the present study was to evaluate the therapeutic effect on oral administration of risedronate in male osteoporotic patients with leprosy. Twenty-three male patients with leprosy, 63-87 years of age, were randomly divided into two administration groups: R group (risedronate, 2.5 mg/day, daily) and P group (placebo, daily). The BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry, and urinary cross linked N-telopeptides of type I collagen (NTX) were assessed at baseline, 6 months, and 12 months after treatment. There were no significant differences in age, body mass index, BMD, or urinary NTX levels at baseline between the two groups. In the present study, oral administration of risedronate apparently prevented vertebral fractures by increasing lumbar BMD and caused a significant reduction in urinary NTX levels, while oral administration of placebo did not increase the lumbar BMD and prevent vertebral fractures due to osteoporosis. The above findings suggested that oral administration of risedronate contributed to the prevention of vertebral fractures by suppressing bone resorption and increasing in lumbar BMD in the elderly male patients with leprosy.

Trochanteric hip fracture in an elderly patient with leprosy during osteoporosis treatment with risedronate and alfacalcidol.

There is no well-established treatment for osteoporosis in male patients with leprosy, because no clinical trials have examined the efficacy of treatment on bone mineral density (BMD) or fracture incidence in patients with leprosy. In this study, we report a case of osteoporosis in a man with leprosy, treated by oral administration of risedronate and alfacalcidol. An 82-year-old man with leprosy presented to our hospital with chronic back pain, due to osteoporosis, in July 2002. To prevent the progression of osteoporosis, oral administration of risedronate and alfacalcidol was started for this patient. An increase in forearm BMD and a decrease in the level of urinary crosslinked N-telopeptides of type I collagen (NTx) were observed in January 2003. The patient suffered a trochanteric fracture of the proximal femur at the end of March 2003. Surgical treatment with a sliding-screw plate was performed 5 days after the injury. Complete bony union of the right proximal femur was confirmed by radiography in July 2003. The above findings suggested that the treatment with risedronate and alfacalcidol contributed to the increase in BMD; however, the treatment did not prevent fracture due to osteoporosis in this male patient with leprosy.

Ender nailing for supracondylar fracture of the femur after total knee arthroplasty: five case reports.

We studied 5 women with supracondylar fractures after total knee arthroplasty (TKA). The mean age at fracture was 67.4 years. Four patients had chronic rheumatoid arthritis, and 1 had osteoarthritis. The range of motion, knee score, femorotibial angle, and component alignment were investigated. Flexion was slightly decreased after Ender nailing, but extension only changed in 1 patient. The knee score decreased, but all patients were ambulatory. The femorotibial angle changed in all patients. Measurement of femoral component alignment showed a postoperative change of angle alpha (1 degrees to 11 degrees ) and angle gamma (0 degrees to 9 degrees ). Union was achieved in all patients. Ender nailing is an acceptable method of treatment for supracondylar fractures of the femur after TKA if the nails can be inserted deeply into the femoral condyles.

Aorsin, a novel serine proteinase with trypsin-like specificity at acidic pH.

A proteinase that hydrolyses clupeine and salmine at acidic pH, called aorsin, was found in the fungus Aspergillus oryzae. Purified aorsin also hydrolysed benzyloxycarbonyl-Arg-Arg-4-methylcoumaryl-7-amide optimally at pH 4.0. The specificity of aorsin appeared to require a basic residue at the P(1) position and to prefer paired basic residues. Aorsin activated plasminogen and converted trypsinogen to trypsin. The trypsin-like activity was inhibited strongly by antipain or leupeptin, but was not inhibited by any other standard inhibitors of peptidases. To identify the catalytic residues of aorsin, a gene was cloned and an expression system was established. The predicted mature protein of aorsin was 35% identical with the classical late-infantile neuronal ceroid lipofuscinosis protein CLN2p and was 24% identical with Pseudomonas serine-carboxyl proteinase, both of which are pepstatin-insensitive carboxyl proteinases. Several putative catalytic residues were mutated. The k (cat)/ K(m) values of the mutant enzymes Glu(86)-->Gln, Asp(211)-->Asn and Ser(354)-->Thr were 3-4 orders of magnitude lower and Asp(90)-->Asn was 21-fold lower than that of wild-type aorsin, indicating that the positions are important for catalysis. Aorsin is another of the S53 family serine-carboxyl proteinases that are not inhibited by pepstatin.

Femoral shaft fracture callus formation after intramedullary nailing: a comparison of interlocking and Ender nailing.

Intramedullary nailing is widely used for the operative treatment of femoral fractures. Recently, the biologic healing of fractures has become better understood from fundamental investigations. However, there has been no clinical comparison between the fracture healing process with these two fixation methods. The purpose of this study was to use radiographs to compare callus formation with two types of intramedullary nailing for femoral shaft fractures: reamed interlocking (IL) nails and Ender nails. Femoral shaft type A fractures (AO classification) were studied. Twenty-seven fractures were treated with reamed IL nailing, and 81 fractures were treated with Ender nailing. The callus area was calculated from the maximum cross-sectional area on the anteroposterior and lateral radiographs. The callus appeared at a mean of 3.9 weeks after surgery in the IL group, and at a mean of 2.8 weeks in the Ender group ( P < 0.05). In the IL and Ender groups, fracture healing was noted at a mean of 3.4 and 2.0 months, respectively. The mean area of callus formation in the IL and Ender nailing groups was 439.5 mm(2) and 699.4 mm(2), respectively ( P < 0.02). Ender nailing results in abundant callus, which forms at an earlier stage after the procedure than in patients treated with IL nailing. Dynamization at the fracture site is reported to increase external callus formation. Our results indicate that the elasticity of the fixation obtained with Ender nailing promotes callus formation.