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Purpose: It is well known that there is a trade-off relationship between image noise and exposure dose in X-ray computed tomography (CT) examination. Therefore, CT dose level was evaluated by using the CT image noise property. Although noise power spectrum (NPS) is a common measure for evaluating CT image noise property, it is difficult to evaluate noise performance directly on clinical CT images, because NPS requires CT image samples with uniform exposure area for the evaluation. In this study, various noise levels of CT phantom images were classified for estimating dose levels of CT images using convolutional neural network (CNN)., Method: CT image samples of water phantom were obtained with a combination of mAs value (50, 100, 200 mAs) and X-ray tube voltage (80, 100, 120 kV). The CNN was trained and tested for classifying various noise levels of CT image samples by keeping 1) a constant kV and 2) a constant mAs. In addition, CT dose levels (CT dose index: CTDI) for all exposure conditions were estimated by using regression approach of the CNN., Result: Classification accuracies for various noise levels were very high (more than 99.9%). The CNN-estimated dose level of CT images was highly correlated (r=0.998) with the actual CTDI., Conclusion: CT image noise level classification using CNN can be useful for the estimation of CT radiation dose.

In patients with cancer, it is difficult to continue medical treatment owing to nausea and vomiting (NV). Therefore, it is important to avoid these problems for improving the patient's QOL. Rikkunshito extract (RK) possesses antiemetic effects and is used in combination in cancer therapy. However, patients with cancer find it difficult to take the medicine orally for the treatment of NV and anorexia owing to the characteristic smell and taste of traditional Chinese medicine. We examined the pharmaceutical properties of RK suppository for hospital use, assessed bioequivalence by using pharmacokinetic parameters, and determined its effectiveness against NV and anorexia in rats. In this study, RK suppository was prepared by using RK formulation (A, B, and C) and Witepsol (H and S) (AH, BH, CH, AS, BS, and CS). Pharmaceutical properties, namely, hardness, dispersibility, long-term stability, and drug (hesperidin and glycyrrhizic acid) release were measured for AH, BH, AH, and AS. The pharmacokinetic parameters, effectiveness of substance P against NV and anorexia, and serotonin-activated ghrelin levels were assessed for BH only. AH, BH, AS, and AS demonstrated uniform and sufficient hardness. The release rate of oleaginous components, such as glycyrrhizic acid, did not change significantly, while that of water soluble components, such as hesperidin, decreased when compared with that in powder formulations A and B. NV and anorexia improved in rats administered BH compared with the control group. BH suppository showed effectiveness in terms of both physicochemical property and bioequivalence for hospital use.

A generic drug is defined as a drug product that is comparable to a brand name drug in terms of dosage, form, strength, route of administration, quality, performance characteristics, and indicated use. Generic drugs for topical use, in the case of sheet-like products, are required to be the same as the original drug in terms of application area and dosage form. The composition of such generic drug formulations may differ from that of the original product. The adhesive of any pharmaceutically-active tape that directly contacts the skin plays a role in delivering the active ingredient into the skin, and affects the sensation and ease of handling. Therefore, adhesives are an important ingredient in these products. Thus, the aim of this study was to characterize original and generic lidocaine tape products, and to evaluate the adhesive properties of each. The tack force, peel strength and shear adhesion were measured as adhesive properties. In addition, in vitro drug releasing profiles and skin permeation profiles of the products were evaluated. In vivo transdermal absorption was also evaluated to predict the possibility of adverse effects. Adhesive properties differed among the three analyzed products. These differences may have been caused by differences in the adhesives. Drug-releasing profiles and skin permeation profiles also differed among the three products, even though the pharmacokinetics were not significantly different. By obtaining an adequate understanding of the characteristics of original and generic products, we will be able to provide better tailor-made medications for drug therapies for patients.

Transdermal Drug Delivery Systems (TDDS), where active drugs must be absorbed into the systemic circulation after penetrating the skin barrier, were first launched in 1979, and about 10 TDDS containing different kinds of drugs were developed during the initial decade. Interestingly, a developmental rush has come again in the present century. Various penetration-enhancing approaches to improve drug permeation of the skin (stratum corneum) have been attempted. These approaches are of two types: chemical and physical. Examples of the chemical approach are enhancers such as alcohol, monoterpenes and fatty acid esters, as well as chemical modification of prodrugs. In contrast, physical approaches include the use of electrical-, thermal- and mechanical-energy, as well as microneedles, needle-free injectors or electroporation to completely or partially evade the barrier function in the stratum corneum. The chemical approaches are mainly effective in increasing the skin permeation of low-molecular chemicals, whereas physical means are effective for these chemicals but also high-molecules like peptides, proteins and nucleotides (DNA or RNA). Marked development has been observed in these physical means in the past decade. In addition, recent developments in tissue engineering technologies enables the use of cultured skin containing keratinocytes and fibroblasts as a TDDS. An effective "cell delivery system" may be a reality in the near future. This paper will look back on the 30-year history of TDDS and evaluate the feasibility of a new generation of these systems.

Neuro-Behçet disease (NBD) can be categorized clinically as the acute type--characterized by meningoencephalitis--and the chronic progressive type- characterized by slowly progressive dementia, ataxia, and dysarthria. We describe a 35-year clinical course of NBD that was characterized by slowly progressive ataxia and dysarthria despite continued corticosteroid treatment. Because of difficulties in swallowing, which interrupted oral corticosteroid therapy, this case was characterized by recurrent manifestations of neurological symptoms and abnormal MRI findings. Resumption of corticosteroid therapy was effective. The patient was a 77-year-old woman who had presented with oral ulceration and dysarthria at the age of 42. She suffered from Entero-Behçet disease at the age of 52 and was treated with corticosteroids for 7 years. Oral corticosteroid therapy was resumed at the age of 64, but her neurological deficit slowly progressed and she developed paraplegia with dysphagia and dysarthria. Corticosteroids treatment was interrupted when she was 76; one year later, she was hospitalized in a state of somnolence. Brain MRI scans revealed new lesions with gadolinium enhancement. We diagnosed acute exacerbation of NBD attacks on the basis of positive findings for HLA-B51, protein elevation, and IL-6 in the cerebrospinal fluid. Corticosteroid treatment was effective. She became alert, and her MRI findings were no longer abnormal. Corticosteroids administration was continued via percutaneous endoscopic gastrostomy. Our case suggested that even if neurological exacertion is not obvious during the clinical course, immunosuppressive therapies should be continued for patients with chronic NBD to prevent acute aggravation.

Respiratory insufficiency is a problem that develops in nearly all people diagnosed with amyotrophic lateral sclerosis (ALS). A 46-year-old man with ALS, who had been in a bedridden state with tracheal ventilation support, complained of faintness and dyspnea. The airway pressure of the ventilator had increased, and bleeding from the trachea had occurred several times. A fiberoptic bronchoscopy showed granulation located on the anterior wall of the trachea and severe airway obstruction of the tracheostomy tube. Although a long tracheostomy tube had been intubated for the initial management of the tracheal granulation, a tumor on the posterior tracheal wall had relapsed and occluded the tracheal lumen. A self-expandable metallic airway stent was placed into the tracheal stenosis. After stenting, his symptoms of dyspnea and syncope imploved, and the increased airway pressure of the ventilator was normalized. We speculated that the tracheal granuloma had occurred due to a tracheal mucosal injury related to endotracheal suctioning. We should pay attention to complaints of dyspnea in ALS patients with tracheostomy and make a careful consideration to airway care including suction management.

Objective: To determine which of the three motor functions (bulbar, upper extremities, lower extremities) was normally preserved at the time that respiratory symptoms occurred in amyotrophic lateral sclerosis (ALS)., Background: Respiratory failure is the major cause of death in ALS. The course of the disease progression to the onset of subjective respiratory symptom can vary from patient to patient and the diversity of this progression in ALS patients is not well understood., Patients/methods: The subjects were 120 Japanese patients with sporadic ALS who were followed-up at our hospital or for whom precise information was available regarding death or the time that the patient required tracheotomy or ventilation assistance. Symptoms started: in the upper limbs in 47 patients; in the lower limbs in 44 patients; in the bulbar region in 22 patients; as the combined type (two regions involved simultaneously on initial presentation) in 6 patients; and with respiratory symptoms in 1 patient., Results: At the time of the appearance of respiratory symptoms, 43 patients (35.8%) had some normally preserved motor function. Significantly fewer patients with progressive bulbar palsy maintained one or more normal motor functions (14%) compared to patients whose disease started in the extremities (43%). Patients were divided into two groups depending on whether they had significant bulbar involvement at the time of the appearance of respiratory symptoms: 88 patients had significant bulbar involvement (B type), and 32 patients did not (R type). Based on the Kaplan-Meier survival curves, no significant difference in the median survival time was noted between the two groups (R type, 29.4 months vs. B type, 32.5 months; p = 0.06). We could not find any difference about clinical characteristics such as gender, onset age, initial site between R and B group. The motor functions that were preserved at the time of respiratory symptom onset included: bulbar function in 32 patients (26.7%); lower extremity function in 12 patients (10%); and upper extremity function in only 3 patients (2.5%). The use of mechanical ventilation in ALS patients with one or more preserved motor functions was significantly higher than in those without any normally preserved motor function (p = 0.03)., Conclusions: From a low rate of upper extremity motor function preservation, respiratory function deterioration appears to be related to upper-limb involvement, likely due to a possible link to diaphragmatic function. Advanced directives should carefully address the use of mechanical ventilation in patients without bulbar symptoms.

Although Japanese encephalitis virus is mainly associated with encephalitis, it does cause other diseases. However, descriptions of symptomatic infections other than encephalitis are limited. In this study, cerebrospinal fluid (CSF) specimens from 21 patients with aseptic meningitis from July to October (in summer season) in each year from 1993 to 2005 were investigated for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified by nested polymerase chain reaction (PCR). Among the specimens, only one product had highest homology with Japanese encephalitis virus genotype III. The patient was a 34-year-old man who complained of headache and fever in July 1998. He was clinically diagnosed with aseptic meningitis, and the symptoms subsided spontaneously without specific treatment in several days. It is suggested that some cases of aseptic meningitis in summer could be caused by Japanese encephalitis virus.

We reported a 52-year-old woman with oculopharyngeal muscular dystrophy (OPMD) harboring expanded (GCG) 13 mutation of the poly (A) binding protein 2 gene. She presented not only ptosis and dysphagia but distal dominant muscle atrophy in four extremities. CT demonstrated distal muscle atrophy with marked fat replacement in the biceps femoris, semitendinosus, membraneous, soleus, and gastrocnemius muscles. Although OPMD is considered to be a muscle disease, this patient showed even neurogenic features in the electrophysiological and pathological findings. Although previous reports indicate that OPMD is genetically homogeneous disease, some cases with OPMD may show some atypical features associated with neurogenic involvement.

Objective: To define changes of clinical features in amyotrophic lateral sclerosis (ALS) over the past 20 years and prognostic indicators of ALS from a single hospital-based retrospective survey., Background: One of the important tasks in ALS research is to determine differences between patients who progress at different rates. Predicting survival time in ALS helps both physicians and patients to make decisions regarding assisted ventilation., Patients/methods: A total of 100 patients (61 men, 39 women) hospitalized between 1980 and 2000 were investigated in the study. Subjects were divided into Groups A and B (Group A: n = 50, diagnosed between 1990 and 2000; Group B: n = 50, diagnosed between 1980 and 1990). Group C comprised 34 patients supported by artificial ventilation between 1980 and 2000. Information was obtained for all patients regarding time of individual primary end-point (PEP, time of death or required ventilation support), secondary end-point (SEP, time of death after artificial ventilation) or being alive with or without ventilation support. Combined type of ALS was defined as two or more regions presenting simultaneously at initial onset. Progression rate was calculated as the time (months) required for a 1-point loss on the ALS functional rating scale (ALS-FRS), using 1/delta FS:1/delta FS = duration (months) from onset to diagnosis/(48-ALSFRS at diagnosis), Results: Mean age at onset has increased in the past 20 years from 59.4 years (group B) to 62.5 years (group A). An increased incidence has been observed in the patients over 70 years with ALS (A:n = 8 vs. B:n = 4). The frequency of assisted ventilation support had been significantly increased for 22 of 44 group A patients (50%) including 5 patients supported by non-invasive positive pressure ventilation, compared to 12 of 48 group B patients (25%, P < 0.01). Two patients in group B and 6 patients in group A who were still alive at time of the investigation were excluded. Mean interval between symptom onset and diagnosis was 14.7 months (A:14.0 months; B:15.4 months). No differences were observed between groups A, B and C regarding sex ratio, mean total ALS-FRS score at diagnosis. Mean survival times were as follows obtained from Kaplan-Meier survival curves; group A:30.8 months, group B:31.0 months until the time of PEP, group C:67.2 months until the time of SEP. Symptoms started in the upper limbs (U) in 37 patients, in the lower limbs (L) in 34, in the bulbar region (B) in 19, as combined type in 9 and in respiratory muscles in 1. Mean survival time until PEP was 33.9 months for U, 34.8 months for L, 28.6 months for B and 18.2 months for C (P < 0.001). Combined-type patients with ALS revealed shorter the time until diagnosis (*P < 0.01) and faster the time until PEP than the other ALS types (P < 0.001 Log-rank test). A significant correlation was found between 1/delta FS and the time until PEP (y = 9.64x + 12.6, r2 = 0.545, p < 0.001, y = PEP, x = 1/delta FS)., Conclusions: Combined type ALS displayed significantly shorter time to PEP than other types. ALS outcome was significantly related to the progression rate of symptoms from total score for ALS-FRS at time of diagnosis.

We report a case of intracerebral pneumocephalus following a head injury. This condition is relatively rare, and only 14 cases, including the present case, have been reported to data. A 40-year-old man fell from a 3rd floor window on June 29, 1999. The patient was admitted to the hospital. Plain skull X-ray films revealed a left basal skull fracture, and CT scan revealed a small contusion at the left frontobasal lobe. The patient was treated conservatively. On July 16, he underwent an MRI, and a small contusion was revealed at the left frontobasal lobe. In addition, the brain appeared to have herniated into the ethmoidal sinus. On July 22, the patient underwent a CT scan, and a intracerebral pneumocephalus was revealed in the left frontal lobe. On August 2, an MRI was performed, and intracerebral pneumocephalus in the left frontal lobe and herniation of the brain into the ethmoidal sinus were noted. In addition, intracerebral pneumocephalus had increased. The patient was admitted to our hospital. Clinotherapy was performed, but intracerebral pneumocephalus increased. On August 9, the patient underwent surgery to repair the skull base. During surgery, it was noted that the left frontal contusion had adhered to the edge of the lacerated dura around the bone defect of the ethmoidal sinus. Following surgery, no recurrence of pneumocephalus was noted. We conclude that once intracerebral air volume increases, early surgical repair should be carried out for intracerebral pneumocephalus. Meticulous MRI investigations of the lesion causing the intracerebral pneumocephalus should be conducted to select an appropriate operative procedure.

We studied that the morphological and histological characteristics, and the content (%DW) of saikosaponins on the root of Bupleurum falcatum cultivated in an Ebb & Flood system (E & F), a kind of soilless culture system, by both the direct sowing and the transplanting methods, and that effects of pinching on the root growth and the content (%DW) of saikosaponins in each part of root. Yield of root and content (%DW) of saikosaponins in each part of root, 8-months-old, cultivated in E & F by both methods were at the same level as that cultivated for the same period in soil condition by generally standard procedures. Morphological characteristics of the root cultivated by the direct sowing method were the same appearance as that by soil condition, but by the transplanting method main root branched off in all direction and the lateral root were more developed than by the direct sowing method. By pinching lignification in xylem on the main root were inhibited, but the dried weight of total root part and content (%DW) of saikosaponins in each part of the root were not shown to be significantly changed.

One hundred patients with carcinoma of the urinary bladder were treated with preoperative intra-arterial anticancer drug infusion in combination with an active carbon-based artificial liver or preoperative radiotherapy (400 rad X 5 days, total 2000 rad) in order to alleviate systemic side effects after preoperative adjuvant therapy and to perform radical cystectomy as soon as possible. Five-year survival was 69.8% in the artificial liver combined preoperative intra-arterial anticancer drug infusion group, and that of the no-pretreatment group and the preoperative irradiated group was 48.6% and 45.8%, respectively. In particular, the CDDP treated group had a higher 5-year survival of 77.4% than did the without CDDP treated group. This was attributable mostly to improved prognosis of T2, whereas either of these preoperative adjuvant therapies failed to ameliorate the prognosis of T3 or T4 stage patients. Therefore, systemic preoperative anticancer chemotherapies such as M-VAC are necessary to destroy "micrometastases" and to improve the prognosis of highly advanced bladder cancer.

This is a case report involving a 9 year old girl with a teratoma that infaced mainly the bilateral hypothalamus. The girl was observed for 14 months after partial surgical removal. During that time she showed aphagia, adipsia, hypopituitarism, and visual and psychiatric disturbances. Severe hypernatremia also was present, even though large amounts of 5% glucose solution without salt were given I.V. Food and water were given by nasal gastric gavage and later gavage via gastric fistula, but the hypernatremia remained unchanged. When pitressin or spironolacton (anti-aldosterone) were administered, remarkable effect on the hypernatremia couldn't be found. Upon autopsy it was discovered that the bilateral hypothalamus, left subthalamus and ventral part of the thalamus were invaded by teratoma. Comparing many similar clinical reports and manifestations of hypothalamic lesions in experimental animals, it is reasonable to assume that the mechanisms of hypernatremia were caused by the disturbances of ADH secretion, thirst centre and osmoreceptor in the hypothalamus.

We report two cases of heterotopic bone formation in the kidney. One patient was a 54-year-old man who consulted his family physician with the complaint of fever-up and nocturia. X-ray examination revealed a calcification in the left kidney and location of the pelvis for outside. Therefore, abdominal CT scan and selective renal angiography were performed. As a malignant renal tumor with hypovascularity could not be neglected, left nephrectomy was performed on August 18, 1980. Grossly, the resected kidney was 230 g in weight and had a 8 X 3 cm mass with a white cut surface and bone-like tendency. Histopathologically, a well-developed bone with erythropoietic bone marrow was found outside of the renal capsule. The other patient was a 52-year-old man with the complaint of painful swelling of left scrotum and lumbago. X-ray examination revealed bilateral renal stones and left ureteral stone. Bilateral nephrolithotomy and left ureterolithotomy were performed, and some stones and a part of bilateral renal pelvis which was bony hard and white in color were resected. Histopathologically, there were well-developed bone formation and infiltration of inflammatory cells in renal pelvic membrane. Among 36 reported cases in Japan, 16 cases were in male and 20 cases in female patients. Our second case was the first cases of bilateral renal heterotopic bone formation complicated with bilateral renal stones in 5 reported cases with renal stones. Including our first case, 5 cases which had heterotopic bone formation in renal capsule have been reported.

A case of pure choriocarcinoma of the testis in a 62-year-old male is reported. The patient consulted his family physician with an enlarged but painless right scrotal containment in November, 1980. Initial diagnosis was right hydrocele testis and chronic epididymitis, and he was treated with antibiotics. However, the tumor continued to enlarge. Right high orchiectomy was performed on March, 15, 1981 under the diagnosis of suspected right testicular tumor. The resected specimen was 10 X 7 X 6 cm and elastic hard. The cut surface was dark reddish with hemorrhagic foci. Serial sections of the entire testis were made and their histopathological examinations revealed the tumor to be a classical pure choriocarcinoma of the testis. The plasma beta-HCG level was remarkably elevated, but the alpha-fetoprotein level was normal. Anticancer chemotherapy (CDDP 125 mg, MTX 20 mg, ADM 50 mg, and EDX 500 mg) was performed in eight courses after the operation. Multiple metastatic foci were present in both lungs during the treatment, and his condition gradually deteriorated. Therefore, he was transferred to our hospital. Aggressive anticancer treatment could not be given because of his poor general condition, and he died on May, 16, 1982 of carcinomatosis. The autopsy revealed multiple nodular metastasis of the tumor to bilateral lungs, bilateral adrenal glands and right kidney. There was no metastasis to the lymph nodes. The metastatic lesions, macrospically dark reddish with hemorrhagic foci, were histopathologically pure choriocarcinoma.

A case of a 19-year-old male with leiomyosarcoma of the prostate is reported. He visited our hospital with the chief complaint of urinary retention in December, 1983. Following overall examination, needle biopsy of the prostate gland was performed with the suspicion of sarcoma. Histology of the prostate revealed leiomyosarcoma. Two courses of combined chemotherapy were given, but the tumor continued to enlarge. The patient died in April, 1984, 5 months after the appearance of the first symptom.

Aspoxicillin (ASPC), a new injectable penicillin, was administered to 5 healthy male adult volunteers once a day at a daily dose of 4 g for 5 consecutive days to study its absorption and excretion. The results of this study are summarized as follows: 1. In consecutive administration of ASPC for 5 successive days, no remarkable changes were observed in serum concentrations and urinary excretion after each administration of ASPC. Therefore, no tendency of accumulation of the drug was recognized. 2. The serum ASPC concentration showed its peak values ranged from 212.3 to 224.8 micrograms/ml at completion of the intravenous drip infusion of ASPC. 3. Urinary recovery rates of ASPC ranged from 70 to 80%. 4. There were neither abnormal findings in subjective and objective symptoms nor abnormal values in physical and clinical laboratory test due to the administration of ASPC.

Computerized tomography accidentally revealed a huge retroperitoneal mass in a 53-year-old male. The mass was located between the liver and the right kidney. Laboratory tests including endocrinological studies were done but the diagnosis was not clearly confirmed before operation. The specimen weighed 410 g, was 12.5 X 8 X 5 cm and did not show any evidence of malignant degeneration histologically. Fourteen cases of the ganglioneuroma of the adrenal gland including our were accumulated from the Japanese literature. A review of the literature showed that cases of this tumor widely ranged from 1 to 65 years of ages, and its incidence was over twice higher in females than in males. Mainly the abdominal mass was the only symptom in these cases. The tumors were generally so well encapsulated that they could be removed completely.