Application of diffusion tensor imaging for the diagnosis of segmental level of dysfunction in cervical spondylotic myelopathy.

STUDY DESIGN: A retrospective study. OBJECTIVES: Diffusion tensor imaging (DTI) reflects pathological change in the spinal cord more sensitively than conventional magnetic resonance imaging (MRI). Electrophysiological examination enables quantitative assessment of spinal cord function. Few studies have addressed the correlation between intraoperative spinal cord-evoked potentials (SCEPs) and DTI. The purpose of this study was to examine whether DTI is an objective index for the diagnosis of the segmental level of dysfunction in cervical spondylotic myelopathy (CSM). SETTING: Yamaguchi University Graduate School of Medicine, Japan. METHODS: Using 3.0-Tesla MRI, DTI values for the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured at the disc level C2/C3 through C6/C7 in 11 normal subjects and 10 subjects with CSM. Subjects with CSM were divided into two groups based on the extent of compression according to conventional MRI: single level (n=3) and multilevel (n=7). Intraoperative SCEPs were measured in subjects with CSM. For each group, the ADC and FA values were compared with SCEPs with respect to the segmental levels of dysfunction. RESULTS: For all three subjects with single-level compression and six of seven with multilevel compression, the maximal ADC value was observed at the segmental level of dysfunction as per the SCEP. Minimum FA values were observed at those sites in two of three patients with single-level compression and in only two of seven with multi-level compression. CONCLUSION: Our results suggest that ADC might serve as a supplementary diagnostic indicator of the segmental levels of dysfunction in CSM.

Characteristics of C6-7 myelopathy: assessment of clinical symptoms and electrophysiological findings.

STUDY DESIGN: This is a single-center retrospective study. OBJECTIVES: The objective of this study was to study the clinical symptoms and electrophysiological features of C6-7 myelopathy. SETTING: This study was conducted at the Department of Orthopedic surgery, Yamaguchi University Graduate school of medicine, Japan. METHODS: A total of 20 patients with cervical compressive myelopathy were determined by spinal cord-evoked potentials or a single level of obvious magnetic resonance imaging (MRI)-documented cervical spinal cord compression. Neurological examinations included manual muscle testing and investigation of deep tendon reflex, including Hoffmann sign, and of sensory disturbance areas. Motor-evoked potentials (MEPs), compound muscle action potentials (CMAPs) and F-wave were recorded from bilateral abductor digit minim and abductor halluces muscles. Central motor conduction time was calculated as follows: MEPs latency-(CMAPs latency+F latency-1)/2 (ms). RESULTS: Eighteen patients (90%) had negative Hoffmann sign. Eight patients (40%) had no sensory disturbance in the upper limbs and 8 patients (40%) had no muscle weakness in the upper limbs. We determined that patients had cervical myelopathy when their central motor conduction time measured in abductor digit minim was longer than 6.76 ms (+2 s.d.). Using this definition, the sensitivity for myelopathy was 42.8%. CONCLUSION: Patients with C6-7 myelopathy may lack clinical symptoms in their hands and central motor conduction time measured in abductor digit minim tended to be less prolonged, and it only showed symptoms in their lower limbs as gait disturbance. Surgeons should bear in mind the possibility of disorders of caudal C6-7 when they encounter patients with no or few symptoms in their hands and with leg weakness or numbness.

Preoperative diagnosis of the responsible level in CCM using CMAPs: comparison with SCEPs.

STUDY DESIGN: A retrospective study. OBJECTIVE: To elucidate the correlation between compound muscle action potentials (CMAPs) amplitudes and responsible level of compressive cervical myelopathy (CCM), and the accuracy of level diagnosis by using CMAPs. SETTING: This study was conducted at the Department of Orthopedic surgery, Yamaguchi University Graduate School of Medicine, Japan. METHOD: A total of 28 patients with CCM were investigated in this study. Erb's point-stimulated CMAPs were measured from deltoid, biceps, triceps in all patients as compared with 88 healthy subjects. We performed a level diagnosis on the basis of CMAPs amplitudes. We performed a level diagnosis on the basis of CMAPs amplitudes and using an index that measures the deviation of CMAPs amplitudes between triceps and deltoid or biceps. RESULTS: Significant correlations between the mean CMAPs amplitudes and responsible level were showed for deltoid (6.82±2.33 mV) at C3/4 (P<0.01) and biceps (8.75±4.42 mV) at C4/5 (P=0.015). Despite considerable individual variability in CMAP amplitudes, there were correlations among CMAPs amplitudes for deltoid, biceps and triceps in the same individual. The sensitivity was 75.0%, specificity 75.0% in the index for diagnosis of C3/4. The sensitivity was 75.0%, specificity 66.7% in the index for diagnosis of C4/5. CONCLUSION: This study showed small CMAPs amplitudes in the deltoid indicated a C3/4 level of myelopathy and in biceps at the C4/5 level and could help exclude clinically silent cord compression and determine the surgical procedure to the suitable level of concern.

Relative vulnerability of various spinal tracts in C3-4 cervical spondylotic myelopathy: multi-modal spinal cord evoked potentials.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the progression of spinal tract lesions in cervical spondylotic myelopathy (CSM) at C3-4 intervertebral level using spinal cord-evoked potensials (SCEPs). SETTING: This study was conducted at the Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Japan. METHODS: A total of 30 patients with CSM were investigated in this study. In all patients, only the C3-4 intervertebral level was symptomatic, as shown by examination of SCEPs. SCEPs were recorded following median nerve stimulation (MN-SCEPs), transcranial electric stimulation (TES-SCEPs) and spinal cord stimulation (spinal-SCEPs). RESULTS: The incidence of abnormalities varied in the order of MN-SCEPs (100%), TES-SCEPs (90%) and spinal-SCEPs (67%). Patients were grouped into three types according to SCEPs: transverse (all SCEPs abnormal), post-erolateral (abnormalities in the MN-SCEPs and TES-SCEPs) and upper limbs sensory (abnormal only for MN-SCEPs). In all, 20 of the 30 patients (67%) were the transverse type, 7 (23%) the post-erolateral type and 3 (10%) the upper limbs sensory type. CONCLUSION: The present study showed the lateral part of the posterior funiculus mediating upper limb sensory function was more vulnerable than the lateral corticospinal tract, which is consistent with numbness tending to appear at an early stage of mild CSM.

EVALUATIONS OF INVENTORY AND ACTIVITY CONCENTRATION OF RADIOCESIUM IN SOIL AT A RESIDENTIAL HOUSE 3 YEARS AFTER THE FUKUSHIMA NUCLEAR ACCIDENT.

Soil samples from the surface to a 5 cm depth were collected at a residential house in Koriyama City, Fukushima Prefecture using a scraper plate every three months from March 2014 to September 2014 to evaluate the vertical distribution profiles and inventories of 134Cs and 137Cs in soil. The vertical distribution profiles of radiocesium (134Cs and 137Cs) in soil showed that greater than 86% of the total radiocesium was absorbed in the upper 2 cm 3 years after the accident. Radiocesium in the surface layer seems to move to the lower layer over time. The migration of radiocesium in surface layer might be influenced by the ground surface runoff by rainfall. Radiocesium inventories in June increased significantly over the short period between March and June. In contrast, the radiocesium inventories in September did not increase significantly compared to the values in June. Radiocesium resuspension and deposition caused by decontamination work and meteorological events might be one possible reason for the increased radiocesium inventories observed in June.

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue.

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose of 3000 rad was performed. On the 11th day, tumor cells and mononuclear cells, which were separated from the low-dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunotherapy.

Expression of cell cycle regulator genes in KB, a human squamous cell carcinoma cell line, after irradiation.

DNA damage induced by irradiation causes overexpression of the p53 gene, and subsequently the upregulation of p53 downstream genes involved in cell cycle modification. Irradiated malignant cells which possess wild-type p53 have been known to undergo G1 arrest due to p21/Cip1/Waf1 upregulation. Other p53 downstream genes related to the modification of the cell cycle such as gadd45 may cause G2 arrest. Many of the genes which regulate the cell cycle progression have been identified, including the G1 phase specific ink4 family of cyclin-dependent kinase inhibitors (CDK-I), another group of CDK-Is, which affect the cyclin-CDK complexes ubiquitously, and S/G2 accelerator genes. The sequential changes in these cell cycle regulator genes after irradiation has not been clarified. We analyzed the appearance of the apoptotic fraction and cell cycle perturbation after irradiation using KB, a human squamous cell carcinoma line derived from oral floor, and examined the alteration of gene expression for cell cycle regulator genes. The KB cells proceeded to undergo apoptosis in a time and dose dependent manner after irradiation and showed G2 arrest accompanied by upregulation of p53, ubiquitous CDK-Is, and S and G2 accelerator genes.

The relative biological effectiveness of 10B-neutron capture therapy for early skin reaction in the hamster.

The relative biological effectiveness (RBE) of 10B-neutron capture therapy (BNCT) on skin was analyzed using hamsters. The Kyoto University Research Reactor, which has a very low contamination of gamma rays and fast neutrons, was used as a thermal neutron source. Boron-10-para-boronophenylalanine hydrochloride ([10B]BPA.HCl) was administered to the hamsters. The evolution and time course of early skin reactions were assessed. These reactions were compared with those produced by electron beams. The maximum safe skin doses (no more than moist desquamation) of BNCT and electron beams were established to be 11 and 21 Gy, respectively. The RBE at this single dose with BNCT was found to be 1.94, assuming that the RBE of the gamma rays was 1.0 and each component of BNCT (mixed radiations) was simply additive.

Acquired cutis laxa concomitant with nephrotic syndrome.

A 41-year-old woman developed laxity and wrinkling of the skin. This process spread slowly to involve the skin of almost the entire body, without any previous inflammatory skin disorder. The skin of her face, neck, and trunk hung in loose folds, leading to a prematurely aged appearance. One year later she noticed edema on her face and legs. Laboratory studies disclosed low C3 and CH50 serum levels and proteinuria. Skin biopsy specimens revealed extensive loss and fragmentation of dermal elastic fibers. A renal biopsy specimen showed membranoproliferative glomerulonephritis (type 2), and an immunofluorescent study disclosed C3 and IgG deposition in the mesangial matrix and along the glomerular basement membrane. We propose that, in this case, cutis laxa may be related to an abnormal immune response.

Selective uptake of para-boronophenylalanine increases in amelanotic melanoma cells transfected by the tyrosinase gene.

To investigate the mechanism of uptake of para-boronophenylalanine (p-BPA), a capture agent for boron neutron capture therapy (BNCT) of melanoma and brain tumour, into melanoma cells, we studied the relationship between melanin synthesis and the concentration of boron using tyrosinase-deficient mouse amelanotic melanoma cells (A1059) and melanotic melanoma cells (TA1059). A1059 was established from mouse B16F10 cells, and TA1059 was constructed by transfecting human tyrosinase cDNA into A1059. The melanin content of TA1059 was 1.5-fold higher than that of B16F10, and was undetectable in A1059. The order of p-BPA uptake was TA1059 > B16F10 > A1059 at the time points examined, and the boron content of TA1059 was approximately 1.5-fold higher than that of B16F10. Our experimental findings indicated that melanin synthesis is a very important factor for characterizing the increase in accumulation of p-BPA in melanoma cells. A significant difference in boron uptake into TA1059 was observed between p-BPA and meta-BPA (m-BPA), but there were no apparent differences in the case of A1059. The difference in accumulation of p-BPA and m-BPA could be due to differences in the properties of p-BPA as a tyrosine analogue needed for melanin synthesis.

X-irradiation enhances the expression of Bcl-2 in HL-60 cells: the resulting effects on apoptosis and radiosensitivity.

Although p53 has been shown to directly activate transcriptional bax gene and to inhibit expression of bcl-2 gene during radiation-induced apoptosis, it is poorly understood how the Bcl-2 family changes in p53-deficient cells during radiation-induced apoptosis. The present work describes the effect of X-irradiation on the apoptosis of p53-deficient HL-60 cells as assessed by means of several methods. Apoptosis of HL-60 cells was induced by X-irradiation in a dose- and time-dependent manner. 18 h after 5 Gy irradiation, G2 cells underwent apoptosis, while 15 Gy X-irradiation induced the death of G1/S cells by 6 h. After X-irradiation, expression of Bcl-2 was elevated, while Bax expression was unchanged. We have isolated a clonal HL-60 variant following twice 5 Gy irradiation of HL-XR3 cells. These cells highly expressed Bcl-2 (about 2-fold), showed a reduced activation of caspase-3, and were not only more resistant to X-irradiation-induced apoptosis but also more radioresistant. These results suggest that HL-60 cells may resist apoptosis and radiation by increasing Bcl-2 expression, and that this elevated Bcl-2 expression might be one of the causes of the phenomenon, often seen clinically, that tumor cells gradually acquire radioresistance during fractionated radiation therapy.

Interstitial brachytherapy for recurrent breast cancer using a high dose rate Ir-192 remote afterloading system: a report of two cases.

We employed interstitial brachytherapy using a high dose rate Ir-192 remote afterloading unit in two breast cancer patients with locoregional recurrence. In the first case, skin metastasis was treated, with favorable control of the infield tumor but subsequent persistent sequelae and multiple outfield metastases. This experience caused us to be cautious when choosing brachytherapy for the second case, in whom a solitary metastasis to an axillary lymph node was successfully treated. Although this method is still investigational, it may play a critical role in the treatment of locoregional recurrence resistant to other treatment modalities.

High dose rate microselectron mould ratiotherapy of a widespread superficial oral cancer.

Treatment of a case of widespread superficial oral squamous cell carcinoma with external beam irradiation, followed by high dose rate Microselectron mould radiotherapy, is reported. The tumor disappeared macroscopically after treatment, but there was infield recurrence in the buccogingival sulcus where the radiation dose might have been inadequate. Apart from some radiation mucositis within the treated area, edema and a superficial ulcer were observed in the tongue. These were considered to be due to radiation overdose. Although there is room for improvement, this mode of treatment has something to offer patients with hard-to-cure cancer.

Radiotherapy of bile duct carcinoma using intracatheter 198Au grains.

Eight patients with bile duct carcinoma were treated with radiotherapy using intracatheter 198Au grains. The intracatheter 198Au grains in an inner tube were inserted into a percutaneous transhepatic catheter. A plastic tip was placed between these grains to improve spatial and temporal dose allocation. This method and 192Ir wire irradiation resemble each other closely in dose distribution, but the former has the following advantages over the latter. 1) The number of 198Au grains used can be changed quite easily in accordance with the length of the stenosis. 2) The half-life of 198Au is about 2.7 days, and a dose of 25-40 Gy at 1.0 cm from the source is delivered over this period. The medical staff can protect themselves from radioactivity when the sources are withdrawn after brachytherapy. 3) 192Ir wire is not used very frequently in spite of its long half-life (74 days) because bile duct carcinoma is uncommon. 4) In Japan, 198Au grains can be purchased on a weekly basis, so treatment plans can be easily made. The eight patients also received external irradiation and the median survival after onset of radiotherapy was 7.9 months. There have been few systemic or local complications.

[A case of clear cell carcinoma of the ovary responding to a paclitaxel-carboplatin combination chemotherapy].

Clear cell carcinoma of the ovary is believed to be chemoresistant; therefore, choosing anticancer agents is often difficult. In this report we present a case of ovarian clear cell carcinoma that showed a significant response to a combination chemotherapy with paclitaxel and carboplatin. The patient is a 51-year-old Japanese female with a history of Gn-RH treatment for endometriosis that was terminated three years before the presentation of this disease. She was referred to our hospital because of a huge abdominal mass. The initial surgery revealed the tumor was a clear cell carcinoma of the left ovary, showing a predominantly solid growth pattern as well as papillary and tubular patterns. Both architectural and nuclear grades were interpreted as 3, and mitotic count was up to 5/10 high-power fields. Therefore, the tumor was considered to be grade 2. A huge para-aortic lymph node metastasis was not resectable. Combination chemotherapy using paclitaxel at 175 mg/m2 in 3 hr intravenous infusion followed by intraperitoneal infusion of carboplatin at AUC of 7.5 as a bolus was administered. The regression rate of the para-aortic lymph node metastasis was 85%, lasting more than 5 months. We believe that the combination of paclitaxel and carboplatin is one treatment choice for clear cell carcinoma of the ovary.

[Pathological evaluation of superselective one-shot intra-arterial infusion chemotherapy for head and neck tumors].

Since 1992, we have treated 43 patients with head and neck tumors by superselective intra-arterial infusion chemotherapy (SIIC) via femoral artery. In 8 patients among then, operation was performed thereafter with/without radiation therapy (RT). CDDP and/or CBDCA were utilized as the chemotherapeutic modality. Only SIIC or RT showed Grade (Gr.) 0-2b pathological effects on Oboshi-Shimosato classification scheme, while a combination of SIIC and RT exhibited Gr. 2b-4 pathological effects. We conclude that a combination of SIIC and RT was most effective and had induced degeneration or necrotic changes in the tumor tissue.

Role of magnetic resonance imaging (MRI) in early cervical cancer.

The aim of this study was to prospectively determine if invasive carcinoma of the cervix can be ruled out by negative magnetic resonance image (MRI) findings. Eligible patients were those who were scheduled to undergo either hysterectomy or conization because of invasive or non-invasive lesions of the cervix. T2-weighted and T1-dynamic enhancement images were reviewed by two radiologists who had no information on these patients except for the preoperative diagnosis. Clinical information regarding location of the disease was not given. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist who was not provided with MRI information. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. Seventy cases were entered and 66 were evaluable. Sensitivities of T2 and dynamic MRI for invasive and non-invasive disease by radiologist 1 were 0.8824 and 0.8235, respectively, and those by radiologist 2 were 0.6296 and 0.7647, respectively. Specificities were 0.8776 and 0.8571, respectively, for radiologist 1 and 0.8974 and 0.8367, respectively, for radiologist 2. When sensitivities and specificities were calculated for prediction of non-invasive plus microinvasive lesions < or = 5 mm vs. invasive lesions > 5 mm, specificities of T2 and dynamic MRI became 1.0000 for both radiologists. Negative findings on T2 and/or dynamic MRI indicated non-invasive or early invasive cervical diseases < or = 5 mm. The dynamic technique provided only limited additional value in the detection of early invasive cervical carcinoma.

Evaluation of nanodispersion of iron oxides using various polymers.

In order to create Fe2O3 and Fe2O3·H2O nanoparticles, various polymers were used as dispersing agents, and the resulting effects on the dispersibility and nanoparticulation of the iron oxides were evaluated. It was revealed that not only the solution viscosity but also the molecular length of the polymers and the surface tension of the particles affected the dispersibility of Fe2O3 and Fe2O3·H2O particles. Using the dispersing agents 7.5% hydroxypropylcellulose-SSL, 6.0% Pharmacoat 603, 5.0% and 6.5% Pharmacoat 904 and 7.0% Metolose SM-4, Fe2O3 nanoparticles were successfully fabricated by wet milling using Ultra Apex Mill. Fe2O3·H2O nanoparticles could also be produced using 5.0% hydroxypropylcellulose-SSL and 4.0 and 7.0% Pharmacoat 904. The index for dispersibility developed in this study appears to be an effective indicator of success in fabricating nanoparticles of iron oxides by wet milling using Ultra Apex Mill.