The aim of this study was to investigate the signal intensity characteristics of highly invasive and highly metastasizing transplanted human squamous cell carcinoma using ultra-small super-paramagnetic iron oxide (USPIO)-enhanced MRI and to correlate them with USPIO distribution to tumour components revealed by histological examination.
13 nude mice with transplanted human squamous cell carcinoma in the oral cavity were imaged before and 24 hours after intravenous administration of USPIO. The difference in signal intensity between pre-contrast and post-contrast MR images was visually evaluated. For quantitative analysis, signal intensity within a region of interest was measured. Histological findings were correlated with MR findings. The approximate USPIO concentration was evaluated using USPIO phantoms.
Seven tumours had an area showing signal intensity increase on post-contrast T1 weighted images. Histopathologically, six of those tumours contained a small amount of iron particles in the stroma. The USPIO concentration was presumed low. Two tumours had an area showing signal intensity decrease on post-contrast T1 and T2 weighted images. The areas had a large amount of iron particles in the stroma and the USPIO concentration was presumed high. There was a minimal amount of iron particles in tumour parenchymal cells.
The amount of USPIO accumulation into tumour stroma was considered to affect MR signal intensity. A small amount increases T1 weighted signal intensity, whereas a large amount decreases T1 and T2 weighted intensity. The USPIO accumulation into the tumour parenchyma was not thought to affect MR signal intensity.
magnetic resonance imaging; contrast media; head and neck neoplasms; carcinoma; squamous cell
The aim of this study was to evaluate the outcome and complications of low-dose-rate brachytherapy (LDR-BT) for oral cancer according to comorbidity.
The records of a total of 180 patients who received LDR-BT for T1-2N0M0 oral cancers between January 2005 and December 2007 were analysed. The comorbidities of the patients were retrospectively graded according to the Adult Comorbidity Evaluation-27, and the relationships between the comorbidity grades and survival, disease control and the incidence of complications were analysed.
The 2 year overall survival rates of patients with no comorbidity, Grade 1, Grade 2 and Grade 3 comorbidity were 87%, 85%, 76% and 65%, respectively, and the reduction in the survival rate according to comorbid severity was significant in a univariate analysis (p = 0.032) but not in a multivariate analysis including other clinical factors. Cause-specific survival, locoregional control and local control were not related to the comorbidity grade, or any other clinical factors. Grade 2 or 3 complications developed in 27% of the patients. The incidence of complications was unrelated to the comorbidity grade.
The disease control of oral cancer and the incidence of complications after LDR-BT were not related to comorbid severity. LDR-BT is a useful and safe treatment for patients regardless of the presence of severe comorbidity.
CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 – ligand interaction may abrogate allergen-induced inflammation.
Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4+CD3+ and CXCR3+CD3+ cells and examined by in situ hybridization for CCR4, IL-4 and IFN-γ mRNA+ cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4+CD4+ cells assessed for actin polymerization in response to the CCR4 ligand macrophage-derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested.
Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3+ T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4+CD3+ protein-positive cells relative to CXCR3+CD3+ cells; CCR4 mRNA+ cells were increased and IL-4 increased to a greater extent than IFN-γ. CCR4+CD4+ T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist.
Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. Blocking CCR4-ligand interaction may provide a novel therapeutic approach in allergic disease.
allergic rhinitis; CCR4; nasal mucosa; Th2-mediated inflammation
For surgical procedures involving the posterior mandible, it is important to be familiar with the details of the bifid mandibular canal. To our knowledge, there have been no systematic studies evaluating the bifid mandibular canal using sectional imaging. The purpose of this study is to evaluate the incidence and configuration of the bifid mandibular canal using cone beam CT.
252 patients (301 mandible sides) underwent cone beam CT between October 2004 and September 2005 and were included in this study. The cone beam CT images were evaluated for the presence and configuration of the bifid mandibular canal. The patterns of bifurcation were classified into four types according to the classification of Nortjé et al (Variations in the normal anatomy of the inferior dental (mandibular) canal: a retrospective study of panoramic radiographs from 3612 routine dental patients. Br J Oral Surg 1977; 15: 55–63). The diameter of the accessory canal was classified into two categories: 50% or more and less than 50% of the diameter of the main mandibular canal.
Of the 301 subjects, 47 (15.6%) demonstrated a bifid mandibular canal. They were Type I in 2, Type II in 40, Type III in 0, and Type IV in 5 cases. The diameter of the accessory canal was greater than or equal to 50% of the main canal in 23, and less than 50% in 24 cases.
On the basis of the cone beam CT, a bifid mandibular canal was found in 15.6% of cases, a markedly higher proportion than found in previous reports using panoramic images. Cone beam CT is considered a suitable modality for detailed evaluation of bifid mandibular canals.
cone beam computed tomography; bifid mandibular canal; panoramic radiography
Diffusion-weighted imaging (DWI) may detect hyperintense lesions in patients with transient hypoglycaemia-induced hemiparesis or coma, which are completely reversible after glucose infusion.1–3 In vivo animal studies have documented the visualisation of such hypoglycaemia-induced changes of signal intensity and the reversal by glucose intake in detail.4 However, the time necessary for hyperintense lesions on DWI to disappear after glucose infusion in humans is still unclear. A 54 year old woman presented comatose with brain stem signs and severe hypoglycaemia. DWI demonstrated hyperintense lesions in the corpus callosum and internal capsules. She was treated with IV glucose. These lesions had resolved significantly on imaging 2 hours later and completely resolved on repeat imaging 2 days later. This report documents the time course of recovery of neurological lesions induced by hypoglycaemia after treatment with IV glucose.
The aim was to investigate the possibility of evaluating the modulation transfer function (MTF) of cone beam CT (CBCT) for dental use using the oversampling method.
The CBCT apparatus (3D Accuitomo) with an image intensifier was used with a 100 μm tungsten wire placed inside the scanner at a slight angle to the plane perpendicular to the plane of interest and scanned. 200 contiguous reconstructed images were used to obtain the oversampling line-spread function (LSF). The MTF curve was obtained by computing the Fourier transformation from the oversampled LSF. Line pair tests were also performed using Catphan®.
The oversampling method provided smooth and reproducible MTF curves. The MTF curves revealed that the spatial resolution in the z-axis direction was significantly higher than that in the axial direction. This result was also confirmed by the line pair test.
MTF analysis was performed successfully using the oversampling method. In addition, this study clarified that the 3D Accuitomo had high spatial resolution, especially in the z-axis direction.
dental; cone beam; computed tomography; modulation transfer function
A 57‐year‐old man with type 2 diabetes mellitus for 10 years showed progressive loss of muscle strength in both legs, pain and muscle atrophy in the femoral region and significant weight loss. On admission, he could not stand alone and used a wheelchair. He also complained of severe pain in the lower extremities. He was diagnosed with proximal diabetic neuropathy (PDN) by characteristic clinical and electrophysiological features. Intravenous immunoglobulin therapy (IVIg 0.4 g/kg×5 days) markedly reduced the severe pain and muscle weakness in the legs. Eventually, pain assessed by the Visual Analogue Scale was relieved by 80% and muscle strength was also well recovered, thereby enabling the patient to walk with a cane. The present case suggests that IVIg therapy may be effective for the relief of pain in PDN.
Forty-two strains of Vibrio parahaemolyticus were isolated from Bay of Bengal estuaries and, with two clinical strains, analyzed for virulence, phenotypic, and molecular traits. Serological analysis indicated O8, O3, O1, and K21 to be the major O and K serogroups, respectively, and O8:K21, O1:KUT, and O3:KUT to be predominant. The K antigen(s) was untypeable, and pandemic serogroup O3:K6 was not detected. The presence of genes toxR and tlh were confirmed by PCR in all but two strains, which also lacked toxR. A total of 18 (41%) strains possessed the virulence gene encoding thermostable direct hemolysin (TDH), and one had the TDH-related hemolysin (trh) gene, but not tdh. Ten (23%) strains exhibited Kanagawa phenomenon that surrogates virulence, of which six, including the two clinical strains, possessed tdh. Of the 18 tdh-positive strains, 17 (94%), including the two clinical strains, had the seromarker O8:K21, one was O9:KUT, and the single trh-positive strain was O1:KUT. None had the group-specific or ORF8 pandemic marker gene. DNA fingerprinting employing pulsed-field gel electrophoresis (PFGE) of SfiI-digested DNA and cluster analysis showed divergence among the strains. Dendrograms constructed using PFGE (SfiI) images from a soft database, including those of pandemic and nonpandemic strains of diverse geographic origin, however, showed that local strains formed a cluster, i.e., “clonal cluster,” as did pandemic strains of diverse origin. The demonstrated prevalence of tdh-positive and diarrheagenic serogroup O8:K21 strains in coastal villages of Bangladesh indicates a significant human health risk for inhabitants.
lysinuric protein intolerance; portal circulation; SLC7A7; nitric oxide; ultrasonography
Tumour samples from 71 patients with stomach cancer, 41 patients with liver metastasis (group A) and 15 patients each in stages II–IV (group B) and stage I (group C) without liver metastasis were analysed. MAGE-A protein expression was evaluated by immunohistochemistry using a 6C1 monoclonal antibody and MAGE-A10 mRNA expression was detected by highly sensitive in situ hybridisation using a cRNA probe. Expressions of MAGE-A protein and MAGE-A10 mRNA in group A were detected in 65.9 and 80.5%, respectively. Both protein and gene showed significantly higher expression in group A than those in groups B (6.7, 26.7%) and C (0, 0%) (P=0.0003, P=<0.0001, respectively). MAGE-A10 mRNA expression in liver metastasis was found in eight (88.9%) out of nine patients. The concordant rate between MAGE-A family protein expression and MAGE-A10 mRNA expression in the primary sites was 81.7% (P<0.0001). MAGE-A10 gene expression was associated with reduced survival duration. The results of this study suggest that MAGE-A10 is a possible target in active immunotherapy for advanced stomach cancer.
MAGE-A protein; MAGE-A10 mRNA; highly sensitive in situ hybridisation; stomach cancer; liver metastasis; active immunotherapy
echocardiography; blood flow; coronary disease; microcirculation
The pandemic spread of Vibrio parahaemolyticus is an international public health issue. Because of the outbreak potential of the organism, it is critical to establish an internationally recognized molecular subtyping protocol for V. parahaemolyticus that is both rapid and robust as a means to monitor its further spread and to guide control measures in combination with epidemiologic data. Here we describe the results of a multicenter, multicountry validation of a new PulseNet International standardized V. parahaemolyticus pulsed-field gel electrophoresis (PFGE) protocol. The results are from a composite analysis of 36 well-characterized V. parahaemolyticus isolates from six participating laboratories, and the isolates represent predominant serotypes and various genotypes isolated from different geographic regions and time periods. The discriminatory power is very high, as 34 out of 36 sporadic V. parahaemolyticus strains tested fell into 34 distinguishable PFGE groups when the data obtained with two restriction enzymes (SfiI and NotI) were combined. PFGE was further able to cluster members of known pandemic serogroups. The study also identified quality measures which may affect the performance of the protocol. Nonadherence to the recommended procedure may lead to high background in the PFGE gel patterns, partial digestion, and poor fragment resolution. When these quality measures were implemented, the PulseNet V. parahaemolyticus protocol was found to be both robust and reproducible among the collaborating laboratories.
Objective: To clarify the progression of autonomic symptoms and functional deterioration in pure autonomic failure (PAF), particularly in comparison with multiple system atrophy (MSA).
Methods: The investigation involved eight patients with PAF (M/F = 7/1; mean age at onset, 57 years) and 22 with probable MSA matched for age at onset (M/F = 14/8; onset 56 years). Subjects were followed up for neurological symptoms, activities of daily living, and autonomic function for more than seven years. Autonomic functional tests were carried out.
Results: In PAF, fainting or sudomotor dysfunction occurred first, followed by constipation and syncope. Urinary dysfunction developed late, and respiratory dysfunction was not evident. This clinical course contrasted sharply with that in MSA, where early urinary dysfunction usually proceeded to sudomotor dysfunction or orthostatic hypotension (p = 0.004), followed by respiratory dysfunction (p = 0.0004). Results of pharmacological tests also distinguished PAF from MSA. Progression and prognosis in patients with PAF did not worsen, unlike the steady progressive autonomic dysfunction in MSA (p<0.0001, p<0.0001, p = 0.0009, and p = 0.003, for progression to modified Rankin scale grade III, IV, V, and death, respectively).
Conclusions: The time course and pattern of progression of autonomic failure differed significantly between PAF and MSA. Patients with PAF had slower functional deterioration and a better prognosis.
This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day−1) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI)=cigarettes per day × years smoked), the better the MST (BI 0: 14.5 months, BI <500: 9.5 months, BI 500 to <1000: 6.9 months, BI ⩾1000: 4.0 months). Positive-EGFR mutation status and PS 0–1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status.
epidermal growth factor receptor (EGFR) inhibitor; EGFR mutations; gefitinib; IRESSA; non-small-cell lung cancer; smoking
Aim: Non-steroidal anti-inflammatory drug (NSAID) enteropathy is a cause of chronic blood and protein loss from the intestine. The aim of this investigation was to compare NSAID enteropathy with enteropathy not related to chronic NSAID use.
Patients/Methods: During the period 1967–97, 12 cases of non-specific small intestinal multiple ulcers were laparotomised because of chronic and persistent blood loss for a prolonged period. The clinical features before and after surgery, and the small intestinal lesions, were compared between NSAID users and non-users.
Results: Three patients were NSAID users and the other nine were not. Initial clinical manifestations, haemoglobin concentrations, serum protein values, and inflammatory reactions were similar in the two groups. In both groups there were multicentric stenoses in the small intestine. In those not using NSAIDs, the stenoses were accompanied by multiple, sharply demarcated small ulcers with minimal and non-specific chronic inflammatory infiltrates. The small intestinal ulcers in NSAID users showed linear and circumferential alignment. NSAID users were free from medication during the subsequent period of observation, whereas repeated laparotomy and medication were required in eight of the nine patients not using NSAIDs.
Conclusion: There appears to be a chronic enteropathy, not related to the use of NSAIDs, in which non-specific multiple ulcers are found. This enteropathy may be a distinct entity that causes persistent blood and protein loss from the intestine.
small intestine; ulcers; stenosis; nonsteroidal antiinflammatory drug
Objectives: To clarify the value of cycle dependent variation of myocardial integrated backscatter (CV-IB) analysis, which non-invasively measures acoustic properties of the myocardium, for early detection of cardiac involvement in patients with sarcoidosis.
Methods: The study population consisted of 22 consecutive patients with biopsy proven sarcoidosis who did not have any abnormal findings on conventional two dimensional echocardiogram. Cardiac sarcoidosis was diagnosed by radionuclide testing including thallium-201 scintigraphy, gallium-67 scintigraphy, and cardiac fluorine-18-deoxyglucose positron emission tomography. The magnitude and delay of the CV-IB were analysed in the basal mid septum and the basal mid posterior wall of the left ventricle of all patients.
Results: The patients were divided into two groups: 8 patients with cardiac involvement and 14 patients without cardiac involvement. In the basal septum, a major reduction in the magnitude (mean (SD) 1.8 (4.4) v 6.6 (1.3), p = 0.012) and an increase in the time delay (1.3 (0.5) v 1.0 (0.1), p = 0.038) of CV-IB were observed in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. The sensitivity for detecting cardiac involvement was such that the magnitude of CV-IB in the basal septum discriminated 75% of patients with cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two dimensional echocardiographic parameters did not discriminate between these two groups.
Conclusions: The CV-IB is decreased in the basal septum in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. Analysis of CV-IB may be a useful method to detect early myocardial involvement in patients with sarcoidosis.
sarcoidosis; ultrasonics; echocardiography
We studied the biochemical characteristics of human knees with deficient anterior cruciate ligaments (ACL) and analysed their relationship to the time after ligamentous injury. Thirty-two patients with isolated ACL-injured knees and six healthy volunteers were enrolled. Synovial fluid samples were centrifuged after aspiration during arthroscopic examination, and aliquots of supernatant were frozen and stored at −80°C. The samples were analysed for interleukin (IL)-1β, tumour necrosis factor (TNF)-α, IL-6, matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 using commercially available sandwich enzyme-linked immunosorbent assay. In fluid from ACL-injured knees, the average concentrations of IL-6, MMP-3 and TIMP-1 were highly elevated in comparison with normal controls. There was a statistically significant correlation between the concentrations of MMP-3 and IL-6. The IL-6 and TIMP-1 concentrations were interrelated. The concentration of MMP-3 remained high, independent of the duration since the injury, whereas the TIMP-1 and IL-6 levels decreased. The results suggest that the timing of the treatment of an ACL-injured knee might be of importance.
Objective: We performed 1H-MR spectroscopy (1H-MRS) on multiple brain regions to determine the metabolite pattern and diagnostic utility of 1H-MRS in multiple system atrophy (MSA).
Methods: Examining single voxels at 3.0 T, we studied metabolic findings of the putamen, pontine base, and cerebral white matter in 24 MSA patients (predominant cerebellar ataxia (MSA-C), n = 13), parkinsonism (MSA-P), n = 11), in 11 age and duration matched Parkinson's disease patients (PD) and in 18 age matched control subjects.
Results: The N-acetylaspartate to creatine ratio (NAA/Cr) in MSA patients showed a significant reduction in the pontine base (p<0.0001) and putamen (p = 0.02) compared with controls. NAA/Cr in cerebral white matter also tended to decline in long standing cases. NAA/Cr reduction in the pontine base was prominent in both MSA-P (p<0.0001) and MSA-C (p<0.0001), and putaminal NAA/Cr reduction was significant in MSA-P (p = 0.009). It was also significant in patients who were in an early phase of their disease, and in those who showed no ataxic symptoms or parkinsonism, or did not show any MRI abnormality of the "hot cross bun" sign or hyperintense putaminal rims. NAA/Cr in MSA-P patients was significantly reduced in the pontine base (p = 0.001) and putamen (p = 0.002) compared with PD patients. The combined 1H-MRS in the putamen and pontine base served to distinguish patients with MSA-P from PD more clearly.
Conclusions:1H-MRS showed widespread neuronal and axonal involvement in MSA. The NAA/Cr reduction in the pontine base proved highly informative in the early diagnosis of MSA prior to MRI changes and even before any clinical manifestation of symptoms.
Objective: To clarify the characteristics of sympathetic vasomotor function in Parkinson's disease by sympathetic neurographic analysis.
Methods: Muscle sympathetic nerve activity (MSNA) was recorded using a microneurographic technique at rest and during head up tilt in 18 patients with idiopathic Parkinson's disease and 21 healthy controls.
Results: Heart rate and blood pressure at rest did not differ between index and control subjects. The increase in these variables and MSNA in response to tilting was slightly blunted in the Parkinson's group. Resting MSNA showed a negative correlation with age in patients with Parkinson's disease (p<0.05) and a positive correlation with age in controls (p<0.01). There was a negative correlation between duration of disease or disability levels and MSNA (p<0.01).
Conclusions: Sympathetic vasomotor function may be related to age and disease duration in Parkinson's disease.
Background: Sulfhydryl (SH) compounds are essential in maintaining mucosal integrity in the gastrointestinal tract. A decrease in colonic mucosal SH compounds affects the redox status of the mucosa, resulting in vulnerability to further attacks. Therefore, there is a strong need for in vivo evaluation of SH compounds in the colonic mucosa.
Aims: The aim of the current study was to establish a method of evaluating levels of SH compounds in the colonic mucosa of live animals before and after induction of colitis.
Methods: Murine experimental colitis was induced by instillation of trinitrobenzene sulphonic acid (TNBS) dissolved in 50% ethanol into the colon via the anus. For evaluation of mucosal SH compounds in the colon, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL), a stable nitroxide radical, was instilled into the colonic lumen of live mice and the spin clearance rate was measured by L-band electron spin resonance (ESR) spectroscopy.
Results: Morphological study showed that mucosal damage was severe one or two days after TNBS instillation. The colonic mucosa started to regenerate at four days, and looked normal at seven days, after induction of colitis. The spin clearance rate of carbamoyl-PROXYL decreased significantly at 0.5, 1, 2, and 4 days after induction of colitis compared with mice before TNBS instillation. Surprisingly, although the colonic mucosa looked normal seven days after TNBS administration, the spin clearance rate still remained significantly slow. The spin clearance rate returned to normal 14 days after induction of colitis. The change in in vivo spin clearance rate was consistent with the time dependent change in mucosal reduced glutathione, a major component of SH compounds.
Conclusion: The spin clearance rate obtained by L-band ESR spectroscopy in combination with carbamoyl-PROXYL can give an estimate of the level of colonic mucosal SH compounds in live animals and is useful for evaluating the mucosal defence system against oxidative stress.
electron spin resonance; experimental colitis; nitroxide radical; sulfhydryl compounds; trinitrobenzene sulphonic acid
Objectives: To elucidate the factors associated with severity of cardiac sympathetic nerve involvement in idiopathic Parkinson's disease (PD).
Methods: 123I-metaiodobenzylguanidine uptake was examined in 88 patients with PD. The ratio of the uptake in the heart (H) to that in the mediastinum (M) (the H/M ratio) was calculated and correlated with age at onset, age at examination, and disease severity and duration. Twenty five healthy people were also examined as a control.
Results: There was a mild but significant negative correlation between H/M ratio and age at onset (early, r = -0.33, p = 0.002; delayed, r = -0.34, p = 0.001) and between Hoehn and Yahr (H-Y) stage (early, r = -0.30, p = 0.006; delayed, r = -0.32, p = 0.003). There was no significant correlation between disease duration and H/M ratio. When patients with PD were classified into four subgroups on the basis of age at onset (> 62 or < 62 years) and disease severity (H-Y > III or H-Y ⩽ II), the median H/M ratio of the older and more severe group was significantly lower than that of the younger and less severe group (p = 0.005).
Conclusion: This study suggests that late onset, high severity PD is associated with myocardial sympathetic dysfunction.