Lateral Asymmetry and Spatial Difference of Iron Deposition in the Substantia Nigra of Patients with Parkinson Disease Measured with Quantitative Susceptibility Mapping.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping is useful for assessing iron deposition in the substantia nigra of patients with Parkinson disease. We aimed to determine whether quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference in iron deposits in the substantia nigra of patients with Parkinson disease. MATERIALS AND METHODS: Our study population comprised 24 patients with Parkinson disease and 24 age- and sex-matched healthy controls. They underwent 3T MR imaging by using a 3D multiecho gradient-echo sequence. On reconstructed quantitative susceptibility mapping, we measured the susceptibility values in the anterior, middle, and posterior parts of the substantia nigra, the whole substantia nigra, and other deep gray matter structures in both hemibrains. To identify the more and less affected hemibrains in patients with Parkinson disease, we assessed the severity of movement symptoms for each hemibrain by using the Unified Parkinson's Disease Rating Scale. RESULTS: In the posterior substantia nigra of patients with Parkinson disease, the mean susceptibility value was significantly higher in the more than the less affected hemibrain substantia nigra (P < .05). This value was significantly higher in both the more and less affected hemibrains of patients with Parkinson disease than in controls (P < .05). Asymmetry of the mean susceptibility values was significantly greater for patients than controls (P < .05). Receiver operating characteristic analysis showed that quantitative susceptibility mapping of the posterior substantia nigra in the more affected hemibrain provided the highest power for discriminating patients with Parkinson disease from the controls. CONCLUSIONS: Quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference of iron deposition in the substantia nigra of patients with Parkinson disease.

Visualization of the Medial and Lateral Geniculate Nucleus on Phase Difference Enhanced Imaging.

BACKGROUND AND PURPOSE: The precise identification and measurement of the medial geniculate nucleus and lateral geniculate nucleus on MR imaging remain technically challenging because the thalamic nuclei are small structures. We compared the visualization of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging with 3D high-resolution phase imaging, 2D-T2WI, STIR, proton attenuation-weighted imaging, and DTI acquired at 3T. We also measured the volume and height of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging. MATERIALS AND METHODS: Phase difference enhanced, 2D-T2-weighted, STIR, proton attenuation-weighted, and DTI were acquired on a 3T MR imaging unit in 10 healthy volunteers. Two neuroradiologists recorded the qualitative visualization scores of the medial geniculate nucleus and lateral geniculate nucleus, specifically the identification of their boundaries, for all images. Measurement differences were assessed with the Wilcoxon signed rank test. The volume and height of the medial geniculate nucleus and lateral geniculate nucleus were measured on phase difference enhanced imaging and compared with previously reported values. RESULTS: The qualitative visualization scores of the lateral geniculate nucleus and medial geniculate nucleus were significantly higher on phase difference enhanced images than on T2-weighted, proton attenuation-weighted, STIR, or DTI (P < .05). On phase difference enhanced imaging, the medial geniculate nucleus and lateral geniculate nucleus were bordered by low-intensity structures: the cerebral peduncle, the origin of the optic radiation, and the superior and inferior quadrigeminal brachia. The volume of the medial geniculate nucleus and lateral geniculate nucleus varied from 74.0 to 183.75 mm(3) (mean, 129.0 ± 34.7 mm(3)) and from 96.5 to 173.75 mm(3) (mean, 135.2 ± 28.0 mm(3)), respectively. CONCLUSIONS: For the depiction of the medial geniculate nucleus and lateral geniculate nucleus on 3T MR imaging, phase difference enhanced imaging is superior to conventional MR imaging. The medial geniculate nucleus and lateral geniculate nucleus volumes vary among individuals.

[Huge right atrial myxoma].

Myxomas are account for approximately half of primary cardiac tumors, and 75% cases originate in left atrium. We report our experience of a right atrial myxoma. A 68-year-old woman was referred to us due to anorexia, general fatigue and facial edema. Echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), and catheter angiocardiogram revealed a huge tumor in right atrium. The tumor was resected completely with the attached right atrial free wall under cardiopulmonary bypass. Pathological examination showed myxomatous tissue. Postoperative course was uneventful. She discharged the hospital on the 37th day after the operation, and is now doing well without any symptoms.

[Valve-in-valve replacement of primary tissue valve failure of bovine pericardial valve minor].

A 73-year-old woman who underwent mitral valve replacement with a 31 mm Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed sudden onset of a grade IV/VI a seagull like diastolic murmur at the apex, and severe hematuria. Echocardiography demonstrated severe mitral regurgitation. These findings were consistent with acute primary tissue valve failure. Therefore we performed emergency reoperation. At operation, valve leaflet was torn at the commissural stitch, and bioprosthesis strut was buried in the left posterior ventricular wall. The mitral prosthetic valve replaced with a 25 mm CarboMedics OptiForm using a technique of valve-in-valve replacement. This procedure would be one option for replacement of bioprosthetic mitral valve.

Mexiletine carbonyloxy beta-D-glucuronide: a novel metabolite in human urine.

1. The study was performed to isolate and characterize a glucuronic acid conjugate of mexiletine that releases mexiletine on acid hydrolysis from urine samples obtained from healthy volunteers following a single oral dose of mexiletine. 2. The [M-H]- ion of the isolated metabolite was observed at m/z 398 in the negative electrospray ionization mass spectrum. This mass number was 44 higher than that of the product generated when mexiletine is subjected to direct glucuronidation. In positive-ion mode, collision-induced dissociation of the quasimolecular ion [M+NH4]+, m/z 417, gave product ions at m/z 224, 180 and 58. These mass spectral data indicated that the metabolite contained a carbonyloxy moiety in its structure in addition to mexiletine and a glucuronic acid moiety. 3. The presence of this carbonyloxy moiety was further supported by the following chemical reactions. When the metabolite was hydrolysed with an aqueous solution of 1 M sodium hydroxide at room temperature, mexiletine was released, whereas the N-methoxycarbonyl derivative of mexiletine was obtained after treatment of the metabolite with methanolic sodium hydroxide solution. 4. The results indicated that the structure of the isolated metabolite was the N-carbonyloxy beta-D-glucuronic acid conjugate of mexiletine.

Interindividual variation in the ratio between plasma morphine and its metabolites in cancer patients.

In 25 cancer patients treated with slow-release oral morphine and in 10 cancer patients treated with continuous infusion of morphine, plasma steady-state concentrations of morphine (M), morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) were determined by high-performance liquid chromatography. Blood samples were withdrawn at 0, 2 and 6 h after oral administration in patients treated with slow-release oral morphine and once or twice a day in patients treated with continuous infusion of morphine. In four cancer patients treated with continuous infusion of morphine, in order to analyze chronopharmacokinetic variability, the M-3-G/M ratio was observed at 12:00 h and 24:00 h. No significant changes were observed in M-3-G/M ratios and M-6-G ratios at 0, 2, and 6 h after oral administration of morphine. The M-3-G/M ratio (38.6 +/- 25.7) in the oral morphine group was significantly higher than that (15.3 +/- 12.9) in the continuous infusion group (p < 0.01). There was an approximately 10-fold interindividual variation in the M-3-G/M ratio both in the continuous infusion group and in the oral morphine group. These results suggest that the activity of UDP glucuronosyltransferase 2B7 in the intestinal metabolism of morphine may play an active part in a large interindividual variation in the ratio of metabolites to morphine. Further studies are needed to clarify this hypothesis.

Synovial histology in three Behçet's disease patients with orthopedic surgery.

Specimens of synovial tissues from 5 affected joints of 3 patients with Behçet's disease were available for histopathological examination. All specimens were infiltrated by lymphocytes and neutrophils, and exhibited marked vascularity and infiltration of lymphoid cells among the vessels. Marked plasma cell infiltration and lymphoid follicle formation were found in one synovial tissue sample. There was no evidence of infection or vasculitis. These findings suggest that the histopathological characteristics of synovial tissue in Behçet's disease may have a wide range, some of which may even resemble the synovial tissue of rheumatoid arthritis.

Detection and cytotoxicity of cisplatin-induced superoxide anion in monolayer cultures of a human ovarian cancer cell line.

Superoxide anions (O2-) generated by cisplatin [cis-diamminedichloroplatinum (II), DDP] were determined by measuring the chemiluminescence from the luminescence probe, 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (methyl Cypridina luciferin analog, MCLA), in monolayer cultures of a human ovarian cancer cell line (A2780) in physiological saline at pH 7.0. In a time-course study, chemiluminescence of MCLA (C-MCLA) showed a peak level at 10 min and a background level at 60 min after the addition of DDP. The intensity of C-MCLA increased with increasing concentrations of DDP or MCLA in a limited concentration range, and was significantly correlated (r = 0.960) with the number of A2780 cells. DDP-induced C-MCLA was completely inhibited by the addition of the O2- scavenger, superoxide dismutase (SOD). However, SOD did not decrease DDP cytotoxicity in terms of clonogenic cell survival. These findings suggest that DDP generates extracellular O2-, probably by interaction with the cellular membrane in A2780 cells, and O2- does not lead to cellular damage.

The progression of invasiveness regarding the role of transforming growth factor beta receptor type II in gastric cancer.

AIMS: Transforming growth factor beta (TGF beta) is a potent growth inhibitor of epithelial cells. The expression of TGF beta receptors is required for the effect of TGF beta. In this study, we used immunohistochemistry to demonstrate the roles of the expression of TGF beta type I (T beta R-I) and type II (T beta R-II) receptors in the progression of gastric carcinoma. METHODS: To evaluate the potential prognostic value of T beta R-I and T beta R-II, 158 consecutive gastric cancer tissues specimens obtained over a 3-year period were examined. RESULTS: A total of 50 (32%) and 28 (18%) patients had T beta R-I(+) and T beta R-II(+), respectively. The 5-year survival rates of the patients with T beta R-I(+) and those with T beta R-I(-) were 74% and 71%, respectively. In contrast, the 5-year survival rates of the patients with T beta R-II(+) and those with T beta R-II(-) were 57% and 75%, respectively, and the difference was statistically significant (P<0.05). The extent of T beta R-II was closely correlated to the macroscopic types based on the Borrmann classification (P<0.01), and curability (P<0.05). However, a significant difference between the 5-year survival rates of the patients with T beta R-II(+) and those with T beta R-II(-) was only obtained in advanced cases (P<0.05) not in either curative cases, non-curative cases, or early cases. CONCLUSIONS: Our data suggest that when T beta R-II expression correlates with the progression of invasiveness in gastric cancer, it may lead to a non-curative resection and a poor prognosis.

Long-term results of corticosteroid administration via appendicostomy in patients with ulcerative colitis involving the entire colon.

BACKGROUND: Ulcerative colitis (UC) of an unknown etiology frequently demonstrates repeated active and inactive stages. As a result, it is difficult to sustain long-term remission under conservative therapy. METHODS: Ten patients who presented suffering from UC involving the entire colon were treated. All patients had been previously treated at other hospitals usually with sulphasalazine and either corticosteroids or steroid enemas for the primary complaints of muco-bloody stool or frequent diarrhea. All patients underwent either an appendicostomy or cecostomy, and were injected with dexamethasone via an artificial fistula twice a day. RESULTS: This treatment led to remission, and, as a result, the symptoms of anal bleeding or muco-bloody stools disappeared in all patients. Radiological, endoscopic, and pathological studies revealed a dramatic response to steroid injection from the fistula. The mean follow-up period was 44.7 months (3-122 months). Eight patients remained free from any symptoms of UC. One underwent a proctocolectomy because of side effects due to steroid treatment. The other patient died suddenly of unknown causes. The mean symptom-free period after cecal injection was 39.5 months (1-119 months). The mean proportion of disease free period from UC, compared with the total follow-up period after surgery, was 88%. After remission, eight patients were able to return to a normal lifestyle at home using a peritoneal button. They could also take a bath and continue their school or social lives in almost the same way as healthy persons. CONCLUSIONS: We thus recommend this new, minimally-invasive therapy for patients with UC involving the entire colon who demonstrate resistance to conventional conservative therapy. As a result of such treatment, all patients were able to achieve a comfortable lifestyle after undergoing minimally-invasive surgery.

Pharmacokinetics of [125I]-recombinant human interleukin-11: 1. Absorption, distribution and excretion after subcutaneous administration to male rats.

Absorption, distribution, metabolism and excretion of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in rats were investigated. After a single administration, the concentration of radioactivity in the tissues was 2-6-fold higher in the liver and kidneys, and slightly higher in the gastrointestinal tract as compared to the plasma concentration. However, since the concentration in the other tissues was lower than the plasma concentration, the transport of rhIL-11 into tissues appeared to be low. Tissue radioactivity rapidly diminished, thus accumulation of rhIL-11 in tissues was thought to be low. Excretion of radioactivity into urine and feces was almost complete 72 h after administration, with 88.5% of the dosed radioactivity being found in urine and 7.9% in feces. When [125I]-rhIL-11 was administered to bile-duct cannulated rats, 44.4% of the dosed radioactivity was excreted into bile up to 48 h after administration. Most radioactivity in bile and urine was found in the TCA supernatant and low molecular weight fraction by HPLC analysis, indicating that rhIL-11 was eliminated from the body by metabolism.

Pharmacokinetics of [125I]-recombinant human interleukin-11: 2. Placental transfer and excretion into milk after subcutaneous administration to rats.

Placental transfer and excretion into milk of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in female rats were investigated. After administration of [125I]-rhIL-11 to rats on the 14th day of gestation, radioactivity in the kidney was the highest among excised tissues, being 3 times higher than that in the plasma at 1.5 h. Radioactivity in other tissues, including the mammary gland, ovary, uterus, placenta and amniotic fluid, was lower than that in the plasma. Although radioactivity in fetuses was detected 6 h after administration, the level was only 2% of the plasma concentration in dams, and the radioactivity was not found in fetal-derived TCA precipitates. These results indicate that rhIL-11 does not readily pass through the placenta into the fetus. After subcutaneous administration of [125I]-rhIL-11 to lactating rats 14 days after delivery, radioactivity in milk was 1.1-1.6 times that in the plasma of dams. Radioactivity in clotted milk in the stomachs of suckling infants was almost equal to that in the dam's milk; however, only a small amount of radioactivity was detected in infant kidneys.

Anthelmintic efficacy of milbemycin oxime against Trichuris vulpis in dogs.

The anthelmintic efficacy of milbemycin oxime against dog whipworm, Trichuris vulpis, was evaluated. A total of 21 T. vulpis positive dogs were divided into 3 groups, one (5 dogs) for control and the other two (8 dogs each) for anthelmintic treatment with oral administration of milbemycin oxime.

Development of microplate-radioluminography for 32P.

Basic research for designing a microplate which can be applied to determination of 32P by radioluminography was carried out. It was proven that 32P can be determined by using the microplate which has plural planchets placed at intervals on a thin plate and a brass collimator that fills the gaps between the planchets. The microplate is joined with the collimator, and exposed to an imaging plate for 24 h. The detection limit of the proposed method was estimated to be 6 m Bq. The cross-talk ratio was negligibly small (0.2%).

Sensitive enzyme-linked immunosorbent assay (ELISA) to measure parasite-specific antibodies of Indian soft-furred rats, Millardia meltada.

Immunoglobulin G (IgG) of Indian soft-furred rat, Millardia meltada, was purified by an immunoaffinity chromatography and antibodies against it was raised in rabbit. Using this rabbit anti-M. meltada IgG antibody, sensitivity of enzyme-linked immunosorbent assay (ELISA) to measure parasite-specific antibodies in the sera of M. meltada was markedly enhanced than the previous method using rabbit anti-mouse IgG and rabbit anti-rat IgG antibodies, which could cross-react to M. meltada IgG. Since M. meltada could effectively produce circulating antibodies against two intestinal helminths, Strongyloides venezuelensis and Nippostrongylus brasiliensis, the high susceptibility of this animal to an array of parasites seems to be not due to general immunological deficiency.

[Cyclophosphamide pulse therapy for refractory rheumatic diseases].

We studied the efficacy of cyclophosphamide pulse therapy (CYP) for refractory rheumatic diseases except for lupus nephritis. Thirty-five patients were included in all, that is 9 patients with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA), 7 with polymyositis/dermatomyositis (PM/DM), 2 with progressive systemic sclerosis (PSS), 2 with anti-phospholipid antibody syndrome (APS), 1 with mixed connective tissue disease (MCTD), 1 with juvenile rheumatoid arthritis (JRA), 1 with Behcet's disease (BD), 1 with Wegener's granulomatosis (WG) and 1 with allergic granulomatous angiitis (AGA). Moderate to marked improvement was noted in 4 patients with SLE (2 with CNS-lupus and 2 with vasculitis), 7 with RA (2 with interstitial pneumonia:IP, 2 with vasculitis and 2 with refractory arthritis), 4 with PM/DM (2 with IP and 2 with refractory myositis), 1 PSS with IP, 2 APS with thrombocytopenia, 1 JRA with vasculitis and BD with CNS disturbance. On the other hand, adverse reactions were observed in 9 out of 35 patients (25.8%). CYP should apply in the treatment for such refractory rheumatic diseases as CNS disturbance, vasculitis, IP and autoimmune thrombocytopenia.

Capabilities of a four-layered feedforward neural network: four layers versus three.

Neural-network theorems state that only when there are infinitely many hidden units is a four-layered feedforward neural network equivalent to a three-layered feedforward neural network. In actual applications, however, the use of infinitely many hidden units is impractical. Therefore, studies should focus on the capabilities of a neural network with a finite number of hidden units, In this paper, a proof is given showing that a three-layered feedforward network with N-1 hidden units can give any N input-target relations exactly. Based on results of the proof, a four-layered network is constructed and is found to give any N input-target relations with a negligibly small error using only (N/2)+3 hidden units. This shows that a four-layered feedforward network is superior to a three-layered feedforward network in terms of the number of parameters needed for the training data.