Detection of ictal and periictal hyperperfusion with subtraction of ictal-interictal 1.5-Tesla pulsed arterial spin labeling images co-registered to conventional magnetic resonance images (SIACOM).

Background: Our recent report showed that 1.5-T pulsed arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging (1.5-T Pulsed ASL [PASL]), which is widely available in the field of neuroemergency, is useful for detecting ictal hyperperfusion. However, the visualization of intravascular ASL signals, namely, arterial transit artifact (ATA), is more remarkable than that of 3-T pseudocontinuous ASL and is easily confused with focal hyperperfusion. To eliminate ATA and enhance the detectability of (peri) ictal hyperperfusion, we developed the subtraction of ictal-interictal 1.5-T PASL images co-registered to conventional MR images (SIACOM). Methods: We retrospectively analyzed the SIACOM findings in four patients who underwent ASL during both (peri) ictal and interictal states and examined the detectability for (peri) ictal hyperperfusion. Results: In all patients, the ATA of the major arteries was almost eliminated from the subtraction image of the ictal-interictal ASL. In patients 1 and 2 with focal epilepsy, SIACOM revealed a tight anatomical relationship between the epileptogenic lesion and the hyperperfusion area compared with the original ASL image. In patient 3 with situation-related seizures, SIACOM detected minute hyperperfusion at the site coinciding with the abnormal electroencephalogram area. SIACOM of patient 4 with generalized epilepsy diagnosed ATA of the right middle cerebral artery, which was initially thought to be focal hyperperfusion on the original ASL image. Conclusion: Although it is necessary to examine several patients, SIACOM can eliminate most of the depiction of ATA and clearly demonstrate the pathophysiology of each epileptic seizure.

Investigation of Endotoxin Positivity in Ascites at the Time of Cell-free and Concentrated Ascites Re-infusion Therapy.

Objective The presence of endotoxin (ET) in ascites at the time of cell-free and concentrated ascites reinfusion therapy (CART) is generally assessed in patients with infectious disease status, but the exact rate of ET positivity in ascites for patients treated with CART is unknown. Methods We evaluated ET levels in ascites at the time of CART, regardless of the presence of infectious symptoms. The analysis was performed for 529 cases in 183 patients in whom ET levels in ascites were measured at 2 time points (pre- and post-processing). Results ET in ascites was positive in 8 of 529 cases. In the positive cases, the ET level after CART was significantly decreased. ET-positive patients had a significantly higher white blood cell count, neutrophil count, and serum CRP level before CART than ET-negative patients. Conclusion Collectively, our data suggest that ET may be present in ascites, regardless of the infectious symptoms, especially in patients with a high white blood cell count, neutrophil count, and serum CRP level. Although the ET level in the re-infusion ascites seems to be decreased by CART, the possibility of endotoxemia after CART should be considered for such patients.

The fluctuation of skin perfusion pressure in hemodialysis patients treated with LDL apheresis therapy: A comparison of LDL adsorption and double filtration plasmapheresis.

BACKGROUND: There have been a number of reports suggesting that LDL apheresis, including LDL adsorption and double filtration plasmapheresis (DFPP), can be applied for the treatment of lower extremity peripheral arterial disease (PAD) in hemodialysis patients, whereas there is no definitive recommendation for the use of LDL apheresis. STUDY DESIGN: The change of skin perfusion pressure (SPP) during LDL apheresis was measured in every single treatment to determine the effect of LDL adsorption and DFPP on improving blood flow in lower extremity PAD hemodialysis patients. Eleven hemodialysis patients treated with more than two series of LDL apheresis were involved in the study. "One series" included 10 treatments of LDL apheresis according to the Japanese health care insurance system. RESULTS: In total, 320 treatments (32 series) of LDL apheresis were performed utilizing either LDL adsorption or DFPP treatment in 11 patients. The SPP values pre- and post-apheresis were recorded in 315 treatments (228 LDL adsorption and 87 DFPP). The SPP was significantly improved after both LDL adsorption (P < .001) and DFPP (P = .002) treatment. The median change of SPP was significantly larger in the LDL adsorption group (12.6 mm Hg, range: -48.5, 77.0 mm Hg) than in the DFPP group (6.7 mm Hg, range: -42.0, 72.5 mm Hg) (P = .003). The LDL adsorption consistently offered a significant increase in the SPP, whereas DFPP treatment seemed to have modest effects on the improvement of SPP compared to the LDL adsorption. CONCLUSIONS: These data indicate that LDL adsorption should be considered the primary LDL apheresis therapy for lower extremity PAD in hemodialysis patients to achieve improvement of blood flow.

Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis.

Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.

Implications and limitations of magnetic resonance perfusion imaging with 1.5-Tesla pulsed arterial spin labeling in detecting ictal hyperperfusion during non-convulsive status epileptics.

Background: Recent our reports showed that 3-T pseudocontinuous arterial spin labeling (3-T pCASL) magnetic resonance perfusion imaging with dual post labeling delay (PLD) of 1.5 and 2.5 s clearly demonstrated the hemodynamics of ictal hyperperfusion associated with non-convulsive status epilepticus (NCSE). We aimed to examine the utility of 1.5-T pulsed arterial spin labeling (1.5-T PASL), which is more widely available for daily clinical use, for detecting ictal hyperperfusion. Methods: We retrospectively analyzed the findings of 1.5-T PASL with dual PLD of 1.5 s and 2.0 s in six patients and compared the findings with ictal electroencephalographic (EEG) findings. Results: In patients 1 and 2, we observed the repeated occurrence of ictal discharges (RID) on EEG. In patient 1, with PLDs of 1.5 s and 2.0 s, ictal ASL hyperperfusion was observed at the site that matched the RID localization. In patient 2, the RID amplitude was extremely low, with no ictal ASL hyperperfusion. In patient 3 with lateralized periodic discharges (LPD), we observed ictal ASL hyperperfusion at the site of maximal LPD amplitude, which was apparent at a PLD of 2.0 s but not 1.5 sec. Among three patients with rhythmic delta activity (RDA) of frequencies <2.5 Hz (Patients 4-6), we observed obvious and slight increases in ASL signals in patients 4 and 5 with NCSE, respectively. However, there was no apparent change in ASL signals in patient 6 with possible NCSE. Conclusion: The detection of ictal hyperperfusion on 1.5-T PASL might depend on the electrophysiological intensity of the epileptic ictus, which seemed to be more prominent on 1.5-T PASL than on 3-T pCASL. The 1.5-T PASL with dual PLDs showed the hemodynamics of ictal hyperperfusion in patients with RID and LPD. However, it may not be visualized in patients with extremely low amplitude RID or RDA (frequencies <2.5 Hz).

Efficacy and Usefulness of New Single-Needle Intensive Granulocyte and Monocyte Adsorptive Apheresis in Active Ulcerative Colitis Patients Without Corticosteroids and Biologics.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

[Usefulness of image fusion for the treatment guidance of cavernous sinus dural arteriovenous fistula].

Before treating an arteriovenous fistula, it is important to understand its features, particularly the shunting point, sinus form, and drainage route. However, this can often be difficult owing to the large number of vessels that accumulate in the fistula region. In this study, we employed image fusion technology to understand the pathology of cavernous sinus dural arteriovenous fistulas (CSdAVFs) prior to treatment. We performed the following three types of fusions on the workstation: three-dimensional rotation angiography (3DRA) images from different feeding arteries to gain a detailed understanding of fistula architecture and shunting points; three-dimensional computed tomography (3DCT) and 3DRA images for determining the correlation between the skull base bone and the sinus shunt to predict the point of shunt access;and time-of-flight magnetic resonance imaging (TOF MRI) scans and 3DRA source images for investigating retrograde leptomeningeal venous drainage. Compared to individual images, the fused images more effectively provided a detailed understanding of CSdAVFs. Herein, we report our experience with image fusion for CSdAVF and review the relevant literature.

Granulomatous interstitial nephritis associated with atypical drug-induced hypersensitivity syndrome induced by carbamazepine.

We report the case of a 70-year-old female patient with granulomatous interstitial nephritis (GIN) induced by carbamazepine (CBZ). The patient had a 22-year history of bipolar disorder. Approximately 50 days before admission to our hospital, she was switched from valproic acid to 200 mg/day CBZ for mood swings. Forty days later, she presented with mild transient platelet depletion and liver dysfunction along with a C-reactive protein (CRP) level of 2.65 mg/dL. At that time, she discontinued CBZ without consulting the doctor. She subsequently developed high fever and a pruritic maculopapular rash. Laboratory tests revealed an elevated CRP level (11.98 mg/dL) and serum creatinine (sCr) of 1.6 mg/dL. Hence, she was admitted to our hospital, where she showed eosinophilia and immunoglobulin suppression. She was diagnosed with atypical drug-induced hypersensitivity syndrome (DIHS). All drugs prescribed by the previous doctor were discontinued. A lymphocyte transformation test showed CBZ positivity; a renal biopsy revealed many granulomatous lesions connected to arterioles, without angionecrotic findings. The patient had no history of allergic disorders or tuberculosis. Because of psychological instability, we treated her conservatively without steroid administration. She had a good recovery except for mild residual renal insufficiency (sCr, 1.0 mg/dL). Although granuloma formation has been observed in kidney biopsy specimens of rare cases with DIHS, no previous studies have reported on the relationship between arterioles and granuloma formation.

[Case of a focal segmental glomerulosclerosis collapsing variant associated with a hypertrophic column of Bertin].

A 59-year-old Japanese man admitted to our hospital complaining of anasarca, body weight gain, and elevation of blood pressure. Serum creatinine(Cre), albumin(Alb), cholesterol(chol), and urinary protein were 1.3 mg/dL, 2.5 g/dL, 527 mg/dL, and 10 g/gCr, respectively. An abdominal echography showed a renal mass, which was diagnosed to be a hypertrophic column of Bertin by enhanced CT. His serum Cre and Alb had worsened to 1.6 mg/dL and 1.7 g/dL, respectively, and a renal biopsy was performed. The results showed a segmental sclerotic lesion associated with hypertrophy and proliferation of podocytes in several glomeruli, hence we diagnosed a focal segmental glomerulosclerosis collapsing variant. After steroid pulse therapy and LDL apheresis, his serum Cre level had decreased to 1.1 mg/dL and the urinary protein level to 2.5 g/gCr. Patients with a focal segmental glomerulosclerosis collapsing variant are poor responders to standard therapies, and have a very poor prognosis. For this case, combined steroid pulse and LDL apheresis therapy was effective.

[Case of lupus vasculopathy associated with lupus nephritis class IV-G (A)].

Various renal vascular lesions are complicated with systemic lupus erythematosus (SLE), and are often overlooked in the actual renal biopsy specimen. We report a case of biopsy-proven lupus vasculopathy, with lupus nephritis class IV-G (A). She developed SLE at 15 years of age, and was treated with prednisolone(PSL) and cyclophosphamide (CTX). Sometimes she experienced a flare-up clinically or serologically, requiring a dose increase of oral PSL. At 40 years of age, she visited our hospital after discontinuation of hospital visits for about 4 months. Oral PSL at 30 mg per day was not effective for urinary abnormalities, increase of anti double-stranded DNA (ds-DNA) antibody titer and decrease in complement components. On admission she had hypertension (180/92 mmHg) and signs of microangiopathic hemolytic anemia. Renal biopsy findings showed the glomerular changes of lupus nephritis, WHO class IV-G (A), and lupus vasculopathy, which is marked luminal narrowing or total occlusion by abundant subendothelial accumulation of immunoglobulins and complement components. In addition to PSL, intravenous pulse CTX promptly achieved clinical remission. When lupus vasculopathy is complicated, CTX may be useful.

Amino terminal cleavage of PTH(1-84) to PTH(7-84) is regulated by serum calcium concentration via calcium-sensing receptor in hemodialysis patients.

BACKGROUND: Secondary hyperparathyroidism is one of the critical complications of end-stage renal disease patients. Conventionally intact parathyroid hormone (iPTH) was used to assess secondary hyperparathyroidism, but this assay measures both PTH(1-84) (full-length parathyroid hormone) and PTH(7-84) (amino (N)-terminal-cleaved parathyroid hormone). PTH(7-84) is biologically inactive or antagonistic for PTH. In this study, we examined the relationship between serum calcium concentration and PTH(7-84)/PTH(1-84) ratio and the effect of calcimimetics on the ratio in hemodialysis (HD) patients. METHODS: Ionized-calcium (iCa), iPTH, and whole PTH (wPTH) were measured at the start of HD sessions on HD patients. Patients were divided into four groups by presence (+) or absence (-) of vitamin D (VD) and calcimimetics (CM). RESULT: PTH(7-84)/PTH(1-84) ratios of the four groups [VD(-)CM(-), VD(+)CM(-), VD(-)CM(+) and VD(+)CM(+)] were 0.735, 0.799, 0.844, and 1.156, respectively. In VD(-)CM(-) and VD(+)CM(-) groups, iCa and PTH(7-84)/PTH(1-84) ratio showed equilateral correlation (r = 0.634, p < 0.001 and r = 0.360, p < 0.01, respectively). In calcimimetics-treated group, iCa and PTH(7-84)/PTH(1-84) ratio did not show correlation. CONCLUSION: Whereas in the absence of calcimimetics cleavage of N-terminal PTH was regulated by serum calcium concentration, this regulation was abolished in the presence of calcimimetics. This suggests that cleavage of N-terminal PTH is regulated by calcium concentration via a calcium-sensing receptor and that calcimimetics may have a novel effect to reduce PTH level.

MRI of glossopharyngeal neuralgia caused by neurovascular compression.

OBJECTIVE: Glossopharyngeal neuralgia is rare but causes severe pain. We retrospectively evaluated preoperative MR images of patients with glossopharyngeal neuralgia caused by neurovascular compression. CONCLUSION: MRI may be beneficial in patients with glossopharyngeal neuralgia and an offending compressing artery. If the offending vessel was the posterior inferior cerebellar artery (PICA), a loop formation at the supraolivary fossette was always seen, whereas if it was the anterior inferior cerebellar artery (AICA), glossopharyngeal neuralgia was difficult to diagnose before surgery.

3-Methylthiopropionic acid ethyl ester, isolated from Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon), enhanced differentiation in human colon cancer cells.

The fully ripened fruit of Katsura-uri Japanese pickling melon ( Cucumis melo var. conomon) has rarely been used for food because the midripened fruit is utilized for making pickles, but the fully ripened fruit is no longer valuable for pickles due to the fruit body being too soft. We have considered the utilization of the fully ripened Katsura-uri fruit that may be used for nonpickling products, particularly if the fully ripened fruit demonstrated health benefits such as anticarcinogenic properties. The phytochemical extract from the fully ripened fruit of Katsura-uri Japanese pickling melon was purified via a bioassay-guided fractionation scheme, which was based on the induction of differentiation in a RCM-1 human colon cancer cell line. On the criteria of two differentiation markers (duct formation and alkaline phosphatase activity), the most potent fraction contained a compound identified as 3-methylthiopropionic acid ethyl ester, based on GC retention time, EI-MS, (1)H NMR, and (13)C NMR spectra. Previously, the role of 3-methylthiopropionic acid ethyl ester was considered as an odor producing compound in many fruits, but this study indicates potential medical benefits of this compound.

[Comparison between serum cystatin C and estimation of GFR by the MDRD study equation for chronic kidney disease].

Glomerular filtration rate(GFR) can be estimated from serum (s-) creatinine using the modification of diet in renal disease (MDRD). However, its calculation is sometimes cumbersome in clinical use. Cystatin C is less influenced by age, gender and muscle mass than serum creatinine, and it has been proposed as an alternative marker for estimating GFR (eGFR). The comparison of s-cystatin C with MDRD-eGFR from 245 Japanese outpatients with chronic kidney disease (CKD)resulted in the equation of eGFR = 82.8/s-cystatin C - 10.7 (r = 0.85, n = 245). Based on this equation, there were 22 patients above + SD, which was the high-group in which s-cystatin C levels were higher than the corresponding eGFR, and there were 21 patients below -SD, which was the low-group in which s-cystatin C levels were lower than the corresponding eGER. Between the two groups there was no significant difference in age, gender, weight, and body mass index. The high-group included 1 case of hyperthyroidism and 7 cases of steroid user. The low-group included 4 cases of hypothyroidism and 1 case of steroid user. In healthy individuals, MDRD-eGFR is unsuitable for estimating GFR. Thyroid dysfunction or glucocorticoid excess are known to influence s-cystatin C levels. An improved eGFR equation was provided from 144 cases excluding 88 with normal renal function (eGFR > 90 mL/min/1.73 m2), 5 with thyroid dysfunction and 8 steroid users. eGFR = 86.1/s-cystatin C - 13.6 (r = 0.94, n = 144). Each GFR estimation provided from males or from females yielded nearly the same results as this equation. The prediction of eGFR using s-cystatin C may be convenient and useful in clinical practice, and the comparison of s-cystatin C with creatinine-based eGFR may reveal some factors that affect s-cystatin C or s-creatinine levels independent of GFR.

ACE inhibitor-induced acute renal failure in a patient with progressive systemic sclerosis: ischemic nephropathy mimicking PSS renal crisis.

A 79-year-old woman with progressive systemic sclerosis (PSS) presented with acute pulmonary edema, hypertension and renal failure. Administration of angiotensin-converting enzyme (ACE) inhibitor under suspicion of PSS renal crisis resulted in worsening of the renal function, which necessitated hemodialysis. Magnetic resonance arteriogram (MRA) demonstrated stenosis of the right renal artery, and ischemic nephropathy was diagnosed. Renal function improved after the discontinuation of ACE inhibitor. ACE inhibitor/angiotensin II receptor blocker (ARB), which is recommended for PSS renal crisis, should be avoided in ischemic nephropathy. In elderly PSS patients, careful exclusion of ischemic nephropathy is warranted before the administration of ACE inhibitor/ARB.

A case of lymphangioleiomyomatosis affecting the supraclavicular lymph nodes.

The case of a 46-year-old woman with lymphangioleiomyomatosis (LAM) involving the supraclavicular, mediastinal, and pelvic lymph nodes in addition to the lungs is reported. Computed tomography incidentally revealed multiple thin-walled pulmonary cysts and low-attenuating masses in the supraclavicular, mediastinal, and retroperitoneal lymph nodes. A biopsy of the supraclavicular mass was performed and diagnosed as LAM histopathologically. The common sites of extrapulmonary LAM include retroperitoneal and mediastinal lymph nodes; however, supraclavicular lymph node involvement is extremely rare.

Novel method to estimate and display cerebral cortical degeneration using diffusion-weighted magnetic resonance imaging.

Previous studies have shown that diffusion-weighted imaging (DWI) is useful for detecting microstructural degradation of neuronal tissue in neurodegenerative diseases. Mapping of cortical degeneration by DWI is potentially useful, but is extremely difficult, mainly because of the partial volume effect resulting from the surrounding cerebrospinal fluid (CSF). In this study a novel method to map and display the cortical damage in neurodegenerative diseases using DWI is proposed. Instead of measuring the cortical diffusivity, the diffusivity of white matter directly beneath the cortex, where neuronal fibers enter or exit the overlying cortex, was measured and mapped onto the cortical surface. The map was viewed in a form of three-dimensional (3D) rendering. Patients with Alzheimer's disease (AD) showed cortical damage in the temporal and parietal cortices, and a patient with frontotemporal dementia showed damage in the frontal lobe, consistent with the typical topographical distribution of histopathological cortical damage in each of these diseases. The results suggest that subcortical diffusivity closely reflects cortical damage, and that the current mapping technique is a promising tool for evaluating neurodegenerative diseases.

[Case of traditional herbal medicine-induced aristolochic acid nephropathy developing to end-stage renal failure].

A 48-year-old male was referred to our university hospital for severe azotemia with muscle cramp. He had been taking Chinese herbs as a traditional medicine to reduce hyperuricemia for about 9 months. Urinalysis showed trace proteinuria and hematuria without any casts. Renal glucosuria was also observed. In addition to azotemia, hyperchloremic metabolic acidosis and severe anemia were revealed. Hemodialysis was conducted and his general condition improved. A renal biopsy specimen revealed severe interstitial fibrosis and tubular atrophy with cellular degeneration. No remarkable glomerular changes were observed except for wrinkling of the basement membrane in a few glomeruli. Aristolochic acid was detected in the Chinese herbs, leading to the diagnosis of aristolochic acid nephropathy (AAN). His renal dysfunction was considered to be irreversible and he underwent maintenance hemodialysis. In Japan, AAN or Chinese herbs nephropathy decreased after an outbreak from 1995 to 2000. The public should be warned again that Chinese herbs, which are not permitted by the Japanese government, may contain aristolochic acid.

Age-related structural changes in the young adult brain shown by magnetic resonance diffusion tensor imaging.

RATIONALE AND OBJECTIVE: Structure of the brain is generally thought to remain stationary over the course of young adulthood. However, there is some evidence that microstructural changes of the brain do occur during this period. Magnetic resonance diffusion tensor imaging (DTI) provides quantitative measures of structural changes in the brain. We used DTI to detect possible age-related structural changes in the brains of young adults. MATERIALS AND METHODS: Twenty-five healthy adults in their 20s and 30s were studied using DTI. Maps of mean diffusivity and fractional anisotropy (FA) were created for subsequent histogram and region-of-interest analyses, and the results were correlated with the respective ages of the subjects. RESULTS: The histogram analysis revealed a significant increase in the mean FA value (r = 0.407, P < .05) and a significant decrease in FA peak height (r = -0.578, P < .002) with increasing age. No age-related changes were observed in indices derived from mean diffusivity maps. Region-of-interest analysis showed no focal white matter regions with significant FA change. CONCLUSION: Quantitative DTI revealed age-related structural changes in the brains of young adults. Changes on FA histograms observed in this study were considered to be related to changes in the relative volumes of gray and white matter and may represent maturational changes.