Spontaneous Regression of Small Cell Lung Carcinoma and Associated Hemichorea.

The spontaneous regression (SR) of cancer is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and this phenomenon is rare in the case of small cell lung carcinoma (SCLC). We herein report an 83-year-old woman who presented with left-sided hemichorea associated with anti-SOX1 (SOX1-Ab) and -CV2/CRMP5 (CV2/CRMP5-Ab) antibodies with SR following a 7-year interval free of disease progression of SCLC. Hemichorea can present with the coexistence of anti-SOX1 and CV2/CRMP5-Ab with SR after a long interval free of SCLC. The immune response associated with these onco-neural antibodies may become independent of the original tumor trigger and remain active for many years.

[A case of spontaneous intracranial hypotension with transient neurological symptoms].

A 41-year-old woman experienced back pain upon waking up. Immediately afterward, she experienced a continual orthostatic headache. Thereafter, right ear fullness and dizziness also occurred. One month later, she became aware of repeated numbness that started in the right hand and spread to the right half of the body and lower limbs and continued for repeated periods of approximately 20-30 min. Neurological examination revealed no abnormal findings except for orthostatic headache. Electroencephalography showed no epileptic discharge. Head MRI revealed left convexal subarachnoid hemorrhage (cSAH) restricted to the prefrontal sulcus, left frontal cerebral venous thrombosis, diffuse dural thickening with gadolinium enhancement, and subdural hematoma in the posterior cranial fossa. Spinal MRI revealed epidural fluid accumulation around the thoracic spine. CT myelography revealed cerebrospinal fluid leakages at the cervical, thoracic, and lumbar vertebrae levels. The patient was diagnosed with spontaneous intracranial hypotension (SIH), which was treated effectively with a blood patch. In this case, cSAH may have resulted from rupturing of the vessel wall as a result of cortical venous thrombosis induced by SIH. The repeated transient neurologic symptoms suggesting migraine aura may have originated from cSAH, which in turn led to cortical spreading depression. The diagnosis and management of SIH can be often difficult; therefore, repeated migraine-aura-like symptoms are a critical sign of complication with cSAH and cortical venous thrombosis.

The effect of small vessel disease on motor and cognitive function in Parkinson's disease.

OBJECTIVES: Small vessel disease (SVD) has been associated with motor and cognitive impairments in neurodegenerative diseases. We investigated SVD markers using brain magnetic resonance imaging (MRI) and the global SVD score in Parkinson's disease (PD). PATIENTS AND METHODS: Seventy-one patients with PD were assessed for vascular risk factors, motor severity, and motor phenotype. Global cognition was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Based on the MoCA score, we categorized cases into normal (>23) or cognitively impaired (≤23). We calculated the total SVD score (range, 0-4) based on white matter hyper intensities (WMHs), lacunae, cerebral microbleeds (MBs), and enlarged perivascular spaces (PVSs). In addition, we evaluated global brain atrophy. RESULTS: There were no significant associations with total SVD score and vascular risk factors, PD severity, and motor phenotype. Increasing age and reduced MMSE and MoCA scores were associated with increased SVD burden. Logistic regression analyses demonstrated that periventricular WMH (PVH), PVS in the basal ganglia (BG-PVS), and atrophy were predictors of cognitive impairment in PD. CONCLUSION: The contribution of SVD may be important in elderly patients with PD. Impaired cognition due to SVD-related brain changes was associated with BG-PVS and PVH. These measures suggest that PD with PVS can provide novel insights into SVD.

Levofloxacin-associated Encephalopathy with Severe Hyperventilation.

A 64-year-old woman with no previous mental illness took a single 500 mg tablet of levofloxacin for cystitis. Two hours later, she developed psychosis with involuntary movement and severe hyperventilation with respiratory alkalosis. Cranial magnetic resonance imaging findings were unremarkable, and an electroencephalogram revealed no epileptiform discharge. Her symptoms improved on the third day after levofloxacin was discontinued. Levofloxacin-associated encephalopathy with psychotic features is a rare adverse event. Disturbance of gamma-aminobutyric acid-ergic (GABAergic) interneurons by levofloxacin may lead to hyperventilation via dysfunction of the brainstem respiratory network. Physicians should be aware of hyperventilation as an additional serious symptom of levofloxacin-associated encephalopathy in acute settings.

Influence of cerebral white matter hyperintensities on cognitive impairment in elderly medical patients.

AIM: We investigated the characteristics of elderly medical patients with white matter hyperintensities on magnetic resonance imaging. METHODS: A total of 213 patients (123 men and 90 women; mean age 74.8 years) reported their history of hypertension, diabetes, dyslipidemia, previous stroke, coronary heart disease and chronic kidney disease (CKD). All patients completed the Mini-Mental State Examination and Geriatric Depression Scale. White matter hyperintensities were evaluated for the periventricular region, basal ganglia (BGH), deep white matter and infratentorial region, and brain atrophy was calculated as bicaudate ratios. RESULTS: Patients with cognitive impairment (Mini-Mental State Examination score < 24) were significantly older (P = 0.001), had periventricular region hyperintensities (P = 0.029) and BGH (P = 0.0015), and showed atrophy (P < 0.0001). Logistic regression showed that cognitive impairment was predicted by stroke (OR 2.5, 95% CI 0.033-0.894, P = 0.036) and atrophy (OR 8.43, 95% CI 5.71-37.0, P = 0.0109). Multiple regressions showed that BGH was associated with CKD (ß = 0.213; P = 0.003), and infratentorial region was associated with stroke (ß = 0.157; P =0.035) and CKD (ß = 0.172; P = 0.016). Periventricular region was associated with age (ß = 0.2; P = 0.011) and Geriatric Depression Scale (ß = 0.151; P = 0.037), and deep white matter hyperintensities with age (ß = 0.189; P = 0.016). CONCLUSIONS: Although cognitive impairment in elderly medical patients is associated with stroke and brain atrophy, white matter hyperintensities, especially BGH and infratentorial region, are associated with cognitive decline in relation to CKD. Geriatr Gerontol Int 2017; 17: 1488-1493.

Effects of planting Phragmites australis on nitrogen removal, microbial nitrogen cycling, and abundance of ammonia-oxidizing and denitrifying microorganisms in sediments.

We examined the effect of planting an emergent aquatic plant (Phragmites australis) on nitrogen removal from sediments using a 42-d pot experiment. The experimental pot systems comprised two types of sediments planted with and without young P. australis. Total nitrogen (total N), total dissolved N, and NH4-N in the sediments decreased markedly after planting. In contrast, those levels decreased only slightly in the unplanted sediments. The decrease in total N in the P. australis-planted sediments was 7-20 times those in the unplanted sediments. Abundances of bacterial 16S rRNA, archaeal 16S rRNA, ammonia-oxidizing bacterial ammonia monooxygenase (amoA), ammonia-oxidizing archaeal amoA, and denitrifying bacterial nitrite reductase (nirK) genes increased significantly in sediments after planting. Phragmites australis appears to have released oxygen and created a repeating cycle of oxidizing and reducing conditions in the sediments. These conditions should promote mineralization of organic N, nitrification, and denitrification in the sediments. Phragmites australis absorbed bioavailable nitrogen generated by microbial nitrogen metabolism. During the 42-d period after planting, 31-44% of total N was removed by microbial nitrogen cycling, and 56-69% was removed via absorption by P. australis. These results suggest that planting P. australis can increase microbial populations and their activities, and that nitrogen removal can be accelerated by the combined functions of P. australis and microorganisms in the sediment. Thus, planting P. australis has considerable potential as an effective remediation technology for eutrophic sediments.

Orthostatic Blood Pressure Changes and Subclinical Markers of Atherosclerosis.

BACKGROUND: Using a simple standing-up test in normotensive subjects, we evaluated orthostatic upright postural blood pressure (BP) changes and autonomic nervous function, as well as the relationship between orthostatic BP changes and subclinical markers of atherosclerosis. METHODS: A total of 515 normotensive subjects aged 35-75 years (58.4±10.0 years) were enrolled. We measured body mass index (BMI), systolic BP (SBP) and diastolic BP (DBP), serum lipids, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and urinary albumin-to-creatinine ratio. Brachial to ankle pulse wave velocity (baPWV) and carotid mean intima-media thickness (IMT) were measured. Participants underwent a simple standing-up test involving sitting then standing for 2 minutes each, followed again by sitting. To evaluate autonomic fluctuations, we calculated the coefficient of variation of the R-R interval, the ratio of low to high frequency heart rate variability (LF/HF), and the coefficient of component variance of high frequency. RESULTS: SBP and DBP decreased when standing, with a reduction of SBP when changing position of -8.0±10.2mm Hg. Orthostatic hypotension (OH) produced a significantly higher SBP than without OH. The baPWV was significantly higher in OH than in without OH. Stepwise regression analysis adjusted for age, sex, BMI, baseline SBP, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, HbA1c, hs-CRP, IMT, late systolic peak of the pressure wave form (SBP2), and baPWV confirmed that baPWV, SBP2, and triglycerides were independently related to orthostatic BP changes. Multiple regression analyses showed that a decrease in SBP as well as baseline SBP, age, BMI, and fasting glucose were independent determinants of PWV. CONCLUSIONS: We have shown that increased arterial stiffness was associated with OH during a standing-up test. Arterial stiffness may contribute to greater BP responses to postural changes from standing.

Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS.

We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high-intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient's symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS.

[A case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion].

A 26-year-old male was admitted because of a fever, headache and disturbance of consciousness with lymph node swelling of the neck two days after developing a rash. A neurological examination revealed restlessness with irritability in response to sensory stimuli, such as an injection. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed a hyperintense ovoid lesion in the splenium of the corpus callosum, which showed a low coefficient in the ADC map: the lesion disappeared after 22 days. An enzyme immunoassay (EIA) of the serum and cerebrospinal IgM were positive for rubella virus. The patient was therefore diagnosed with rubella encephalitis. He recovered gradually and was discharged on day 19 after the onset of symptoms without any sequelae. To our knowledge, this is the first case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Although the exact mechanism underlying the development of rubella encephalitis is not well established, this case indicated that our patient had an immune-mediated secondary encephalitis. According to the survey of the pandemic of rubella from 2012 to April 2013 in Japan, the incidence of rubella encephalitis is thought to be relatively higher than was previously noted. This emphasizes the importance of vaccination for preventing encephalitis.

[A case of subacute parkinsonism presenting as bilateral basal ganglia legions by MRI in diabetic uremic syndrome].

A 60-year-old male was admitted because he had developed tremulous movement in both upper and lower limbs and gait disturbance over the course of 3 months. He had been on continuous ambulatory peritoneal dialysis almost 1 year earlier due to end-stage diabetic nephropathy. A neurological examination revealed a mild disturbance of his consciousness, asterixis in the upper limbs, bilateral extensor plantar responses and parkinsonism, which were characterized by bradykinesia, akinesia, rigidity, and bilaterally tremors at rest. Cranial magnetic resonance imaging (MRI) revealed swollen bilateral basal ganglia legions, which appeared hyperintense on T2-weighted images. The patient was treated for metabolic acidosis and continued hemodialysis three times a week; however, the parkinsonism remained 1 year later. Follow-up MRI revealed decreased swelling of the basal ganglia, and the pattern of diffusion-weighted images and the apparent diffusion coefficient (ADC) map indicated vasogenic and cytotoxic edema in bilateral globus pallidus. The case was diagnosed as encephalopathy due to diabetic uremic syndrome, initially characterized by Wang et al. (2003). Only 17 cases with parkinsonism have been reported. Diabetic uremic syndrome is characterized by acute or subacute onset consciousness disturbance and movement disorders such as parkinsonism, chorea and the other extrapyramidal signs to various degrees related to bilateral lesions of the basal ganglia.

Moderate renal dysfunction may not require a cisplatin dose reduction: a retrospective study of cancer patients with renal impairment.

OBJECTIVE: The aim of this study was to assess the tolerability of cisplatin (CDDP) in patients with moderate renal dysfunction. METHODS: To investigate the relationship between CDDP dose and nephrotoxicity, a retrospective chart review was conducted of patients with a creatinine clearance (Ccr) of 30-60 mL/min. Subjects were classified into three groups according to the CDDP dose, as determined by the physician, and the nephrotoxicity among these groups was compared. Additionally, we investigated the correlation coefficients between maximum serum creatinine (Scr) level or minimum estimated glomerular filtration rate (eGFR) and baseline Ccr. RESULTS: Fifty-six patients were included in this study. Among these patients, 13 patients received 30-40 mg/m(2) CDDP (group I), 18 patients received 40-70 mg/m(2) (group II), and 25 patients received 70-80 mg/m(2) (group III). No significant difference in nephrotoxicity was observed (median Scr 1.53, 1.61, and 1.53 mg/dL, respectively), and no correlation was observed between baseline Ccr and maximum Scr (r = 0.004, p = 0.979) or minimum eGFR (r = 0.21, p = 0.119). Only two patients (3.5 %) experienced grade 3 or 4 Scr elevation-one patient with a Ccr of 52.6 mL/min received 60 mg/m(2) CDDP, and the other patient with a Ccr of 52.1 mL/min received 70 mg/m(2) of CDDP. Hemodialysis was not observed. CONCLUSION: CDDP was tolerated at doses of 35-80 mg/m(2) among patients with moderate renal impairment. Empiric dose reduction might create a risk of under-treatment.

Spatial frequency differentially affects habituation in migraineurs: a steady-state visual-evoked potential study.

A lack of habituation in visual-evoked potentials (VEPs) is the main abnormality observed in migraineurs. However, no study of steady-state VEPs has yet evaluated pattern-reversal stimuli with respect to habituation behavior or spatial frequency. The aim of this study was to clarify habituation behavior in migraineurs between attacks and to establish characteristics of VEPs in these patients. Steady-state VEPs were sequentially recorded as checkerboard patterns in four consecutive blocks from 12 patients with migraine without aura (MO), 12 patients with migraine with aura (MA), and 12 healthy controls (HC) at four spatial frequencies of 0.5, 1.0, 2.0, and 4.0 cycles per degree (cpd) with a stimulus rate of 7.5 Hz (15 reversal/s). VEP amplitudes were consistently higher in migraineurs. However, habituation was not demonstrated in HCs, and migraineurs did not reveal a clear lack of habituation. MAs exhibited high-amplitude VEPs, depending on spatial frequency. In the MA patients, amplitude differences reached statistical significance at 2.0 cpd. The sequential amplitude changes at 0.5 cpd were significantly different in MAs compared with HCs. Migraine patients exhibited high-amplitude VEPs, which were dependent on spatial frequency, and may be related to altered excitability in pre-cortical and cortical visual processing.

Isolated homonymous hemianopsia due to lateral posterior choroidal artery region infarction: a case report.

An 86-year-old, right-handed, hypertensive man suddenly experienced blurring of vision predominating in the left visual field. Neurological examinations were normal, except for left homonymous hemianopsia. Goldmann visual field testing revealed a left congruent incomplete homonymous hemianopsia with macular splitting. Brain MRI, with a T2-weighted image, demonstrated a lesion of high intensity in the right lateral geniculate body (LGB), as well as the posterior part of the caudate nucleus, posterolateral thalamus, and dorsolateral thalamus. MRA revealed severe stenosis at the second segment of right posterior cerebral artery (PCA). SPECT revealed significantly decreased blood perfusion in the striate cortex. To the best of our knowledge, this is the first case of an isolated, congruent, incomplete, homonymous hemianopsia due to lateral posterior choroidal artery (LPChA) region infarction. The LPChA possibly supplied the LGB through the PCA system. A horizontal, homonymous sectoranopia is typically the hallmark of an LPChA region infarction. However, a homonymous hemianopsia may also occur when the entire LGB has been affected. In the case of homonymous hemianopsia, LGB damage due to LPChA region infarction should be considered, in addition to lesions of the visual pathway, such as the optic tract, optic radiations, and occipital cortex.

Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer.

Primary liver cancers are classified into three types based on their morphology and cytogenetic characteristics hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (CHC). It is often difficult to distinguish these liver tumors. Glypican-3 (GPC3) is serological and histochemical marker of hepatocellular carcinoma. In order to separate these three types of liver cancers, we analyzed the GPC3 expression in 85 liver resection specimens, including 46 HCCs, 28 ICCs and 11 CHCs. GPC3 immunohistochemical staining was used to distinguish HCC from ICC by comparing with the conventional biomarker, alpha-fetoprotein (AFP). The immunostaining of GPC3 was identified in 78.3% (36/46) of HCCs, 60% (9/15) of well differentiated, 88.9% (16/18) of moderately differentiated and 84.6% (11/13) of poorly differentiated HCCs. It was negative in the ICCs. We confirmed that GPC3 expression is specific to HCC component (8/11, 72.7%) but few samples also showed weakly in ICC component (2/11, 18.2%) of CHC sections among 11 cases compared with HCC biomarkers including AFP and hepatocyto paraffin 1 (HepPar1), and ICC biomarkers cytokeratin (CK) 7 and CK19. Three cases in which the macroscopic features resembled ICC did not express GPC3 even in the pathological HCC component. Most (10/11, 91%) of the pathological cholangiocarcinoma components in CHC showed positive staining for CK7 and CK19. The results of this study suggest that GPC3 is a biomarker that is sensitive and specific to HCC component of CHC, and CK7 and CK19 are markers for pathological cholangiocarcinoma component of CHC.

Study of intra-abdominal fat distribution in sigmoid colon cancer in Japanese patients by use of MDCT data.

To assess the relationship between intra-abdominal fat and sigmoid colon cancer, we investigated the intra-abdominal fat distribution in 172 examples of sigmoid colon cancer and 767 examples of various other pathologies by using data from multidetector-row computed tomography. One significant finding was that the intra-abdominal fat area in sigmoid colon cancer presents a small secondary peak in the pelvis on the profile of the intra-abdominal fat, which we called the pelvic sub-peak. The presence or absence of the pelvic sub-peak was determined based on the sub-peak ratio, which was calculated by dividing the maximum peak by the sub-peak value on the profile of the intra-abdominal fat area. The pelvic sub-peak was defined as having a sub-peak ratio >or=0.1. The pelvic sub-peak frequency was higher for all male patients than for female patients. The frequency of the pelvic sub-peak in sigmoid colon cancer was 77.5% (79/102) for men and 50.0% (35/70) for women. Among both men and women, frequencies of the pelvic sub-peak were significantly higher in patients with sigmoid colon cancer than in non-tumor cases (P < 0.001). Furthermore, the frequency of the pelvic sub-peak was almost the same in sigmoid colon cancer as in rectal cancer. No causal relationship between sigmoid colon cancer and a pelvic sub-peak could be confirmed in the present study; however, patients with sigmoid colon cancer tended to exhibit a unique pattern of fat accumulation.

Butyrate induces necrotic cell death in murine colonic epithelial cell MCE301.

Recent findings have suggested that organic acids produced by anaerobic intestinal bacteria might contribute to the pathogenesis of colonic ulcers. In this study, it was shown that butyrate caused potent cytotoxicity in the murine normal colonic epithelial cells MCE301 at physiological concentrations. Several markers of apoptosis, such as phosphatidyl serine externalization, cytochrome c release, DNA fragmentation, and chromatin condensation were negative after butyrate exposure. Inhibitor of caspases failed to protect against butyrate cytotoxicity. By transmission electron microscopy, marked swollen mitochondria and vacuolization within the cytoplasm was observed by treatment of butyrate. Collective, these data indicated that butyrate-induced cell death caused through a necrosis-like process. Butyrate induced cell death was reduced partially by treatment with prednisolone or 5-aminosalicylates in a concentration dependent manner. These results suggest that (1) butyrate induces necrotic cell death but not apoptotic cell death, and (2) the necrotic cell death induced by butyrate may be useful as a novel in vitro model of ulcerative colitis to screen useful drugs for the treatment of the disease.

Nascent peptide-mediated translation elongation arrest coupled with mRNA degradation in the CGS1 gene of Arabidopsis.

Expression of the Arabidopsis CGS1 gene that codes for cystathionine gamma-synthase is feedback regulated at the step of mRNA stability in response to S-adenosyl-L-methionine (AdoMet). A short stretch of amino acid sequence, called the MTO1 region, encoded by the first exon of CGS1 itself is involved in this regulation. Here, we demonstrate, using a cell-free system, that AdoMet induces temporal translation elongation arrest at the Ser-94 codon located immediately downstream of the MTO1 region, by analyzing a translation intermediate and performing primer extension inhibition (toeprint) analysis. This translation arrest precedes the formation of a degradation intermediate of CGS1 mRNA, which has its 5' end points near the 5' edge of the stalled ribosome. The position of ribosome stalling also suggests that the MTO1 region in nascent peptide resides in the ribosomal exit tunnel when translation elongation is temporarily arrested. In addition to the MTO1 region amino acid sequence, downstream Trp-93 is also important for the AdoMet-induced translation arrest. This is the first example of nascent peptide-mediated translation elongation arrest coupled with mRNA degradation in eukaryotes. Furthermore, our data suggest that the ribosome stalls at the step of translocation rather than at the step of peptidyl transfer.