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Case: A 52-year-old man developed a cerebral infarction from the right middle cerebral artery occlusion, and the infarction extensively damaged the right insula. Three months after the onset of the cerebral infarction, persistent hiccups appeared, occurring during sleep. The thoracic and abdominal cavities showed no lesions; hence, the hiccups were considered to be caused by central nervous system dysfunction. Administration of metoclopramide, chlorpromazine, and diazepam were ineffective, while levetiracetam had a partial effect. Combining perampanel with baclofen finally suppressed the symptoms., Discussion: Lesions at the right insula impair respiratory reflex and may present with hiccups as a symptom of respiratory reflex disinhibition. Here, we review similar cases of treatment-resistant hiccups, as well as perampanel and baclofen efficacy in myoclonus cases., Conclusions: Our patient's case suggested that perampanel with baclofen may be effective for myoclonus due to respiratory reflex disinhibition and can be used to treat hiccups derived from cerebral infarctions., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The effectiveness of Japanese helicopter emergency medical services (HEMS) and interventions at the scene is not clear as regard children. For effective use of HEMS at the clinical scene, we need to clarify the characteristics of pediatric patients cared for by HEMS. Therefore, the objective of this study was to describe the characteristics of pediatric scene flights and to describe the procedures performed on the patients., Methods: This was a retrospective cohort study based on the database for children aged younger than 18 years who were cared for by physician-staffed HEMS of Ibaraki prefecture, in Japan. We reviewed the database for air medical transports conducted at our institution from July 2010 to December 2016., Results: During the 6.5-year period, the Ibaraki HEMS attended to 288 children. The median age of the children was 11 (interquartile range, 5-14) years. Of the total, 196 (68.1%) of the children had trauma-related injuries. The head was the most common site of significant injuries (12.4%). The most common cause of nontrauma incidents was seizure (9.0%). In 65.9% of the patients, the injury or illness was of mild or moderate severity at the scene. An intervention was applied at the scene in 76.0% of the cases: 75.1%, intravenous route; 6.9%, intubation; and 13.4%, drug administration. Of those patients, 29.1% were discharged from the emergency department. In-hospital mortality accounted for 1.5% (n = 2) of the cases., Conclusions: Although the condition at the scene of most of the pediatric patients transported by the physician-staffed HEMS was not severe, an intervention was frequently applied from the scene. Improving the dispatch criteria and monitoring compliance are needed for appropriate use of HEMS., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Slow wave with frequency <0.5 Hz are recorded in various situations such as normal sleep, epileptic seizures. However, its clinical significance has not been fully clarified. Although infra-slow activity was recently defined as activity between 0.01 and 0.1 Hz, we focus on the activity recorded with time constant of 2 seconds for practical usage. We defined short "infraslow" activity (SISA) less than 0.5 Hz recorded with time constant of 2 seconds and investigated the occurrence and clinical significance of SISA in acute anoxic encephalopathy., Methods: This study evaluated the findings of electroencephalography in consecutive 98 comatose patients with acute anoxic encephalopathy after cardiac arrest. We first classified electroencephalography findings conventionally, then investigated SISA by time constant of 2 second and a high-cut filter of 120 Hz, to clarify the relationship between SISA and clinical profiles, especially of clinical outcomes and occurrence of acute posthypoxic myoclonus or acute symptomatic seizures., Results: Short infra-slow activity was found in six patients (6.2%), superimposed on the burst phase of the burst-suppression pattern. All six patients showed acute posthypoxic myoclonus or acute symptomatic seizures (generalized tonic-clonic seizures) and its prognosis was poor. This 100% occurrence of acute posthypoxic myoclonus or acute symptomatic seizures was significantly higher than that in patients without SISA (39.1%; P < 0.05)., Conclusions: Short infra-slow activity in acute anoxic encephalopathy could be associated with acute posthypoxic myoclonus and acute symptomatic seizures. Short infra-slow activity could be a practically feasible biomarker for myoclonus or seizures and poor prognosis in acute anoxic encephalopathy, if it occurs with burst suppression.

Objectives: In addition to motor symptoms, bladder dysfunction is a major clinical issue in patients with Parkinson disease (PD). Istradefylline is adenosine A2A receptor antagonist approved for PD patients with wearing-off symptoms. The aim of this study was to determine the long-term effects of istradefylline on lower urinary tract symptoms (LUTSs) in PD patients., Methods: We enrolled 14 male PD patients. The mean age of patients was 73 years (61-77 years), the Hoehn-Yahr stage was 2 (2-3), and disease duration was 9 years (3-28 years). The effects of istradefylline (20 mg/d) on LUTSs in PD patients with motor complications after 3, 6, and 12 months of therapy were evaluated based on the International Prostate Symptom Score and Overactive Bladder Symptom Score before and after its administration., Results: Motor symptoms significantly improved at 12 months' administration (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III: 30.0 ± 12.9 vs 13.8 ± 8.1; P < 0.01). Significant improvements were also observed in the answers provided on urinary questionnaires (International Prostate Symptom Score, 14.4 ± 7.6 vs 8.5 ± 6.8; Overactive Bladder Symptom Score, 6.9 ± 2.8 vs 5.5 ± 3.7; P < 0.05). Nighttime urinary frequency and the percentage of the nocturnal urine volume also improved significantly at 3 months' administration (P < 0.01)., Conclusions: Istradefylline effectively improved not only motor symptoms, but also LUTSs in patients with PD.

Objective: Plasma platelet-activating factor (PAF) acetylhydrolase (AH) is an enzyme bound with lipoproteins that degrades not only PAF but also PAF-like oxidized phospholipids that are proposed to promote atherosclerosis. In this study, we investigated the distribution of PAF-AH protein among lipoprotein classes by using adenovirus-mediated gene transfer in mice, and we examined its effects on lipoprotein oxidation and foam cell formation of macrophages., Methods and Results: Adenovirus-mediated overexpression of PAF-AH in mice resulted in a 76- to 140-fold increase in plasma PAF-AH activity. Contrary to the previous report, overexpressed human PAF-AH protein was bound to very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and high density lipoprotein (HDL). All the lipoproteins with overexpressed human PAF-AH revealed more resistance against oxidative stress, which was associated with lower levels in autoantibody against oxidized low density lipoprotein in the plasma. In addition, HDL with human PAF-AH inhibited foam cell formation and facilitated cholesterol efflux in macrophages., Conclusions: These results suggest that human plasma PAF-AH exerts an antiatherogenic effect by binding to all the lipoproteins and thereby protecting them from oxidation, producing less proatherogenic lipoproteins and preserving HDL functions.

Objective: Apolipoprotein E (apoE) mediates cellular cholesterol efflux and plays a crucial role in the inhibition of atherogenesis. We investigated whether there is an isoform-specific difference in its function for cholesterol efflux from cholesterol-loaded RAW264.7 cells, a murine macrophage cell line that lacks endogenous apoE expression., Methods and Results: When human apoE was expressed in RAW264.7 cells, apoE2 reduced cellular total cholesterol (TC) and esterified cholesterol (EC) levels significantly, whereas apoE3 and apoE4 had no effect. However, treatment of cells with 4-methylumbelliferyl-7-beta-D-xyloside (beta-DX) resulted in all 3 isoforms' reducing cellular TC and EC contents significantly. We also investigated the effect of exogenously derived apoE on cholesterol efflux by utilizing the medium harvested from HeLa cells expressing apoE. ApoE2 and E3 reduced both cellular TC and EC contents significantly, whereas apoE4 did not. However, treatment of the cells with beta-DX resulted in all 3 exogenously derived apoE isoforms' reducing TC and EC contents significantly. The binding ability of apoE to heparan sulfate proteoglycans examined by heparinase I treatment revealed less binding ability of apoE2 compared with that of apoE3 or apoE4., Conclusions: The present study clarified the differential cellular cholesterol-modulating effect of apoE isoforms in macrophages, which would be due to the difference in their binding to proteoglycans.

Objective: We examined the possible association between insulin resistance and carotid arteriosclerosis in subjects who had both normal fasting glucose and normal glucose tolerance after intake of a glucose load., Methods and Results: Our subjects were individuals who underwent general health screening at our institute, which included carotid ultrasound and oral glucose tolerance testing. Of the 1238 subjects enrolled in our study, 738 (60%) were classified as normal, defined as a normal fasting glucose level and normal glucose tolerance, and 334 (27%) and 166 (13%) were classified as borderline and diabetic, respectively, according to the criteria of the Japan Diabetes Society. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to measure insulin resistance. In normal-type subjects, univariate analysis showed that insulin resistance, but not insulin secretion, was associated with the presence of carotid plaque. Multivariate analysis showed that HOMA-IR was positively associated with carotid plaque in normal-type subjects, with an odds ratio of 1.19 (95% confidence interval, 1.00 to 1.41; P<0.05)., Conclusions: These data suggest the possibility that the presence of higher insulin resistance could be a risk factor for carotid arteriosclerosis in subjects with normal fasting glucose and normal glucose tolerance.

Objective: Heme oxygenase (HO) is important in the defense against oxidative stress and as a factor in an antiatherogenic mechanism. Compared with long (GT)(n) repeats, short (GT)(n) repeats in the human HO-1 gene promoter were shown to have higher transcriptional activity in response to oxidative stress. There is a strong link between oxidative stress and the pathogenesis of coronary artery disease (CAD)., Methods and Results: We screened the allelic frequencies of (GT)(n) repeats in the HO-1 gene promoter in 577 patients who underwent coronary angiography. Because the distribution of numbers of (GT)(n) repeats was bimodal, we divided the alleles into 2 subclasses: class S included shorter (<27) repeats, and class L included longer (> or =27) repeats. Multivariate logistic regression models including standard coronary risk factors revealed that the genotypes were significantly related to CAD status in hypercholesterolemic, diabetic patients or in smokers. In this study, the patients with shorter GT repeats were less likely to have CAD., Conclusions: Length polymorphism in the HO-1 gene promoter is related to CAD susceptibility in Japanese people who also have coronary risk factors such as hypercholesterolemia, diabetes, and smoking. HO-1 may play an antiatherogenic role in Japanese patients with these coronary risk factors.