Effects of pendant-like hydrophilic monomers on the adsorption properties of reversed-phase-type sorbents for solid-phase extraction.

Solid-phase extraction (SPE) has been extensively employed as a pretreatment method. In SPE, reversed-phase-type sorbents have been widely applied for the pretreatment of environmental or biological samples. Hydrophilic-lipophilic balance (HLB)-type sorbents, constituting the copolymers used as reversed-phase-type sorbents, have been applied for various sample pretreatment methods. In HLB-type sorbents, the hydrophilic monomer contributes to the improved wettability of sorbents and increase of polar interactions. In this study, three pendant-like hydrophilic monomers, viz. N-vinylpyrrolidone (NVP), 4-acryloylmorpholine (AMO), and 4-vinyl-1,3-dioxolan-2-one (VDO), respectively, exhibiting different Log P values and possibly causing different polar interactions, were selected to improve the adsorption properties of polar compounds, and divinylbenzene (DVB)-based HLB-type sorbents containing each hydrophilic monomer were synthesized and examined. By the optimization of the molar ratio of DVB and the hydrophilic monomer (i.e. HLB), the inert diluent, and the degree of cross-linking, the developed sorbents exhibited higher recoveries for various polar compounds (viz. cytosine, uracil, cytidine, uridine, 2'-deoxycytidine, 2'-deoxyguanosine, adenine, thymidine, adenosine, and 2'-deoxyadenosine) compared to commercially available HLB-type sorbents.

[Paraneoplastic Cerebellar Degeneration with Lambert-Eaton Myasthenic Syndrome: A Report of an Effectively Treated Case and Systematic Review of Japanese Cases].

A 63-year-old female who developed dizziness, diplopia and subsequent gait disturbance from September X-1 year was analyzed. The first neurological findings in May X year revealed cerebellar ataxia, weakness in the proximal limbs, decreased tendon reflexes, and autonomic symptoms (ADL:mRS 3). Furthermore, an incremental phenomenon was observed in the repetitive nerve stimulation test, and she was diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) based on the serum P/Q-type calcium channel (VGCC) antibody positivity. In addition, small cell lung cancer was detected by chest CT and bronchoscopy, and her cerebellar ataxia was diagnosed as paraneoplastic cerebellar degeneration (PCD). Therefore, the patient underwent chemotherapy and radiotherapy from June in X year. Six months after initiation of treatment, her cerebellar ataxia had almost disappeared and she could walk without assistance (ADL:mRS 1). The P/Q-type VGCC antibodies were also negative at that time. Cases wherein cerebellar ataxia resolved almost completely in parallel with disappearance of the serum P/Q-type VGCC antibodies are of great interest. We conducted a systematic literature review of PCD-LEMS cases in Japan reported since P/Q-type calcium channel antibody measurement was reported in 1995. As a result, 13 cases (including our study) that concurrently displayed cerebellar ataxia and LEMS were selected. The average age of the 13 patients (10 males and 3 females) was 61.5 years. Small cell carcinoma was complicated in 11 patients (10 in the lung and 1 in the oropharynx); in the other 2 patients, cancer was not found at the time of reporting (the observation period was as short as 1-2 months). The time from onset to treatment ranged between 1 week and 10 months. While 1 of the 13 patients developed cerebellar ataxia during the subsequent course of the treatment, the remaining 12 had already developed cerebellar ataxia and LEMS symptoms, although their main neurologic finding was cerebellar ataxia and they were subsequently diagnosed with LEMS after electrophysiological testing and autoantibody detection. Small cell carcinoma was found in 11 patients. We define the pathology following such a certain clinical course as PCD-LEMS. The P/Q-type VGCC antibodies were positive in 11 of the 13 cases, although their antibody titers were not necessarily very high. Treatment for the associated small cell carcinoma might have improved the neurological findings in 9 of the 11 PCD-LEMS patients. The P/Q-type VGCC antibodies were measured before and after the treatment. The PCD-LEMS symptoms improved in all patients and their antibody titers decreased. These findings indicate that P/Q-type VGCC antibodies are involved in the pathology of PCD-LEMS. Appropriate and timely treatment, at least in PCD-LEMS patients in Japan, that actively treats any associated cancer can be expected to improve not only life prognosis but also cerebellar ataxia. (Received October 15, 2018; Accepted November 5, 2018; Published January 1, 2019).

Effects of hydrophilic monomers on sorptive properties of divinylbenzene-based reversed phase sorbents.

Solid phase extraction (SPE) has been extensively used as a pretreatment method. In SPE methods, commercially available reversed phase type sorbents, which consist of macroporus styrene-divinylbenzene or copolymers including divinylbenzene (DVB) and hydrophilic monomers, have been applied to a variety of samples. The later sorbents are called hydrophilic lipophilic balanced (HLB) type sorbents. Hydrophilic monomers in hydrophilic lipophilic balanced type sorbents contribute to the increase in retention of polar compounds, because hydrophilic monomers improve the wettability and increase the interaction with polar compounds as analytes. In this study, three different methacrylate monomers (ethylene glycol dimethacrylate (EGDMA), glycerol dimethacrylate (GDMA) and trimethylolpropane trimethacrylate (TMPTMA)), which are expected to improve the retention of polar compounds, were chosen, and DVB-based copolymetric sorbents including the three monomers were newly synthesized. Among them, the sorbents including GDMA or TMPTMA gave higher recoveries to polar compounds such as uridine and adenine than that including EGDMA. The optimization studies of hydrophilic lipophilic balance, inert diluent and the purity of DVB improved the sorptive abilities of the sorbents. The developed sorbents have higher recoveries for variety of polar compounds (cytosine, uracil, cytidine, uridine, 2'-deoxycytidine, 2'-deoxyguanosine, adenine, thymidine, adenosine and 2'-deoxyadenosine) than commercially available hydrophilic lipophilic balanced type sorbents, while the recoveries for theophylline were comparable between the proposed sorbents and the commercial sorbents.

Optimal cut-off value and clinical usefulness of the Adherence Starts with Knowledge-12 in patients with asthma taking inhaled corticosteroids.

BACKGROUND: Non-adherence to inhalation regimens is common in asthmatic patients. The Adherence Starts with Knowledge-12 (ASK-12) survey was developed to detect and address patient-specific barriers to medication adherence. Our objective is to investigate the clinical usefulness of the ASK-12 for assessing and addressing adherence to inhalation therapy in asthma. METHODS: The ASK-12 was administered to 138 asthmatic patients. Using pharmacy-refill data, we examined the cut-off value of the ASK-12 to identify patients who were non-adherent to inhalation regimens and identify factors associated with non-adherence. To verify the usefulness of the ASK-12, inhalation regimens were prospectively switched to less-expensive and simpler (once-daily) dosing regimens in eight non-adherent asthmatic patients who reported specific-barriers in "inconvenience of twice-daily inhaler use" and "cost". RESULTS: Valid responses were received from 114 (82.6%) patients. A significant correlation was found between pharmacy-refill rates and the ASK-12 total score (r=-0.55, P<0.0001). The optimal cut-off value of the ASK-12 total score to discriminate non-adherent patients (defined by pharmacy-refill rate <80%) was 23, with 71.4% specificity and 93.3% sensitivity. Using this value, 52 (45.6%) patients were classified as non-adherent. Univariate followed by multivariate analysis identified younger age as a predictor of non-adherence to inhalation regimens (odds ratio, 2.67; 95% CI, -0.95 to -0.06; P=0.027). Switching inhaled medicines in eight patients resulted in significant improvements in both ASK-12 scores and asthma control. CONCLUSIONS: The ASK-12 is a brief, practical, and clinically useful measure for assessing and addressing adherence to inhalation regimens in asthma.

Correlations between Cognitive Impairments and Employment Status in Patients with Diffuse Axonal Injury.

Patients with diffuse axonal injury (DAI) may initially present with prominent physical impairments, but their cognitive dysfunctions are more persistent and are attributable to later unemployment. In this study, we analyzed how the findings of early and delayed neuropsychological assessments correlated with employment outcome of patients with DAI. A total of 56 patients with DAI without motor or visual dysfunction were included in this study. The neuropsychological battery consisted of the Wechsler Adult Intelligent Scale - Revised (WAIS-R), Wechsler Memory Scale - Revised (WMS-R), Trail Making Test (TMT), Wisconsin Card Sorting Test (WCST), and Word Fluency Test (WFT). This battery of tests was administered twice in early stage after injury and in later stage. The results of all of the neuropsychological tests improved significantly (P <0.001) between the early and later assessments. All scores other than TMT part A and B improved to the normal range (Z-score ≥ 2). The patient characteristics (age, gender, initial Glasgow Coma Scale, and duration of posttraumatic amnesia) had no relationship to the outcome. The results of TMT part B, however, were significantly correlated with employment outcome in both the early and later assessments (P = 0.01, 0.04). Given that TMT evaluates visual attention, we surmise that a lack of attention may be the core symptom of the cognitive deficit and cause the re-employment failure in patients with DAI. TMT part B in both early and later assessments has the potential to accurately predict chronic functional outcome.

Efficacy of the American Heart Association/American Stroke Association guidelines for ultra-early, intentional antihypertensive therapy in intracerebral hemorrhage.

Whether the intentional antihypertensive therapy recommended by the American Heart Association/American Stroke Association (AHA/ASA) guidelines has clinical benefit for patients who have acute spontaneous intracerebral hemorrhage (ICH) has yet to be proven. We retrospectively reviewed the clinical charts of 175 patients with putaminal or thalamic ICH with acute hypertension to examine the correlation between the efficacy of antihypertensive therapy within 3 hours of onset, hematoma expansion (HE) after hospitalization and clinical outcome. The aim of the antihypertensive therapy was to achieve and maintain a systolic blood pressure of 120 mm Hg to 160 mm Hg until the second CT scan. The mean arterial pressure (MAP) after admission was the average MAP values measured every hour for the first 3 hours of hospitalization or until the second CT scan, if this was performed within the same timeframe. Thirty-two (18.3%) patients were found to have HE. Prior to the second CT scan, antihypertensive medications were administered to all patients without any major complications. A multiple logistic regression analysis revealed that a MAP of >110 mm Hg after admission was the only variable independently associated with HE (odds ratio [OR] = 3.455; 95% confidence interval [CI] = 1.510-8.412; p = 0.004). Modified Rankin Scale scores of < or = 3 on day 30 were significantly more common in those patients without HE (p = 0.002). Our findings suggest that there are clinical benefits, by the prevention of subsequent HE, in maintaining a MAP level lower than that recommended by the AHA/ASA (110 mm Hg) after hospitalization for patients who have ICH.

[Long-term problems associated with emergency neurological medicine].

Japanese medical care systems suffered from a number of long-term problems associated with emergency neurological medicine; moreover, with decreasing birthrate and aging society, these problems are rapidly worsening. The problems include shortage and uneven distribution of the necessary convalescent beds required for the treatment of stroke patients, scarcity of beds for treatment heavy work load of in-house healthcare staff, and shortage of human resources, furthermore, back-up emergency wards for acute treatment have not been developed. Medical facilities should be easily available to the general public; however, in a free economy, it is difficult to modify these facilities according to social needs. Moreover, presently, patients with higher brain dysfunction are supported only through nationwide system. It is necessary to recognize the current situation in which many patients have no other choice but to stay at home. In the light of this situation, the medical doctors in charge of emergency neurological medicine should discuss their future mode of action.

[Endosaccular embolization of an intrasellar aneurysm with hypopituitarism: case report].

An 81-year-old male presented with weight loss and hyponatremia. A baseline endocrinological examination revealed anterior pituitary dysfunction. A computed tomography and MRI revealed a large, unruptured intrasellar aneurysm protruding from the right internal carotid artery and pushing the pituitary stalk leftward. The patient developed polyuria and polydipsia from 10 days after commencing corticosteroid supplementation and was diagnosed with partial central diabetes insipidus (DI). Balloon assisted endosaccular embolization was performed about one month after the posterior pituitary dysfunction was identified. The unruptured aneurysm was successfully embolized with Guglielmi detachable coils (GDCs) without narrowing of the parent vessel. DI resolved completely and the posterior pituitary dysfunction improved soon after endosaccular embolization. The remission of DI after coil embolization suggested that the DI might have been induced by the progressive mass effect of the aneurysm rather than by the steroid. An endocrinological evaluation and cerebral angiography confirmed partial recovery of anterior pituitary dysfunction and almost complete obliteration of the aneurysm, respectively at 1 year after the operation. We report a case of hypopituitarism secondary to the large intrasellar aneurysm. This aneurysm was embolized with GDCs, resulting in partial recovery of anterior pituitary dysfunction and complete recovery of posterior pituitary dysfunction.

Neural injury and recovery near cortical contusions: a clinical magnetic resonance spectroscopy study.

OBJECT: Proton magnetic resonance (MR) spectroscopy can detect neural metabolic alterations noninvasively after traumatic brain injury (TBI) even in areas that appear normal. Unlike metabolic depression in diffuse TBI, focal metabolic alterations near cortical contusions in humans have not been previously investigated in a longitudinal study. The object of this study was to identify these alterations and examine their course. METHODS: At 1 week and 1 month after mild to moderate TBI involving cortical contusion, 30 patients underwent 1H MR spectroscopy examination that focused bilaterally on normal-appearing frontal and temporal white matter. Levels of N-acetylaspartate (NAA), choline (Cho) compounds, and creatine (Cr) were measured to obtain two metabolite ratios, NAA/Cr and Cho/Cr. The ratios were compared with those of 11 healthy individuals. At 1 week after TBI, the NAA/Cr ratio was significantly lower near cortical contusions than it was in white matter remote from the injury or in controls, while the Cho/Cr ratios did not differ significantly. At 1 month, the decreased NAA/Cr ratios near contusions had increased significantly from 1 week, as had the Cho/Cr ratio. CONCLUSIONS: Metabolic depression reflecting neural injury was apparent in subjacent normal-appearing white matter at 1 week after cortical contusion; this had normalized substantially at 1 month.

[Stent-assisted coiling of an acutely ruptured large aneurysm of the internal carotid artery: case report].

A 48-year-old female was referred to our hospital for the management of a ruptured 22-mm-diameter internal carotid aneurysm, located immediately distal to the ophthalmic artery. The right internal carotid artery was completely involved in the aneurysm. Because the right carotid siphon was relatively nontortuous stent-assisted coiling of the aneurysm was attempted 4 days after subarachnoid hemorrhage. A new coil-type coronary stent, a DRIVER stent, was deployed after microcatheter insertion into the aneurysm dome under systemic heparinization, followed by dome packing using Guglielmi detachable coils. Systemic heparinization was continued for 18 hours postoperatively, and aspirin (100 mg/day) was administered orally immediately after the embolization. However, 4 hours after heparin administration cessation, left hemiparesis became apparent. Immediate magnetic resonance angiography revealed a right internal carotid artery occlusion. Diffusion-weighted images demonstrated ischemic spots in the watershed zones of the right cerebral hemisphere. Following an immediate thrombolysis of the right internal carotid artery, systemic heparinization was continued for 5 days, and aspirin and ticlopidine were administrated orally. The patient was discharged on day 37, following the recovery from left hemiparesis within ten days. A DRIVER stent is a low profile coil-type coronary stent, which can be used for the stent-assisted coiling of large internal carotid aneurysms, located distal to the carotid siphon. It seems necessary to continue systemic heparinization for more than 2 days and to administer increased dose or two types of antiplatelet after the stent-assisted coiling of large cerebral aneurysms.