Search

Introduction Management of elderly patients with cancer has become a global issue. We investigated the safety and tolerability of lenvatinib in hepatocellular carcinoma (HCC) patients ≥80 years old. Methods We retrospectively evaluated 61 HCC patients and divided them into 2 groups: an elderly group (n = 13, ≥80 years old) and a younger group (n = 48, Results The discontinuation of lenvatinib due to AEs was more frequent in the elderly group (8/13, 61.5%) than in the younger group (10/48, 20.8%) (P = 0.0043). Fatigue and appetite loss accounted for half of the cases discontinued due to AEs in the elderly group. The elderly group had a significantly lower 8-week-delivered dose intensity/body surface area ratio (147.2) and 8-week-relative dose intensity (50.0%) than those in the younger group (267.4, 67%) (P = 0.003, 0.029). The objective response rate was significantly lower in the elderly group (15.4%) than in the younger group (61.5%) (P = 0.021). The PFS in the elderly group tended to be shorter than that in the younger group (P = 0.058, hazard ratio [HR] 1.98). The modified albumin-bilirubin (mALBI) grade (hepatic function) (HR, 2.60; P = 0.01) and objective response (HR, 0.41; P = 0.011) were independently associated with the PFS in the multivariate analysis. Conclusion The management of AEs is crucial for adherence and maintaining the dose intensity of lenvatinib in elderly HCC patients.

Background/Aim: We aimed to investigate the association between The Geriatric Nutritional Risk Index (GNRI) and the tolerability of lenvatinib in patients with hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively evaluated 61 HCC patients treated with lenvatinib and compared those with low GNRI (≤98, n=26) to those with high GNRI (>98, n=35). Results: The discontinuation of lenvatinib due to adverse events was more frequent in the low GNRI group (46.2%) than in the high GNRI group (17.1%) (p=0.014). Multivariate analysis revealed that low GNRI (p=0.014), hypothyroidism (model 1 p=0.021, model 2 p=0.013), and advanced age (p=0.026) were independently associated with the discontinuation of lenvatinib. The progression-free survival in the low GNRI group was significantly shorter than that in the high GNRI group (p=0.047). Conclusion: The GNRI might be independently associated with the tolerability of lenvatinib in patients with HCC.

Background Differential diagnosis between acute ischemic stroke (AIS) and epilepsy-related stroke mimics is sometimes difficult in the emergency department. We investigated whether a combination of diffusion-weighted imaging (DWI) and arterial spin labeling imaging (ASL) is useful in distinguishing AIS from epileptic disorders. Methods The study included suspected AIS patients who underwent emergency MRI including both DWI and ASL, and who exhibited DWI high-intensity lesions corresponding to neurological symptoms. We investigated the relationship between the ASL results from within and/or around DWI lesions and the final clinical diagnosis. Results Eighty-five cases were included (mean age, 71 ± 13 years; 47 men). The time from onset to the MRI examination was 493 ± 536 minutes. ASL showed hyperintensity in 13 patients, isointensity in 43, and hypointensity in 29. All ASL hyperintensities were observed in the cortex, with 4 patients (31%) presenting with AIS and 9 (69%) with an epileptic disorder. All of the AIS patients with ASL hyperintensity were diagnosed with cardioembolic stroke (4/4, 100%), with magnetic resonance angiography demonstrating recanalization of the occluded artery in all cases (4/4, 100%). In the 9 patients with an epileptic disorder, the area of ASL hyperintensity typically extended beyond the vascular territory (7/9, 78%) and involved the ipsilateral thalamus (7/9, 78%). All patients with ASL isointensity and hypointensity were diagnosed with AIS; none had epileptic disorders. Conclusions Although cortical ASL hyperintensity can indicate cardioembolic stroke with recanalization, hyperintensity beyond the vascular territory may alternatively suggest an epileptic disorder in suspected AIS patients with DWI lesions.

Background The hemodynamic state of the posterior dominant vasogenic edema in posterior reversible encephalopathy syndrome (PRES) is controversial. The aim of this retrospective study was to examine the contribution of epileptic ictal hyperperfusion in patients with PRES using combined magnetic resonance perfusion imaging with arterial spin labeling (ASL) and diffusion-weighted magnetic resonance imaging (MRI). Methods A detailed review of chronological MRI findings in 2 patients, including diffusion-weighted imaging (DWI) and ASL, with special reference to clinical and electroencephalographic findings, was performed. At the onset of PRES, both patients developed secondary generalized seizures. Results At the first PRES episode in Case 1, ASL and DWI clearly depicted "ictal hyperperfusion" and prolonged epilepsy-induced cytotoxic edema in the left parieto-occipital lobe cortex, located around the vasogenic edema of the PRES lesion in the left occipital lobe (hypoperfused area). At the second and third episodes (2 and 7 months after the first episode, respectively), although recurrent PRES was ruled out, ASL and DWI clearly demonstrated ictal hyperperfusion in the left posterior temporal and parieto-occipital lobes associated with partial nonconvulsive status epilepticus, which developed around the PRES-related old hematoma lesion. In Case 2, peri-ictal MRI findings of ictal ASL hyperperfusion and cortical hyperintensity on DWI were also noted in the left parieto-occipital lobe, but were mild compared with Case 1. Conclusions Combined use of DWI and ASL can provide information on hemodynamic state associated with epileptic ictal hyperperfusion in the various phases of PRES.

We report the first use of endoscopic submucosal dissection (ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus (EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution, and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor, primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion, an 8 mm submucosal tumor. Immunohistologically, tumor cells differentiating into ductal epithelium and myoepithelium were observed, and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall, vertical stump or horizontal margin invasion with pT1b-SM2 staining (1800 μm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC.

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.

A 73-year-old man was admitted to our hospital because of a decrease in spontaneity. His medical history included two stroke episodes, probably related to hypertension. Brain MRI on admission demonstrated acute infarction in the right caudate nucleus and left putamen. Intravenous infusion of a low molecular-weight heparin added to oral antiplatelets was started. Following admission, he developed a low grade fever and severe inflammatory reaction. The focus of infection was not evident, and none of the antibiotics tried were effective. Ten days after admission, he developed right hemiparesis, and an additional brain MRI showed new multiple infarctions. We also determined the presence of a high MPO-ANCA titer (57 EU), and we diagnosed the patient's condition to be ANCA-associated vasculitis (AAV). Steroid therapy improved his inflammatory reaction and stroke recurrence was not observed. We suggest that vasculitis should be considered as a potential risk factor for repeated small infarctions with fever of unknown origin, especially those of perforating artery territories.

A 76-year-old woman was referred to our hospital with anorexia. Computed tomography revealed a tumor lesion measuring 110mm in the liver at S4/5 with calcification and swelling of a paraaortic lymph node. The gallbladder was not visualized. Histological examination of a biopsy specimen from the liver tumor revealed squamous cell and undifferentiated carcinomas, and several tumor markers were elevated. Therefore, we diagnosed the patient with gallbladder adenosquamous cell carcinoma T3N2M0 stage III. Because the serum parathyroid hormone-related protein (PTHrP) and granulocyte-colony stimulating factor (G-CSF) levels were significantly elevated, we suspected that PTHrP and G-CSF production occurred because of adenosquamous cell carcinoma in the gallbladder. We initiated chemotherapy with S-1.

Patients with severe intracranial hemorrhage (ICH) often develop infectious complications during the acute stage. Animal experiments have demonstrated that enteral immunonutrition with a dietary fluid containing whey peptide (WP) enhances immunoactivity and prevents infection. The aim of the current study was to investigate the infection control effect of WP in the clinical management of patients with severe ICH.Fourteen patients with ICH were given enteral nutrition from January 2012 to December 2012. Nine patients were given WP (WP group) and the other five were given control dietary fluid (Non-WP group) for two weeks. We retrospectively analyzed the incidence of infectious complications and chronological changes in white blood cell (WBC) count, C-reactive protein (CRP), and total lymphocyte count.All patients in the Non-WP Group experienced infectious complications, whereas 5 out of 9 patients in the WP Group did not experience them. There was a tendency for a decrease in WBC count and CRP value in the WP group. In contrast, WBC and CRP increased in 3 patients in the Non-WP Group. Total lymphocyte count tended to increase earlier in the WP Group; however this tendency was not noted in the Non-WP Group.Although the number of cases was small, our study suggests that WP might have an infection control effect, capable of preventing infectious complications associated with severe ICH in the acute stage.

Brain hypoxia or ischemia causes acidosis and the intracellular accumulation of Ca(2+) in neuron. The aims of the present study were to elucidate the interaction between intracellular pH and Ca(2+) during transient acidosis and its effects on the viability of neuronal and glial cells. Intracellular Ca(2+) and pH were measured using the fluorescence of fura-2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester in neuroblastoma (IMR-32), glioblastoma (T98G), and astrocytoma (CCF-STTG1) cell lines. The administration of 5 mM propionate caused intracellular acidification in IMR-32 and T98G cells but not in CCF-STTG1 cells. After the removal of propionate, the intracellular pH recovered to the resting level. The intracellular Ca(2+) transiently increased upon the removal of propionate in IMR-32 and T98G cells but not in CCF-STTG1 cells. The transient Ca(2+) increase caused by the withdrawal of intracellular acidification was abolished by the removal of external Ca(2+), diminished by a reduction of external Na(+), and inhibited by benzamil. Transient acidosis caused cell death, whereas the cells were more viable in the absence of external Ca(2+). Benzamil alleviated cell death caused by transient acidosis in IMR-32 and T98G cells but not in CCF-STTG1 cells. These results suggest that recovery from intracellular acidosis causes a transient increase in cytosolic Ca(2+) due to reversal of Ca(2+) transport via Na(+)/Ca(2+) exchanger coactivated with Na(+)/H(+) exchanger, which can cause cell death.

The aims of the present study were to investigate the mechanisms of Ca 2+ signaling caused by hydrogen peroxide in CNS pericytes. In cultured human brain microvascular pericytes, cytosolic Ca 2+ concentration was measured by means of fura-2 fluorescence. Reverse transcription and polymerase chain reaction was performed to examine the expression of mRNA. Knockdown of Na + /H + exchanger (NHE) was done by transfecting the cells with specific double-strand siRNAs for NHE. Externally applied hydrogen peroxide dose-dependently (100 μM–10 mM) increased cytosolic Ca 2+ in human CNS pericytes. Cytosolic Ca 2+ remained high after wash-out of hydrogen peroxide. However, the addition of dithiothreitol rapidly reversed cytosolic Ca 2+ to the resting level. The hydrogen peroxide-induced Ca 2+ increase was not inhibited by nicardipine, Gd 3+ , La 3+ , or omission of external Ca 2+ . Neither thapsigargin nor carbonyl cyanide 4-trifluoromethoxyphenylhydrazone attenuated the hydrogen peroxide-induced Ca 2+ rise. Amiloride and its derivatives, benzamil and hexamethylene amiloride reversed the hydrogen peroxide-induced Ca 2+ increase. Human CNS pericytes expressed acid sensing ion channel (ASIC) 1a, Na + /Ca 2+ exchanger (NCX) 1, Na + /H + exchanger (NHE) 1, and NHE7. However, the removal of external Na + , treatment with KB-R 7943 and mibefradil, or knockdown of NHE1 and NHE7 did not affect the hydrogen peroxide-induced Ca 2+ increase. Hydrogen peroxide releases Ca 2+ from intracellular Ca 2+ pool via an amiloride-sensitive protein, which is controlled by oxidation of thiol group in human CNS pericytes.

Background and Purpose: Lymphotoxin α (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population. Methods: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study. Results: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke. Conclusions: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.

The C242T polymorphism of p22 phox , a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi-squared test revealed that the T-allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate-adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72-1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS-7 cells cotransfected with Nox4 and p22 phox of each genotype. The superoxide-producing activity in those cells expressing p22 phox with the T allele was not significantly different from that in cells expressing p22 phox with the C allele. The present results suggest that the p22 phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan.

Objective: The aims of the present study were to elucidate the interaction of reactive oxygen species (ROS) and Ca2+ response in central nervous system (CNS) pericytes. Methods: The intracellular Ca2+ concentration was measured using fluorescent Ca2+ indicator, fura-2, in cultured CNS pericytes. Results: Hydrogen peroxide evoked a dose-dependent increase in cytosolic Ca2+, which was completely inhibited by catalase. Removal of external Ca2+ or addition of nicardipine (1 μM) during application of hydrogen peroxide did not affect Ca2+ response. Incubation of the cells in Ca2+ free solution did not abolish but slightly reduced Ca2+ response by hydrogen peroxide. Ca2+ response to hydrogen peroxide was not altered by the depletion of intracellular Ca2+ by thapsigargin (1 μM). Pretreatment of the cells with tyrosine kinase inhibitor genistein (100 μM) or tyrphostin A47 (30 μM) significantly reduced Ca2+ increase by hydrogen peroxide. Conclusions: These results indicate that hydrogen peroxide evokes Ca2+ increase predominantly by release from intracellular Ca2+ store, which may be regulated by tyrosine kinases.

We report a patient with dissection of the bilateral intracranial vertebral artery (VA) that did not present any symptoms other than occipital headache, which was probably associated with sleeping overnight in a car seat with unsteady head position. Although cerebral angiography revealed extensive dissection of the bilateral VA after branching of the posterior inferior cerebral artery, retrograde flow to the basilar artery (BA) via the right posterior communicating artery contributed to preserved posterior circulation. These findings indicate that even in patients without neurological deficits, the involvement of BA cannot be excluded and that accurate evaluation using radiological techniques should be considered.

A 54-year-old Japanese woman with a 6-year history of systemic lupus erythematosus (SLE) was admitted to our hospital suffering from acute blindness in her right eye. Her condition recovered after steroid pulse therapy, however, 18 months later she suffered from nuchal pain for 2 weeks after which right hemiparesis with urinary incontinence developed. A spinal magnetic resonance imaging (MRI) revealed cord swelling from C2 to C7. She was diagnosed with neuromyelitis optica (NMO) and intravenous steroid administrations were immediately commenced. Her condition promptly improved. This case was unique because the steroid treatment was quite effective for this case of myelitis, which had passed the acute phase. We supposed that, because most of the lesion was not necrotic or demyelinated, but rather showed edematous change caused by vasculitis based on autoimmune pathogenesis, the symptoms progressed rather gradually and improved promptly in response to glucocorticoid treatment.

Here, we report two cases with rapidly progressive renal failure, caused by cholesterol crystal embolism (CCE), after an angiography for carotid artery stenosis. The diagnosis was determined by histological examination and from clinical symptoms, including livedo reticularis and eosinophilia. Neurologists and neuroradiologists tend to underdiagnose CCE, which results from the same atherosclerotic risk factors as cerebrovascular disease. We need to understand more about CCE and identify its unique clinical symptoms to enable an early diagnosis and treatment.

Recently, the number of patients with severe carotid stenosis is increasing in Japan. During these 2 years (2001-2002), 205 patients with severe internal carotid stenosis were admitted to our hospital, of whom 94 patiens (45.9%) underwent carotid endarterectomy (CEA). According to our criteria of carotid ultrasound sonogram (US), we recommend the precise examination and CEA for the patients with>90% stenosis on the US axial view, over 200cm/sec in peak sysytolic velosity at the most stenotic lesion, and>1.3 in endodiastolic flow velosity ratio of common carotid artery (intact/lesion side). Transoral carotid ultrasonograpy are essential for the assessment of distal internal carotid artery, and trascranial color coded doppler ultrasonography are also useful for the management of the CEA patients to protect against hyperperfusion. Stroke internists should play the coordinator for the comprehensive assessment of the patients with systemic vascular disease with the various medical specialists, to establish the treatment strategy and management of patients with carotid artery disease.

Hemimedullary infarction, which presents Babinski-Nageotte syndrome, has been mainly reported to result from atherosclerotic occlusion of the vertebral artery. A 54-year-old housewife with right nuchal pain developed Wallenberg's syndrome followed by left hemiparesis. Diffusion-weighted magnetic resonance imaging documented fresh infarcts in the right hemimedulla and right dorsal cerebellum. Angiography revealed dissection of the right vertebral artery as a cause of the infarcts. Anterograde progression of the dissection might cause stepwise evolution of her neurological symptoms.

A 60-year-old man was admitted to our hospital complaining of fever, headache and vertigo. Neurological examination on admission showed mild ataxic gait. Brain magnetic resonance imaging showed linear high intensity in the left parietal lobe on diffusion-weighted imaging (DWI) and laboratory data revealed elevated serum lactate dehydrogenase and soluble interleukin-2 receptor. Although intravascular lymphoma was suspected from these findings, bone marrow and skin biopsies were negative. Two months later, he presented with sensory disturbance of the left upper limb, and new lesions in the right frontal and bilateral parietal lobes were detected on DWI. A systemic evaluation showed multiple low-density lesions in the bilateral kidneys on computed tomography. Based on the results of a renal biopsy, we made a histological diagnosis of intravascular large B-cell lymphoma (IVLBCL). As IVLBCL is quite rare and often has a poor prognosis, a systemic evaluation to determine the proper biopsy site is needed for early diagnosis.

Background and Purpose— The purpose of this study was to clarify the differences in the acute blood pressure course among different ischemic stroke subtypes. Methods— We divided 588 consecutive patients with acute brain infarction into four clinical subgroups to study the blood pressure levels during the initial 6 hospital days. Results— During the 6 days, systolic blood pressure of lacunar and atherothrombotic patients was higher ( P =0.0001) and diastolic blood pressure of lacunar patients was higher ( P =0.0371) than of patients with the other subtypes. Preexisting hypertension was associated with elevated acute systolic blood pressure in all patients and in each subtype and with elevated acute diastolic blood pressure in all patients, cardioembolic patients, and patients with stroke of other etiology. After adjustment by preexisting hypertension, diabetes mellitus with a hemoglobin A1c >7.0% was associated with elevated systolic blood pressure in all, lacunar, and cardioembolic patients and with diastolic blood pressure in all patients. Conclusions— Blood pressure course of patients sustaining acute stroke varied widely according to stroke subtypes. Poorly controlled diabetes mellitus, as well as preexisting hypertension, appeared to influence blood pressure during the initial week of stroke.

An unruptured intracranial aneurysm is an uncommon but possible embolic source to the brain. We report a young patient who developed recurrent ischemic strokes occurring mainly in the left internal carotid arterial territory within a short interval; the first stroke occurred midway through a long-distance race, and the second stroke occurred immediately following a bowel movement. The angiographical contrast deficit indicated a thrombus in the left anterior cerebral artery as a result of the embolism. A saccular aneurysm of the left distal internal carotid artery was the only detectable potential embolic source. Initially anticoagulant therapy was given, and then surgical clipping of the aneurysm was performed. The patient has been free from stroke recurrence. As a cause of ischemic stroke in young adults, a carotid saccular aneurysm should be considered. Hard exercise and a Valsalva maneuver may be important triggers of thrombus detachment from the aneurysm.

AIM Malnutrition is common in the hospitalized elderly with hip fractures and has been linked to poorer recovery and increased complications. Hence, the aim of this study is to investigate whether nutrition support team (NST) intervention has a beneficial effect on rehabilitation outcome in the elderly, especially in the oldest-old patients with hip fracture using the Functional Independence Measure (FIM). METHOD Patients were classified into two groups before and after NST intervention, and we evaluated FIM gain, FIM efficacy, and discharge outcomes. Every item was compared in low-ADL patients with an FIM of 54 or less on admission. RESULTS The numbers of patients were 18 in the non-NST and 22 in the NST group. Although nutritional indicators on admission showed no significant difference in the groups, FIM gain and FIM efficacy were significantly higher (p

An 86-year-old woman developed cardioembolic stroke three times. In the last one, she fell into sudden coma and fatal outcome due to acute occlusion of bilateral internal carotid arteries (ICAs) and the basilar artery. Diffusion-weighted magnetic resonance imaging (MRI) delineated brain ischemia in the whole bilateral cerebral hemisphere soon after the stroke onset. Signal intensity of the brain parenchyma increased in whole the hemisphere. Especially, all the cortical rims glittered. This is the first report of the cardioembolic stroke due to simultaneous occlusion of the three major arteries to the brain.

The central nervous system (CNS) pericytes play an important role in brain microcirculation. Na+/H+ exchanger isoform 1 (NHE1) has been suggested to regulate the proliferation of nonvascular cells through the regulation of intracellular pH, Na+, and cell volume; however, the relationship between NHE1 and intracellular Ca2+, an essential signal of cell growth, is still not known. The aim of the present study was to elucidate the role of NHE1 in Ca2+ signaling and the proliferation of human CNS pericytes. The intracellular Ca2+ concentration was measured by fura 2 in cultured human CNS pericytes. The cells showed spontaneous Ca2+ oscillation under quasi-physiological ionic conditions. A decrease in extracellular pH or Na+ evoked a transient Ca2+ rise followed by Ca2+ oscillation, whereas an increase in pH or Na+ did not induce the Ca2+ responses. The Ca2+ oscillation was inhibited by an inhibitor of NHE in a dose-dependent manner and by knockdown of NHE1 by using RNA interference. The Ca2+ oscillation was completely abolished by thapsigargin. The proliferation of pericytes was attenuated by inhibition of NHE1. These results demonstrate that NHE1 regulates Ca2+ signaling via the modulation of Ca2+ release from the endoplasmic reticulum, thus contributing to the regulation of proliferation in CNS pericytes.

Lymphotoxin alpha (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population.Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study.The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke.Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.

Carotid arterial stenosis is a major risk factor for ischemic stroke and is increasing in Japan as the life-style has been westernized. The purpose of this study was to clarify the detailed process of diagnosis and treatment of patients with carotid arterial stenosis. Of the consecutive 1,889 hospitalized patients in our cerebrovascular center during 2001 and 2003, 293 patients had carotid stenosis 50% or more in diameter by the NASCET method; 82 patients were hospitalized during the acute stage of ischemic stroke and 211 patients with or without past history of ischemic stroke were admitted in the chronic stage. Among acute ischemic stroke patients, 62 patients (76%) had mild neurological symptoms of NIH Stroke Scale scoreor = 4 on admission. As the initial treatment during the acute phase, all patients underwent antithrombotic medication; 33 of them underwent carotid endarterectomy (CEA) or carotid arterial stenting (CAS) in the chronic stage. Of 211 chronic patients, 123 (58%) did not have a history of symptomatic ischemic stroke, and instead had nonspecific symptoms, including carotid bruit, headache, and vertigo, or were diagnosed as having carotid artery stenosis by examinations of preoperative screenings. One hundred and thirty-five chronic patients underwent CEA/CAS and all the others except for a patient with serious gastrointestinal bleeding underwent anti-thrombotic medication. Statin treatment was chosen for 59 acute patients and 66 chronic patients. Because many patients with carotid arterial stenosis had mild symptoms during the acute phase or did not have ischemic episodes, we might overlook carotid lesions unless we performed screening examinations using ultrasound or magnetic resonance angiography.

Several infectious agents, such as Chlamydia pneumoniae , cytomegalovirus (CMV), herpes simplex virus (HSV), and Helicobacter pylori , have been implicated in the pathogenesis of atherosclerosis; however, but the contribution of infection may vary among races and geographic conditions. The present study investigates the association between the presence of these pathogens and carotid atherosclerosis and examines the relevance of an infectious burden during atherogenesis in Japanese patients undergoing carotid endarterectomy. We investigated a total of 50 carotid atherosclerotic plaques resected during carotid endarterectomy by polymerase chain reaction (PCR) for C. pneumoniae , CMV, HSV, and H. pylori and by immunocytochemistry (ICC) for C. pneumoniae . We also examined the presence of antibodies to IgG and/or IgA for each pathogen in blood samples. We detected HSV DNA in 2 specimens (4%) and positive ICC for C. pneumoniae in 8 (16%). The results of PCR, ICC, or serum antibodies, as well as the number of seropositive antibodies, did not correlate with severely stenotic, ulcerative, or symptomatic plaques. Our findings indicate that the detection rate of infectious agents within atherosclerotic plaques was significantly lower in our patients than that in other studies. Thus, an inflammatory mechanism might not correlate with the pathogenesis of carotid atherosclerosis among Japanese patients with severe carotid artery stenosis.

Hyperhomocysteinemia is thought to cause ischemic strokes. We report two middle-aged widowers with frequent recurrences of small-artery strokes, two capsular infarcts and a thalamic hemorrhage in one patient, and two thalamic and pontine infarcts in the other. Blood tests following the final stroke showed hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T gene mutation, with low concentration of vitamin B6. Multivitamin supplementation normalized plasma homocysteine levels in both patients. Hyperhomocysteinemia is treatable; therefore, serum homocysteine should be measured as a potential risk factor for stroke recurrence in relatively young patients with recurrent small-artery infarctions or hemorrhage, especially those with insufficient lifestyle factors.

Dural arteriovenous fistulas (AVFs) cause several types of intracranial hemorrhage, but rarely cause primary intraventricular hemorrhage (IVH). We report a 67-year-old man with sudden headache and a long history of a pulsatile bruit who developed intraventricular hemorrhage without any parenchymal hemorrhage. Cerebral angiogram revealed dural arteriovenous fistulas in transverse and sigmoid sinuses. Severe retrograde venous drainage seemed to have caused backward flow into the subependymal veins with their consequential rupture. Transvenous embolization was successful.

We report a 56-year-old woman suffering from an embolic brain infarction in her right frontal lobe. Carotid ultrasonogram showed a mass-shaped thrombus with little atherosclerotic change of underlying intima-media in the right common carotid artery. The thrombus was reduced with treatment and changed to mobile slender thrombus on admission. No other embolic sources were detected even using transesophageal echocardiography. Her blood test indicated existence of antiphospholipid antibody syndrome (APS) complicated with mixed connective tissue disease as an etiology of this uncommon carotid thrombus. The thrombus disappeared completely after two-week intensive antithrombotic therapy. This is a valuable report that arterial thrombi accompanied by APS could be detected by carotid ultrasound and observed until thrombus was disappeared. When we manage APS patients, it is important to rule out thrombus formation in the carotid artery using ultrasonography from the point of stroke prevention.

Two aged women suddenly suffered from severe cervical and back pain followed by ipsilateral hemiparesis sparing the face. One woman had taken anticoagulant for prosthetic mitral valve and another had taken antiplatelet for prevention of recurrent brain infarction. On admission, MRI did not document any definite lesions in the brain, and revealed epidural hematoma compressing the cervical spinal cord for both patients. We promptly stopped their anticoagulants and antiplatelets use, because the agents seemed to be the leading cause of hematoma. In addition, we performed emergent laminectomy and evacuation of hematoma for the former patient. These cases suggest dual warnings against recently prevalent antithrombotic therapy for patients with histories of thromboembolic accidents. First, we should be careful about spinal epidural hematoma as a hemorrhagic complication of antithrombotic therapy. Second, we should not misdiagnose spinal epidural hematoma as ischemic stroke nor select hyperacute thrombolytic therapy. Cervical pain and hemiparesis sparing face are important signs for distinction of spinal epidural hematoma from stroke.

A 76-year-old diabetic woman received epidural catheterization for sigmoid colectomy. Four months later she started to complain of fever and severe lumbago, and finally fell into coma and tetraplegia. She had severe neck stiffness, and lumbar puncture yielded yellowish pus. Methicilin-resistant Staphylococcus aureus (MRSA) was detected in a culture of the epidural pus and blood as a causative organism. Magnetic resonance imaging showed extensive abscess in the posterior epidural space at the level between Th1 and L5. We diagnosed her disease as iatrogenic spinal epidural abscess due to epidural catheterization. After emergent laminectomy and evacuation of abscess, inflammation was gradually improved. She returned to normal except for slight gait disturbance. Spinal epidural abscess often develops rapidly after Staphyloccocus aureus infection. In our case, however, neurological deficits appeared 144 days after insertion of epidural catheter. We must remember that spinal epidural abscess is an important cause of lumbago with high fever, even several months after surgical or catheterial intervention to the spine, for immunocompromised patients with diabetes or neoplasm.

We evaluated a rapid diagnostic kit that detects influenza type A and B viral antigens by immunochromatography, Quick Vue Influenza Test (Quidel Corp., San Diego, CA, USA), with 425 specimens collected from patients with influenza-like symptoms at three hospitals between January and March 2001. The specimens included 184 nasal aspirates, 140 nasal swabs, and 101 throat swabs. The test correctly identified 179 of the 204 culture positive specimens and 203 of the 221 culture negative specimens; the sensitivity and specificity compared with the culture were 87.7% and 91.9%, respectively. The sensitivity of the test was 92.6% (112/121) for nasal aspirates, 83.7% (41/49) for nasal swabs, and 76.5% (26/34) for throat swabs, which is similar to the results for conventional rapid enzyme immunoassay kits for influenza virus infection. The sensitivity and specificity of the QuickVue Influenza Test were equivalent to those of Flu OIA (BioStar, Inc., Boulder, CO, USA), with the agreement of 84.2%. Although the QuickVue Influenza Test does not differentiate between influenza A and B viruses, the easy-to-use kit detects both types in the physician's office, allowing physicians to make a decision on prescription of neuraminidase inhibitor therapy during the initial visit.

The Directigen Flu A + B kit, a rapid diagnostic device for influenza virus A and B was evaluated. The nasopharyngeal aspirates were obtained from 239 patients who visited our hospital, between January and March, 2000, presenting flu-like symptoms. Influenza virus AH1: 77 and AH3: 51 were isolated from 128 specimens and none from 111 specimens. Directigen Flu A + B showed 115 specimens positive and 106 specimens negative. The sensitivity and specificity of this kit were 89.8% (115/128) and 95.5% (106/111) compared with viral isolation. Agreement on positive and negative interpretations between Direction Flu A and this kit was 97.9% (234/239). In the evaluation of this kit for influenza B virus, 60 frozen nasopharyngeal aspirates collected from February to April, 1999 were used. The sensitivity and specificity of this kit were 88.9% (16/18) and 88.1% (37/42) compared with viral isolation. Agreement on positive and negative interpretations between FLU OIA and this kit was 91.7% (55/60). The Directigen A + B demonstrated sensitivity and specificity equivalent to the conventional kits in nasopharingeal aspirates. This kit can also differentiate influenza A and B viruses, a feature which is useful for treatment using anti-viral agents such as amantadine and neuraminidase inhibitor. To date, the kit is the most effective tool for the rapid diagnosis of influenza.

We investigated the usefulness of a rapid antigen detection kit using optical immunoassay for influenza virus (FLU OIA, BioStar, USA). Nasal aspirates were taken from 92 influenza suspected outpatients between March to April of 1999. Compared with virus isolation and PCR, the sensitivity of FLU OIA was 88.5% and 81.6%, and the specificity was 65.2% and 72.2%. All isolated viruses were influenza type B virus. It was difficult to differentiate the weak-positive and negative cases, leading to the rather low specificity, although the assay procedure was easy and quick. FLU OIA may be a useful rapid diagnosis kit for influenza in pediatric outpatient clinics and wards, because it can detect both influenza type A and type B viruses.

A determination method for choline-containing phospholipids in serum lipoproteins was established by application of the HPLC method [Hara et al. (1980) J. Biochem. 87, 1863-1865; (1981) 89, 879-887] developed for cholesterol quantitation. The concentration of choline-containing phospholipids in the fraction separated by HPLC using gel permeation columns was determined through colorimetric detection using a commercial enzymatic kit. The optimum conditions for enzymatic reaction in the flow diagram were examined. The concentration calculated from the A500 peak area was found to reflect very precisely the concentration of choline-containing phospholipids in all lipoprotein fractions, and the quantitation of each lipoprotein fraction can be performed with only 10-20 microliters of whole serum. Monitoring the elution patterns by detecting choline-containing phospholipids can give much more information about lipoprotein distributions according to particle size than analyses done by detecting cholesterol.

A combination method consisting of separation by HPLC using gel permeation columns and selective detection of cholesterol or choline-containing phospholipids was applied to the identification and quantitation of subclasses of high density lipoproteins in human serum. The frequency distribution of peaks in the elution patterns on detection of choline-containing phospholipids in a group (n = 71) of normal males and females showed five maxima. Their particle sizes were determined from the relation between Stokes' diameter and elution volume to be as follows: 122.0 +/- 2.8 A, 110.1 +/- 2.1 A, 97.5 +/- 1.8 A, 86.7 +/- 1.3 A, and 76.3 +/- 16 A. The two larger fractions were found to correspond to HDL2 subclasses, i.e., HDL2b and HDL2a. The other three peaks were found to reflect the subclasses of HDL3 and choline-containing phospholipids in the very high density lipoprotein fraction which sedimented at the bottom on ultracentrifugation at the density of 1.21. Moreover, the existence of these five subclasses in the HDL fraction was confirmed by rechromatography using this combination HPLC method. Our results for the particle sizes of HDL subclasses were confirmed by electron microscopy.

We have developed a quantitation method for cholesterol in each lipoprotein fraction of blood serum through separation by HPLC and selective detection by enzymatic reaction. Enzymatic reactions can be applied in general to quantitation of serum lipoprotein components other than cholesterol. We have succeeded in the quantitation of choline-containing phospholipids using this kind of technique. The optimum method of preparing the quantitation reagent for HPLC use was determined by a bulk test using a commercial kit (PL kit K “f” Nippon Shoji Co., Ltd., Osaka Japan). This reagent was confirmed to be quantitatively usable for a flow system of HPLC analysis. Similar reactivities to this reagent were observed among lipoprotein fractions (Chylomicron+VLDL, LDL, HDL2 and HDL3). Therefore, using this reagent, quantitation of choline-containing phospholipids in each lipoprotein fraction of blood serum was found to be possible.