Cerebrospinal fluid levels of interleukin-6 and interleukin-12 in children with meningitis

Purpose  Certain cytokines play important roles in the pathophysiology of meningitis. The main purpose of this study was to investigate if the levels of interleukin-6 (IL-6) and interleukin-12 (IL-12) in cerebrospinal fluid (CSF) could be diagnostic predictors of bacterial meningitis in children. Methods  CSF was obtained from 95 patients suspected with meningitis. These cases were classified to the bacterial meningitis (n = 12), aseptic meningitis (n = 41), and nonmeningitis (n = 42) groups. The levels of IL-6 and IL-12 in CSF were measured using the enzyme-linked immmunosorbent assays test. Results  The CSF IL-6 levels in the bacterial meningitis group (45.2 ± 50.0 pg/ml) were significantly higher than those in the aseptic meningitis group (12.9 ± 10.2 pg/ml) and the nonmeningitis group (6.5 ± 7.8 pg/ml; p < 0.05). The CSF IL-12 levels in the bacterial meningitis group (69.8 ± 67.1 pg/ml) were significantly higher than those in the aseptic meningitis group (22.9 ± 10.8 pg/ml) and the nonmeningitis group (15.3 ± 11.2 pg/ml; p < 0.05). With regard to diagnosis, the measurement of CSF IL-6 and IL-12 levels showed sensitivities of 96% and 96%, respectively, and specificities of 51% and 75%, respectively. Conclusion  It is suggested that the CSF IL-6 and IL-12 levels are useful markers for distinguishing bacterial meningitis from aseptic meningitis.     

Soluble lectin-like oxidized low-density lipoprotein receptor-1 as a novel biomarker for large-artery atherosclerotic stroke

Background: Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown associated with the progression of atherosclerosis in endothelial cells. We sought to assess whether the baseline serum sLOX-1 levels are correlated with the presence and short-term functional outcome of large-artery atherosclerotic (LAA) stroke. Methods: The study recruited 241 subjects, including 148 consecutive patients with acute ischemic stroke with the subtype of LAA and 93 non-stroke controls. Clinical and laboratory data, including serum concentration of sLOX-1, were collected within 24 h of admission, and the severity of LAA stroke patients was evaluated by National Institutes of Health Stroke Scale score. And functional outcome was assessed by modified Rankin Scale three months after stroke. The association between sLOX-1 level and the functional outcome at three months was analyzed by multiple logistic regression models. Results: Serum levels of sLOX-1 in the LAA stroke patients were significantly higher as compared to normal controls (2.48 ± 0.93 ng/ml vs. 2.22 ± 0.79 ng/ml in the controls, t = 2.301, p = 0.022). The levels of serum sLOX-1 in patients with good outcome were significantly lower than those with poor outcome (2.39 ± 0.94 ng/ml vs. 2.77 ± 0.84 ng/ml, p = 0.032). After adjusting for potential confounders, sLOX-1 was still an independent predictor for the function outcome with an adjusted OR of 3.39 (95% CI, 1.61–7.11, p = 0.001). Conclusions: The serum sLOX-1 level was higher in patients with LAA stroke, and it was an independent predictor of functional outcome in patients with LAA ischemic stroke.     

Outcomes of long-term iron supplementation in pediatric restless legs syndrome/periodic limb movement disorder (RLS/PLMD)

ObjectivesRestless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are thought to center around a genetically mediated sensitivity to iron insufficiency. Previous studies have shown the effectiveness of short-term iron therapy in children with low iron storage. Little is known, however, about long-term iron treatment in children with RLS and PLMD. Therefore, we performed this study to assess the long-term effect of iron therapy in children with RLS and PLMD.MethodsA retrospective chart review was performed for children who met the following criteria: A) diagnosed as having either RLS or PLMD, B) started on iron supplementation, C) followed up for >2 years in a sleep clinic. Baseline values for iron, ferritin, and periodic limb movement of sleep index (PLMS index) were defined in the three months leading up to the initiation of iron therapy. Values were also computed for follow-up periods of 3–6 months, 1–2 years, and >2 years. Serum iron and ferritin levels and PLMS index were compared between baseline and all subsequent follow-ups.ResultsIn total, 105 patients met inclusion criteria, of whom 64 were diagnosed with PLMD alone, seven with RLS alone, and 35 with both RLS and PLMD. The average age was 10.2 ± 5.3 years. Compared to the baseline (27.4 ± 12.1 ng/ml), the average ferritin values at 3–6 months (45.62 ± 21.2 ng/ml, p < 0.001, n = 34), 1–2 years (52.0 ± 48.3 ng/ml, p <0.001, n = 63), and >2 years (54.7 ± 40.5 ng/ml, p <0.001, n = 67) were all significantly increased. Inversely, compared to baseline (21 ± 27.0/h, n = 66), PLMS index values at 3–6 months (7.5 ± 9.5/h p < 0.05, n = 11), 1–2 years (6.9 ± 8.9/h, p <0.001, n = 29), and >2 years (10 ± 14.5/h, p <0.001, n = 31) were all significantly decreased. No significant change in serum iron levels was noted at any time point.ConclusionWhile retrospective in nature, this study demonstrates a sustained improvement in PLMS index and maintenance of adequate ferritin levels >2 years after iron therapy initiation in our RLS/PLMD cohort with a long-term follow-up. Iron therapy appears to lead to long-lasting improvements in children with RLS/PLMD.     

Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients

Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R ² = 0.048, p < 0.001 and R ² = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.     

Randomized,placebo‐controlled trial of incobotulinumtoxina for upper‐limb post‐stroke spasticity

Introduction: Efficacy and safety of incobotulinumtoxinA in post‐stroke upper‐limb spasticity were studied. Methods: Subjects randomized 2:1 to incobotulinumtoxinA (fixed dose 400 U) or placebo, with fixed doses for the primary target clinical pattern (PTCP; flexed elbow, 200 U; flexed wrist, 150 U; clenched fist, 100 U). Doses for non‐primary patterns were flexible within predefined ranges. Results: At week 4, incobotulinumtoxinA led to larger improvements in PTCP Ashworth scale (AS) scores than placebo [least‐squares mean change ± standard error: –0.9 ± 0.06 (n = 171) vs. –0.5 ± 0.08 (n = 88); P < 0.001], and more subjects were PTCP AS responders (≥1‐point improvement) with incobotulinumtoxinA (69.6%) than with placebo (37.5%; P < 0.001). Investigator's Global Impression of Change confirmed superiority of incobotulinumtoxinA vs. placebo (P = 0.003). IncobotulinumtoxinA was associated with functional improvements, as demonstrated in responder rates for Disability Assessment Scale principal target at week 4 (P = 0.007). Adverse events were mainly mild/moderate, and were reported by 22.4% (incobotulinumtoxinA) and 16.8% (placebo) of subjects. Conclusions: IncobotulinumtoxinA significantly improved upper‐limb spasticity and associated disability, and was well‐tolerated. Muscle Nerve 53: 415–421, 2016     

A precise,simple, convenient and new method for estimation of intracranial hematoma volume–the formula 2/3Sh

Abstract

Objectives: The formula 1/2abc was a relatively reliable technique for the estimation of mostly intracranial hematoma volume, but its accuracy was prone to be affected by some particular shapes of hematoma, such as multinodular, separated and so on. In this work, we aimed to validate a more accurate method for the estimation of intracranial hematoma volume, which were free limitations of axial slices shapes.

Methods: We investigated the computed tomography (CT) scans of 186 patients with intracranial hematoma. The volume values of 186 intracranial hematomas were respectively assessed using five different methods.

Results: For the formula 2/3Sh, the excellent correlation coefficient obtained using Pearson and Spearman's coefficients were 0.990 and 0.990, respectively. Meanwhile, the estimated intracranial hematoma volume using the formula 2/3Sh was fairly precise, with a <1% (?0.00±0.14, p>0.05) underestimation. However, the intracranial hematoma volume values were estimated by the formulas 1/2abc, Tada and 1/3abc, in comparison with the gold standard (43.16±37.55 ml), were 45.98±39.97 ml (p>0.05) with a 5% (0.05±0.25, p<0.05) overestimation, 48.12±41.84 ml (p>0.05) with 10% (0.10±0.26, p<0.05) overestimation and 30.65±26.65 ml (p<0.05) with a nearly 29% (?0.29±0.16, p<0.05) underestimation, respectively.

Discussions: Owing to the area, length and width of the largest axial hematoma slice clearly marked in CT imaging, the formula 2/3Sh in comparison with other methods was a precise, simple and convenient estimation technique.     

Plasma and cerebrospinal fluid substance P in post-stroke patients with depression

Aims: To investigate the correlation between the incidence of post‐stroke depression (PSD) and the levels of substance P (SP) in the plasma and cerebrospinal fluid (CSF). Methods: Ninety‐one stroke patients were divided into PSD (n = 46) and post‐stroke (without depression) groups (n = 45). PSD must have occurred 2–4 weeks after the onset of the stroke and was determined by the Hamilton Rating Scale for Depression (HAMD). In addition, the subjects were divided into anterior (n = 67) and posterior circulation stroke groups (n = 24) based on the location of the focus as determined by computed tomography. All recruited patients were graded by the National Institutes of Health Stroke Scale (NIHSS). Results: The results included the following findings: (i) the level of plasma SP in the PSD group (58.47 ± 14.39) was higher than that of the PS group (36.98 ± 9.49; P = 0.000), while the level of CSF SP in the PSD group (72.13 ± 13.06) was higher than that of the post‐stroke group (37.30 ± 12.57; P = 0.03); (ii) the level of plasma SP was positively correlated with the HAMD and NIHSS score; (iii) the level of plasma SP (38.45 ± 12.23), the HAMD score (9.08 ± 8.72), and the NIHSS score (3.25 ± 1.90) of the anterior stroke group (51.21 ± 16.27, 17.46 ± 15.96, and 6.91 ± 3.30, respectively) were higher than those of the posterior stroke group (38.45 ± 12.23, 9.08 ± 8.7, and 3.25 ± 1.90, respectively; P = 0.017, P = 0.001, and P = 0.000, respectively). Conclusions: SP in the plasma and CSF of patients exhibited a close correlation with neural damage and the incidence of PSD. This study also suggested that anterior hemispheric strokes may play a significant role in development of PSD.     

Increased serum soluble interleukin-2 receptors in schizophrenic monozygotic twins

Summary There is a confusing history of immune findings associated with schizophrenia. At least some of these discrepant results may be artifacts caused by heterogeneity. In an attempt to decrease heterogeneity, we studied three groups of monozygotic twins who were either discordant for schizophrenia, concordant and ill, or concordant and well. This comparison minimizes environmental and genetic variance, and heightens differences that are actually due to the disorder. Overall, schizophrenic subjects had higher levels of serum soluble interleukin-2 receptors (SIL-2Rs) than unaffected individuals (480.8, SD 238.6 U/ml vs 380.9, SD 170.6 U/ml;F=5.256,df=1.61,P=0.02). When data from discordant and concordant twin groups were analysed separately, both the discordant ill twins (P=0.06) and concordant ill twin pairs (P=0.08) showed trends towards higher serum SIL-2R levels than their respective control groups. These data contribute to the growing body of evidence that immune activation is associated with some forms of schizophrenia.The Metabolism Branch of the National Cancer Institute     

Distribution of growth hormone and thyroid-stimulating hormone in cerebrospinal fluid and pathological compartments of the central nervous system

Human growth hormone (HGH) radio-immunoassay (RIA) was adapted for an accurate measurement of immunoreactive HGH concentrations in the CSF in different cases of hypothalamic-somatotropin dysfunctions.In control subjects (n = 43) mean HGH levels were 0.35 ± 0.03 ng/ml in CSF and 1.95 ± 0.2 ng/ml in plasma with a $\text{CSF}\text{plasma}$ ratio of 17%. The thyroid-stimulating hormone (TSH) RIA gave in controls mean basal levels of 2.65 ± 0.2 μU/ml in CSF and 5.95 ± 0.3 μU/ml in plasma with a $\text{CSF}\text{plasma}$ ratio of 44%. HGH and TSH concentrations in CSF and plasma show a very good correlation; but the regression curves for both hormones are distinctly different and appear specific for each polypeptide hormone.Hypothalamic-somatotropin hyperreactivity was reported in diabetic retinopathy (DR). CSF and plasma HGH concentrations in a group of diabetic patients with progressing retinopathy (n = 27) were not different from those in normal subjects (respectively 0.35 ± 0.05 in CSF and 2.10 ± 0.25 ng/ml in plasma with a $\text{CSF}\text{plasma}$ ratio of 16%). The HGH regression curve obtained in diabetics is similar to that of controls. These data do not substantiate the hypothesis of an HGH hyperreactivity in diabetic retinopathy.In somatotropin hypersecretion (acromegaly) without adenoma suprasellar extension, higher HGH concentrations recorded in CSF than in plasma cannot be attributed to an anatomical break-down of the CSF blood-brain barrier and suggest an active transport process of pituitary hormones to the CNS.HGH and TSH concentrations were measured in the cystic fluid of CNS tumors. In 1 case of a cystic dysembryoma, the HGH and TSH of CF were considerably increased. In gliomas (n = 8) the HGH and TSH cystic fluid concentrations were more elevated (respectively 0.72 ± 0.2 ng/ml and 3.6 ± 0.7 μU/ml) than in the CSF of controls.     

Blood levels of histamine,IL-1β, and TNF-α in patients with mild to moderate alzheimer disease

In this study, we have evaluated the levels of blood histamine, serum interleukin-1 beta (IL-1β), and plasma tumor necrosis factor-alpha (TNF-α) in 20 patients with mild to moderate Alzheimer disease (AD; 13 early onset and 7 late-onset AD subjects) and in 20 agematched control subjects (C). AD patients showed higher concentrations of histamine (AD=452.9±237.9 pmol/mL; C=275.3±151.5 pmol/mL;p<0.05) and IL-1β (AD=211.2±31.1 pg/mL; C=183.4±24.4 pg/mL;p<0.01), and lower values of TNF-α (AD=3.59±2.02 pg/mL; C=9.47±2.64 pg/mL;p<0.001) than elderly controls. Increased levels of histamine and decreased levels of TNF-α were observed in both early onset AD (EOAD) and late-onset AD (LOAD) patients, but only EOAD subjects had elevated serum IL-1β values compared with age-matched controls. Age negatively correlated with histamine (r=?0.57;p<0.05) and positively with IL-1β levels (r=0.48;p<0.05) in healthy subjects, but not in AD, whereas a positive correlation between TNF-α scores and age was only found in AD patients (r=0.46;p<0.05). Furthermore, histamine and TNF-α values correlated negatively in AD (r=?0.50,p<0.05). In addition, cognitive impairment increased in patients with lower TNF-α and higher histamine and IL-1β levels, as indicated by the correlations between mental performance scores and histamine (r=?0.37, ns), IL-1β (r=?0.33, ns) and TNF-α levels (r=0.42,p<0.05). Finally, histamine concentrations decreased as depression scores increased in AD (r=?0.63,p<0.01). These data suggest a dysfunction in cytokine and histamine regulation in AD, probably indicating changes associated with inflammatory processes.     

Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized,placebo‐controlled and dose‐finding study

Background Lubiprostone is a prostone analog with a novel mechanism of action involving type‐2 chloride channel activation. The aim of this work was to perform a dose‐finding study for lubiprostone for the treatment of constipation with or without irritable bowel syndrome (IBS) in Japan. Methods A total of 170 patients (128 without IBS and 42 with IBS) with chronic idiopathic constipation (CIC) randomly received a placebo (n = 42) or 16 μg (n = 41), 32 μg (n = 43), or 48 μg (n = 44) of lubiprostone daily for 2 weeks. Key Results There was a statistically significant and dose‐dependent increase in change from baseline in the weekly average number of spontaneous bowel movements at week 1 (placebo: 1.5 ± 0.4; 16 μg: 2.3 ± 0.4, 32 μg: 3.5 ± 0.5; and 48 μg: 6.8 ± 1.1, per week, mean ± SE; P < 0.0001). These primary endpoint results were significant on stratified analysis when patients were limited to those without IBS (P < 0.0001). The primary endpoint in patients with IBS treated with 48 μg of lubiprostone was significantly better than those given placebo (P = 0.0086). Dose dependency was also seen for the secondary efficacy endpoints. Lubiprostone produced no serious side effects. Conclusions & Inferences Our results suggest that lubiprostone produced a steady and effective improvement in the symptoms of CIC with or without IBS in a dose‐dependent manner with a good safety profile and tolerability in a Japanese population.     

Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus

Abstract

Objectives. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious but potentially treatable disease. However, biological markers such as IgG index or IL-6 do not always reflect the severity of the psychotic symptoms of NPSLE. We hypothesized that serum BDNF levels may be a biological marker for reflecting the severity of the psychiatric symptoms of NPSLE. Methods. The participants enrolled in this study were 28 healthy volunteers and 54 Japanese SLE inpatients at the University Hospital of Occupational and Environmental Health, all of whom fulfilled the criteria for the classification of SLE. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms including an acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder, and psychosis (NP group); NPSLE without psychiatric symptoms (NN group); and SLE without neuropsychiatric symptoms (S group). The serum BDNF levels were measured by ELISA. Results. Serum BDNF levels were significantly increased in the NP group (mean ± SE = 37.0 ± 5.46 ng/ml) compared with those in the other three groups (NN group; mean ± SE=9.1 ± 2.44 ng/ml, P < 0.0001, S group; mean ± SE=10.4 ± 2.51 ng/ml, P < 0.0001, healthy control; mean ± SE= 11.44 ± 0.69, P < 0.0001). Subsequently, serum BDNF levels were decreased in parallel with the improvement of psychiatric symptoms in the NP group. Conclusion. These results suggest that serum BDNF is a biological marker for the severity of psychiatric symptoms in NPSLE patients.     

Aldehyde dehydrogenase 2 polymorphism as a protective factor for intracranial vascular stenosis in ischemic stroke in Han Chinese

Aim: Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that metabolizes acetaldehyde to acetic acid. ALDH2 gene polymorphism modifies its activity and the mutation of ALDH2 gene has been reported to be associated with the protection against ischemic stroke. However, the potential association of allelic variation of ALDH2 with intracranial vascular stenosis and the clinical characteristics of ischemic stroke without coronary artery disease remains unclear. Methods: In this study, ischemic stroke patients were recruited, National Institutes of Health Stroke Scale scores were analyzed, intracranial arterial stenosis were evaluated by magnetic resonance angiography and gene typing of ALDH2 was determined by polymerase chain reaction and sequencing. Results: We found that the rate of heavy drinking was significantly lower in the ALDH2 mutation group (^*1/^*2 and ^*2/^*2) than in wild-type group (^*1/^*1) (18.6% vs. 38.0%, p = 0.01). Plasma homocysteine (Hcy) levels were significantly different in the two groups (15.45 ± 6.39 vs. 13.14 ± 4.45, p = 0.015). The ALDH2 mutation genotype was negatively correlated with severe intracranial vascular stenosis (OR, 0.34; p = 0.002), even after adjustment for high-density lipoprotein cholesterol, Hcy, and heavy drinking (adjusted OR, 0.44; p = 0.03). Conclusion: ALDH2^*2 could be a protective factor and negative predictor for severe intracranial vascular stenosis in ischemic stroke in Han Chinese.     

Rapid induction of prostaglandin synthesis in piglet astroglial cells by interleukin 1α

We examined effects of interleukin 1α (IL-1α) on prostaglandin production in piglet cultured astroglia. Immuno-and morphologically identified polymorphic and process-bearing astrocytes were collected from cerebral cortex and white matter from piglets (1–3 days of age). Levels of Prostaglandins were determined using enzyme immunoassay. Baseline levels for prostaglandin (PG) F_2α, were 631 ± 332 pg/ml and increased to 1417 ± 353 pg/ml 20 min after addition of 11 μg/ml IL-1α (p < 0.05) and to 2280 ± 391 pg/ml 20 min after addition of 22 μg/ml IL-1α (p < 0.05) (n = 7). Only small amounts of 6-ketoPGF_2α or PGE₂ were detected in medium under baseline conditions or in the presence of IL-1α. Medium alone did not change PGF_2α levels (n = 3). Coapplication of cycloheximide (10⁻³ M) blocked the increase in PGF_2α (n = 3). We conclude that IL-1α causes a rapid increase in prostaglandin production by astroglia, and this process involves a step requiring continued or increased protein synthesis.     

Type I interferon and proinflammatory cytokine levels in cerebrospinal fluid of newborns with rotavirus-associated leukoencephalopathy

Objective

The purpose of this study was to identify whether there is an increase in type I interferon and proinflammatory cytokine levels in the cerebrospinal fluid of newborns with rotavirus-associated leukoencephalopathy.

The Telephone Interview for Cognitive Status (TICS): Reliability and validity in a stroke sample

The Telephone Interview for Cognitive Status (TICS) is an 11-item screening test (maximum score=41 points) that was developed for the assessment of cognitive function in patients with Alzheimer's disease who are unwilling or unable to be examined in person. To investigate the 1-month test-retest reliablility and validity of the TICS in a stroke sample, we administered it twice by telephone to 36 stroke patients (age = 72.3 ± 8.9; education = 9.7 ± 4.7) and 36 stroke-free non-demented control subjects (age = 71.8 ± 6.8; education = 13.1 ± 4.1). Dementia was diagnosed in six stroke patients based on neuropsychological and functional examinations performed during an outpatient visit and the Mini-Mental State Examination (MMSE) was also given. Multiple regression analyses determined that stroke status was significantly related to performance on the TICS (β= ?0.26, p = 0.006), while adjusting for demographic variables. Among stroke patients, test-retest reliability was excellent (r = 0.90, p < 0.001) and performance was significantly correlated with MMSE score (r = 0.86, p <0.001). A TICS cutoff score <25 best distinguished between demented and non-demented patients; sensitivity (1.00) and specificity (0.83) were excellent and comparable to the sensitivity (0.83) and specificity (0.87) of the MMSE, with dementia defined as a score <24/30. We conclude that the TICS is a reliable mental status test that can provide accurate information regarding cognitive function in stroke patients who cannot be assessed in person.     

The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke

Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. Materials and Methods: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post-stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. Results: People with acute stroke had significantly lower FMD (4.2% ± 4.6%) than control participants (8.5% ± 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% ± 4.6% stroke-affected vs. 5.3% ± 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke-affected limb, r = ?0.62, p = 0.03; non-affected limb, r = ?0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. Conclusions: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response.     

Cognitive function and insulin resistance in elderly patients with type 2 diabetes

Purpose: To explore the relationship between cognitive impairment and insulin resistance (IR) in elderly patients with type-2 diabetes mellitus.

Materials and methods: Two hundred and twelve elderly patients with type-2 diabetes were enrolled in this study and assigned into either the cognitive impairment group (n = 100) or the normal cognitive group (n = 112). Gender, age, education, body mass index (BMI), total cholesterol, triglyceride, low-density lipoprotein cholesterol, creatinine (Cr), fasting plasma glucose, fasting insulin (FINS) and homeostasis model of assessment for IR index (HOMA-IR) were compared between the two groups. Multifactorial logistic regression analysis was performed.

Results: In cognitive impairment group, education level (33.00 vs 53.57%, p < 0.01) was lower, the level of BMI [(28.7 ± 4.5) kg/m² vs (23.9 ± 3.7) kg/m², p < 0.01], FINS [(21.8 ± 5.3) mU/L vs (12.9 ± 3.9) mU/L, p < 0.01], HOMA-IR [(6.9 ± 1.7) vs (3.9 ± 0.9), p < 0.01] were higher than the control group. In the logistic regression, education level (B = –0.996, p = 0.03), FINS (B = 1.120, p < 0.01) and HOMA-IR (B = 1.301, p < 0.01) were independent factors.

Conclusions: Our study demonstrates that the education level, FINS and HOMA-IR were independent factors of cognitive impairment in elderly patients with type-2 diabetes. IR is an important risk factor and higher education level in a protective factor for the cognitive impairment in elderly patients with type-2 diabetes.     

Experimental ischemic neuropathy: Salvage with hyperbaric oxygenation

Hyperbaric oxygenation is effective in augmenting the delivery of oxygen to tissue, but also causes oxidative stress. As part of our focus on improving peripheral nerve salvage from ischemic fiber degeneration, we evaluated whether hyperbaric oxygenation rescues peripheral nerve, rendered ischemic by microembolization, from ischemic fiber degeneration. The supplying arteries of rat sciatic nerve were embolized with microspheres of 14 μm diameter at moderate (2 × 10⁶) and high (5.6 × 10⁶) doses. Rats were randomized to receive hyperbaric oxygenation treatment (2.5 atm 100% oxygen for 2 hours/day for 7 days beginning within 30 minutes of ischemia), or room air. End points for the embolized limb were (1) behavioral scores (0–11 in increasing levels of limb function), (2) nerve action potential of sciatic-tibial nerve, (3) nerve blood flow, and (4) histological grade as percentage of fibers undergoing ischemic fiber degeneration (0 = <5%; 1 = 5–25%; 2 = 26–50%; 3 = 51–75%; 4 = >76%). Nerve blood flow and nerve action potential were uniformly absent and more than 90% of fibers had degenerated in both control and treatment groups receiving high doses. Control and treatment groups receiving moderate doses were well matched by level of ischemia (8.5 ± 0.3 [N = 18] vs 7.7 ± 0.4 ml/100 gm/min [N = 18], P > 0.05) but were significantly different by behavior score (5.6 ± 0.7 vs 9.2 ± 0.5 [N = 19], p < 0.001), nerve action potential (1.4 ± 1.0 vs 3.9 ± 0.5 [N = 6], p < 0.05), and histology (2.4 ± 0.4 [N = 5] vs 0.8 ± 0.5 [N = 4], p < 0.05). On single teased fiber evaluation, the predominant abnormality was E (axonal degeneration). We conclude that hyperbaric oxygenation will effectively rescue fibers from ischemic fiber degeneration, providing the ischemia is not extreme.