Elevated plasma levels of soluble CD40 in incipient Alzheimer's disease

CD40 is a member of the tumor necrosis factor receptor super-family and has been suggested to play a role in the metabolism of beta-amyloid (Abeta) in Alzheimer's disease (AD). However, the role of CD40-signalling in incipient AD has not yet been studied. We investigated the plasma levels of soluble CD40 (sCD40) and the soluble CD40 ligand (sCD40L) at baseline in 136 subjects with mild cognitive impairment (MCI) and 30 age-matched controls. Sixty of the 136 MCI cases converted to AD (MCI-AD) during a clinical follow-up period of 4-7 years. The baseline levels of sCD40, but not sCD40L, were elevated in MCI-AD cases when compared to age-matched controls (Mann-Whitney U-test, p=0.02). However, MCI patients who were cognitively stable or developed vascular dementia during follow-up did not have significantly increased levels of sCD40 or sCD40L when compared to controls. The levels of sCD40 correlated to decreased baseline performance on mini-mental state examination (MMSE) in both controls (r(s)=-0.37, p<0.05) and MCI-AD cases (r(s)=-0.29, p<0.05). Finally, the plasma levels of sCD40 correlated with the levels of soluble amyloid precursor protein-alpha (sAPP-alpha) (r(s)=0.28, p<0.01) and sAPP-beta (r(s)=0.23, p<0.05) in cerebrospinal fluid. In conclusion, CD40-signalling might play a role in the pathogenesis of early AD.     

Serum levels of platelet released CD40 ligand are increased in early onset occlusive carotid artery disease

Objective: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls. Methods: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age-matched controls using ELISA. Degree of stenosis of the internal carotid artery (ICA), and intima-media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean ± SD. Results: Mean age was 50.9 ± 3.5 and 50.1 ± 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 ± 0.14 vs. 0.78 ±0.12 mm, p = 0.0003). Serum levels of sCD40L were significantly higher (6.9 ± 5 vs. 4.5 ± 3.0 ng/mL, p = 0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 ± 56.9 vs. 79.3 ± 18.7 pg/mL, p = 0.34). IMT did not correlate with sCD40L or sCD40 levels (R = −0.03, p = 0.77; and R = 0.109, p = 0.308, respectively). Conclusions: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis.     

Serum CD40/CD40L system in Graves' disease and Hashimoto's thyroiditis related to soluble Fas, FasL and humoral markers of autoimmune response

Activated CD4 T cells' express CD40 ligand (CD154) interacting with CD40 on the B cells surface, protecting them from Fas-mediated apoptosis and in this study, influence humoral response. The aim of the study was to assess soluble CD40 and CD154 in Graves' disease (GD) and Hashimoto's thyroiditis (HT) in relation to Fas and FasL and to the markers of humoral response: aTPO, aTG and aTSHR. The study was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on methimazol (euGD), 2/20 patients with hyperthyroid GD (hrGD), 3/15 patients with HT in euthyreosis on levothyroxine (euHT), 4/16 patients with hypothyroid Ht (hoHT), 5/12 healthy volunteers, age and sex-matched to groups 1-4. The serum levels of CD40, CD154, Fas and FasL, aTPO and aTG were determined by ELISA and aTSHR was determined by the RIA method. CD40 serum concentration was significantly higher in hoHT individuals: 55.8 (24.0-83.2) pg/ml (p<0.01) and euHT patients: 51.2 (20.0-80.1) (p<0.05) as compared to the controls. Also sCD40L values were significantly increased in euHT individuals: 5.1 (1.0-11.8) (p<0.05) and hoHT patients: 3.9 (0.7-11.2) ng/ml (p<0.05) as compared to the controls. There was a positive correlation between sCD40 and sCD154 in the patients studied (r=0.36, p<0.001). In HT patients we found positive correlations between sCD40 and aTPO (r=0.45, p<0.001) and sFas (r=0.36, p<0.05) as well as a negative correlation between sCD40 and FasL (r=-0.24, p<0.05). In GD patients there was a positive correlation between sCD40 and aTSHR (r=0.28, p<0.05). In summary, our results suggest that CD40/CD154 interaction plays an important role in the regulation of autoimmune humoral response, both in Hashimoto's thyroiditis and Graves' disease. Fas-mediated apoptosis seems to be involved in this process especially in Hashimoto thyroiditis. Soluble CD40 may serve as a marker of the active stage of autoimmune thyroid disease.     

Soluble CD40 in the serum of healthy donors, patients with chronic renal failure, haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) patients.

CD40 and its ligand CD40L are key players in T cell-B cell interaction and T cell-antigen-presenting cell (APC) interaction. Inhibition of CD40-CD40L interaction leads to severe humoral and cellular immunodeficiency. In this study we examined the presence of soluble CD40 (sCD40) in the serum of haemodialysis (HD) patients, CAPD patients, chronic renal failure (CRF) patients and healthy donors in order to evaluate the possible involvement of CD40 in uraemic immunodeficiency. Soluble CD40 was detected in the serum of healthy donors (n = 41) with a mean of 0.14 +/- 0.12 ng/ml and in the urine of healthy donors with a mean of 1.80 +/- 0.74 ng/ml. Soluble CD40 was highly elevated in all patients with impaired renal function. HD patients (n = 22) had up to 100-fold elevated sCD40 levels with a mean concentration of 8.32 +/- 4.11 ng/ml, whereas CAPD patients (n = 10) had considerably lower levels of sCD40 with a mean of 3.58 +/- 2.40 ng/ml. A strong correlation between sCD40 and serum creatinine levels was noted in CRF patients (n = 66). The highly elevated levels of sCD40 may point to the involvement of CD40 and its ligand CD40L in the clinical manifestation of uraemic immunodeficiency.     

Soluble CD44 splice variants and pelvic lymph node metastasis in ovarian cancer patients

Alternative splicing of CD44 and aberrant levels of soluble CD44 protein in the serum of cancer patients has been correlated to tumor progression and metastasis. To examine the clinical value of CD44 serum levels (sCD44) in ovarian cancer we determined concentrations of the soluble, variable isoforms sCD44std, sCD44v5 and sCD44v6 with a sensitive ELISA. Pre-operative serum samples from 66 patients with histologically diagnosed invasive disease as well as sera taken from 40 healthy blood donors were analyzed. In sera of ovarian cancer patients we detected elevated concentrations of overall CD44 serum levels represented by sCD44std (p=0.001), but decreased levels of the specific isoforms CD44v5 (p=0.0002) and v6 (p=0.0001). This is the first report demonstrating that ovarian cancer patients with pelvic lymph node metastasis at the time of diagnosis showed specifically elevated sCD44v6 (p=0.073) serum concentrations in comparison to patients without lymph node involvement, whereas overall sCD44 serum levels did not differ. Decreased serum levels of sCD44v5 were found in progesterone receptor-positive tumors (p=0. 059) and postmenopausal patients (p=0.032). Increased concentrations of sCD44v6 were detectable in estrogen receptor-positive tumors but not significantly (p=0.138). Serum CD44v5 levels were associated with shortened relapse-free survival time. No association was found between serum CD44 isoforms and the classical clinicopathological parameters stage and grading or overall survival. CD44 splice variants are possibly involved in a complex interaction with the hormonal environment during tumorigenesis and metastasis of ovarian cancer.     

Carotid atherosclerosis and cognitive decline in patients with Alzheimer's disease

Aim of the study was to explore the correlation between the progression of carotid atherosclerosis and the evolution of cognitive impairment in 66 patients with Alzheimer's disease (AD). They underwent cognitive status evaluation and ultrasonography (US) to investigate carotid arteries intima-media thickness (IMT) and plaque index (PI). After a 12-month follow-up period, neuropsychological and US examinations were repeated to assess the progression of carotid atherosclerosis and of cognitive decline [in terms of changes in Mini Mental State Examination (MMSE) scores]. MMSE score changes were related to baseline IMT (p=0.018), changes in IMT (p<0.001) and PI (p=0.006), and "antihypertensive drug intake" (p<0.001). While the first three variables correlated with increased cognitive impairment, the last one was associated with a reduced extent of MMSE score decline. Results show a link between progression of carotid wall changes and of cognitive decline, and suggest a possible protective role of antihypertensive therapy. Given the potential clinical implications, our preliminary findings could stimulate further investigations into the role of vascular impairment in patients with AD.     

Levels of soluble CD40 ligand (CD154) in serum are increased in human immunodeficiency virus type 1-infected patients and correlate with CD4(+) T-cell counts

CD40 ligand (CD40L or CD154) is a costimulatory molecule expressed mainly on activated CD4(+) T cells. Concentrations of the soluble form of CD40L (sCD40L) in serum were determined for a cohort of 77 human immunodeficiency virus type 1 (HIV-1)-infected patients before and after initiation of highly active antiretroviral treatment (HAART) by a quantitative enzyme-linked immunosorbent assay. Circulating sCD40L levels were higher by twofold in untreated patients than in healthy controls (means +/- standard deviations [SD]: 1.41 +/- 1.48 versus 0.69 +/- 0.59 ng/ml; P < 0.001). HIV-1-infected patients classified as CD4 T-cell category 1 had significantly higher sCD40L levels than patients classified as CD4 categories 2 and 3 (mean +/- SD: 2.08 +/- 1.46 ng/ml versus 1.57 +/- 1.58 [category 2] and 0.94 +/- 1.25 ng/ml [category 3]; P = 0.046), while no correlation with clinical categories A, B, and C was found. Individual serum sCD40L levels correlated with CD4(+) T-cell counts (P = 0.039) but not with viral load, gamma globulin levels, or acute-inflammatory-response markers. After 8 to 12 months of HAART, a further threefold increase of serum sCD40L levels, which paralleled the increase of CD4(+) T-cell counts, was observed. These novel findings suggest that sCD40L measurement in HIV-1-infected patients could serve as a new surrogate marker useful in the assessment of treatment efficacy, especially in settings where well-equipped laboratories and funding required for CD4(+) T-cell count and viral load measurements are not available.     

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.     

Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer's disease

Serum apolipoprotein (apo) AI concentration was studied in 98 Alzheimer's disease (AD) patients (77.56+/-8.83 years) and 59 healthy, elderly controls (75.37+/-5.27 years). ApoAI levels were significantly lower (p<10(-7)) in AD patients. An apoAI cutoff value of 1.50 g/L, could distinguish between the two groups with a sensitivity of 71% and a specificity of 69%. ApoAI levels were highly correlated with mini-mental state (MMSE) scores of patients (p<0.0001). These relationships remained significant after adjustment for multiple testing. Our findings raise the question of the potential implication of apoAI in the etiopathology of AD and bring serum apoAI concentration to the fore as an important biochemical marker.     

Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease

Magnesium deficiency is present in several chronic, age-related diseases, including cardiovascular, metabolic and neurodegenerative diseases. Alzheimer's disease (AD) is the most common cause of dementia. The aim of the present study was to study magnesium homeostasis in patients with mild to moderate AD. One hundred and one elderly (≥65 years) patients were consecutively recruited (mean age: 73.4±0.8 years; M/F: 42/59). In all patients, a comprehensive geriatric assessment was performed including cognitive and functional status. Admission criteria for the AD group (diagnosed according to the DSM-IV and the NINCDS-ADRDA criteria) included: mild to moderate cognitive impairment (MMSE score: 11-24/30, corrected for age and education). Blood samples were analyzed for serum total magnesium (Mg-tot) and serum ionized magnesium (Mg-ion). AD patients had significantly lower MMSE scores (20.5±0.7 vs 27.9±0.2; p<0.001), and for the physical function tests. Mg-ion was significantly lower in the AD group as compared to age-matched control adults without AD (0.50±0.01 mmol/L vs 0.53±0.01 mmol/L; p<0.01). No significant differences were found in Mg-tot between the two groups (1.91±0.03 mEq/L vs 1.95±0.03 mEq/L; p=NS). For all subjects, Mg-ion levels were significantly and directly related only to cognitive function (Mg-ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this group of patients between magnesium and ADL or IADL. Our results show the presence of subclinical alterations in Mg-ion in patients with mild to moderate AD.     

Efficacy and safety of galantamine (reminyl) for dementia in patients with Parkinson's disease (an open controlled trial)

An open controlled trial of the use of galantamine at a maximum dose of 16 mg/day included 41 patients with Parkinson's disease with dementia randomized to a galantamine treatment group (21 patients) and a control group (20 patients). Cognitive, neuropsychiatric, and motor symptoms were assessed clinically before the trial and at 4, 12, and 24 weeks, using the Mini Mental State Examination (MMSE), the cognitive Alzheimer's Disease Assessment Scale (ADAS-cog), the clock drawing test, the Frontal Assessment Battery (FAB), and the Neuropsychiatric Inventory (NPI) with assessment of distress in relatives. Patients treated with galantamine had better scores on the MMSE (p < 0.05),ADAS-cog (p < 0.05), the clock drawing test (p < 0.05), and the FAB (p < 0.01) at the end of the study period as compared with the control group. Changes in total point scores on the NPI-12 at the ends of weeks 12 and 24, as compared with the beginning of the trial, were in favor of the group treated with galantamine, with significant changes in the hallucinations (p = 0.0002), anxiety (p = 0.04), sleep disturbance (p = 0.04), and apathy (p = 0.006) sections. Galantamine treatment was accompanied by decreases in the level of distress in patients' relatives (p = 0.007) and improvements in daily activity (p = 0.003). Improvements in gait and decreases in freezing and falls were seen in the galantamine treatment group. However, two patients of this group showed minor increases in tremor. Side effects (drooling, postural hypotension, nausea, dysuria) occurred in seven patients (30%). __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 107, No. 12, pp. 25–33, December, 2007.     

急性冠脉综合征患者血浆炎性标志物及血脂水平分析

目的:检测分析急性冠脉综合征(ACS)患者血浆sCD40L、高敏C反应蛋白(hs-CRP)和血脂水平及临床意义。方法:检测68例ACS患者,28例稳定性心绞痛(SA)患者及33例对照组血浆sCD40L、hs-CRP水平,分析比较各组炎性标志物的水平及与血脂的相关性。结果:ACS组血浆sCD40L、hs-CRP与SA组及对照组比较,差异有统计学意义(均P<0.01);急性心肌梗死(AMI)组血浆sCD40L、hs-CRP显著高于不稳定性心绞痛(UA)组、SA组及对照组(均P<0.01),UA组血浆sCD40L、hs-CRP水平显著高于SA组及对照组(均P<0.01);而血浆sCD40L、hs-CRP在SA组及对照组比较,差异没有统计学意义(P>0.05);血浆sCD40L与hs-CRP呈正相关(r=0.452,P<0.01);hs-CRP与HDL-C呈负相关(r=-0.263,P<0.05);sCD40L与HDL-C呈负相关(r=-0.234,P<0.05),与TG呈正相关(r=0.254,P<0.05)。结论:血浆sCD40L、hs-CRP与ACS及血脂有一定关系,对判断ACS病情严重程度有重要意义。     

可溶性CD40在肝病患者血清中的表达及其临床意义

目的:研究可溶性CD40(solubleCD40,sCD40)在急性肝炎、重型肝炎和原发性肝癌患者血清中的表达,探讨其与生化指标和疾病预后的关系。方法:使用酶联免疫吸附实验(ELISA)检测急性肝炎(49例)、重型肝炎(22例)和原发性肝癌(13例)患者入院次日清晨空腹血清标本和健康体检者(44例)血清标本中sCD40浓度,分析其与急性肝炎患者丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的关系,并初步探讨sCD40水平与重型肝炎患者疾病预后的关系。流式细胞术检测患者血清sCD40与CD40配体(CD40L)的结合活性。结果:三种肝脏疾病患者血清中sCD40水平(149.70±86.82)pg/mL较健康对照组(47.33±27.49)pg/mL显著升高(P<0.001),但各组患者之间无统计学意义(P=0.475)。重型肝炎死亡患者血清sCD40浓度较存活患者显著升高(P<0.05)。急性肝炎患者血清sCD40浓度与ALT、AST水平呈显著正相关(r=0.50,P<0.001;r=0.47,P<0.01)。体外实验显示患者血清sCD40具有与CD40L结合的活性。结论:肝脏疾病患者血清异常高表达sCD40,这是评价急性肝细胞损伤的辅助指标,有助于判断重型肝炎患者的病情和预后。CD40-CD40L作用可能参与了肝细胞损伤和免疫失调的病理过程。     

Soluble CD30: a serum marker for Epstein-Barr virus-associated lymphoproliferative diseases

The soluble form of CD30 (sCD30), a member of tumor necrosis factor receptor superfamily, has been used as a marker of disease activity in various lymphomas. Epstein–Barr virus (EBV) is a potent stimulator of CD30 expression. The study aims to evaluate whether sCD30 can be used as a diagnostic marker for EBV‐associated infectious mononucleosis (IM) and post‐transplant lymphoproliferative disease (PTLD). Plasma from EBV seropositive healthy controls (N = 90), acute IM patients (n = 90), non‐PTLD heart/lung transplant recipients (N = 30) and EBV‐positive PTLD patients (N = 23) was tested for sCD30 using a commercially available ELISA kit. EBV DNA was tested by real time quantitative polymerase chain reaction assay. Significantly higher sCD30 levels were observed in acute IM patients (median 242.9 ng/ml) compared to EBV seropositive controls (median 15.7 ng/ml; P < 0.0001). These levels were highest in IM patients within 14 days of onset of illness. PTLD patients had significantly higher sCD30 levels (median 94 ng/ml) than healthy controls (P < 0.0001) and transplant patients (median 27 ng/ml; P = 0.0007). EBV DNA was detected mostly in acute IM and PTLD patients. In both cases there was a significant correlation between sCD30 and EBV DNA levels in plasma (P < 0.0001). This study demonstrates that sCD30 and EBV DNA levels can be used as potential markers for diagnosis of IM and PTLD. J. Med. Virol. 83:311–316, 2011. © 2010 Wiley‐Liss, Inc.     

Factors associated with parietal cell autoantibodies in the general population

The presence in serum of parietal cell autoantibodies (PCA) is a characteristic of autoimmune gastritis. We determined the prevalence of PCA in the general population and investigate their association with type 2 diabetes, insulin resistance and lifestyle factors related with autoimmune gastritis. A cross-sectional study was performed, involving 429 individuals enrolled in a cohort study of the general population of the Canary Islands. All participants underwent physical examination, provided a blood sample and responded to a questionnaire regarding health and lifestyle factors. Serum concentrations of PCA, soluble CD40 ligand (sCD40L), C-peptide and glucose (to determine insulin resistance) were measured. The association of PCA with the other factors was determined with bivariate analysis, and logistic regression models were used to adjust the associations for age and sex. The prevalence of PCA was 7.8% (95% CI=10.3-5.3). The factors associated with PCA were female sex (p=0.032), insulin resistance (p=0.016), menopause (p=0.029) and sCD40L (p=0.019). Alcohol consumption (p=0.006) and smoking (p=0.005) were associated with low prevalences of PCA. After adjustment for age and sex, the association with PCA was confirmed for smoking (OR=0.1 [0.0-0.9]), alcohol consumption (OR=0.3 [0.1-0.9]), insulin resistance (OR=2.4 [1.1-4.9]), female sex (OR=2.4 [1.1-5.3]), sCD40L (OR=3.7 [1.2-11.4]) and menopause (OR=5.3 [1.2-23.3]). In conclusion, smoking and alcohol consumption acted as protective factors against the appearance of PCA in the general population, whereas female sex, menopause, insulin resistance and elevated serum sCD40L were risk markers for PCA. In patients who smoke or drink alcohol, clinicians should be cautious when using PCA to rule out autoimmune gastritis.     

Use of Memantine (akatinol) for the Correction of Cognitive Impairments in Parkinson’s Disease Complicated by Dementia

This study addresses the effects of 52 weeks of treatment with the NMDA glutamate receptor antagonist memantine on motor, cognitive, and mental disorders in patients with Parkinson’s disease complicated by dementia, as compared with a control group of patients not treated with memantine. Patients of the experimental group (32 subjects) received memantine (20 mg/day), while patients in the control group continued on antiparkinsonism treatment alone. Cognitive, psychiatric, and motor symptoms were assessed before the study and then at the ends of weeks 12, 24, and 52, using clinical assessment, rating scales, and neuropsychological tests. Plasma homocysteine levels were measured by HPLC. Patients treated with memantine had better measures on the MMSE (p < 0.05), ADAS-cog (p < 0.05), clock drawing test (p < 0.05), and FAB (p < 0.01) as compared with the control group by the end of study week 24. Members of the group of patients with high homocysteine levels mounted significantly better responses with memantine treatment, as compared with patients of the control group with high homocysteine levels but not receiving memantine, at the ends of study weeks 24 and 52, in terms of all rating scales (UPDRS, MMSE, ADAS-cog, D-KEFS Verbal Fluency Test, FAB. NPI, and DAD, p < 0.05). By the end of week 52, significant changes in points scores on the NPI-12 scale from baseline were in favor of patients receiving memantine, this applying to the disinhibition (p = 0.006), irritability (p = 0.04), anxiety (p = 0.04), and hallucinations (p = 0.048) subscales. The presence of hyperhomocysteinemia may indicate faster progression of both motor and cognitive impairments in Parkinson’s disease. Prolonged memantine treatment of patients with Parkinson’s disease complicated by dementia leads to improvements in cognitive functions, stabilization of motor impairments, and decreases in the severity of mental disorders, especially in patients with hyperhomocysteinemia.     

Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting: analysis of inflammatory response and hemodilution

We compared the inflammatory response, hemodilution, and blood loss in patients who underwent mini-cardiopulmonary bypass (CPB) or conventional CPB during coronary artery bypass grafting (CABG). Ninety-eight consecutive patients with ischemic heart disease were randomly assigned to mini-CPB (n = 34) or conventional CPB (n = 64). Interleukin (IL) -8 and neutrophil elastase levels were measured before and after surgery. Hemodilution during CPB, blood loss during and after surgery were also evaluated. Compared with the conventional group, the mini-CPB group had lower levels of IL-8 on postoperative day 1 (8.3 +/- 6.4 vs. 19 +/- 11 pg/mL, p = 0.016) and of neutrophil elastase on postoperative days 1 (127 +/- 52 vs. 240 +/- 100 microg/L, p = 0.013) and 2 (107 +/- 17 vs. 170 +/- 45 micro/L, p = 0.0001). The mini-CPB group also has less blood loss during (620 +/- 595 vs. 978 +/- 658 mL, p = 0.012) and after the operation (578 +/- 310 vs. 1,002 +/- 651 mL, p = 0.0034) and a hemodilution ratio of 14 +/- 2 vs. 25% +/- 3%, p < 0.0001. Thus, mini-CPB attenuated the inflammatory response and hemodilution, resulting in blood conservation in patients undergoing CABG.     

Elevated serum soluble CD44 level in sarcoidosis

Sarcoidosis is a chronic multi-organ granulomatous disease of unknown etiology. Several studies have suggested an involvement of immunologic background in sarcoidosis. The lymphocyte surface marker CD44 is a multifunctional molecule which mediates the adhesion of lymphocytes to the extracellular matrix. Recently, we developed a system to quantitate soluble CD44 (sCD44) which we employed to determine serum and bronchoalveolar lavage fluid (BALF) levels of sCD44 to obtain further insights into immunologic aspects of sarcoidosis. Serum sCD44 levels were measured in 13 consecutive patients with sarcoidosis and 56 normal healthy controls using enzyme-linked immunoabsorbent assay. BALF sCD44 levels were also measured in 11 patients with sarcoidosis and 10 normal healthy controls. In patients with sarcoidosis, the serum sCD44 level was significantly higher than that of normal controls (348.5+/-164.2 ng/ml vs 145.4+/-22.9 ng/ml; p<0.001). Also BALF sCD44 levels tended to be higher in sarcoidosis than in normal controls (23.7+/-13.4 ng/ml vs 18.1+/-8.4 ng/ml), but no statistically significant difference was recognized. We also found that there was a positive correlation between the serum sCD44 and angiotensin converting enzyme (r=0.78). Our data indicate that sCD44 may be related to immunologic background and may be a useful new marker of sarcoidosis.     

Cutoff values of preoperative s-CEA levels for predicting survivals after curative resection of colorectal cancer

Serum carcinoembryonic antigen (s-CEA) is used to detect recurrence and predict prognosis in colorectal cancer. However, the cutoff values of s-CEA for prognosis have not been determined. We therefore tried to determine the preoperative s-CEA levels predictive of survivals in colorectal cancer patients. We retrospectively analyzed the medical records of 989 patients who underwent curative resection for colorectal cancer between July 1990 and December 1997, with a mean followup of 46 months (range, 3-129 months). When patients were divided into four subgroups with the cutoff values of s-CEA at 3,6, and 17 ng/mL, their 5-yr diseasefree survival rates were 85.3% (<3.0 ng/mL), 70.0% (3-6 ng/mL), 64.2% (6-17 ng/mL), and 55.2% (>17 ng/mL) (p<0.001). Multivariate analysis showed that factors predictive of survival included age (p=0.028), tumor stage (p<0.001), cell differentiation (p=0.016), and gross type (p=0.007), location (p=0.003) and preoperative s-CEA (p<0.001). Using the above-described cutoff levels, a significant difference in survival was observed only in patients with stage III tumors (p=0.007) when analyses were performed by stage. We can suggest the new cutoff values of s-CEA used in the present study.     

Decreased EEG synchronization and its correlation with symptom severity in Alzheimer's disease

BACKGROUND: Global field synchronization (GFS) has recently been introduced to measure functional synchronization in frequency-domain EEG data. This study explored GFS values and its clinical significance in patients with Alzheimer's disease (AD). METHOD: EEGs were recorded from 22 AD patients and 23 age-matched healthy controls. GFS values were computed in the delta, theta, alpha, beta1, beta2, beta3, gamma, and full frequency bands. The Mini-Mental Status Examination (MMSE) and the Clinical Dementia Rating scale (CDR) were used to assess the symptom severity in AD patients. RESULTS: GFS values in the beta1, beta2, beta3, and full bands were lower in AD patients than in healthy controls. GFS values in the alpha, beta1, beta2, beta3, and full bands were positively correlated with the MMSE and CDR scores in combined group (AD patients and healthy controls). In AD patients, GFS values were positively correlated with MMSE scores in the beta1, beta 3, and full bands, and with CDR scores in the delta band. CONCLUSION: GFS values were significantly lower in AD patients than in healthy controls, and they were positively correlated with MMSE and CDR scores. Our results suggest that GFS values are a useful biological correlate of cognitive decline in AD patients.