Principal component analysis of proton nuclear magnetic resonance spectra of lipoprotein fractions from patients with coronary heart disease and healthy subjects.

Blood plasma was drawn from 12 healthy subjects and 12 patients with coronary heart disease (CHD). The lipoproteins were fractionated by serial ultracentrifugation. The methyl and methylene regions of proton nuclear magnetic resonance (1 H NMR) spectra of the lipoproteins very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were analysed by principal component analysis (PCA). Grouping patterns in the score plots and the profiles of the principal components revealed several characteristics of the spectra. LDL subparticle size among the CHD group was consistently skewed against smaller, denser subparticles. This feature was independent of the concentration of LDL cholesterol. Analysis of the LDL spectra by soft independent modelling of class analogy (SIMCA) showed that none of the samples from the CHD group could be assigned as healthy subjects (p < 0.05). We also found that the samples from the healthy subjects were associated with a higher concentration of HDL cholesterol and larger VLDL subparticles. The approach presented, in which PCA is used in combination with NMR spectroscopy, might be implemented in clinical studies to give information about lipoprotein subparticle distribution and lipid content.     

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a 'haemodynamic instability score' (HIS). Aim: To assess HIS sensitivity and specificity in the diagnosis of CFS. DESIGN:Prospective controlled study. METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT. RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%. DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.     

拉曼光谱在妊娠糖尿病诊断中的应用价值

目的 探讨拉曼光谱在妊娠糖尿病(GDM)中的应用价值.方法 选取29名非孕体检健康者(正常对照组)、29例正常妊娠妇女(正常妊娠组)和42例GDM患者,建立拉曼光谱诊断GDM的方法 .另选取78例GDM患者和70名体检健康者进行方法 验证.采用正交偏最小二乘回归(OPLS)、主成分分析(PCA)-支持向量机(SVM)及...     

Raman difference spectroscopy: a non-invasive method for identification of oral squamous cell carcinoma

The feasibility of shifted-excitation Raman difference spectroscopy (SERDS) as a label-free and non-invasive technique for an objective diagnosis of oral cancer (OSCC) was investigated by analyzing 12 ex vivo OSCC samples. 72 mean SERDS spectra from each three physiological tissue points and pathological lesions were correlated with the histo-pathological diagnosis. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed excellent results with an area under the curve of 94.5% and a classification error of 9.7% (sensitivity: 86.1%; specificity: 94.4%). The SERDS Raman spectra of malignant and benignant tissues were discriminable with respect to the spectral features of proteins, lipids and nucleic acids. The presented method is capable of a highly accurate identification of OSCC. These findings suggest a high validity and reproducibility of SERDS combined with PCA and LDA analysis regarding oral cancer tissue.OCIS codes: (170.0170) Medical optics and biotechnology, (170.5660) Raman spectroscopy, (170.6935) Tissue characterization, (170.3890) Medical optics instrumentation     

Gray matter volume reduction in the chronic fatigue syndrome

The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities. We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities. We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.     

Identification and application of marker genes for differential diagnosis of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a complex disease and has no laboratory biomarkers, which makes diagnosis of CFS difficult. Several research groups challenged to identify genes specific for CFS; however, there are no overlaps between studies. The U.S. Centers for Disease Control and Prevention reported remarkable gene expression profiles of a large scale cohort study recruited 227 people. Reported genes were mostly different from the previously reported genes, again featuring the complexity of CFS. Separately, we identified 9 genes that were significantly and differentially expressed between CFS patients and healthy subjects using an original microarray. The changes in expression of 9 genes were confirmed by quantitative PCR. We also demonstrated the usefulness of 9 genes for differential diagnosis of CFS.     

Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome

A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature, it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level.     

Tired of being inactive: a systematic literature review of physical activity,physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome

A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature, it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level.     

Symptoms of autonomic dysfunction in chronic fatigue syndrome

BACKGROUND: Chronic fatigue syndrome (CFS) is common and its cause is unknown. AIM: To study the prevalence of autonomic dysfunction in CFS, and to develop diagnostic criteria. DESIGN: Cross-sectional study with independent derivation and validation phases. METHODS: Symptoms of autonomic dysfunction were assessed using the Composite Autonomic Symptom Scale (COMPASS). Fatigue was assessed using the Fatigue Impact Scale (FIS). Subjects were studied in two groups: phase 1 (derivation phase), 40 CFS patients and 40 age- and sex-matched controls; phase 2 (validation phase), 30 CFS patients, 37 normal controls and 60 patients with primary biliary cirrhosis. RESULTS: Symptoms of autonomic dysfunction were strongly and reproducibly associated with the presence of CFS or primary biliary cirrhosis (PBC), and correlated with severity of fatigue. Total COMPASS score >32.5 was identified in phase 1 as a diagnostic criterion for autonomic dysfunction in CFS patients, and was shown in phase 2 to have a positive predictive value of 0.96 (95%CI 0.86-0.99) and a negative predictive value of 0.84 (0.70-0.93) for the diagnosis of CFS. DISCUSSION: Autonomic dysfunction is strongly associated with fatigue in some, but not all, CFS and PBC patients. We postulate the existence of a 'cross-cutting' aetiological process of dysautonomia-associated fatigue (DAF). COMPASS >32.5 is a valid diagnostic criterion for autonomic dysfunction in CFS and PBC, and can be used to identify patients for targeted intervention studies.     

Study of proteomic changes associated with healthy and tumoral murine samples in neuroblastoma by principal component analysis and classification methods

BACKGROUND: The adrenal gland is the election organ forming primary neuroblastoma (NB) tumours, the most common extracranial solid tumours of infancy and childhood. METHODS: Samples of adrenal gland belonging to healthy and diseased nude mouse were analysed by 2D gel-electrophoresis. The resulting 2D-PAGE maps were digitized by PDQuest and investigated by principal component analysis (PCA). RESULTS: The analysis of the loadings of the first principal component (PC) permitted the evaluation of the spots characterising each class of samples. Moreover, the soft-independent model of class analogy (SIMCA) method confirmed the separation of the samples in the two classes and allowed the identification of the modelling and discriminating spots. Very good correlation was found between the data obtained by analysis of 2D maps via the commercial software PDQuest and the present PCA analysis. In both cases, the comparison between such maps showed up- and down-regulation of 84 polypeptide chains, out of a total of 700 spots detected by a fluorescent stain, Sypro Ruby. Spots that were differentially expressed between the two groups were analysed by matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry and 14 of these spots were identified so far.     

Spontaneous and coherent anti-Stokes Raman spectroscopy of human gastrocnemius muscle biopsies in CH-stretching region for discrimination of peripheral artery disease

Peripheral Artery Disease (PAD) is a common manifestation of atherosclerosis, characterized by lower leg ischemia and myopathy in association with leg dysfunction. In the present study, Spontaneous and coherent anti-Stokes Raman scattering (CARS) spectroscopic techniques in CH-stretching spectral region were evaluated for discriminating healthy and diseased tissues of human gastrocnemius biopsies of control and PAD patients. Since Raman signatures of the tissues in the fingerprint region are highly complex and CH containing moieties are dense, CH-stretching limited spectral range was used to classify the diseased tissues. A total of 181 Raman spectra from 9 patients and 122 CARS spectra from 12 patients were acquired. Due to the high dimensionality of the data in Raman and CARS measurements, principal component analysis (PCA) was first performed to reduce the dimensionality of the data (6 and 9 principal scores for Raman and CARS, respectively) in the CH-stretching region, followed by a discriminant function analysis (DFA) to classify the samples into different categories based on disease severity. The CH₂ and CH₃ vibrational signatures were observed in the Raman and CARS spectroscopy. Raman and CARS data in conjunction with PCA-DFA analysis were capable of differentiating healthy and PAD gastrocnemius with an accuracy of 85.6% and 78.7%, respectively.OCIS codes: (300.0300) Spectroscopy, (300.6230) Spectroscopy, coherent anti-Stokes Raman scattering, (300.6450) Spectroscopy, Raman, (170.0170) Medical optics and biotechnology     

Antinuclear antibodies in patients with chronic fatigue syndrome

Significance of antinuclear antibodies (ANA) in the patients with chronic fatigue syndrome (CFS) was reviewed. When indirect immunofluorescence with the HEp-2 cells as the substrates was used, prevalence of the positive ANA was reportedly 15-25%. The ANA titers were low and the immunofluorescent staining patterns were heterogeneous. One group in the USA reported that 'nuclear envelope staining pattern' was found in more than 50% of the patients with CFS. This results, however, have not been confirmed by any other research groups. Clinical significance of the positive ANA in the CFS patients resides in differential diagnoses of systemic lupus erythematosus and other diffuse connective tissue diseases. Recently, several ANAs specific to CFS have been described. We reported anti-68/48kD protein antibodies utilizing SDS-PAGE/ immunoblot method. These autoantibodies were found in 13% of 114 CFS patients and 0% in healthy subjects (p < 0.05). Hypersomnia and difficulty in concentration were found more frequently in the CFS patients with this specific autoantibody.     

Chronic fatigue syndrome: physical and cardiovascular deconditioning

We investigated whether chronic fatigue syndrome (CFS) patients have physical and/or cardiovascular de-conditioning, in 273 CFS patients and 72 healthy controls. We used laboratory tests to assess haematological, biochemical, endocrinological and immunological systems. The cardiovascular system was assessed by echocardiography and carotid echography. Body composition was determined by dual energy X-ray absorptiometry (DEXA). CFS patients had smaller left ventricular end systolic (p < 0.001) and diastolic (p = 0.008) dimensions but thinner posterior walls (p = 0.02) than corresponding values in healthy controls. Left ventricular mass was also reduced in CFS patients (p = 0.006). Both maximum (p < 0.001) and minimum (p < 0.008) diameter of the carotid artery were smaller in CFS patients. The laboratory screening tests showed significant differences in serum albumin (p = 0.05), phosphate (p = 0.02), HDL-cholesterol (p = 0.03), HDL:total cholesterol ratio (p = 0.01), triglycerides (p = 0.02), neutrophils (p = 0.01) and thyroid-stimulating hormone (p = 0.04) between CFS patients and controls. Male CFS patients had an increased percentage of fat mass compared with healthy male subjects (p = 0.02). This large group of CFS patients had evidence of physical and cardiovascular de-conditioning, suggesting that in these patients a graded exercise programme could lead to physical reconditioning and could increase their ability to perform physical activities.      

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow

Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder. Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.     

Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome

Some of the symptoms reported by people with CFS (chronic fatigue syndrome) are associated with various cardiovascular phenomena. Markers of cardiovascular risk, including inflammation and oxidative stress, have been demonstrated in some patients with CFS, but little is known about the relationship between these and prognostic indicators of cardiovascular risk in this patient group. In the present study, we investigated the relationship between inflammation and oxidative stress and augmentation index, a measure of arterial stiffness, in 41 well-characterized patients with CFS and in 30 healthy subjects. AIx@75 (augmentation index normalized for a heart rate of 75 beats/min) was significantly greater in patients with CFS than in control subjects (22.5+/-1.7 compared with 13.3+/-2.3% respectively; P=0.002). Patients with CFS also had significantly increased levels of CRP (C-reactive protein) (2.58+/-2.91 compared with 1.07+/-2.16 mug/ml respectively; P<0.01) and 8-iso-prostaglandin F(2alpha) isoprostanes (470.7+/-250.9 compared with 331.1+/-97.6 pg/ml respectively; P<0.005). In patients with CFS, AIx@75 correlated significantly with logCRP (r=0.507, P=0.001), isoprostanes (r=0.366, P=0.026), oxidized LDL (low-density lipoprotein) (r=0.333, P=0.039) and systolic blood pressure (r=0.371, P=0.017). In a stepwise multiple regression model, including systolic and diastolic blood pressure, body mass index, CRP, tumour necrosis factor-alpha, interleukin-1, oxidized LDL, high-density lipoprotein-cholesterol levels, isoprostanes, age and gender, AIx@75 was independently associated with logCRP (beta=0.385, P=0.006), age (beta=0.363, P=0.022) and female gender (beta=0.302, P=0.03) in patients with CFS. The combination of increased arterial wave reflection, inflammation and oxidative stress may result in an increased risk of future cardiovascular events. Assessment of arterial wave reflection might be useful for determining cardiovascular risk in this patient group.     

Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome

Contradictory reports have suggested that serum free carnitine and acylcarnitine concentrations are decreased in patients with chronic fatigue syndrome (CFS) and that this is a cause of the muscle fatigue observed in these patients. Others have shown normal serum free carnitine and acylcarnitines in similar patients. We report here studies on free, total and esterified (acyl) carnitines in urine and blood plasma from UK patients with CFS and three control groups. Plasma and timed urine samples were obtained from 31 patients with CFS, 31 healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Samples were analysed using an established radioenzymatic procedure for total, free and esterified (acyl) carnitine. There were no significant differences in plasma or urinary total, free or esterified (acyl) carnitine between UK patients with CFS and the control groups or in renal excretion rates of these compounds. The data presented here show that, in the CFS patients studied, there are no significant abnormalities of free or esterified (acyl) carnitine. It is thus unlikely that abnormalities in carnitine homeostasis have any significant role in the aetiology of their chronic fatigue.     

Diagnosis of HIV-1 infection by near-infrared spectroscopy: analysis using molecular clones of various HIV-1 subtypes

BackgroundPreviously, we investigated the possibility of using near-infrared (NIR) spectroscopy for the diagnosis of human immunodeficiency virus type-1 (HIV-1) infection. Here, we further analyze NIR spectra using molecular clones of various HIV-1 subtypes.MethodsCulture supernatants of pNL4-3- (HIV-1 molecular clone) or pUC18- (empty vector) transfected 293 T cells were used. In addition, culture supernatants obtained using pBal (HIV-1 subtype B molecular clone) or pIndieC (HIV-1 subtype C molecular clone) were used. Near-infrared radiation (NIR) spectra, obtained using the culture supernatants, were subjected to principal component analysis (PCA) to extract and analyze their properties.ResultsThe PCA demonstrated that HIV-1 in medium altered wavelength absorption at around 950 and 1030 nm, suggesting that the HIV-1 altered OH vibration in water. In addition, absorption varied among subtypes at around 950, 1030 and 1060 nm, suggesting that the interaction between HIV-1 and water varies among subtypes.ConclusionsThese differences in the NIR spectra may make it possible to delineate HIV-1 subtypes spectroscopically.     

Estimation of fatigue state in patient with CFS using actigraph and R-R interval power spectrum analysis

OBJECTIVES: In this study, we try to estimate the fatigue state using actigraphy and R-R interval power spectrum analysis. RESULTS: Actigraphy analysis showed that mean awake activity was decreased and duration of sleep was prolonged in patients with chronic fatigue syndrome (CFS), significantly (p < 0.001). Both of sleep episodes in wake period and wake episodes in sleep period were significantly increased in CFS patients in comparison with healthy volunteers (p < 0.001) In autonomic nerve analysis, sleep/awake ratio of high frequency component was significantly decreased in patients with CFS (p < 0.05). CONCLUSION: The quality of sleep in patients with CFS was decreased because of increase of wake episodes in sleep period. Also the lack of parasympathetic activation during sleep period might be associated with the deterioration of sleep quality in patients with CFS.     

Plasma metabolic profiling of Alzheimer's disease by liquid chromatography/mass spectrometry

ObjectivesThe identification of Alzheimer's disease (AD) biomarkers may allow for a less invasive and more accurate diagnosis as well as serve as a predictor of future disease progression and treatment response. The aim of this study was to map potential biomarkers in plasma for AD.Design and methodsPlasma metabolic perturbations between AD and healthy old person were investigated using ultra performance liquid chromatography/mass spectrometry (UPLC/MS) and metabonomics approach. The principal component analysis (PCA) of UPLC/MS spectra showed that metabolic changes between two groups.ResultsThe PCA of UPLC/MS spectra showed that metabolic changes observed between AD and control were clear. Nine potential biomarkers in correlation with the extent of AD were found.ConclusionsBased on PCA, several potential biomarkers (LPCs, sphingosine and tryptophan) were found and further identified by the following LC/MS/MS analysis. All of them could be the potential early markers of AD.