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Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration.

UNLABELLED: Degenerative disc disease (DDD) is a common finding in MRI scans and X-rays. However, their correlation to morphological and biochemical changes is not well established. In this study, radiological and MRI parameters of DDD were assessed and compared with morphological and biochemical findings of disc degeneration. Thirty-nine human lumbar discs (L1-S1), age 19-86 years, were harvested from eight cadavers. Within 48 h postmortem, MRIs in various spin-echo sequences and biplanar radiographs of intact spines were obtained. Individual discs with endplates were then sectioned in the mid-sagittal plane and graded according to the morphological appearance. Samples from the nucleus of each disc were harvested for biochemical analysis including water and proteoglycan contents. On MRIs, T2-signal intensity, Modic changes, disc extension beyond the interspace (DEBIT), nucleus pulposus shape, annular tears, osteophytes and endplate integrity were graded. On radiographs, an independent observer classified the parameters disc height, endplate sclerosis, osteophytes, Schmorl's nodes, intradiscal calcifications and endplate shape. General linear-regression models were used for statistical analysis. Backward elimination with a 10% significance cut-off level was used to identify the most significant parameters, which then were summed to create composite scores for radiography, MRI and the combination of both methods. The grading was performed by three observers, and a reliability analysis using Cronbach's alpha model was used to control interobserver agreement. The three radiographic parameters height-loss, osteophytes and intradiscal calcifications correlated significantly with the morphological degree of degeneration (p<0.001, R2=642). Significant differences of even one morphological grade could also be differentiated in the composite radiological score (p<0.05), except at the extremes between grades 1 and 2 and grades 4 and 5. All MRI parameters correlated significantly with the morphological grade (p<0.05); however Modic changes, T2-intensity and osteophytes accounted for 83% of the variation in the data. T2-signal intensity correlated significantly with H2O and proteoglycan content (p<0.001), and was best for detecting highly degenerated discs. Regression showed that the combined score was better correlated with the morphological grade (p<0.001, R2=775) than either the composite radiographic (p<0.001, R2=642) or composite MRI (p<0.001, R2=696) alone. Based on the combined score, a backwards elimination of the regression was performed, in which the parameters Modic changes, and T2-intensity loss (MRI) as well as calcifications (X-ray) accounted for 87% of the variability. The interobserver validation showed a high correlation for all three scores (Cronbach's alpha values ranging from 0.95 to 0.97). CONCLUSION: Selective imaging parameters and a newly created scoring scheme were found to correlate with disc degeneration as determined in a morphological manner. Surprisingly, radiographic parameters were able to distinguish different stages of degeneration, whereas MRI could only detect advanced stages of disc degeneration. We conclude that X-rays may remain a cost-effective, non-invasive in vivo-grading method to detect early disc degeneration, and, combined with MRI, correlate best with morphological and biochemical assessment of disc degeneration.

Adult↗

Correlation of cyclooxygenase-2 and aromatase immunohistochemical expression in invasive ductal carcinoma, ductal carcinoma in situ, and adjacent normal epithelium.

The purpose of our study was to evaluate the correlation between cyclooxygenase-2 (COX-2) and aromatase immunohistochemical expression in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast, as well as in adjacent stroma and normal epithelium, we still correlated with nuclear grade, histologic grade, presence or absence of comedonecrosis, tumor size, and age at diagnosis. Forty-seven cases were evaluated through the use of anti-aromatase and anti-COX-2 polyclonal antibodies. Making the correlation of COX-2 and aromatase expression, we observed that COX-2 expression in IDC was correlated with aromatase expression in IDC (p < 0.001), DCIS (p < 0.001), normal epithelium (p = 0.024), and stroma tumor (p < 0.001). When the correlation was made between COX-2 expression in DCIS with aromatase, we observed positive correlation in IDC (p < 0.001), DCIS (p < 0.001), normal epithelium (p = 0.013), and stroma tumor (p < 0.001). In the correlative analysis of COX-2 expression in normal epithelium with aromatase in different evaluated tissues, we observed the following statistical results: IDC (p < 0.001), DCIS (p < 0.001), normal epithelium (p = 0.005), and stroma tumor (p = 0.047). Our results demonstrate the high correlation between COX-2 and aromatase expression in IDC, DCIS and normal epithelium, showing the importance of these two enzymes in the induction, promotion and progression of breast cancer.

Adult↗

Visual field and multifocal electroretinography and their correlations in patients on hydroxychloroquine therapy.

PURPOSE: To evaluate the effects of hydroxychloroquine on visual field and multifocal electroretinography (mfERG) and their correlations in patients taking hydroxychloroquine. METHODS: This was a cross-sectional study in which patients on hydroxychloroquine therapy underwent automated 10-2 threshold static visual field examination and mfERG recordings. Non-parametric unadjusted and age-adjusted Spearman correlation coefficients rho were calculated between the cumulative dose of hydroxychloroquine and the visual field mean deviation (MD) and pattern standard deviation (PSD) values; and the mfERG response amplitudes and peak latencies. Correlation analysis was also performed between the visual field MD and PSD values and the mfERG response amplitudes and peak latencies. RESULTS: A total of 26 eyes in 13 patients were analyzed. The mean duration of hydroxychloroquine therapy was 4.9 years and the mean cumulative dose was 574 g. No significant correlation was found between the cumulative dose of hydroxychloroquine and the visual field MD and PSD values. There were significant correlations between the cumulative dose of hydroxychloroquine and mfERG N1 and P1 response amplitudes for the central rings (ring 1-3). The correlations between the dose of hydroxychloroquine and mfERG N1 and P1 response amplitudes were strongest for the paracentral ring 2 (rho =-0.63 and rho =-0.62, respectively, P = 0.001). Significant correlations were also found between the visual field MD values and mfERG response amplitudes of various ring eccentricities. CONCLUSIONS: In patients on hydroxychloroquine, mfERG response amplitude correlated with both the 10-2 visual field MD values and with the cumulative dose of hydroxychloroquine used. The use of mfERG can provide objective measurement of retinal function in patients on hydroxychloroquine and may provide supplementary quantitative information to visual field findings.

Adult↗

Correlation of urodynamic measures of urethral resistance with clinical measures of incontinence severity in women with pure genuine stress incontinence. The Continence Program for Women Research Group.

OBJECTIVE: Our aim was to correlate multiple measures of urethral resistance with five clinical measures of incontinence severity in women with pure genuine stress incontinence. STUDY DESIGN: Seventy-five women with pure genuine stress incontinence underwent passive and dynamic urethral pressure profilometry and Valsalva leak point pressure determinations. The standardized and validated measures of incontinence severity included (1) the number of incontinent episodes, (2) the number of continence pads used recorded in a prospective 1-week urinary dairy, (3) grams of fluid loss on a pad quantitation test, and (4) two condition-specific quality-of-life scales, the urogenital distress inventory and the incontinence impact questionnaire. The urodynamic and severity measures were compared with Pearson product-moment correlation analysis. RESULTS: There were no significant correlations between dynamic urethral pressure profile pressure transmission ratios and any measure of incontinence severity. Passive urethral pressure profile variables correlated significantly with incontinence episodes and pad use. Valsalva leak point pressures correlated significantly with pad use and quantitation testing. None of the urodynamic measurements was significantly correlated with either of the quality-of-life scales, but our power to demonstrate a correlation was limited. CONCLUSIONS: Both passive urethral pressure profile measures and Valsalva leak point pressures correlate with some severity measures of genuine stress incontinence. Although inefficient pressure transmission during stress is critical to the pathogenesis of genuine stress incontinence, the severity of the pressure transmission defect is not related to clinical severity. Conversely, impairment of intrinsic urethral resistance is not essential to the pathogenesis of genuine stress incontinence, but the degree of sphincteric impairment is related to severity once the condition exists.

Adult↗

A comparative study of ERP correlates of psychometric and Piagetian intelligence measures in normal and hyperactive children.

Verbal and performance scores of the Wechsler Intelligence Scale for Children-Revised (WISC-R 1981) and of a Piagetian battery, the Cognitive Development Scale for Children (EDC 1984), were obtained on 30 normal control and 19 hyperactive 6-8-year-old children. Amplitudes and latencies of a fronto-central P250 and of the parieto-occipital N250, P350 and P500 were measured concurrently in 4 categorization tasks derived from tests of the WISC-R and EDC batteries. Spearman correlations were computed between the intelligence and the ERP factor scores. Results showed that age-related and age-corrected Wechsler's scores were correlated with similar ERP changes (reduced amplitude, decreased latency). With regard to the amplitude changes, each type of intelligence was associated with a specific ERP pattern. The verbal scores were correlated with the P350 and the P500 amplitudes, and the performance scores with the frontal P250 and occipital N250 amplitudes. By contrast, Piagetian development and intelligence scores yielded ERP correlates in the opposite direction: P500 amplitude was negatively correlated with raw EDC scores, but positively with scaled EDC scores. In addition, Piagetian intelligence was not related to the general peak latency decrease with age. In hyperactive children, additional negative correlations were found between P250 amplitude and the subjects' verbal test scores. Correlations with some performance tests that were negative in normal controls, were positive in hyperactive children. In addition, latency-based correlations found in normal controls were lacking in hyperactive children. These findings provide strong evidence that intelligence comprises different components related to different subsets of cognitive processes, as indexed by different ERP waves. They also suggest that the development and intelligence do not always rely on the same changes, and that intelligence forms may not be referred to the same use of the same processes in hyperactive and normal children.

Attention Deficit Disorder with Hyperactivity↗

Spatio-temporal correlations in human gamma band electrocorticograms.

Animal electrocorticogram (ECoG) studies have shown that spatial patterns in the gamma band (>20 Hz) reflect perceptual categorization. Spatio-temporal correlations were investigated in the 20-50 Hz range in search for similar phenomena in human ECoG. ECoGs were recorded in a somatosensory discrimination task from 64-electrode subdural grid arrays, with inter-electrode spacing of 1 cm, overlying somatosensory, motor and superior temporal cortices in 2 patients with intractable epilepsy. Bootstrap techniques were devised to analyze the spatial and temporal characteristics of the correlations. Despite an extensive search, no evidence was found for globally correlated activity related to behavior either in narrow (1.e., 35-45 Hz) or broad (i.e., 20-50 Hz) bands. Spatial patterns, extracted using principal component analysis, could not be classified with respect to stimulus type in any time interval. Instead, spatially and temporally intermittent synchronization was observed between pairs of electrodes in 1 cm X 1 cm regions with high variability within and across trials. The distribution of correlation coefficients differed substantially from background levels at inter-electrode distances of 1 cm and 1.4 cm but not 2 cm or more. The minimum duration of correlation, the decorrelation time, of the ECoG was about 50 msec; the average correlation duration at 1 cm inter-electrode distance was about 150 msec; and the recurrence rate of significant correlation peaks was about 1.3/sec. The findings suggest that the surface diameters of domains of spatially correlated activity underlying perceptual categorization in human gamma band ECoG are limited to less than 2 cm and that the intermittent synchronization observed across separations of 1 cm and 1.4 cm is not solely due to volume conduction. Thus, if such gamma band spatial patterns exist in the human brain, no existing technology would be capable of measuring them at the scalp, and subdural electrode arrays for cortical surface recording would have to have spacings under 5 mm.

Adult↗

Alcohol and beer consumption in relation to cancers of bowel and lung: an extended correlation analysis.

Some extensions to simple international correlation analyses are examined with reference to beer consumption and bowel and lung cancers in 29 countries. Simple correlation of cross-sectional data for beer consumption and rectal cancer yields a coefficient of 0.77 in males and 0.75 in females. Lagged correlation analyses show a different temporal relationship between beer and colon cancer (little change over time) and rectal cancer (maximal correlation for contemporaneous, i.e. cross-sectional, data sets). Lagged correlation analysis of beer consumption and lung cancer shows a similar pattern to that for rectal cancer and beer, and markedly different from that for lung cancer and cigarettes, the former showing maximal correlation for contemporaneous data, the latter peaking 15 yr prior to date of mortality. Changes in beer consumption over time correlate with subsequent changes in rectal cancer, particularly amongst younger age groups. The sex-ratio of rectal cancer varies from around 1 in low beer consumption countries to about 1.75 in high consumption countries. The utility of these extensions to the usual simple correlation analyses is considered. The biologic plausibility of beer-bowel cancer relationships, and possible mechanisms, are discussed in the light of the findings.

Adult↗

Correlation between calculated local stability and hydrogen exchange rates in proteins.

The attempt is made to find new correlations between local structural characteristics of proteins and the hydrogen exchange rates of their individual main-chain amides, and to relate such correlations to possible mechanisms of hydrogen exchange. It is found that in bovine pancreatic trypsin inhibitor (BPTI) the surface area buried by a particular residue and its neighbors correlates with the exchange rate of the main-chain amide of that residue. As the area buried by a particular fragment can be associated with the stabilization of the protein structure by this fragment, the correlation suggests a role for the energetics of the local unfolding in the mechanism of hydrogen exchange. Calculations based on the assumption that the exchange mechanism involves local unfolding lead to quantitative agreement between the calculated and experimentally measured exchange rates for 80% of the amides of BPTI that are buried or hydrogen bonded to the main-chain or to internal water molecules. The same degree of correlation is found between the calculated exchange rates and partial exchange data for ribonuclease S, hen lysozyme and cytochrome c. A similarly strong correlation is found between calculated exchange rates and the exchange rates of ribonuclease A determined by neutron diffraction in the crystal. The criteria of correlation are, however, less stringent in this case because of the experimental errors, which are larger than for solution data. It is suggested that the observed correlation be used for predictions of hydrogen exchange rates in proteins.

Animals↗

Correlations among assays of porcine semen quality following cryopreservation.

Correlations between in vitro tests of semen quality, used to predict the in vivo fertilizing potential of sperm, indicate that the tests may substitute for each other in predicting fertilizing potential. Lack of correlation between tests suggest that both tests should be used to estimate the fertilizing potential. The purpose of this study was to establish correlations between several in vitro tests of porcine semen quality following freezing. Tests of motility with and without caffeine, spermatozoa with normal apical ridges, sephadex filtration with and without caffeine and acrosin activity were all correlated with each other. Correlations among these tests ranged from 0.45 to 0.83 (P<0.05). Assays for glutamic oxalacetic transaninase (GOT) were not consistently correlated with other tests. None of these tests of semen quality were correlated with the sperm penetration assay except for the test of motility without caffeine, which was correlated with the number of penetrations per hamster oocyte (r = 0.71, P<0.05).

Journal Article↗

Cross-modal correlation of dichotic and tachistoscopic language laterality tasks: the importance of familial sinistrality.

Previous studies have found little if any correlation between dichotic and tachistoscopic language laterality task performance asymmetries. Problems with these studies have been that quite dissimilar auditory and visual tasks have often been used, and the reliability of the asymmetry measures has generally been unknown or, when known, relatively poor. We assessed the cross-modal correlation for two tasks, the Bilateral Object Naming Latency Task (BONLT) and the Dichotic Object Naming Latency Task (DONLT). These tasks are highly similar and have demonstrated high reliabilities. A significant, though rather small, cross-modal correlation was found (r = +.28). When cross-modal correlations were computed for FS- and FS+ subjects separately, no correlation was found for FS+ subjects (r = +.02), but the correlation for FS- subjects was highly significant (r = +.54, p less than .004). This led us to reexamine some previously collected data (P.L. Van Eys and W. F. McKeever, 1988, Brain and Cognition, 4, 413-429) which had administered two highly reliable language laterality tasks (the BONLT and the Dichotic Consonant Vowel Task), but had not assessed cross-modal correlation. A significant cross-modal correlation was found for FS- but not for FS+ subjects. The results are consistent with the hypothesis of H. Hecaen, M. De Agnostini, and A. Monzon-Montes (1981, Brain and Language, 12, 261-284) which suggests that one effect of FS+ is to induce a greater heterogeneity of localizations of different language processes.

Adult↗

Biochemical and histologic correlates of ventricular end-diastolic pressure.

The associations of elevated left ventricular (LV) and right ventricular (RV) end-diastolic pressure (EDP) were evaluated in 28 patients with non-ischemic congestive cardiomyopathy. Right-sided endomyocardial biopsies from each patient were evaluated for ATP content, percent fibrosis and myocardial fiber diameter. The resting RVEDP and LVEDP and the post-angiographic LVEDP were correlated with the results from the biopsies. There was a correlation of the LVEDP with the RVEDP (r = 0.67, P less than 0.001) by a linear plot. There was no correlation of any EDP measurement with the percent fibrosis. There was, however, a rough correlation of the myocardial fiber diameter with RVEDP (r = 0.40, P less than 0.05). Myocardial ATP content correlated with the RVEDP (r = -0.53, P less than 0.005), the LVEDP (r = -0.65, P less than 0.001) and the post-angiographic LVEDP (r = -0.72, P less than 0.001). These data demonstrate that an elevated ventricular EDP correlates most closely with depressed levels of myocardial ATP. The myocardial cell diameter correlated less well and there was no correlation of EDP with fibrosis. Metabolic factors may be more important than histologic parameters in the elevated ventricular EDP of non-ischemic congestive cardiomyopathy.

Adenosine Triphosphate↗

Computation of a location shift between two subsequent intra vascular ultrasound registrations by cross-correlation analysis of the lumen area functions.

For longitudinal studies on atherosclerosis and restenosis after angioplasty by intravascular ultrasound (IVUS), it is essential that repeated studies are performed at exactly the same location along an arterial section. In human femoral arteries, lumen and plaque area functions of two subsequent IVUS pullback maneuvers were compared by cross-correlation analysis. In cross-correlation analysis of two functions with equal abscissa values, the data sets are repetitively correlated after incremental shifts of the two functions along the abscissa. This results in multiple correlation coefficients with a maximum at the relative position where the two functions show the closest match. In group A (12 patients), both pullbacks were performed after angioplasty and in group B (17 patients) one pullback was performed before angioplasty and the second immediately after angioplasty. In group A, cross-correlation showed a shift between lumen area functions of 5 mm in one patient and no shift in the other patients. Maximum correlation coefficients in group A ranged from 0.644 to 0.978. Four patients from group B showed shifts from 2.5 to 35 mm. Maximum coefficients were significantly smaller than in group A: 0.259-0.864 (p < 0.01). Plaque area functions in group B showed higher correlations (0.468-0.862, p = 0.034) and only two shifts. Cross-correlation of lumen and plaque area functions may be used to compute location shifts between two subsequent IVUS registrations and to correct such shifts.

Aged↗

Growth in the first four years: IV. Correlations with parental measures in small-for-dates and large-for-dates babies.

Parent-child correlations for weight, height and head circumference on eight occasions between birth and 4 years were estimated within groups of 212 small-for-dates (SFD), 208 average-for-dates (AFD) and 221 large-for-dates (LFD) children. For mothers and fathers in the SFD and AFD groups, and fathers in the LFD group, correlations for weight were generally low in the first year, with moderate increases up to 4 years. No correlations for weight at any age were found between mothers and LFD children. There was a gradual rise in correlations for length in all three groups for both mothers and fathers between birth and 4 years. Head circumference correlations in the AFD and LFD groups were relatively high at birth and showed little change thereafter. Mother-child correlations for head circumference in the SFD group were absent at birth, but then rose sharply to a value comparable with the AFD parents' correlations at 18 months, with the little change thereafter. No SFD father-child correlations for head circumference were found at any age. Children's standards of weight and head circumference adjusted for mid-parental measures would, in some cases, be misleading.

Adult↗

Cardiopulmonary exercise testing and six-minute walk correlations in pulmonary arterial hypertension.

In a clinical trial of 178 patients with pulmonary arterial hypertension, treatment improved the 6-minute walk (6MW) distance but not the peak VO2. To clarify this discrepancy, we examined the exercise data from all study sites. Patients received either the endothelin receptor antagonist sitaxsentan or placebo and underwent serial 6MW and cardiopulmonary exercise testing (CPET). In 518 pairs of body weight-adjusted and unadjusted 6MW and CPET data, the correlation between 6MW and peak VO2 was 0.48. In the 4 sites with the highest overall correlation at baseline (r = 0.62 compared with 0.46 for the other 19 sites, p = 0.04), the correlations at baseline (0.66) and at week 12 (0.65) were similar (p = 0.90). However, the correlation increased significantly from baseline (0.34) to week 12 (0.54, p = 0.0005) for the other 19 sites. The correlations between weight-adjusted 6MW distance and peak VO2 for all centers (0.76) were significantly higher than the unadjusted correlations (0.48, p < 0.0001). Improvement in the correlations over time between the 6MW and CPET data at less-experienced sites was most consistent with improved technical skill with increasing experience. Weight adjustment of the 6MW improved its correlation with peak VO2. In conclusion, in future multicenter trials, CPET expertise should be validated at all sites before subject enrollment.

Adolescent↗

Correlation between mRNA and protein abundance in Desulfovibrio vulgaris: a multiple regression to identify sources of variations.

Parallel profiling of mRNA and protein on a global scale and integrative analysis of these two data types could provide additional insights into the metabolic mechanisms underlying complex biological systems. However, because mRNA and protein abundance are affected by many cellular and physical processes, there have been conflicting results on their correlation. Using whole-genome microarray and LC-MS/MS proteomic data collected from Desulfovibrio vulgaris grown under three different conditions, we systematically investigate the relationship between mRNA and protein abundance by a multiple regression approach, in which some of the key covariates that may affect mRNA-protein relationship were included. The results showed that mRNA abundance alone can explain only 20-28% of the total variation of protein abundance, suggesting mRNA-protein correlation can not be determined by mRNA abundance alone. Among various covariates, analytic variation of protein abundance is the major source for the variation of mRNA-protein correlation, which contributes to 34-44% of the total variation of mRNA-protein correlation. The cellular functional category of genes/proteins contributes 10-15% of the total variation of mRNA-protein correlation, with a more pronounced correlation of the two properties was observed for "central intermediary metabolism" and "energy metabolism" categories. In addition, protein stability also contributes 5% of the total variation of mRNA-protein correlation. The study presents the first quantitative analysis of the contributions of various biochemical and physical sources to the correlation of mRNA and protein abundance in D. vulgaris.

Bacterial Proteins↗

Long-range temporal correlations in alpha and beta oscillations: effect of arousal level and test-retest reliability.

OBJECTIVE: The aim of the present study was to evaluate test-retest reliability and condition sensitivity of long-range temporal correlations in the amplitude dynamics of electroencephalographic alpha and beta oscillations. METHODS: Twelve normal subjects were measured two times with a test-retest interval of several days. Open- and closed-eyes conditions were used, representing different levels of arousal. The amplitude of the alpha and beta oscillations was extracted with bandpass filtering and the Hilbert transform. The long-range temporal correlations were quantified with detrended fluctuation analysis. RESULTS: The amplitude dynamics of the alpha and beta oscillations demonstrated power-law long-range temporal correlations lasting for tens of seconds. These correlations were degraded in the open- compared to the closed-eyes condition. Test-retest statistics demonstrated that the long-range temporal correlations had significant reliability, which was greatest in the closed-eyes condition. CONCLUSIONS: The presence of long-range temporal correlations indicates that the amplitude of neuronal oscillations at a given time is dependent on the amplitude at times as remote in the past as tens of seconds. The reliability of long-range temporal correlations suggests that the mechanisms generating the amplitude fluctuations are not perturbed over several days. The systematic changes in the scaling exponents at different levels of arousal indicate that these changes occur on many time scales (5-80 s) as a result of modifications in the intrinsic dynamics of the neuronal oscillations. SIGNIFICANCE: This study demonstrates that the dynamics of spontaneous neuronal oscillations possess long-range temporal correlations with properties suitable for functional and clinical studies.

Adult↗

Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients.

BACKGROUND: In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. METHODS: A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). RESULTS: Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). CONCLUSIONS: Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.

Aged↗

Characterization of patterns of expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta and their correlations to p53, galectin-3, the retinoic acid receptor-beta and the macrophage migration inhibitory factor (MIF) in human cholesteatomas.

Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin in the middle ear cavity. Due to roles in cell proliferation, apoptosis and differentiation members of the protein kinase C (PKC) family could be involved in disease progression. This study focuses on the expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta in the epithelial tissues of 56 human cholesteatomas and their correlations with those of previously characterized distributions of p53, galectin-3, retinoic acid receptor-beta (RARbeta) and macrophage migration inhibitory factor (MIF). We have previously reported this marker set to be correlated with keratinocyte differentiation in human cholesteatomas. Our present data clearly show that the percentage of PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta)-immunopositive cells in epithelial tissue fro recurrent cholesteatomas was significantly higher than in non-recurrent cases. Correlations between the PKC isoenzymes and the biological markers were non-uniform. PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta) expression in epithelial cholesteatoma cells correlated significantly and positively with the percentages of p53-immunopositive cells. The patterns of PKC-alpha and -delta expression, but not of PKC-gamma, -eta and -zeta, correlated significantly and positively with galectin-3 expression. In addition, the correlation levels between the expression of PKC-alpha and -delta and that of galectin-3 varied depending on the infection and recurrence status. Presence of RARbeta correlated significantly (and positively) with the expression of PKC-gamma and -zeta and also in relation to the infection and recurrence status. MIF correlated presence significantly (and positively) with that of the five PKCs under study, depending on whether the cholesteatomas were non-infected or infected as well as non-recurrent or recurrent. In conclusion, the present study suggests that modifications occurring at the level of keratinocyte differentiation in human cholesteatomas involve distinct effectors, to which the activation of PKC-alpha, -delta, -eta, -gamma and -zeta can be added.

Adolescent↗