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Results for “Biomarker variability”

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PubMed2007

Comparison between urinary o-cresol and toluene as biomarkers of toluene exposure.

The characteristics of urinary o-cresol (o-C) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene were comparatively evaluated. One hundred healthy male rotogravure printing workers and 161 male and female control subjects were studied. Personal exposure to airborne toluene (TOL-A) during the shift was determined as a time-weighted average. Simple analytical procedures based on solid phase microextraction followed by gas chromatography/mass spectometry analysis were applied to the determination of end-shift o-C and TOL-U. Median TOL-A was 48 (6.0-162.0) mg/m3 in printers and 0.021 (<0.003-0.137) mg/m3 in controls. o-C was 0.185 (0.032-0.948) mg/g creatinine in printers and 0.027 (<0.006-0.330) mg/g creatinine in the controls. TOL-U was 7.6 (1.8-23.9) microg/L in printers and 0.140 (0.094-0.593) microg/L in the controls. According to all indices, exposure to toluene was higher in printers than in the controls. Nevertheless, the distribution of o-C in the two groups partially overlapped, whereas such behavior was not found in TOL-U. Both o-C and TOL-U in printers were correlated with TOL-A (Pearson's on log10-transformed variables r = 0.704 and 0.844, respectively) and with each other (r = 0.683). Smoking habits significantly increased the excretion of o-C but not of TOL-U. From the point of view of sampling conditions and analytical requirements, TOL-U and o-C showed similar properties, but comparison of their intrinsic characteristics showed that TOL-U had higher specificity and sensitivity, lower background values, was better correlated with airborne exposure, and was not influenced by cigarette smoking. Therefore TOL-U may be considered superior to o-C as a biomarker of occupational exposure to toluene.

Adult↗

PubMed2004

Biomarker responses during and after treatment with nesiritide infusion in patients with decompensated chronic heart failure.

BACKGROUND: Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion. METHODS: NT-proBNP and BNP were measured in a nonconsecutive patient cohort receiving clinically indicated intravenous nesiritide. Blood samples were drawn before, at 6 and 24 h during, and at 6 h after infusion. A reduction in NT-proBNP was defined as a decrease from baseline during infusion ("infusion responders") of >3 SD of the variability of the assay measurement (approximately 20%). Patients with decreases >20% in both NT-pro BNP and BNP at 6 h post infusion were designated "biochemical responders". RESULTS: Forty patients [27 males; mean (SE) age, 68 (2) years; mean (SE) left ventricular ejection fraction, 25 (1.4)%] were studied. All patients improved clinically. Overall, the changes in NT-proBNP were a 18 (4.6)% [mean (SE)] and 19.8% (median) decrease from baseline at 24 h of infusion and a 22 (6.0)% and 17.8% decrease at 6 h post infusion (P <0.001 compared with baseline). In a large number of patients, decreases in NT-proBNP were, however, within the variability of the assay. Subgroup analysis showed that 22 of 40 patients were infusion responders with a >20% decrease from baseline in NT-proBNP during nesiritide infusion, whereas only 12 patients were biochemical responders with >20% decreases from baseline postinfusion for both NT-proBNP and BNP. CONCLUSIONS: In this study, many patients had decreased NT-proBNP and BNP values after therapy with nesiritide, but the majority of patients did not demonstrate biochemically significant decreases in analytes despite a clinical response. Until we know more about the responses of natriuretic peptides to therapies such as nesiritide, a strategy of monitoring NT-proBNP and BNP to guide therapy cannot be universally advocated.

Aged↗

PubMed1995

Glutathione S-transferase activity and glutathione S-transferase mu expression in subjects with risk for colorectal cancer.

The glutathione S-transferases (alpha, mu, and pi), a family of Phase II detoxication enzymes, play a critical role in protecting the colon mucosa by catalyzing the conjugation of dietary carcinogens with glutathione. We investigated the efficacy of using the glutathione S-transferase (GST) activity of blood lymphocytes and GST-mu expression as biomarkers of risk for colorectal cancer. GST activity was measured in the blood lymphocytes of control individuals (n = 67) and in the blood lymphocytes (n = 60) and colon tissue (n = 34) of individuals at increased risk for colon cancer. Total GST activity was determined spectrophotometrically with the use of 1-chloro-2,4-dinitrobenzene as a substrate. The ability to express the um subclass of GST was determined with the use of an ELISA. Although interindividual variability in the GST activity of blood lymphocytes was greater than 8-fold (range, 16.7-146.8 nmol/min/mg), the GST activity of blood lymphocytes and colon tissue within an individual was constant over time and was unrelated to sex, age, or race. The GST activity of blood lymphocytes from high-risk individuals was significantly lower than that of blood lymphocytes from control individuals (P < or = 0.004). No association was observed between the frequency of GST-mu phenotype and risk for colorectal cancer. Blood lymphocytes from high-risk individuals unable to express GST-mu had lower levels of GST activity than did those from control subjects with the GST-mu null phenotype; however, this difference was significant in male subjects only (P < or = 0.006). Analysis of paired samples of blood lymphocytes and colon tissue indicated a strong correlation between the GST activity of the two tissue types (Spearman's rank correlation, r = 0.87; P < or = 0.0001). The GST activity of blood lymphocytes may be used to identify high-risk individuals with decreased protection from this Phase II detoxication enzyme who may benefit from clinical trials evaluating GST modulators as chemopreventive agents for colorectal cancer. The GST activity of blood lymphocytes may also be used in colorectal cancer chemoprevention trials to monitor the responsiveness of colon tissue to regimens that modify Phase II detoxication enzymes.

Adult↗

PubMed2006

Association of left-heart dysfunction with severe exacerbation of chronic obstructive pulmonary disease: diagnostic performance of cardiac biomarkers.

RATIONALE: Cardiac biomarkers are used to distinguish acute dyspnea due to left-heart dysfunction from that of pulmonary origin. However, they have not been assessed in the specific setting of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), where they might be released without left-heart impairment. OBJECTIVE: To assess the accuracy of troponin T and of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD associated with left ventricular (LV) dysfunction. METHODS: Both biomarkers were measured in 148 consecutive patients on intensive care unit admission for AECOPD. A panel of physicians adjudicated blindly the cause of AECOPD to be unlikely, possibly associated, or definitely associated with LV dysfunction. MEASUREMENTS AND MAIN RESULTS: The final diagnosis was AECOPD definitely associated with acute left-heart dysfunction in 31.1%, possibly associated with LV dysfunction in 13.5%, and probably not associated with LV dysfunction in 55.4%. Both NT-proBNP and troponin T levels were significantly different among the three groups. The area under the receiver operating characteristic curve was greater for NT-proBNP (0.95 vs. 0.67). A cutoff of 1,000 pg/ml was accurate to rule out left-heart involvement in AECOPD (sensitivity, 94%; negative predictive value, 94%; negative likelihood ratio, 0.08). A cutoff of 2,500 pg/ml had the best operating characteristics to rule in the diagnosis (positive likelihood ratio, 5.16). Left-heart involvement in AECOPD was the only variable independently associated with increased secretion of NT-proBNP (odds ratio, 74; 95% confidence interval, 15-375; p = 0.0001). CONCLUSION: NT-proBNP and troponin T are useful in excluding AECOPD associated with left ventricular dysfunction. NT-proBNP was the more accurate of the two.

Aged↗

PubMedDate not supplied

[Neurogenic stunned myocardium].

The existence of stunned myocardium and reversible myocardial dysfunction is widely described and accepted in patients suffering ischemic heart disease. However, it cannot be exclusive to coronary disease. Classically, the appearance of electrocardiographic changes in the critical neurological disease has been described. However, at present, it seems to be observed that some of these patients with critical neurological disease could have variable grades of myocardial dysfunction, which is generally reversible in the surviving patients. This myocardial dysfunction, which could affect critically ill neurological patients, has traits similar to stunned myocardium generated in coronary patients since: a) it is generally associated to electrocardiographic changes, b) it can be accompanied by segmental contractility disorders and even c) it may be accompanied by a certain increase of cardiac biomarkers. Although its etiopathogeny is unknown, it could be related with the severity of the primary neurological disease. Its prophylaxis and prognosis are also unknown. It could be related with neurogenic edema, with hemodynamic instability, and could also play a very important role in brain death and in organ donation.

Brain Injuries↗

PubMed2000

Assessments of physical activity and cancer risk.

The assessment of physical activity is one of the most important methodological issues in research into physical activity and cancer risk. A sedentary Western lifestyle has been observed to influence biological mechanisms promoting development of certain types of cancer. At present the totality of evidence supports a protective effect against cancers of the colon and probably the breast, while further data concerning carcinoma of other cancers are required. Thus, physical activity represents a powerful public health measure for reducing cancer risk. Studies of the association between physical activity and cancer risk have used a great variety of methods, but have most often included work and/or leisure time activity. Questionnaires are the method most often used and various components of physical activity such as type, frequency, intensity and lifetime physical activity have been recorded. However, the measurements used when assessing physical activity have been hampered by lack of accuracy as regards validity and reliability, missing information on the various components of physical activity and sparse information of lifetime exposure, and often no repeat assessments in cohort studies. Discrepancies between studies elaborating the association between physical activity and site-specific cancer risk may be explained through real differences or lack of information on the various components of physical activity (type, intensity, duration) and incomplete information about the cancer type studied (localization, histological type). The complicated nature of the variable physical activity, combined with incomplete understanding of the pathogenesis of most cancer and lack of knowledge regarding possible biological mechanisms operating between physical activity and cancer, warrants further studies. In these studies methodological improvements in measuring physical activity, combined with inclusion of physiological markers (heart rate, energy balance, hormonal levels, etc.) reflecting the variety of physical activities performed are of particular interest. Assessing biomarkers and intermediate steps for site-specific cancer risk may give us further insight into the relation between physical activity and cancer that will be of enormous interest for public health recommendations.

Breast Neoplasms↗

PubMed2005

High serum concentration of YKL-40 is associated with short survival in patients with acute myeloid leukemia.

PURPOSE: YKL-40 is secreted by cancer cells, macrophages, and neutrophils. It may be a growth or differentiation factor, play a role in angiogenesis, or protect against apoptosis. High serum YKL-40 is associated with poor prognosis in solid carcinomas. The aim was to examine serum YKL-40 in patients with acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: YKL-40 was measured by ELISA in serum from 77 patients recently diagnosed with AML before and during the first month of chemotherapy. RESULTS: Forty (52%) of the AML patients had elevated serum YKL-40 (compared with age-matched healthy subjects) and their survival was shorter than in patients with normal serum YKL-40 (median, 128 days; interquartile range, 18-629 days versus 386 days; interquartile range, 180-901; P=0.018 Mann-Whitney test). Univariate analysis of serum YKL-40 (logarithmically transformed and treated as a continuous covariate) showed significant association with survival within the first month after start of chemotherapy [hazard ratio (HR), 1.7; 95% confidence interval (CI), 1.2-2.4; P=0.002], first 12 months (HR, 1.6; 95% CI, 1.2-2.0; P=0.0002), and overall survival (HR, 1.3; 95% CI, 1.1-1.6; P=0.003). Multivariate Cox analysis showed that serum YKL-40 was an independent prognostic variable for survival (first month: HR, 1.7; P=0.011; 12 months: HR, 1.6; P=0.0002; overall survival: HR, 1.4; P=0.002). High serum YKL-40 at start of chemotherapy was a risk factor for pneumonia within the first month, and serum YKL-40 increased (P=0.002) at time of pneumonia and was unchanged in patients without infections. CONCLUSIONS: Serum YKL-40 is a prognostic biomarker of survival in AML patients. Its role in AML and infections needs to be determined.

Acute Disease↗

PubMed2002

Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer.

PURPOSE: The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G(1)-S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (e.g., HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study. PATIENTS AND METHODS: We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (i.e., performance status, extent of disease, and prior therapy) were also examined. RESULTS: In univariate analysis, Karnofsky performance status > or = 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P =.003 and P =.041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P =.075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy. CONCLUSION: The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Polymorphisms of microsomal epoxide hydrolase in French vinyl chloride workers.

OBJECTIVES: The purpose of this study was to determine if polymorphisms in microsomal epoxide hydrolase, an enzyme involved in the metabolism of reactive intermediates of vinyl chloride (VC), contribute to the variable susceptibility to the mutagenic effects of vinyl chloride among exposed workers. MATERIALS AND METHODS: Polymorphisms at codons 113 and 139 were determined in DNA samples from 211 French vinyl chloride workers. Genotypes were stratified into low, medium and high activity groups and odds ratios and 95% confidence intervals were determined for the presence of one or both of two VC-induced mutant biomarkers (mutant ras-p21 and mutant p53) by logistic regression adjusting for age, smoking, drinking and cumulative VC exposure. RESULTS: Compared to the low-activity microsomal epoxide hydrolase genotype stratum, the odds ratio for the presence of the VC-induced mutant biomarkers increased to 1.16 (95% CI: 0.64-2.10) in the medium-activity genotype stratum and to 1.35 (95% CI: 0.66-2.77) in the high-activity genotype stratum. The test for trend was not statistically significant and was in the opposite direction from that expected based on increasing removal of reactive intermediates with increasing activity. CONCLUSIONS: The results suggest that polymorphisms in microsomal epoxide hydrolase do not play a significant role in susceptibility to the mutagenic effects of vinyl chloride.

Adult↗

PubMed1999

Yolk PCB and plasma retinol concentrations in shag (Phalacrocorax aristotelis) hatchlings.

To evaluate the possibilities of applying plasma retinol as a biomarker of response in seabirds exposed to chronic low levels of organochlorines, the relationship between yolk content of polychlorinated biphenyls (PCBs) and plasma retinol levels were studied in newly hatched shag chicks (Phalacrocorax aristotelis) from the coast of central Norway. The mean concentration of 29 PCB-congeners (SigmaPCB) in the yolk sac was 1.22 microgram/g ww (wet weight basis) (SD = 0.57, n = 10), or 17.99 ng/g lw (lipid weight basis) (SD = 6.26, n = 10). Expressed as TCDD-equivalents (SigmaTEQ), the exposure in the yolk sac was 43.9 pg/g ww (SD = 19.5, n = 10), or 637.1 pg/g lw (SD = 240.8, n = 10), considerably lower than the levels that have been associated with clear-cut lethal and sublethal effects such as egg mortality, hatchability, or live deformity in Phalacrocoracidae species. There were significant negative correlations between SigmaPCB ww and the variables egg volume, yolk mass, and hatchling mass. We suggest that these relationships are passive causes of a higher lipid concentration in small eggs, rather than the PCB affecting the variables. Analyses showed that there was a borderline significant positive correlation between SigmaPCB lw in yolk and plasma retinol concentration. Although the results indicate that plasma retinol level alone is a poor indicator of PCB exposure in shag hatchlings, the result may be related to the low level of contaminant exposure and the low sample size of the study.

Animals↗

PubMed2006

Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans.

BACKGROUND: Lipocalin-2, a 25-kDa secreted glycoprotein, is a useful biomarker for early detection of various renal injuries. Because lipocalin-2 is abundantly expressed in adipose tissue and liver, we investigated its relevance to obesity-related pathologies. METHODS: We used real-time PCR and in-house immunoassays to quantify the mRNA and serum concentrations of lipocalin-2 in C57BL/KsJ db/db obese mice and their age- and sex-matched lean littermates. We analyzed the association between serum lipocalin-2 concentrations and various metabolic and inflammatory variables in 229 persons (121 men and 108 women) recruited from a previous cross-sectional study, and we evaluated the effect of the insulin-sensitizing drug rosiglitazone on serum lipocalin-2 concentrations in 32 diabetic patients (21 men and 11 women). RESULTS: Compared with the lean littermates, lipocalin-2 mRNA expression in adipose tissue and liver and its circulating concentrations were significantly increased in db/db diabetic/obese mice (P <0.001). These changes were normalized after rosiglitazone treatment. In humans, circulating lipocalin-2 concentrations were positively correlated (P <0.005) with adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index, but negatively correlated (P = 0.002) with HDL cholesterol. There was also a strong positive association between lipocalin-2 concentrations and high sensitivity C-reactive protein (hs-CRP), independent of age, sex, and adiposity (P = 0.007). Furthermore, rosiglitazone-mediated decreases in lipocalin-2 concentrations correlated significantly with increases in insulin sensitivity (r = 0.527; P = 0.002) and decreases in hs-CRP concentrations (r = 0.509; P = 0.003). CONCLUSIONS: Lipocalin-2 is an inflammatory marker closely related to obesity and its metabolic complications. Measurement of serum lipocalin-2 might be useful for evaluating the outcomes of various clinical interventions for obesity-related metabolic and cardiovascular diseases.

Acute-Phase Proteins↗

PubMed2000

Tenascin-A marker for the malignant potential of preinvasive breast cancers.

OBJECTIVE: Up to now, the mechanisms responsible for progression from noninvasive to invasive breast cancer have remained obscure. Tenascin is an extracellular matrix glycoprotein, present in embryonal and fetal tissues, which is also found in the stroma of various benign and malignant pathologies. We studied the expression and immunohistochemical behavior of tenascin in specimens of invasive and preinvasive breast cancer in order to assess its potential role as a marker for tumor invasion. MATERIALS AND METHODS: Sixty-eight specimens including 29 noninvasive ductal cancers, 12 invasive ductal cancers, 5 adenoses, 7 fibroadenomas, and 15 samples of normal human breast tissue were evaluated. An immunofluorescent microscopic technique was used for analysis of the localization and distribution of tenascin. Paraffin-embedded biopsies were incubated with primary monoclonal anti-tenascin antibodies (1:25, Dako-tenascin, TN2). Subsequently, trimethylrhodamine-isothiocyanate-conjugated secondary antibodies (rabbit anti-mouse immunglobulins (Dakopatts, Denmark) were added to visualize the protein. RESULTS: A significant tenascin expression was observed around the ducts in all samples of patients with preinvasive breast cancers. Intensive staining was also found in the periductal stroma of all specimens of patients with invasive breast cancers. Benign breast lesions showed weaker reactivity. No tenascin expression was detectable in normal human breasts, while tissue samples of in situ cancers presented variable staining intensities positively correlating with the degree of differentiation. CONCLUSION: Tenascin immunofluorescence may prove a suitable and helpful adjunct for diagnosing malignant disease and for predicting the invasive potential of premalignant breast lesions.

Aged↗

PubMed2004

Diagnostic molecular markers in thyroid cancer.

The use of molecular assays to analyze clinical tissues in the diagnosis and management of thyroid cancer, similar to other tumors, will likely allow for more accurate characterization of the aggressiveness of individual tumors and may allow for the early diagnosis of recurrence. The application of these methods to thyroid nodules and nodal metastases is less encumbered by difficulties arising from amplification of transcripts in non-thyroid cells. For these tissues, these assays are likely to be used clinically in the near-future. New data arising from cDNA arrays identifying novel markers of malignancy or tumor aggressiveness make this a growing area of interest. The use of molecular assays in diagnosing distant metastases is more problematic due to issues with ectopic expression of either full length or splice variants of genes thought to be thyroid-specific. Assay quantitation is a complex problem owing to variability in the level of expression of "housekeeping" genes and the variety of phlebotomy and RT-PCR methods reported. Additional research in this area is clearly required before a recommendation can be given regarding clinically applicability of these tests.

Biomarkers, Tumor↗

PubMed1992

Glycosidically bound sialic acid levels as a predictive marker of postoperative adjuvant therapy in gastric cancer.

A group of 293 gastric cancer patients were examined to see if the preoperative value of glycosidically bound sialic acid is a predictor of prognosis and effectiveness of postoperative adjuvant therapy. All patients had gastrectomies and were histologically confirmed to have primary adenocarcinoma of the stomach. Some patients then received either postoperative adjuvant chemotherapy or immunochemotherapy. Patients with sialic acid levels less than 74.5 mg/dl survived significantly longer than those with sialic acid levels of 74.5 mg/dl or of 85.3 mg/dl and over. No significant differences in survival were found among patients treated by gastrectomy alone, gastrectomy plus chemotherapy and gastrectomy plus immunochemotherapy. However, patients with abnormally elevated levels of sialic acid survived significantly longer when they were treated with immunochemotherapy after gastrectomy than those treated by gastrectomy alone or with chemotherapy after gastrectomy. By using Cox's multivariate regression model, pTNM stages, postoperative adjuvant therapy (chemotherapy and immunochemotherapy) and preoperative serum levels of sialic acid were examined as prognostic variables. Postoperative therapy was a significant prognostic variable in patients with abnormally elevated levels of sialic acid. The preoperative serum level of sialic acid is a promising predictive marker of the response to postoperative adjuvant immunochemotherapy.

Adult↗

PubMed2005

Smad4 protein expression correlates with grade, stage, and DNA ploidy in prostatic adenocarcinomas.

The tumor suppressor gene Smad4 (DPC4) has been localized to chromosome 18q21.1 and is a member of the Smad family that mediates the transforming growth factor beta signaling pathway suppressing epithelial cell growth. However, variable expression of this protein has been reported, with a loss in some cancers and increased expression in others. Given both the variability and lack of consensus reported regarding Smad4 expression in prostate cancer, we assessed Smad4 immunoreactivity in prostatic adenocarcinomas (PACs). Formalin-fixed, paraffin-embedded tissue sections from 133 PACs were immunostained by a manual method using indirect biotin streptavidin horseradish peroxidase and diaminobenzidine detection using a monoclonal mouse antihuman Smad4 antibody (sc-7966; Santa Cruz Biotechnology Inc, Santa Cruz, Calif). Nuclear immunoreactivity and cytoplasmic immunoreactivity were each semiquantitatively scored based on intensity and percentage of positive cells. Deoxyribonucelic acid ploidy was determined on Feulgen-stained tissue sections by static image analysis. Results were correlated with morphological and prognostic variables. Variable nuclear and cytoplasmic Smad4 positivity was noted in the adjacent benign glands in all cases. Of 133 PACs, 64 (48%) featured increased nuclear and 68 (51%) featured increased cytoplasmic protein expression. Nuclear Smad4 overexpression correlated with tumor grade (P = .02), stage (P = .04), and DNA ploidy (P = .04). Cytoplasmic overexpression correlated with tumor grade (P = .04) and DNA ploidy (P = .04) while showing a trend for correlation with tumor stage (P = .08). Neither nuclear nor cytoplasmic Smad4 overexpression correlated with postsurgical biochemical disease recurrence. Smad4 protein expression persists in PACs compared with benign glands, with both nuclear and cytoplasmic overexpression correlating with prognostic variables indicative of aggressive tumor behavior. Given the significant reported variability of Smad4 in several different cancers, further studies in prostate and other tumors are warranted to elucidate its role in tumorigenesis.

Adenocarcinoma↗

PubMed2004

Exhaled nitric oxide as a marker of airway inflammation for an epidemiologic study in schoolchildren.

BACKGROUND: Exhaled nitric oxide (eNO) levels are increased in airway inflammatory disorders, such as asthma. OBJECTIVE: We sought to determine whether eNO could serve as a noninvasive marker of allergic airway inflammation for an epidemiologic study in schoolchildren. METHODS: Two hundred seventy-eight schoolchildren aged 10 to 12 years answered a modified American Thoracic Society questionnaire, and eNO levels and pulmonary function were measured. In 246 subjects serum nonspecific IgE levels and levels of IgE specific to house dust mite, cat, cedar, and mold were also measured. Correlation analysis was used to examine eNO levels, nonspecific IgE levels, antigen-specific IgE levels, and pulmonary function. In addition, we compared these variables between subjects with (recurrent wheezers) and without (nonwheezers) recurrent wheeze. Finally, multiple logistic regression analysis was used to find possible predictors for recurrent wheezers. RESULTS: eNO showed significant positive correlations with nonspecific IgE (r=0.62, P <.001) and mite-specific IgE (r=0.74, P <.001) and weak positive correlations with specific IgE to cat and cedar. Only eNO showed a weak but significant inverse correlation with pulmonary function (%FEV(1), P=.035; FEV(1)/forced vital capacity, P=.018). eNO, nonspecific IgE, and mite-specific IgE levels in recurrent wheezers were greater (P <.001), and %FEV(1) was less (P=.06) when compared with values seen in nonwheezers. Finally, eNO was determined by means of multiple logistic regression analysis to be the best predictor for recurrent wheezers compared with other variables (odds ratio, 11.2; 95% CI, 1.33-94.0). CONCLUSION: eNO can be used in epidemiologic studies as a noninvasive marker of allergic airway inflammation in schoolchildren.

Asthma↗

PubMed2004

Temperament types are associated with weak self-construct, elevated distress and emotion-oriented coping in schizophrenia: evidence for a complex vulnerability marker?

Knowledge concerning temperament factors involved in vulnerability to schizophrenia is limited. We hypothesized that temperament and self-variables (emotional distress, coping styles, self-efficacy and self-esteem) might present a complex trait marker for underlying vulnerability to schizophrenia. We sought to (1) assess temperament dimensions and types in schizophrenia patients and healthy controls using the Tridimensional Personality Questionnaire (TPQ), and (2) explore their association with symptom dimensions, emotional distress, coping styles, self-constructs, demographic and background variables. We evaluated 90 consecutively recruited DSM-IV schizophrenia patients and 136 healthy controls matched for gender and age. We found that the harm avoidance (HA) factor was higher, while reward dependence (RD) was lower in schizophrenia patients than in healthy controls. Relationships of negative symptoms to novelty seeking (NS) and general psychopathology with both NS and HA show a confounding relation to self-variables. TPQ temperament types were defined by dichotomization into high and low according to medians of the three TPQ temperament dimensions. The odds ratios for the HA and HA/NS temperament types were significantly higher, while the NS/RD type was lower in schizophrenia patients than in healthy controls. HA/NS, HA/RD and high-HA/NS/RD types revealed higher scores for emotional distress, emotion-oriented coping and lower scores on self-constructs. No links were found between temperament types and schizophrenia symptom dimensions, task and avoidance oriented coping, or demographic and background variables. Thus, our findings strengthen the hypothesis that temperament types, when associated with elevated emotional distress, emotion-oriented coping and weak self-constructs, might represent a complex trait marker for underlying vulnerability to schizophrenia.

Adaptation, Psychological↗

PubMed2004

Preoperative neural network using combined magnetic resonance imaging variables, prostate-specific antigen, and Gleason score to predict positive surgical margins.

OBJECTIVES: To assess whether artificial neural network analysis (ANNA) predicts for positive surgical margins (PSMs) more effectively than logistic regression analysis (LRA) according to the combined use of the findings of pelvic coil magnetic resonance imaging (pMRI) and other preoperatively available tumor variables in patients with clinically organ-confined prostate cancer after radical prostatectomy. METHODS: A total of 205 patients with clinically localized prostate cancer, who underwent retropubic radical prostatectomy were evaluated. The predictive variables included clinical TNM stage, prostate-specific antigen (PSA) level, PSA density, biopsy Gleason score, percentage of cancer in biopsy specimens, and pMRI findings. The predicted outcome was PSMs. The patient data were randomly split into four cross-validation sets and used to develop and validate the ANNA and LRA models. For comparison, the area under the receiver operating characteristic curve was used. RESULTS: The overall PSM rate was 22% (n = 45). Using all input parameters, the accuracy of the ANNA and LRA was 84% and 75% for the prediction of PSMs, respectively. The area under the receiver operating characteristic curve of the ANNA (0.872 +/- 0.014) was significantly greater statistically (P <0.001) than that for LRA (0.791 +/- 0.006). The simplified ANNA models that used the pMRI findings in addition to PSA and Gleason score were as accurate as the model that used all the variables (P = 0.89). A high percentage of cancer in the biopsy specimens, pMRI findings, and high PSA density were equally the most influential predictors (relative weight 1.881, 1.964, and 1.493, respectively). CONCLUSIONS: All the ANNA models in this study were superior to LRA in the prediction of PSMs. The ANNA using pMRI findings, PSA level, and Gleason score as input variables performed as well as the ANNA using all the input parameters. Additional studies seem warranted.

Adenocarcinoma↗