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Results for “Biomarker variability”

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PubMed1999

Serum interleukin 10 and interleukin 11 in patients with acute pancreatitis.

BACKGROUND: Proinflammatory and anti-inflammatory cytokines are involved in the pathogenesis of acute pancreatitis. AIMS: To measure the serial serum levels of interleukin 10 and interleukin 11 in patients with acute pancreatitis and analyse the relation of these anti-inflammatory cytokines to disease severity. METHODS: In 50 patients with acute pancreatitis, the serum concentrations of interleukin 10 and interleukin 11 were determined on days one, two, three, four, and seven after admission. Serum C reactive protein levels were evaluated on days one and two. Severity of pancreatitis was determined according to the Atlanta criteria. RESULTS: Serum concentrations of interleukin 10 on days one to seven were significantly higher in patients with severe pancreatitis than in those with mild pancreatitis. Patients with severe attacks had significantly elevated serum interleukin 11 concentrations on days two to four compared with those with mild attacks, but not on days one and seven. With cut off levels of 30 pg/ml for interleukin 10, 10.5 pg/ml for interleukin 11, and 115 mg/l for C reactive protein, the accuracy rates for detecting severe pancreatitis were 84%, 64%, and 78% respectively on day one and 82%, 74%, and 84% respectively on day two. CONCLUSIONS: Serum interleukin 10 and interleukin 11 concentrations reflect the severity of acute pancreatitis. Interleukin 10 is a useful variable for early prediction of the prognosis of acute pancreatitis.

APACHE↗

PubMed2000

Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis.

BACKGROUND: Infected pancreatic necrosis (IPN) is the main cause of death in patients with severe acute pancreatitis. Therefore an early prediction of IPN is of utmost importance. AIM: Analysis of new blood variables as potential early predictors to differentiate between IPN and sterile pancreatic necrosis (SPN). PATIENTS: 64 consecutive patients with acute pancreatitis were enrolled in this prospective study; 29 were suffering from acute oedematous pancreatitis (AIP), and 35 from necrotising disease (NP) as diagnosed by contrast enhanced computed tomography. METHODS: Procalcitonin (PCT) and granulocyte colony stimulating factor (G-CSF) in the serum were examined and compared with C reactive protein (CRP). CRP was measured with a turbidimetric immunoassay (Autokit CRP; Wako, Osaka, Japan), and PCT and G-CSF by ELISA (Lumitest PCT; Brahms Diagnostica, Berlin, Germany; G-CSF-Elisa; R&D Systems, Abingdon, Oxon, UK). Monitoring was performed daily and related to the onset of symptoms. RESULTS: Within the first week, all three variables (CRP, PCT, and G-CSF) were significantly higher in patients with NP than in those with AIP (CRP, p<0.001; G-CSF, p<0. 001; PCT, p<0.001). During the course of the study, 12 of the 35 patients with NP developed late IPN after a median of 20.5 (range 3-49) days. Neither the peak nor the lowest concentrations during the monitoring period were of any value for predicting IPN (median peak values in SPN v IPN: PCT, 0.93 v 1.93 ng/ml; G-CSF, 347 v 421 pg/ml; CRP, 270 v 325 mg/l). CONCLUSIONS: Serum PCT, G-CSF, and CRP concentrations are of similar value for early differentiation between mild and severe acute pancreatitis. However, these variables are not suitable for the early prediction of IPN.

Acute Disease↗

PubMed2006

Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer.

Macrophage inhibitory cytokine-1 (MIC-1), a transforming growth factor-beta superfamily cytokine, is involved in tumor pathogenesis, and its measurement can be used as a clinical tool for the diagnosis and management of a wide range of cancers. Although generally considered to be part of the cell's antitumorigenic repertoire, MIC-1 secretion, processing, and latent storage suggest a complex, dynamic variability in MIC-1 bioavailability in the tumor microenvironment, potentially modulating tumor progression and invasiveness.

Animals↗

PubMed2001

Detecting disseminated solid tumor cells in hematopoietic samples: methodological aspects.

Detection of tumor cell dissemination in solid tumor patients recently became essential to determine the prognosis of the disease and to monitor response to the therapy. Accurate detection of disseminated tumor cells in hematological samples requires tumor-specific target molecules, which allow sensitive and specific assays and, further, enable the quantification of tumor cells. Currently, numerous applications are in use, including immunological and molecular biological approaches. Theoretically, both ways are sensitive enough to detect less than one tumor cell in 1 million hematopoietic cells. With the improved sensitivity, however, the likelihood that unspecific events will be amplified is also increased. Moreover, biological and analytical variables may fundamentally influence the findings in a particular case. Basic methods, significant pitfalls and the most recent developments in this field are discussed in this overview.

Biomarkers, Tumor↗

PubMed2002

Tissue hypoxia in sleep apnea syndrome assessed by uric acid and adenosine.

STUDY OBJECTIVE: Although the overnight increase in urinary uric acid/creatinine ratio (DeltaUA/Cr) is considered by some to be a marker of tissue hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), this index is not universally accepted. The purpose of this study was to confirm the validity of DeltaUA/Cr as a marker of tissue hypoxia by measuring the plasma level of adenosine during sleep, and also to test the hypothesis that the heart rate (HR) response to apnea is a determinant of tissue hypoxia. DESIGN: Intergroup comparative study. SETTING: A university hospital, Sapporo, Japan. PATIENTS: Eighteen patients with OSAS who had apnea-associated, moderate-to-severe arterial desaturation. The patients were classified into two groups: the DeltaUA/Cr-positive group, who were considered to have tissue hypoxia, and the DeltaUA/Cr-normal group, who were not. MEASUREMENTS AND RESULTS: Although there were no significant differences between two groups of the patients in either arterial desaturation parameters or the apnea-hypopnea index, the plasma level of adenosine during sleep was significantly higher in the DeltaUA/Cr-positive group than in the DeltaUA/Cr-normal group. Successful treatment with nasal continuous positive airway pressure significantly decreased both DeltaUA/Cr and the plasma level of adenosine only in the DeltaUA/Cr-positive group. The magnitude of the HR increase after the termination of apnea was significantly smaller in the DeltaUA/Cr-positive group. CONCLUSIONS: DeltaUA/Cr is a marker of tissue hypoxia, which does not necessarily parallel arterial desaturation indexes in OSAS. Intersubject variability in the HR response to apnea may explain the discrepancy between tissue hypoxia and arterial desaturation indexes.

Adenosine↗

PubMed2002

Comparative measurement of N-terminal pro-brain natriuretic peptide and brain natriuretic peptide in ambulatory patients with heart failure.

It is not clear whether brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) is superior as a diagnostic and prognostic indicator in cardiac diseases. Here, we compare the clinical correlations of both peptides in a population of 92 ambulatory patients with heart failure, using a well-established immunoradiometric assay (IRMA) for BNP and an automated electrochemiluminescence immunoassay for NT-proBNP. The analytical correlation between the two peptides was satisfactory over a wide range of concentrations (1-686 pM for BNP) with the equation: NT-proBNP = 3.48 x BNP -19 and a correlation coefficient r2=0.94. In addition, the concentration of both peptides increased in a similar fashion according to the severity of the disease New York Heart Association (NYHA) functional class, left ventricular ejection fraction, etiology) and age; for instance, the ratios between median levels measured in NYHA class III vs. class II patients were comparable for BNP (383 vs. 16 pM, ratio 24) and NT-proBNP (1306 vs. 57 pM, ratio 23). We conclude that N-terminal proBNP, as assayed in the present study, correlates equally to BNP with clinical variables in patients with heart failure.

Adult↗

PubMed1998

Etiopathogenesis of cardiovascular disease: hemostasis, thrombosis, and vascular medicine.

The role of hemostatic variables (which promote hemostatic plugs and thrombi) and rheological variables (which affect blood flow) in the pathogenesis of vascular diseases (ischemic heart disease, stroke, and peripheral arterial disease) is reviewed, with emphasis on epidemiological studies. Rheological variables are consistently associated with both prevalent and incident cardiovascular disease. These associations are only partly explained by conventional risk factors. The predictive value of plasma viscosity for cardiovascular events is partly explained by fibrinogen, and partly by lipoproteins. The associations of whole blood viscosity with cardiovascular disease are partly explained by plasma viscosity and partly by hematocrit. White cell count, but not platelet count, predicts ischemic heart disease events. Cigarette smokers have higher levels of rheological variables than non-smokers, these increases are partly or wholly reversible in ex-smokers. Lipoprotein reduction by pravastatin lowers plasma and whole-blood viscosity, which may be one mechanism through which lipid lowering produces an early reduction in cardiovascular events. Data from the Edinburgh Artery Study suggest that viscosity is related both to the extent of atherosclerosis, and to ischemia in the presence of a given degree of atherosclerotic stenoses. Among hemostatic variables, fibrinogen, factor VIII: vWF complex, tpA antigen, and fibrin D-dimer are associated with both prevalent and incident cardiovascular disease. Again, these associations are only partly explained by conventional risk factors They suggest that endothelial disturbance and increased fibrin turnover may play roles in cardiovascular disease. Hemostatic and rheological variables are therefore associated with both prevalent and incident cardiovascular disease, and may be mechanisms through which risk factors such as smoking, hyperlipidemia and infections (including oral infections) promote vascular events.

Biomarkers↗

PubMed2001

Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity.

BACKGROUND: Tartrate-resistant acid phosphatase (AcP) 5b is a marker of osteoclastic activity and bone resorption. Immunoassays for serum TRAcP may lack sensitivity and specificity because of the presence of non-bone isoform 5a. The purpose of this study was to isolate the serum isoforms, quantify their disease-related expressions, and test an improved immunoassay for TRAcP 5b. METHODS: We separated TRAcP isoforms chromatographically from pooled sera of healthy, rheumatoid arthritis (RA) and endstage renal disease (ESRD) subjects. TRAcP isoforms were identified by electrophoresis and quantified by biochemical and immunochemical assays. Serum TRAcP activity in healthy, RA, and ESRD cohorts was assessed at pH 5.5 and 6.1, and compared with bone alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTx). RESULTS: TRAcP isoforms 5a and 5b were present in all sera; 5b was identical to osteoclastic TRAcP. In serum from healthy subjects, 5a accounted for 87% of the enzyme protein but only 55% of the activity. In RA, both isoforms were increased two- to threefold in protein, but their specific activities were subnormal. In ESRD, only 5b was abnormal, being increased fivefold in protein and threefold in activity. In RA sera, TRAcP activity did not correlate with either BAP or NTx. In ESRD sera, TRAcP activity correlated with BAP and NTx only when measured at pH 6.1. CONCLUSIONS: All sera contained both TRAcP isoforms 5a and 5b, but only 5b was present in bone. TRAcP isoform expression was variable in different diseases. Measurement of TRAcP activity at pH 6.1 improves the specificity of immunoassay for isoform 5b.

Acid Phosphatase↗

PubMed1989

[Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for sialyl Tn antigen: (1). Evaluation of assay conditions and normal values. STN Study Group].

An immunoradiometric competitive inhibition assay of the serum levels of the sialyl Tn antigen using "STN Otsuka" kits is described. The assay required only duplicate 50-microliters samples, and the concentration of sialyl Tn antigen in serum was determined by reference to a standard curve ranging from 0 to 400 arbitrary units/ml. The intra-and inter-assay reproducibilities were largely satisfactory. The serum levels of the antigen in normal individuals were not affected by ABO and Lewis blood type status of the tested individuals. Normal values were 25.5 +/- 9.8 in male, and 21.3 +/- 8.0 in female, and the difference was statistically significant at p less than 0.001. The serum level of the antigen was not affected by menstrual cycle or pregnancy in female, whereas the level of other tumor markers such as CA 125 was highly variable depending upon these conditions.

Adult↗

PubMed2005

Logical analysis of diffuse large B-cell lymphomas.

OBJECTIVE: The goal of this study is to re-examine the oligonucleotide microarray dataset of Shipp et al., which contains the intensity levels of 6817 genes of 58 patients with diffuse large B-cell lymphoma (DLBCL) and 19 with follicular lymphoma (FL), by means of the combinatorics, optimisation, and logic-based methodology of logical analysis of data (LAD). The motivations for this new analysis included the previously demonstrated capabilities of LAD and its expected potential (1) to identify different informative genes than those discovered by conventional statistical methods, (2) to identify combinations of gene expression levels capable of characterizing different types of lymphoma, and (3) to assemble collections of such combinations that if considered jointly are capable of accurately distinguishing different types of lymphoma. METHODS AND MATERIALS: The central concept of LAD is a pattern or combinatorial biomarker, a concept that resembles a rule as used in decision tree methods. LAD is able to exhaustively generate the collection of all those patterns which satisfy certain quality constraints, through a systematic combinatorial process guided by clear optimization criteria. Then, based on a set covering approach, LAD aggregates the collection of patterns into classification models. In addition, LAD is able to use the information provided by large collections of patterns in order to extract subsets of variables, which collectively are able to distinguish between different types of disease. RESULTS: For the differential diagnosis of DLBCL versus FL, a model based on eight significant genes is constructed and shown to have a sensitivity of 94.7% and a specificity of 100% on the test set. For the prognosis of good versus poor outcome among the DLBCL patients, a model is constructed on another set consisting also of eight significant genes, and shown to have a sensitivity of 87.5% and a specificity of 90% on the test set. The genes selected by LAD also work well as a basis for other kinds of statistical analysis, indicating their robustness. CONCLUSION: These two models exhibit accuracies that compare favorably to those in the original study. In addition, the current study also provides a ranking by importance of the genes in the selected significant subsets as well as a library of dozens of combinatorial biomarkers (i.e. pairs or triplets of genes) that can serve as a source of mathematically generated, statistically significant research hypotheses in need of biological explanation.

Combinatorial Chemistry Techniques↗

PubMed1998

The F value cannot be ruled out as a chromosomal fingerprint of radiation quality.

The F value, the ratio of inter- to intrachromosomal interchanges, as a biomarker for densely ionizing radiation which was proposed by Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) has been a matter of repeated discussion. We examined our experimental data on radiation-induced chromosome aberrations in human peripheral blood lymphocytes for the F value as measured by the ratio of dicentrics to centric rings. Because of the rarity of aberrations, the F value showed a considerable variability, with a large error range particularly in the low-dose range of low-LET radiation. However, the data showed a general trend that the F value tended to be lower for high-LET than low-LET radiations. The differential F value was more pronounced at low doses and diminished with increasing dose; the F values of all radiations tended to converge toward a similar value at high doses. The limiting F value at the lowest doses, or the F0 value, was dependent on LET for high-energy radiations that can produce an array of DNA double-strand breaks along the track of the charged particle. However, LET and dose dependence were not seen for the low-energy photons, where spatially uncorrelated random breaks were produced by independent photoabsorption events.

Biomarkers↗

PubMed2002

alpha-Methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation.

alpha-Methylacyl-CoA racemase (AMACR) has previously been shown to be a highly sensitive marker for colorectal and clinically localized prostate cancer (PCa). However, AMACR expression was down-regulated at the transcript and protein level in hormone-refractory metastatic PCa, suggesting a hormone-dependent expression of AMACR. To further explore the hypothesis that AMACR is hormone regulated and plays a role in PCa progression AMACR protein expression was characterized in a broad range of PCa samples treated with variable amounts and lengths of exogenous anti-androgens. Analysis included standard slides and high-density tissue microarrays. AMACR protein expression was significantly increased in localized hormone-naive PCa as compared to benign (P < 0.001). Mean AMACR expression was lower in tissue samples from patients who had received neoadjuvant hormone treatment but still higher compared to hormone-refractory metastases. The hormone-sensitive tumor cell line, LNCaP, demonstrated stronger AMACR expression by Western blot analysis than the poorly differentiated cell lines DU-145 and PC-3. AMACR protein expression in cells after exposure to anti-androgen treatment was unchanged, whereas prostate-specific antigen, known to be androgen-regulated, demonstrated decreased protein expression. Surprisingly, this data suggests that AMACR expression is not regulated by androgens. Examination of colorectal cancer, which is not hormone regulated, demonstrated high levels of AMACR expression in well to moderately differentiated tumors and weak expression in anaplastic colorectal cancers. Taken together, these data suggest that AMACR expression is not hormone-dependent but may in fact be a marker of tumor differentiation.

Biomarkers, Tumor↗

PubMed2026

Prognostic value of circulating tumor DNA and copy-number alterations in patients receiving tandem [225Ac]Ac-/[177Lu]Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer: a prospective observational study.

BACKGROUND: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) demonstrates clinical efficacy in metastatic castration-resistant prostate cancer (mCRPC), yet robust biomarkers for dynamic treatment monitoring and resistance remain lacking. We investigated circulating tumor DNA (ctDNA)-derived tumor fraction (TFx) and genome-wide copy-number alterations (CNAs) as non-invasive biomarkers of treatment response and resistance biology. METHODS: Seventy-eight patients with advanced mCRPC receiving tandem [225Ac]Ac-/[177Lu]Lu-PSMA-617 were prospectively enrolled. Plasma samples collected longitudinally (n = 172) underwent ultra-low-pass whole-genome sequencing. TFx was estimated using ichorCNA, and recurrent CNAs were identified using GISTIC2.0. Associations with progression and overall survival (OS) were assessed using Cox proportional hazards models, including time-dependent analyses. RESULTS: Baseline TFx differed across metastatic disease stages (p = 0.027) and dynamic TFx changes paralleled PSA kinetics during early treatment. Modelled as a time-dependent variable, TFx was associated with a significantly increased risk of progression (HR 4.9, 95% CI 1.2-20.1, p = 0.026). Unsupervised clustering identified distinct high- and low-CNA burden groups strongly correlated with TFx (p = 8.09 × 10⁻8). High CNA burden was associated with shorter median OS (8.3 vs 13.8 months). Multivariable analysis identified baseline logPSA and logALP as independent predictors of OS. Recurrent CNAs affected key tumor suppressors (PTEN, RB1, BRCA2, ATM) and were enriched in pathways related to TP53 signalling, homologous recombination repair, and oncogenic signaling. Longitudinal analyses demonstrated persistence and expansion of specific amplifications at progression. CONCLUSIONS: ctDNA-derived TFx represents a dynamic biomarker of treatment response and progression risk, while CNA profiling provides insight into resistance mechanisms in mCRPC treated with PSMA-RLT. These findings support the integration of ctDNA-based biomarkers into clinical stratification and real-time monitoring strategies.

Humans↗

PubMed2001

A preliminary study of serum concentrations of soluble epidermal growth factor receptor (sErbB1), gonadotropins, and steroid hormones in healthy men and women.

Soluble ErbB (sErbB) growth factor receptors are being investigated as cancer biomarkers. Gonadotropic and steroid hormones have been shown to modulate the expression of ERBB family members in vivo. Accordingly, the range of sErbB1 values and their relationship to gonadotropic and steroid hormones need to be established in healthy subjects to provide a baseline for future clinical studies. We assayed sera from healthy men and women to determine p110 sErbB1 concentrations by acridinium-linked immunosorbent assay (ALISA). Follicle-stimulating hormone (FSH), estradiol, and testosterone concentrations were measured using the ACS:180 Immunoassay Analyzer. Luteinizing hormone (LH) and progesterone concentrations were quantified using the Access Immunoassay System. Unadjusted for age, p110 sErbB1 concentrations in healthy men and women do not differ significantly. However, sErbB1 concentrations show a strong age-gender interaction, increasing with age in men but decreasing with age in women. Consequently, sErbB1 concentrations are significantly higher in premenopausal women compared with either postmenopausal women or age-matched men and in age-matched men compared with postmenopausal women. Serum sErbB1 concentrations show significant negative associations with both FSH and LH concentrations in healthy women and a significant positive association with FSH concentrations in healthy men. Univariate linear regression models show that these respective gonadotropic hormones and age are independent predictors of sErbB1 concentrations in men and women. Multivariate models show that when age and FSH and LH concentrations are mutually adjusted for each other, they account for 22% of the variability observed in sErbB1 concentrations in healthy women. These data support the hypothesis that gonadotropic and steroid hormones may modulate ERBB1 expression in vivo and suggest that age- and gonadotropin-adjusted sErbB1 concentrations may be of clinical utility. Furthermore, these data demonstrate that gender, age, menstrual cycle phase, menopausal status, and exogenous hormone use must be considered when using serum p110 sErbB1 concentrations as cancer biomarkers.

Adult↗

PubMed2002

Prediction of pathological stage in patients with clinical stage T1c prostate cancer: the new challenge.

PURPOSE: We developed an algorithm for predicting the likelihood of organ confined disease in patients with clinical stage T1c prostate cancer using biopsy pathology, computer assisted image analysis and serum prostate specific antigen (PSA). MATERIALS AND METHODS: Of the 557 consecutive men enrolled in this study between October 1998 and January 2000 scheduled for radical prostatectomy at a single institution 386 (69%) presented with clinical stage T1c disease. Study exclusion criteria included neoadjuvant hormonal treatment with luteinizing hormone-releasing hormone, antiandrogen or 5alpha-reductase inhibitors. Preoperative serum, biopsy histology slides, clinical demographic information, prostatectomy pathology and prostate weight data were obtained. Biomarkers assessed included total PSA, complexed PSA, free PSA, the free-to-total PSA ratio, quantitative nuclear grade determined by image analysis, complexed PSA density, and biopsy Gleason grade and score. To determine patient specific quantitative nuclear grade values, images from approximately 125 cancer nuclei were captured per patient from the area of the biopsy section with the highest Gleason score. The variance in 60 nuclear size, shape and chromatin texture descriptors was calculated for each gallery of nuclei. Logistic regression was done to determine the most accurate combination of variables for predicting organ confined prostate cancer. RESULTS: Complete results and data were available on 255 of the 386 men (66%) with an average age plus or minus standard deviation of 58.8 +/- 6 years who had stage T1c disease, including 49 (19%) with pathologically nonorgan confined disease. Logistic regression analysis revealed that quantitative nuclear grade, biopsy Gleason score, total PSA, the calculated free-to-total PSA ratio, complexed PSA and complexed PSA density were univariately significant for predicting organ confined disease (p <0.05). On backward stepwise logistic regression only quantitative nuclear grade, complexed PSA density and Gleason score remained in a model yielding an area under the receiver operating characteristics curve of 82.4%. CONCLUSIONS: The quantitative nuclear grade biomarker was the strongest independent predictor of pathological stage in men with clinical stage T1c prostate cancer when combined with biopsy Gleason score and complexed PSA density data.

Aged↗

PubMed1997

Lycopene and myocardial infarction risk in the EURAMIC Study.

A multicenter case-control study was conducted to evaluate the relations between antioxidant status assessed by biomarkers and acute myocardial infarction. Incidence cases and frequency matched controls were recruited from 10 European countries to maximize the variance in exposure within the study. Adipose tissue needle aspiration biopsies were taken shortly after the infarction and analyzed for levels of carotenoids and tocopherols. An examination of colinearity including all covariates and the three carotenoids, alpha-carotene, beta-carotene, and lycopene, showed that the variables were sufficiently independent to model simultaneously. When examined singularly, each of the carotenoids appeared to be protective. Upon simultaneous analyses of the carotenoids, however, using conditional logistic regression models that controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease, lycopene remained independently protective, with an odds ratio of 0.52 for the contrast of the 10th and 90th percentiles (95% confidence interval 0.33-0.82, p = 0.005). The associations for alpha- and beta-carotene were largely eliminated. We conclude that lycopene, or some substance highly correlated which is in a common food source, may contribute to the protective effect of vegetable consumption on myocardial infarction risk.

Adipose Tissue↗

PubMed2006

Effect of garlic powder on C-reactive protein and plasma lipids in overweight and smoking subjects.

BACKGROUND: Epidemiologic studies suggest that garlic may have beneficial effects on risk factors associated with cardiovascular disease (CVD). However, these findings are not unambiguously supported by randomized placebo-controlled clinical trials. OBJECTIVE: We sought to investigate the effects of a chemically well-characterized garlic preparation on biomarkers for inflammation, endothelial function, and lipid metabolism in subjects with risk factors for CVD. DESIGN: This was a double-blind, randomized, placebo-controlled trial in 90 overweight [body mass index (in kg/m2) > 24.5] subjects aged 40-75 y who smoked >10 cigarettes/d. The subjects were randomly assigned to 3 parallel treatment groups: garlic powder (2.1 g/d), atorvastatin (40 mg/d), or placebo. Duplicate measurements were performed at baseline and after 1 and 3 mo of treatment. Treatments were compared with analysis of covariance with baseline as the covariate, and differences between the treatments were reported as mean percentage difference and corresponding 97.5% CI. RESULTS: None of the variables showed significant differences between the garlic-treated and the placebo groups. In contrast, compared with the placebo group, atorvastatin treatment resulted in significantly lower plasma concentrations of C-reactive protein (20.2%; 1.7%, 35.3%), total cholesterol (37.2%; 33.1%, 41.1%), LDL cholesterol (52.7%; 47.9%, 57.1%), triacylglycerols (31.9%; 20.8%, 41.5%), and tumor necrosis factor alpha (TNF-alpha; 41.9%; 19.0%, 58.3%) and increased the ratio of ex vivo whole blood lipopolysaccharide-stimulated to nonstimulated TNF-alpha concentrations (109.7%; 37.9%, 218.9%). CONCLUSION: We conclude that a chemically well-characterized garlic preparation has no significant effect on inflammatory biomarkers, endothelial function, or lipid profile in normolipidemic subjects with risk factors for CVD.

Adult↗

PubMed1992

Cell kinetics evaluation of colorectal tumors after in vivo administration of bromodeoxyuridine.

Although several biomarkers have been tested, Dukes' (or TNM) stage at diagnosis is still considered the only prognostic factor of clinical relevance in colorectal cancer. Among the various biomarkers, the fraction of cells engaged in DNA synthesis has been extensively investigated as an indicator of tumor aggressiveness. Bromodeoxyuridine (BUdR) is a non-radioactive thymidine analogue which is incorporated into DNA during the S-phase of cycling cells. In order to evaluate the relationships between cell kinetics and morphologic variables, 500 mg of BUdR were given i.v. to 46 patients with colorectal cancer prior to surgery. After operation, a large tumor sample was taken and processed for immunohistochemical detection of BUdR-labeled cells in various regions of the neoplasm and in normal colorectal mucosa. Smaller superficial tumor specimens were also incubated with 3H-thymidine (3H-TdR) for the autoradiographic identification of labeled cells. In the 43 evaluable tumors, the overall BUdR labeling index (BLI, percent of labeled cells) was significantly higher in carcinoma (20.30 +/- 0.86%, SEM) than in normal colonic mucosa (6.51 +/- 0.49%). BLIs in central and peripheral regions of carcinoma were closely correlated (r = 0.48, p = 0.003). In 21 neoplasms a high correlation between overall BUdR and 3H-TdR labeling index in the same tumor was observed (r = 0.57, p = 0.007). No evident association between overall BLI and clinical or morphologic parameters of the tumor was seen, including number of capillaries and ras-p21 protein expression. We conclude that BUdR immunostaining after in vivo administration of BUdR is a simple method for studying cell kinetics in various regions of colorectal cancer. BUdR labeling data are comparable to those obtained with in vitro incorporation of 3H-TdR.

Adult↗