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At least 973 records · Page 54Linked to original sources
PubMed2003

Putative biomarkers for evaluating antibiotic treatment: an experimental model of porcine Actinobacillus pleuropneumoniae infection.

Biomarkers of infection were screened for their possible role as evaluators of antibiotic treatment in an aerosol infection model of porcine pneumonia caused by Actinobacillus pleuropneumoniae (Ap). Following infection of 12 pigs, clinical signs of pneumonia developed within 20 h, whereafter the animals received a single dose of either danofloxacin (2.5mg/kg) or tiamulin (10 mg/kg). To test the discriminative properties of the biomarkers, the dosage regimens were designed with an expected difference in therapeutic efficacy in favour of danofloxacin. Accordingly, the danofloxacin-treated pigs recovered clinically within 24h after treatment, whereas tiamulin-treated animals remained clinically ill until the end of the study, 48 h after treatment. A similar picture was seen for the biomarkers of infection. During the infection period, plasma C-reactive protein (CRP), interleukin-6 and haptoglobin increased, whereas plasma zinc, ascorbic acid and alpha-tocopherol decreased. In the danofloxacin-treated animals, CRP, interleukin-6, zinc, ascorbic acid and alpha-tocopherol reverted significantly towards normalisation within 24h of treatment. In contrast, signs of normalisation were absent (CRP, zinc and ascorbic acid) or less marked (interleukin-6 and alpha-tocopherol) in the tiamulin-treated animals. Plasma haptoglobin remained elevated throughout the study in both groups. This indicates that CRP, zinc, ascorbic acid and to a lesser extent interleukin-6 and alpha-tocopherol might be used to evaluate antibiotic treatment of acute Ap-infection in pigs. The present model provides a valuable tool in the evaluation of antibiotic treatments, offering the advantage of clinical and pathological examinations combined with the use of biochemical infection markers.

Actinobacillus Infections↗
PubMed2003

Breast cancer: new technologies for risk assessment and diagnosis.

In the US, one in every eight women will develop breast cancer in her lifetime. Despite the advances made in treating breast cancer, the causal mechanisms underlying this disease have yet to be fully elucidated; 85% of breast cancer cases occur sporadically without any known genetic mutation. Too little is known about the pathogenesis of breast cancer for primary prevention to be feasible in the near- to mid-term. Secondary prevention through screening offers an alternative that has been widely adopted. For decades, breast self-examination has been touted as a technique for the early identification of breast cancer. However, it has been recently suggested that this technique is a waste of time and resources for both doctors and patients. Mammography finds breast cancer earlier than breast self-examination, and will reduce the risk of death from breast cancer by approximately 30% in women over 50 years old. Mammography is limited in that cancer, like breast tissue, appears white on the x-ray; therefore lesions may be difficult to detect in women with very dense breasts, and a tumor may not cast a significant shadow until it is quite large. Some cancers are so aggressive that they can spread quickly, before routine screening can detect them. Despite these limitations, mammography is still viewed as the best tool currently available for screening and early diagnosis. Improved methods to detect and diagnose breast cancer early, when it is most curable, are required if a significant impact on morbidity and mortality from breast cancer is to be made. Various new and innovative technologies are being investigated for improving the early detection and diagnosis of breast cancer. About 85% of breast cancers begin in the milk ductal system of the breast. As cancer develops in the breast, abnormalities occur, including atypical hyperplasia, ductal carcinoma in situ, and invasive breast carcinoma. Thus, the early screening of ductal cells can provide a parallel benefit to the 'Pap' smear, which is used virtually universally to identify the abnormal cells that can lead to cervical cancer. Two technologies to monitor for atypical ductal epithelial cells are Cytyc Corporation's FirstCyte Ductal Lavage system and Nastech Pharmaceutical Company's Mammary Aspiration Cytology Test. Matritech, Inc. is searching for biomarkers linked to breast cancer. Researchers at Matritech have detected the presence of nuclear matrix protein (NMP) in the blood of women at the early stage of breast cancer, which is absent in the blood of healthy women, as well as those with fibroadenoma, a benign breast disease. NMP66 has been selected as a marker for further development and clinical trials of a test for use in the detection and monitoring of women with, or at risk for, breast cancer have been initiated. Technologies developed by the US Department of Defense are under investigation as breast cancer screening. Advanced Image Enhancement, Inc. has licensed naval sonar technology for digital image enhancement of mammograms. New thermography applications are also being investigated in two separate projects sponsored by the US Department of Defense using military thermal surveillance tools adapted for cancer detection. Both are enhancements of older thermal imaging technology based on the principle that heat equates to unwanted activity, in the case of breast cancer, abnormal cell proliferation.

BRCA1 Protein↗
PubMed2003

Use of biomarkers of heavy drinking in health care practice.

Several biochemical tests are available to screen for heavy drinking in patients. Most of these (e.g., liver function tests and macrocytic volume) rise due to adverse effects of alcohol on organs or the organ's functions. Carbohydrate-deficient transferrin, however, seems to elevate because of the direct action of alcohol or one of its metabolites. A second valuable contribution of biomarkers is identification of relapse events in recovering alcoholics that either would not be voluntarily reported or reported only much later. Finally, providing feedback to patients in treatment based on their biomarker values and changes in them during the course of treatment can enhance motivation, a key component in recovery from alcohol problems. The current article offers a clinical rationale for routine use of biomarkers of heavy drinking in health care practice and proposes recommendations on how they might be best used.

Alanine Transaminase↗
PubMed2004

Assessment of risk factors and human papillomavirus (HPV) related pathogenetic mechanisms of CIN in HIV-positive and HIV-negative women. Study design and baseline data of the HPV-PathogenISS study.

OBJECTIVES: In women with HIV-associated immunosuppression, HPV infections have an increased risk of progression to high-grade cervical intraepithelial neoplasia (CIN). With the HAART-induced prolonged survival and more protracted clinical course of AIDS, progression of CIN to cervical cancer (CC) has become a clinically relevant issue, and the mechanisms responsible for HIV-HPV interactions need further elucidation. The study design and analysis of the baseline data of our new project are presented. MATERIAL AND METHODS: This project is a combination of a prospective cohort study of HIV- and HIV+ women, and a retrospective analysis of CIN lesions and cervical cancer. Up to the present, 244 women have been enrolled (17 HIV+) and subjected to epidemiological interview, colposcopic examination, sampling for HPV testing and typing (PCR, InnoLiPA), and HPV serology. The retrospective series of biopsies were analysed for 13 biomarkers (monitoring key molecular events) using immunohistochemistry and tested for HPV by PCR and TaqMan. RESULTS: HIV- and HIV+ women differ in their exposure status to many of the key epidemiological risk factors of cervical cancer, the most significant ones being number of sexual partners (p = 0.0001), age at onset of sexual activity (p = 0.002), and contraception (yes-no) (p = 0.009). The differences in the baseline clinical observations are less dramatic; HIV-positive women had more frequent HSIL PAP tests (p = 0.040), CIN2 or higher in cervical biopsy (p = 0.049), and external genital warts (p = 0.019). The factors predicting intermediate endpoint markers of cervical cancer, i.e., HSIL PAP smear, ATZ2 in colposcopy, and high-grade CIN in biopsy were analysed in univariate and multivariate regression models. All factors significant in univariate analysis were entered in the multivariate model; HIV-status and Pap smear history maintained their independent predictive power of the HSIL Pap test. The most powerful predictor of ATZ2 colposcopy was HSIL in Pap test. Only the HSIL Pap test and ATZ2 colposcopy remained significant independent predictors of high-grade CIN (p = 0.0001 and p = 0.008, respectively) in the multivariate model. CONCLUSIONS: The three intermediate endpoint markers are closely interrelated, but predicted in part by different covariantes in the causal pathway to cervical cancer. To elucidate whether the increased risk of HIV-positive women to high-grade CIN is due a) to their different exposure status to the risk factors, b) to the direct effects of HIV, or c) to molecular interactions between HIV and HPV, we need to complete these analyses separately in HIV+ and HIV- women.

Adult↗
PubMed2005

Effective use of autoantibody tests in the diagnosis of systemic autoimmune disease.

Screening for disease-specific autoantibodies may be useful in asymptomatic ANA-positive individuals as a means of evaluating the risk of developing a systemic autoimmune disease such as systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), scleroderma (SSc), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or primary biliary cirrhosis (PBC) in the future. In patients with known or suspected systemic autoimmune disease, a panel of disease-specific markers may help to establish a diagnosis and to assess the prognosis. The great strides in autoantibody testing over the last 20 years make it feasible to use specific autoantibody markers to improve diagnostic accuracy in systemic autoimmune disease. New technology enabling screening for multiple autoantibodies may further enhance the clinical usefulness of autoantibody testing, making it possible to diagnose autoimmune disease in its earliest stages and to intervene before serious end organ damage occurs.

Antibodies, Antinuclear↗
PubMedDate not supplied

The role of serum liver enzymes in the diagnosis of choledocholithiasis.

BACKGROUND/AIMS: The introduction of laparoscopic cholecystectomy has increased the need for preoperative diagnosis of common bile duct stones. The purpose of this study is to verify the sensitivity of the liver function tests in the detection of duct stones. METHODOLOGY: We evaluated 438 patients (223 retrospectively and 215 prospectively) who underwent endoscopic papillotomy for bile duct stones in two different services. In every case, blood samples for liver function tests levels were collected prior to endoscopic retrograde cholangiopancreatography. RESULTS: The most sensitive test was gamma-glutamyl transpeptidase, that was abnormal in 92.2% of the cases. Alkaline phosphatase was elevated in 74.7% of the patients with choledocholithiasis. The least sensitive parameter was AST, altered in only 50.8% of times. The sensitivity of all liver tests for the diagnosis of choledochal stones taken together was 94.3%. CONCLUSIONS: Liver function tests are very sensitive in the detection of common bile duct stones, however these blood tests are in the normal range of about 5% of endoscopically treated patients.

Adolescent↗
PubMed2000

Transforming growth factors-beta are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system.

Using a carcinogen-initiated rat model of mammary tumorigenesis, we tested the hypothesis that transforming growth factor (TGF)-betas are useful biomarkers of chemopreventive efficacy in the breast. The chemopreventive agents tested were tamoxifen and the retinoids 9-cis-retinoic acid (9cRA) and N-(4-hydroxyphenyl)retinamide (4-HPR), because both antiestrogens and retinoids have previously been shown to upregulate TGF-betas in vitro. Despite demonstrable chemopreventive efficacy in this model, none of these agents, alone or in combination, had any significant impact on the expression of TGF-betas in the mammary ductal epithelium or periductal stroma as determined by immunohistochemistry. These data suggest that TGF-betas are not likely to be useful biomarkers of chemopreventive efficacy in a clinical setting.

Animals↗
PubMed2004

Diagnosis of atrophic body gastritis in Chinese patients by measuring serum pepsinogen.

OBJECTIVE: Atrophic body gastritis (ABG) is common in China. Although histology via endoscopy is an efficient and reliable means of diagnosing ABG, it is an invasive procedure. Therefore, in the present study serum pepsinogen (PG) was used as a biomarker to develop a novel noninvasive test as the first option for screening of ABG in certain groups of Chinese. METHODS: The study population consisted of 81 selected dyspeptic patients (mean age, 64.8 +/- 0.7 years; M:F, 43:38) who underwent diagnostic gastroscopy. At least four biopsy specimens were taken from the antrum and corpus of the stomach (two specimens from each site) for histological diagnosis. Blood samples for ELISA assays of serum pepsinogen I (PGI), pepsinogen II (PGII) and IgG antibodies against Helicobacter pylori (Hp IgG) were drawn after endoscopy. Cut-off points were calculated using receiver operating curves (ROC). RESULTS: There was no correlation between serum PG and atrophy in the antral mucosa. The mean serum concentration of PGI was lower (P < 0.05) in patients with ABG (89.9 microg/L) than in those with normal mucosa (NM) and non-ABG (123.7 microg/L and 139.1 microg/L). The mean ratio of PGI:PGII was also lower (P < 0.01) in patients with ABG (6.2) than in those with NM and non-ABG (11.6 and 11.7). There was no difference in serum PGI or the PGI:PGII ratio between patients with and without H. pylori infection. For diagnosing ABG, the area under the ROC of PGI and the PGI:PGII ratio was 0.741 (95% CI: 0.627-0.856) and 0.874 (95% CI: 0.788-0.961), respectively. The maximum of the Youden's index (YI) of PGI and the PGI:PGII ratio was 0.426 and 0.722, respectively. The best cut-off point for PGI was 97.1 microg/L with sensitivity of 67% and specificity of 76%, and for PGI:PGII ratio was 8.1 microg/L, with sensitivity of 89% and specificity of 83%. CONCLUSIONS: The serum PGI:PGII ratio appears to be a sensitive and specific assay for corpus atrophy, thus providing a noninvasive and indicative test for diagnosis of atrophic gastritis.

Aged↗
PubMed1999

Intrinsic and extrinsic biomarkers for the assessment of risks from environmental UV radiation.

In the last decades the knowledge of the effects of UV radiation on human health, especially in skin cancerogenesis, but also in immunsuppression, photoaging, eye damages, has enlarged strongly. The increasing solar UV radiation and changes in life style strengthen the necessity to identify and quantitate intrinsic biomarkers which are indicative for the individual UV susceptibility and the accumulated individual UV burden. For the risk assessment of potentially deleterious UV effects extrinsic biomarkers have to be developed and tested as personal biological UV dosimeters. One example for such a well characterized biological UV dosimeter is the DLR-biofilm which consists of spores of the bacterium Bacillus subtilis as UV sensitive target.

Adolescent↗
PubMed2003

Evolving strategies for prostate cancer chemoprevention trials.

Prostate cancer chemoprevention (CP) can be defined as the use of natural and synthetic agents that inhibit, reverse or regress precancer and delay progression to invasive cancer. During the past two decades several CP strategies have evolved. The first generation of CP trials tested the efficacy of antioxidants and vitamins including B-carotene, vitamin A, retinol, 13 cis retinoic acid, vitamins E, C and selenium. Although these trials were disappointing, provocative hypotheses were generated for selenium and vitamin E that set the stage for future prostate trials. In the 1990s, the NCI launched a second generation of large CP trials aimed at breast and prostate cancer. One of these trials is the PCPT, testing the efficacy of a 5 alpha-reductase inhibitor-finasteride to prevent prostate cancer in 18,000 men. Although PCPT is still in progress, the NCI recently launched a second large primary prostate CP trial called SELECT, testing the efficacy of selenium and vitamin E in 32,400 men. The Prostate Cancer Progress Report to the Director of NCI in 1998 challenged the research community to design more efficient CP trials for prostate cancer. In response, the NCI has evolved a third generation of CP trials. This involves pharmacologically driven translational science research including agents and their targets, biomarker endpoints, suitable clinical models for testing agents and efficient trial designs employing high risk cohorts and surrogate endpoints. In summary, a dual strategy for CP is being developed which includes public health measures and a medical intervention approach.

Antioxidants↗
PubMed2000

Ammonia toxicity as a criterion for the evaluation of larval quality in the prawn Macrobrachium rosenbergii.

The feasibility of a short-term ammonia toxicity test as an evaluation criterion for larval quality was assessed in three trials. In each one, Macrobrachium rosenbergii larvae originating from the same spawn were nutritionally differentiated in two groups by feeding them either a nutrient-rich (Artemia nauplii enriched for 24 h with n-3 highly unsaturated fatty acids (HUFA) and ascorbic acid (AA)) or a nutrient-poor diet (Artemia nauplii starved for 24 h). Throughout their development, larvae from both treatments were exposed during 24 h to six concentrations of total ammonia (NH(4)(+)+NH(3)) and a control (no ammonia added). Based on mortality rates, the median lethal concentration for 50% of the population (LC(50)) was estimated. As expected from earlier work, larvae fed the optimal diet presented higher n-3 HUFA and AA contents as well as higher growth and metamorphosis rates. From the moment the effect of diet quality was analytically detectable in the tissues of the larvae, the ammonia test was able to distinguish both groups of larvae. Differences in ammonia tolerance were observed as early as larval stage 4 and remained evident throughout larval development. The short-term ammonia toxicity test proved to be a valuable, sensitive and reproducible criterion for the establishment of larval quality.

Age Factors↗
PubMed2003

Incorporation of in situ and biomarker assays in higher-tier assessment of the aquatic toxicity of insecticides.

This study was designed to test the feasibility of integrating in situ, single species exposures and biomarker analysis into microcosm studies. Experimental ponds were dosed with pirimiphos methyl (PM) and lindane. C. riparius fourth instar larvae were deployed for 48h on nine separate occasions during the study period before and after treatment. Surviving larvae were analysed for acetylcholinesterase activity (AChE). Survival and biomarker data were compared to chironomid assemblage analysis by monitoring insects emerging from the microcosms. Survival of chironomids within the in situ systems commenced on day +16 after treatment with 31.6% and 53.3% survival in the lindane and PM treated ponds, respectively. In contrast, the first emergence from the microcosms occurred on days +27, in respect to lindane, and +59 for the PM treated ponds. Thus the in situ bioassay was able to demonstrate gradual reduction in toxicity within the sediment before this was evident from macroinvertebrate monitoring. Significant AChE inhibition was only detected on exposure to PM. Levels decreased from 75% on day +16 to 26% by day +29. The biomarker analysis confirmed that, by the end of the study, the insecticide was no longer exerting an effect. We discuss how the use of in situ bioassays could also aid comparison of microcosm studies by adding a standardized dimension.

Acetylcholinesterase↗
PubMed2006

Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker Working Group Report.

Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials.

Biomarkers↗
PubMed2005

N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic pulmonary arterial hypertension.

Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test. A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample. A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%). These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.

Adult↗
PubMed2003

Validation of a new biomarker of fetal exposure to alcohol.

OBJECTIVE: To test the sensitivity and specificity of fatty acid ethyl esters (FAEEs) extracted from meconium to identify alcohol-using pregnant women with a sensitive and specific methodology, gas chromatography-tandem mass spectroscopy (GC/MS/MS). Study design Twenty-seven samples of meconium were obtained from infants from the mixed race community in Cape Town, South Africa, who were enrolled in a longitudinal neurobehavioral study. Maternal alcohol use was reported prospectively during pregnancy. FAEEs were isolated from meconium and quantitated by GC/MS/MS. RESULTS: Ethyl oleate was the FAEE that correlated most strongly with maternal self-reported drinking, especially with the average ounces of absolute alcohol ingested per drinking day. Ethyl oleate was most strongly related to drinking in the second and third trimesters (Pearson r=.55 and.40, respectively). At a threshold of 1.5 average ounces of absolute alcohol ingested per drinking day, the area under the receiving operator characteristic curve was.92 (95% confidence interval, 0.74-0.97). Using a cut-off value of 32 ng/g, sensitivity was 84.2% and specificity was 83.3%. CONCLUSIONS: Ethyl oleate concentration in meconium assayed by GC/MS/MS provides a highly sensitive and specific indicator of maternal alcohol use during pregnancy.

Adult↗
PubMed1993

Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction.

Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool for myocardial damage. A blinded prospective multicentre study representing 298 patients suspected of having acute myocardial infarction (AMI), and admitted to the coronary care units of six Scandinavian Hospitals was undertaken to assess the diagnostic performance and prognostic efficacy of a new cardiospecific TnT immunoassay. We used a discriminator TnT value of 0.20 microgram l-1. One hundred and fifty five patients (52%) had definite AMI, based on WHO criteria (all had peak S-TnT values of > or = 0.20 micrograms l-1); 127 patients (43%) had ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all had peak S-TnT values of < 0.20 microgram l-1). The 127 IHD-patients without definite AMI could be subdivided into a group of 44 patients with S-TnT peak values of > or = 0.20 microgram l-1, and a group of 83 patients with TnT below this level. An equal identification of these patients among the centres was seen (mean +/- SD 35 +/- 13%; range 20-55%). A follow-up study was able to define the clinical significance of these findings. The cumulative 6 months probability of suffering cardiac death or AMI was significantly higher in the subgroup with increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the patients with definite AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗