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PubMed1998

[Echocardiographic and hematological variables as a risk factor for stroke in chronic nonvalvular atrial fibrillation].

The relationship between echocardiographic variables and the incidence of ischemic stroke in patients with atrial fibrillation was investigated by transthoracic and transesophageal echocardiography in 67 patients with chronic nonvalvular atrial fibrillation. Hematologic variables were also measured simultaneously, including plasma levels of D-dimer and thrombin-antithrombin III complex in these patients. There was a prior history of ischemic stroke in 13 patients (stroke group), but not in the other 54 patients (nonstroke group). There were no significant differences in age, sex, left ventricular ejection fraction, left ventricular end-diastolic diameter, left atrial diameter or hematologic parameters between the groups. The left atrial appendage emptying flow velocity was lower in the stroke group than in the nonstroke group (21 +/- 5 vs 32 +/- 3 cm/sec, p < 0.05), and the incidence of left atrial spontaneous echo contrast was significantly higher in the stroke group than in the nonstroke group (69% vs 26%, p < 0.01). There was no significant difference in the incidence of left atrial thrombi between the groups (23% vs 12%). These findings suggest that transesophageal echocardiographic variables are correlated with the risk of ischemic stroke in patients with chronic nonvalvular atrial fibrillation.

Adult↗

PubMed2003

Quinine 3-hydroxylation as a biomarker reaction for the activity of CYP3A4 in man.

OBJECTIVE: To investigate the usefulness of the 3-hydroxylation of quinine as a biomarker reaction for the activity of CYP3A4 in man and to study the interindividual variation in the metabolic ratio (MR), i.e. quinine/3-hydroxyquinine. METHODS: Data from a previous study (A) was used for determination of the MR of quinine in plasma and urine at different time points. In study B, 24 healthy Swedish subjects received 250 mg quinine hydrochloride first alone and later together with four other CYP probe drugs [losartan (CYP2C9), omeprazole (CYP2C19), debrisoquine (CYP2D6) and caffeine (CYP1A2)] administered on the same day. Plasma and urine samples were collected before quinine intake and 16 h thereafter and analysed for quinine and 3-hydroxyquinine using high-performance liquid chromatography. Plasma and/or urine were collected for the other probes at different time points. MRs of all the probes were determined and correlations to quinine MR were studied. RESULTS: In study A, the MR in plasma was stable over 96 h. The ratio increased from 5.8 to 12.2 (P=0.006) during co-administration with ketoconazole, whereas no significant difference (P=0.76) was observed during co-administration with fluvoxamine (from 5.8 to 6.0). In study B, there was no significant difference (P=0.36) between the mean MRs when quinine was given alone (4.7) or together with the four other drugs (4.5). There was a significant correlation between the MR of quinine and omeprazole sulphone formation (r=0.52, P<0.01), but not to the MRs of the other probes. There was a fivefold interindividual variability in the MR. CONCLUSIONS: The MR of quinine in plasma or urine may serve as a stable measure of the activity of CYP3A4 in man. These results together with in vitro data show that quinine is also a specific CYP3A4 probe.

Adult↗

PubMed2005

Analgesia and anesthesia for neonates: study design and ethical issues.

OBJECTIVE: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. METHODS: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. RESULTS: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. CONCLUSIONS: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field.

Analgesia↗

PubMed2001

Immunological response to oxidized LDL occurs in association with oxidative DNA damage independently of serum LDL concentrations in dyslipidemic patients.

Oxidative modification of LDL induces immunogenic epitopes in the LDL molecule, and the presence of antibodies against oxidized LDL (anti-Ox-LDL) has been demonstrated in human sera. However, little is known about the clinical significance of anti-Ox-LDL. To elucidate a clinical relationship between the immunological response to oxidized LDL and cellular oxidative stress, we measured serum titers of anti-Ox-LDL in 45 unselected patients with hypercholesterolemia and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), considered a biomarker of the oxidative damage to DNA. The anti-Ox-LDL titer was not correlated with the serum LDL-C concentration, but was correlated with the 8-OHdG concentration (r = 0.300, P < 0.05) in a simple linear regression. Multiple regression analysis indicated that 8-OHdG was independently correlated with anti-Ox-LDL (r = 0.429, P < 0.05), but no other variables, including LDL-C concentrations and smoking habit, were correlated with anti-Ox-LDL. In 16 subgroup patients, the concentrations of TC, TG and LDL-C decreased and the HDL-C concentration increased after cholesterol-lowering therapy with fluvastatin. In addition, both the anti-Ox LDL titer (14.0 +/- 9.5 to 11.4 +/- 6.6 AcU/ml, P < 0.05) and the 8-OHdG concentration (1.19 +/- 0.41 to 0.85 +/- 0.43 ng/ml, P < 0.05) also decreased after fluvastatin therapy. The immunological response to LDL oxidation on vascular wall tissues or cells appear to occur in association with oxidative DNA damage. The measurement of anti-Ox-LDL may be a useful indicator for lipid-lowering therapy.

Anticholesteremic Agents↗

PubMed2000

A real-time PCR assay for the quantification of residual malignant cells in B cell chronic lymphatic leukemia.

Several new therapeutic approaches for the treatment of monoclonal B cell lymphomas are currently being investigated. In parallel with new therapeutic modalities, more sensitive diagnostic methods are needed. These methods should be highly sensitive in detecting very low amounts of malignant cells and should be specific for the malignant clone. In addition, these methods should allow the quantification of residual tumor cells. In this study a new real-time polymerase chain reaction (LightCycler) was evaluated to quantify residual tumor cells in monoclonal B cell malignancies. This technology combines the advantages of rapid cycling PCR with the online detection of PCR products using fluorescent dyes. Our assay is based on immunoglobulin heavy chain (IgVH)-specific PCR with allele-specific primers complementary to hypervariable CDRII and CDRIII regions. A set of framework region III (FRIII)-specific hybridization probes was used for detection of the specific amplification product, and IgVH copy number was quantified with the cloned IgVH sequence as an external standard. The approach was evaluated with the Hodgkin lymphoma cell line L428 in order to quantify L428 dilutions. L428 cells mixed with peripheral blood mononuclear cells (PBMNCs) were detected and quantified with a sensitivity of one cell within 1 x 10(5) PBMNCs. Sample DNA from the peripheral blood and from the bone marrow of two patients with B-CLL was analyzed in the new set up at different time points before and after therapy. Statistically significant changes in IgVH copy numbers were documented in both patients. We conclude that this technology offers an additional opportunity to detect and quantify residual tumor cells in B-CLL over several log steps with a high sensitivity. The kinetics of residual tumor cell counts in B-CLL can be analyzed by this method.

Antibodies, Monoclonal↗

PubMed2024

A framework for block-wise missing data in multi-omics.

High-throughput technologies have generated vast amounts of omic data. It is a consensus that the integration of diverse omics sources improves predictive models and biomarker discovery. However, managing multiple omics data poses challenges such as data heterogeneity, noise, high-dimensionality and missing data, especially in block-wise patterns. This study addresses the challenges of high dimensionality and block-wise missing data through a regularization and constrained-based approach. The methodology is implemented in the R package bwm for binary and continuous response variables, and applied to breast cancer and exposome multi-omics datasets, achieving strong performance even in scenarios with missing data present in all omics. In binary classification task, our proposed model achieves accuracy in the range of 86% to 92%, and F1 in the range of 68% to 79%. And, in regression task the correlation between true and predicted responses is in the range of 72% to 76%. However, there is a slight decline in performance metrics as the percentage of missing data increases. In scenarios where block-wise missing data affects multiple omics, the model performance actually surpasses that of scenarios where missing data is present in only one omics. One possible explanation for this might be that the other scenarios introduce a greater diversity of observation profiles, leading to a more robust model. Depending on the specific omics being studied, there is greater consistency in feature selection when comparing block-wise missing data scenarios.

Humans↗

PubMed2006

Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function.

Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most significant predictors of chronic allograft nephropathy. Protocol biopsies, both in deceased- and living-donor renal grafts, have shown that cortical tubulointerstitial fibrosis correlates with graft survival and function. The impact of not treating subclinical acute rejection (SAR) is less clear. In this study, 126 de novo renal transplant recipients were randomly assigned to receive area-under-the-curve-controlled exposure of either a cyclosporine or a tacrolimus-based immunosuppressive regimen that included steroids, mycophenolate mofetil, and basiliximab induction. Protocol biopsies were taken before and 6 and 12 mo after transplantation. The prevalence of SAR was determined retrospectively. Fibrosis was evaluated by quantitative digital analysis of Sirius red staining in serial biopsies. Donor age correlated significantly with tubulointerstitial fibrosis in pretransplantation biopsies and inferior graft function at month 6 (rtau = -0.26; P = 0.033). Acute rejection incidence was 11.5%, and no clinical late rejection occurred. The prevalence of SAR at 6 mo was 30.8% but was not associated with differences in serial quantitative Sirius red staining at 6 or 12 mo, proteinuria, or progressive loss of GFR up to 2 yr. No differences were found in donor variables, histocompatibility, rejection history, or exposure of immunosuppressants. Controlled individualized calcineurin inhibitor exposure and subsequent tapering resulted in a low early acute rejection rate and prevented late acute rejection. Because, by design, we did not treat SAR, these results provide evidence that asymptomatic infiltrates in 6-mo surveillance biopsies may not be deleterious in the intermediate term. There is need for reliable biomarkers to prove that not all cell infiltrates are equivalent or that infiltrates may change with time.

Adult↗

PubMed2003

Rapid ecotoxicological assessment of heavy metal combined polluted soil using canonical analysis.

Quick, simple to perform, and cheap biomarkers were combined in a rapid assessment approach to measure the effects of metal pollutants, Cu, Cd, Pb and Zn in meadow burozem on wheat. Analysis of orthogonal design showed that the significant zinc factor indicated both the inhibition rate of shoot mass and that of root elongation were affected by zinc (P < 0.05 and P < 0.01, respectively). The first toxicity canonical variable (TOXI), formed from the toxicity data set, explained 49% of the total variance in the toxicity data set; the first biological canonical variable (BIOL) explained 42% of the total variation in the biological data set. The correlation between the first canonical variables TOXI and BIOL (canonical correlation) was 0.94 (P < 0.0001). Therefore, it is reliable and feasible to use the achievement to assess toxicity of heavy metal combined polluted soil using canonical analysis. Toxicity of soil combined polluted by heavy metals to plant community was estimated by comparing the IC50 values describing the concentration needed to cause 50% decrease with grow rate compared to no metal addition. Environmental quality standard for soils prescribe that all these tested concentration of heavy metals in soil should not cause hazard and pollution ultimately, whereas it indicated that the soils in second grade cause more or less than 50% inhibition rates of wheat growth. So environmental quality standard for soils can be modified to include other features.

Analysis of Variance↗

PubMed2006

[Application of new method for data processing in metabonomic studies].

AIM: To search for and application of new method for data processing in metabonomic studies. METHODS: The paper proposed that in the processing of metabonomic data, robust PCA method can be used to diagnose outliers; and unstable variables judged by comparison between difference within class and difference among classes should be excluded before data analysis; moreover, the data should be properly scaled before further processing. The proposed methods were used to preprocess metabolomic data of four genotypes of the Arabidopsis thaliana plants. RESULTS AND CONCLUSION: The outcome demonstrated that the application of these methods can obviously improve clustering and biomarker identifying results.

Algorithms↗

PubMed2006

Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients.

p63 and cytokeratin (CK) 5/6 are markers of basal and squamous differentiation in several normal epithelia and human tumors and are also suggested to be markers of progenitor or stem cells in certain stratified epithelia. In endometrial carcinoma, there is very limited information about the expression pattern of p63 or CK5/6 and no prognostic information. The aim of our study was to examine whether the expression of these markers was associated with a certain tumor phenotype in terms of other biomarkers, clinicopathologic characteristics and patient prognosis. Immunohistochemical expression of p63 and CK5/6 was examined using tissue microarrays (TMAs) in a large population-based series of 276 endometrial carcinomas with long and complete follow-up. Selected cases of normal and hyperplastic endometrium were examined for comparison (n = 15). Absence of p63 expression (70%) was significantly associated with nonendometrioid carcinomas, high histologic grade (FIGO), higher mitotic count and tumor cell proliferation by Ki-67, microsatellite instability (MSI) and loss of hMSH6 expression. A tendency toward reduced patient survival was also seen (p = 0.098). Presence of CK5/6 expression was more frequent in endometrioid tumors with squamous differentiation, while loss of CK5/6 expression (54%) was significantly associated with high FIGO stage, reduced beta-catenin expression, MSI and reduced patient survival (p = 0.0001); the latter was also found within the endometrioid subgroup (p = 0.0004). Multivariate survival analysis revealed that loss of CK5/6 expression had an independent prognostic impact in addition to well-known prognostic variables. Expression of both markers was increased in simple hyperplasia compared with normal endometrium. In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only. Thus, loss of p63 or CK5/6 was associated with features of aggressive tumors, and lack of CK5/6 was significantly associated with reduced survival in multivariate analysis.

Biomarkers, Tumor↗

PubMed2006

Online immunoaffinity liquid chromatography/tandem mass spectrometry determination of a type II collagen peptide biomarker in rat urine: Investigation of the impact of collision-induced dissociation fluctuation on peptide quantitation.

Proteolytic fragments of type II collagen, a major component of joint tissue, have recently been identified as biomarkers for osteoarthritis, a progressive disease associated with cartilage degeneration. A liquid chromatography/tandem mass spectrometry (MS/MS) assay that utilizes online immunoaffinity chromatography and column switching was developed in our laboratory for the neoepitope of type II collagen (NET2C). During method development, peptide collision-induced dissociation (CID) was found to be a significant source of assay variation, which exceeded 10% CV, despite the fact that a stable-isotope-labeled (SIL) internal standard was used to minimize imprecision. This phenomenon was studied in detail using peptides and associated SIL internal standards of varying lengths and amino acid compositions. Variability in peptide CID necessitated the monitoring of multiple MS/MS transitions to obtain acceptable assay precision. The assay was subsequently validated to measure NET2C concentrations in rat urine over the range of 0.1 to 10 ng/mL. The interday accuracy and precision ranged from 3.9 to 13.1 (%CV) and 10.7 to 5.3 (%RE), respectively, across the range of validated concentrations. A specific application of the assay is presented in which the role of estrogen deficiency in the development and progression of osteoarthritis was investigated. In this study, the effect of estrogen on lowering NET2C concentrations in urine in ovariectomized rats was demonstrated.

Animals↗

PubMed2006

Pregnancy-associated plasma protein A: a biomarker in acute ST-elevation myocardial infarction (STEMI).

BACKGROUND: Elevated circulating levels of pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque instability, are associated with increased risk of future cardiac events in patients with acute coronary syndromes (ACS). However, little is known of the kinetics or clinical significance of circulating PAPP-A after plaque rupture in acute ST-elevation myocardial infarction (STEMI). AIM: To evaluate the 48-hour release of pregnancy-associated plasma protein A (PAPP-A) and its association with 12-month outcome in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Sixty-two consecutive STEMI patients were included (40 men and 22 women, median age 67.5 years (range 34-84)), of whom 54 (87.1%) received reperfusion therapy. PAPP-A was measured at admission and 6-12, 24 and 48 hours thereafter. In 14 patients, samples were obtained also at 1, 2 and 4 hours. RESULTS: There was an early peak of circulating PAPP-A during the first 12 hours from symptom onset, followed by rapid normalization. A second, late PAPP-A elevation was noticed in 20/62 patients (32.3%). Admission PAPP-A >10.0 mIU/L (highest tertile) was associated (P = 0.049) with increased 12-month risk of cardiovascular death or non-fatal myocardial infarction. Moreover, the combination of failed early reperfusion together with late PAPP-A elevation was strongly (7/13 versus 10/49 patients, P = 0.016) associated with adverse outcome. Admission PAPP-A did not correlate with admission C-reactive protein or cardiac troponin I. CONCLUSIONS: PAPP-A is elevated early in STEMI and then declines rapidly, a pattern consistent with release from the ruptured plaque. The variability of PAPP-A kinetics at 48 hours reflects the success of reperfusion. This study also shows that PAPP-A may have prognostic value in STEMI.

Adult↗

PubMed2006

Relation of quantitative indexes of concurrent alpha-synuclein abnormalities to clinical outcome in autopsy-proven Alzheimer disease.

BACKGROUND: Lewy bodies (LBs) and Lewy neurites are frequent concomitant neuropathologic observations in clinical and neuropathologically defined Alzheimer disease (AD), but their relation to clinical features in AD is uncertain. Most studies used semiquantitative measures to determine the presence or absence of LB abnormalities. OBJECTIVE: To determine the clinical consequences of LB abnormalities in the setting of AD. DESIGN: Prospective study. SETTING: Three outpatient research and treatment centers. PARTICIPANTS: Fourteen autopsy cases with a pathologic diagnosis of AD abnormalities and concomitant LBs followed semiannually for up to 8 years (mean age at intake, 72 years; mean age at death, 77 years; mean education, 15 years; 12 women). MAIN OUTCOME MEASURES: The modified Mini-Mental State Examination was used to assess cognitive function. The Unified Parkinson Disease Rating Scale was used to rate extrapyramidal motor signs. Hallucinations were evaluated using the Columbia University Scale for Psychopathology in Alzheimer's Disease. Time from the first evaluation in which diagnostic criteria for probable AD were met to death was used to determine illness duration. Quantitative measures of LB abnormalities were obtained for the frontal cortex, entorhinal cortex, substantia nigra, and hippocampus. RESULTS: Independent-samples t tests were used to assess whether the degree of LB abnormality varied as a function of the presence or absence of hallucinations and extrapyramidal signs. Pearson r correlations were run to examine whether there was a relation among LB abnormalities, cognitive function, and illness duration. There was no relation between quantitative neuropathologic indexes of LB abnormalities and clinical outcome. CONCLUSION: The variability of clinical features in AD was not related to the presence or degree of LB abnormalities.

Aged↗

PubMed1997

Gastrointestinal carcinoid tumors: current management strategies.

BACKGROUND: Carcinoid or neuroendocrine tumors of the gastrointestinal tract, although characteristically indolent, are also quite heterogeneous both with respect to histologic and endocrine features and with respect to clinical presentation and behavior. PURPOSE: This study was undertaken to review and summarize the current literature on classification controversies, site-specific carcinoid presentation and behavior, and diagnostic and management strategies for primary and advanced carcinoid tumors and the carcinoid syndrome. RESULTS: For carcinoid tumors, oncologic results depend on the location of the primary tumor, extent of locoregional and metastatic disease, functioning status of the tumor, and the feasibility of complete surgical extirpation. Whereas favorable survival rates are typically observed for appendiceal and rectal primaries, less favorable rates are often observed for colonic and ileal tumors. A search for additional tumors is generally advised because multiple carcinoids and second neoplasms are not uncommon. Because of the indolent nature of the tumor and because these therapies have been shown to improve quality and quantity of life, otherwise fit patients with advanced carcinoid disease should be treated with aggressive medical and surgical therapies. Development of a malignant carcinoid syndrome indicates the presence of a functionally active carcinoid tumor and portends a poor prognosis. CONCLUSION: Gastrointestinal carcinoids, although malignant, behave differently from other carcinomas. Results are highly variable and must be individualized according to the site of the primary tumor, extent of spread, and general condition of the patient. A prolongation of quality life can often be accomplished through aggressive medical and surgical therapies.

Biomarkers↗

PubMed2006

Podoplanin is expressed in subsets of tumors of the central nervous system.

Immunohistochemical analyses with the monoclonal antibody D2-40 were performed to ascertain the expression of podoplanin (a.k.a. T1-alpha, gp36, or aggrus) in tumors of the central nervous system (CNS) and to determine the diagnostic utility of the antibody. The analyses were performed on 325 tumors of various histologic types. The chief finding was almost constant immunoreactivity in ependymal tumors (37/40, 92.5%), choroid plexus papillomas (8/8, 100%), and meningiomas (100/100, 100%). The reactivity was considered "tissue-specific," as the corresponding normal tissue of each tumor was also found to express podoplanin. In addition, expression, not committed to the lineages, was found in many other tumor types, including astrocytic tumors, medulloblastomas, and hemangioblastomas, with variable frequency and intensity. The way of expression was not fully understood, but the expression in astrocytic tumors seemed to be associated with pronounced fibrous properties or malignant phenotype, as was shown by high-frequent expression in pilocytic astrocytomas (12/12, 100%) and glioblastomas (29/35, 82.9%). The present study has shown that podoplanin is expressed in several types of CNS tumors with variable frequency and intensity. Given the widespread expression of podoplanin, the antibody D2-40 is of little use in diagnostic practice for CNS tumors.

Animals↗

PubMed2026

Novel HLA class I and II insights into the pathogenesis of systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of mortality in systemic sclerosis (SSc), yet its genetic architecture remains incompletely understood. Therefore, given the key role of the major histocompatibility complex (MHC) in SSc, we aimed to perform a comprehensive MHC-wide association study in the largest SSc-ILD cohort to date. METHODS: We analysed 2412 patients with SSc-ILD⁺, 3550 patients with SSc-ILD⁻, and 15,076 controls of European ancestry from 10 international cohorts. After quality control, the MHC region was imputed, and inverse variance weighted meta-analysis was performed. Subsequently, conditional stepwise analyses, adjustment for antitopoisomerase autoantibody (ATA) status, and functional annotation of significant single-nucleotide polymorphisms were performed. Finally, we constructed a composite score combining genetic, clinical, and demographic variables to predict SSc-ILD. RESULTS: After conditional analysis, we detected 12 significant associations within class I and class II human leukocyte antigen (HLA) genes. ATA adjustment reduced the significance of class II HLA variants, whereas class I HLA variants remained unaffected. Finally, the built composite score had an area under the curve of 0.754, significantly outperforming the models including any of the variables alone. CONCLUSIONS: In this study, we identify genetic mechanisms underlying SSc-ILD that support the potential implication of CD8+ T cells and ATAs in its pathogenesis. Moreover, we also demonstrate the enhanced efficacy of integrating genetic information into predictive models to detect patients at high risk of SSc-ILD. These findings provide new insights into disease pathogenesis and suggest potential biomarkers and therapeutic targets for improved patient management.

Humans↗

PubMed2005

Oxidized low-density lipoprotein as a predictor of outcome in patients with unstable coronary artery disease.

BACKGROUND: The prognostic value of circulating oxidized low-density lipoprotein (OxLDL) in patients with unstable coronary artery disease (CAD) is unknown. METHODS: Plasma levels of OxLDL were measured in 433 patients with unstable CAD included in FRISC-II (Fragmin and fast Revascularisation in Instability in Coronary artery disease trial) and in 233 of these patients at follow-up 4-7 weeks later. Mortality and myocardial infarction (MI) at 2 years of follow-up was related to above (n=226) or below (n=207) the median level of OxLDL (76 U/L) at study entry. RESULTS: After adjustment for other well-known predictors of risk, OxLDL levels >76 U/L were associated with a higher risk for recurrent MI (Odds Ratio [95% CI]: 1.90 [1.05-3.39]). When patients were divided according to troponin T (TnT) status, the prognostic value of OxLDL was most evident in the TnT negative group with a risk of MI of 16.9% in patients with elevated OxLDL compared to 1.7% (p=0.004) in those without. No association was found between levels of OxLDL and mortality. At follow-up levels of OxLDL were similar to levels during the acute phase unless patients were treated with statins in which levels were significantly lower. CONCLUSIONS: Elevated levels of OxLDL may identify patients with unstable CAD, at increased risk for future MI independent of other risk variables, particularly those without evidence of myocardial damage. OxLDL levels appear to be similar in patients during the unstable and stable phase of CAD unless statin therapy is initiated.

Aged↗

PubMed2001

Serum acid phosphatase level and biochemical recurrence following radical prostatectomy for men with clinically localized prostate cancer.

OBJECTIVES: Serum acid phosphatase (ACP) was once used as the marker for advanced prostate cancer. However, with the development of assays for prostate-specific antigen (PSA), a more sensitive and specific tumor marker, the use of ACP has diminished. We investigated the prognostic value of preoperative serum ACP in predicting prognosis for men with localized prostate cancer following radical retropubic prostatectomy (RRP). METHODS: Of 2293 men treated from 1982 to 1998, 1681 men had a preoperative ACP measurement using an enzymatic assay. We analyzed the actuarial freedom from biochemical (PSA) progression following RRP according to ACP levels. We used multivariate logistic regression and proportional hazards models to determine the independent prognostic value of ACP level with respect of pathologic stage and biochemical recurrence. RESULTS: ACP was not an independent predictor of organ confinement or lymph node involvement in the multivariate logistic regression models using preoperative variables. However, in the proportional hazards model, ACP was an independent predictor of tumor recurrence following RRP, and there was a statistically significant improvement in biochemical recurrence-free survival for men with lower levels of ACP (P <0.001). Furthermore, the normalized hazard ratios of ACP and PSA for predicting biochemical recurrence were similar. CONCLUSIONS: Stratification of men according to their preoperative ACP levels was predictive of patient outcome after RRP. Proportional hazards modeling using preoperative variables demonstrated that the serum ACP level is an independent predictor of tumor recurrence following RRP.

Acid Phosphatase↗