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Results for “Biomarker variability”

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PubMed2000

Human neutrophil lipocalin (HNL) and myeloperoxidase (MPO). Studies of lung lavage fluid and lung tissue.

Myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) are proteins which are stored in neutrophil granulocytes, in the primary and secondary granules, respectively. These granules or their contents of MPO and HNL are secreted upon activation of the cells, and measurement of these soluble markers in biological fluids, such as bronchoalveolar lavage (BAL), has been proposed to mirror the degree of neutrophil activity in the tissue. We conducted a BAL study in 10 healthy volunteers, with the aim to evaluate the intra-individual variability of the concentration of HNL and MPO recovered in sequential aspirations, during a time period when the concentrations of HNL and MPO in BAL fluids were considered to have equilibrated with those in the underlying tissues. The concentrations of HNL were less variable than those of MPO (coefficients of variability 0.33 +/- 0.07 vs. 0.92 +/- 0.28; P = 0.01), suggesting HNL to be a more useful marker of neutrophil activity within the airspace. The specificity of HNL as a selective index of neutrophil cells was confirmed by means of immunohistochemical staining of uninvolved lung tissue specimens obtained from patients referred to pulmonectomy due to carcinoma. While HNL was located only to intracellular spaces of neutrophils, MPO was in addition located to other cells as well. We speculate that the dynamic changes of pressure across the membranes and flow of solutes during a lavage process might mobilize particulate matter and adherent cells, some of which may be loaded with MPO, and that this may introduce larger variability in the recovery of MPO than of HNL. We conclude that using HNL as a soluble indicator of neutrophil presence is more feasible than using MPO.

Acute-Phase Proteins↗

PubMed1998

Resuscitation with hypertonic saline dextran improves cardiac function in vivo and ex vivo after burn injury in sheep.

In a 24 h, double-blind, prospective trial, we tested the hypothesis that two 4 mL/kg doses of hypertonic saline dextran (HSD; 7.5% NaCl/6% dextran 70) given in addition to isotonic fluid treatment would produce both immediate and sustained benefit for the heart after large burn injury. 12 instrumented sheep were subjected to a 40% total body surface area full-thickness flame burn under halothane anesthesia. 1 h after burn, when the animals had recovered from anesthesia, the first dose of either HSD (n=6) or normal saline (NaCl .9%; n=6) was infused over 30 min. The test solution was immediately followed by lactated Ringer's solution infused to maintain a urine output of 1-2 mL/kg x h throughout the study. The second dose of test solution was started at 12 h and was infused over 5 h. The initial dose of HSD corrected the burn-induced reduction in cardiac output, cardiac work, an index of myocardial contractility, and restored myocardial blood flow, as measured by the colored microsphere technique, to preburn values. Plasma concentrations of troponin I, creatine kinase (CK), and CK isoenzyme CKMB were increased 1 h after burn, but were not altered after HSD treatment. After euthanasia at 24 h, myocardial glutathione concentrations were higher in HSD-treated animals, whereas other markers of oxidative injury in heart or in plasma did not show systematic differences. The maximum contraction force measured in isolated right papillary muscles ex vivo was significantly greater in HSD-treated than normal saline-treated animals. In conclusion, the first dose of 4 mL/kg HSD infused 1 h after burn improved cardiac function, whereas the second dose of HSD infused at 12 h was without apparent effect on dynamic variables. An overall effect of the HSD treatments was a lasting increase in papillary muscle contraction force.

Animals↗

PubMed2003

Mucin expression in nonneoplastic and neoplastic glandular epithelia of the uterine cervix.

Although it is well known that the uterine cervix contains mucin-producing glandular epithelium, only a few studies have described the changes in mucin that accompany malignant transformation. In this study the authors evaluated the characteristics of mucin expression in the normal endocervical epithelium and mucinous and endometrioid adenocarcinomas of the uterine cervix. The normal endocervical epithelium was characterized by predominant sulfomucin and MUC1 expression in all sites and MUC5AC expression in the surface epithelium, while MUC2 was not detected at all and pyloric gland type mucin (using antibody HIK1083) was detected in less than 1% of cases. Cervical adenocarcinomas, especially mucinous adenocarcinomas, showed marked variability in mucin expression that included mucins of pyloric gland and intestinal type.

Adenocarcinoma, Mucinous↗

PubMed2004

A longitudinal study of bone-related biochemical changes at the menopause.

OBJECTIVE: To evaluate the effects of the menopause on bone-related biochemical variables in a longitudinal study. DESIGN: Recruitment by advertisement of premenopausal women over the age of 44 for measurement of selected variables and collection of blood and urine samples for deep freezing, followed by annual check of menopausal status and repeat collection of blood and urine samples for deep freezing after the menopausal transition. PATIENTS: A total of 104 women with confirmed premenopausal status and on no treatment likely to affect calcium or bone metabolism were admitted to the study over a period of 2 years. After 8 years, 43 of the volunteers had passed through the menopause and the study was closed. MEASUREMENTS: Radiocalcium absorption was measured at the first attendance and again after the menopausal transition. Calcium and other relevant variables were measured consecutively on paired thawed-out samples of blood and urine. RESULTS: The data were complete in 34 subjects. In these women, there were highly significant correlations between the first and second measurements of most variables - serum calcium and fractions, radiocalcium absorption, vitamin D metabolites, PTH and others - indicating significant 'tracking' of these variables across the menopause. Within that framework there were significant rises in serum total and calculated ionized calcium (both P < 0.001) without change in mean serum parathyroid hormone (PTH). Radiocalcium absorption fell (P < 0.001) without change in serum 1,25D. There was a rise in fasting urinary calcium (P < 0.001) which could not be explained by the rise in filtered load and therefore represented a fall in TmCa (P < 0.001). There were significant rises in urinary bone resorption markers, pyridinoline and deoxypyridinoline (P < 0.001). CONCLUSIONS: We conclude that the menopausal rise in calculated serum ionized calcium without fall in PTH, indicates a change in PTH set-point, and that the falls in gastrointestinal absorption and renal tubular reabsorption of calcium reflect the loss of an oestrogen action at these two sites. Although these changes are sufficient to explain the rise in calcium requirement at the menopause, the association of high bone resorption with normal serum PTH suggests also an increased sensitivity of bone to the action of parathyroid hormone. There is significant 'tracking' of many variables across the menopause despite very significant changes in their absolute values.

Adult↗

PubMed2005

Survivin is a negative prognostic marker in medulloblastoma.

Survivin is a member of the inhibitor of apoptosis protein family, which is over-expressed in many human cancers. Our aim was to analyse survivin expression in medulloblastoma, its association with aberrant activation of the WNT (wingless) pathway and to test the prognostic significance of survivin expression. We immuno histochemically analysed survivin expression and localization of beta-catenin, a downstream mediator of the WNT pathway, in 56 cases of medulloblastoma. Survivin was detected in the nuclei of tumour cells in all cases, but the proportion of positive nuclei varied from 0.5 to 31.3%. Survivin expression tended to be higher in medulloblastomas with an aberrant activation of the WNT pathway (nuclear localization of beta-catenin), but did not correlate with histological type, age group or dissemination via cerebrospinal fluid pathways. Survivin expression and dissemination status were two independent negative prognostic variables for the overall survival of patients with medulloblastoma. In conclusion, survivin is up-regulated in medulloblastomas. It is a negative prognostic marker and a potential therapeutic target.

Adolescent↗

PubMed2006

Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice.

Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of transgenic mice seems critical. Due to technical difficulty associated with performing cardiac IP in mice, we developed an in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion. This technique has the major advantage of eliminating the necessity of intermittently occluding the coronary artery with a knotted suture. To systematically evaluate this model, we first demonstrated correlation of ischemia times (10-60 min) with infarct sizes [3.5 +/- 1.3 to 42 +/- 5.2% area at risk (AAR), Evan's blue/triphenyltetrazolium chloride staining]. IP (4 x 5 min) and cold ischemia (27 degrees C) reduced infarct size by 69 +/- 6.7% and 84 +/- 4.2%, respectively (n = 6, P < 0.01). In contrast, lower numbers of IP cycles did not alter infarct size. However, infarct sizes were distinctively different in mice from different genetic backgrounds. In addition to infarct staining, we tested cardiac troponin I (cTnI) as marker of myocardial infarction in this model. In fact, plasma levels of cTnI were significantly lower in IP-treated mice and closely correlated with infarct sizes (R(2) = 0.8). To demonstrate transcriptional consequences of cardiac IP, we isolated total RNA from the AAR and showed repression of the equilibrative nucleoside transporters 1-4 by IP in this model. Taken together, this study demonstrates highly reproducible infarct sizes and cardiac protection by IP, thus minimizing the variability associated with knot-based coronary occlusion models. Further studies on cardiac IP using transgenic mice may consider this technique.

Animals↗

PubMed2003

Antioxidant and oxidative stress indices in dialysis-dependent acute renal failure.

BACKGROUND: Experimental animal models and in vitro studies have established a role for reactive oxygen species and the therapeutic potential for free radical scavengers in acute renal failure (ARF). Little is known of the effects of hemodialysis and other clinical variables on antioxidant defenses and oxidative stress among patients with ARF. METHODS: We examined antioxidant defenses and oxidative stress status in 24 patients with ARF requiring hemodialysis (HD). Blood samples were drawn prior to the first dialysis session (baseline), as well as before and after the third and sixth dialysis sessions. At each time point, the following parameters were measured: plasma alpha-tocopherol (vitamin E), plasma glutathione peroxidase (GSH-Px), serum total oxygen radical absorbance capacity (ORAC), plasma thiobarbituric acid reactive substances (TBARS), plasma tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10). Multivariate linear regression analyses were performed to examine clinical/laboratory variables associated with antioxidant/oxidative stress indices. The changes in antioxidant/oxidative stress indices over time after initiation of hemodialysis was evaluated in a subgroup of patients (n = 11) who completed six dialysis sessions. Intradialytic changes in antioxidant/oxidative stress indices and the differential impact of cellulose acetate vs. polysulfone dialyzers were also evaluated. RESULTS: Factors associated with alpha-tocopherol level were serum albumin (301 microg/dl upward arrow for each 1 g/dl upward arrow in albumin) and ORAC (188 microg/dl upward arrow for each 1,000 micromol Trolox Eq/l upward arrow in ORAC). Age was independently associated with plasma GSH-Px levels (55 U/l downward arrow for each 10-year age upward arrow ). Factors associated with ORAC were alpha-tocopherol (85 micromol Trolox Eq/l upward arrow for each 100 microg/dl upward arrow in alpha-tocopherol) and total bilirubin (30 micromol Trolox Eq/l downward arrow for each 1 mg/dl upward arrow in total bilirubin). Total bilirubin was independently associated with TBARS (0.2 microM upward arrow for each 1 mg/dl upward arrow in total bilirubin). GSH-Px and ORAC levels declined over time between baseline and the sixth dialysis session (p < 0.05 for both). Finally, there was a significant intradialytic decline in ORAC levels, which appeared to be more pronounced with use of cellulose acetate compared with polysulfone dialyzer membranes (p < 0.05). CONCLUSIONS: These observations indicate that antioxidant and oxidative stress indices in ARF patients are associated with several clinical and laboratory variables as well as the dialysis procedure. Further studies are needed to investigate the therapeutic role of anti-oxidant therapy in these patients.

Acute Kidney Injury↗

PubMedDate not supplied

p53 expression, DNA ploidy and mitotic index as prognostic factors in patients with epithelial ovarian carcinoma.

AIMS AND BACKGROUND: Biological variables linked to genomic instability were examined and related to survival in 52 patients affected by ovarian carcinoma and nine patients with low malignant potential tumors (LMP). METHODS: DNA ploidy was measured by image cytometry in isolated neoplastic cells; the mitotic index was measured in Feulgen-toluidine blue-stained sections and p53 was investigated by immunohistochemistry. RESULTS: Twenty-five tumors (4 LMP) were peridiploid (ploidy < 2.25c), 22 tumors (4 LMP) were hyperdiploid (2.25c > ploidy < 2.9c) and 14 (1 LMP) had high ploidy (> or = 2.9c). MI ranged from 0.3 to 24.2 with a mean of 1.8 for LMP and 6.8 for carcinomas (P<0.001). Widespread p53 overexpression was detected in 49% of carcinomas and in none of the LMP tumors. CONCLUSIONS: Survival analysis performed in patients with carcinomas indicated that, of the examined biological variables, only MI was moderately associated with survival in a subgroup of early-stage patients.

Adult↗

PubMed2002

Relationships between serum markers of monocyte/macrophage activation in type 1 Gaucher's disease.

We studied 44 patients with type 1 Gaucher's disease (16 non-treated patients and 28 treated with enzyme replacement therapy). We measured serum levels of chitotriosidase (ChT), neopterin, angiotensin-converting enzyme (ACE), adenosine deaminase (ADA) and beta-hexosaminidase (Hex) and its major isoenzymes Hex A and Hex B. In the untreated group of patients, the increase in serum levels was ChT>neopterin>ACE> ADA>Hex, with all decreasing significantly in treated patients (p< 0.001). Highly significant correlations were obtained between the markers of monocyte/macrophage activation which were tested (p<0.001). However, partial correlations between serum Hex B (with Hex A constant) and ChT, ACE, neopterin and ADA did not reach statistical significance. This suggests that hepatocytes are the major cellular source of this isoenzyme. Similarly, partial correlation of ChT with neopterin, with the other variables constant, was not significant, which would suggest a different expression of these two markers in Gaucher's disease.

Adenosine Deaminase↗

PubMed1992

Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Serum tumour markers in human prostatic carcinoma. The value of a marker panel for prognostic information.

Serum from 102 patients was analysed with regard to its content of prostatic acid phosphatase (PAP), prostate specific antigen (PSA), neopterin, osteocalcin, thymidine kinase, C-reactive protein, and of tissue polypeptide antigen (TPA). The levels were related to the short-term survival (death from cancer within 3 years) and compared by statistical means. A comparison was also made with tumour grade and stage and the presence or not of metastatic lesions. In this study neopterin was found to be most closely related to the clinical course followed by tumour grade, thymidine kinase and PSA. When all these four variables were in the equation no other parameter added any information of statistical significance. The importance of selecting appropriate cut off values ('normal' vs 'elevated') when using the serum marker as a prognostic indicator is also discussed.

Biomarkers, Tumor↗

PubMedDate not supplied

CEA, CA125 and CA19-9 levels in congenital gastrointestinal anomalies.

Preoperative and postoperative serum samples of 35 patients with different congenital gastrointestinal anomalies were analyzed for the markers CEA, CA 125 and 19-9 by immunoradiometric assay during a period of three years. The majority of the anomalies were aganglionic megacolon and hypertrophic pyloric stenosis. CA 125 and CA 19-9 were likely to indicate logistic model probabilities for babies with anomalies, while CEA was not (F=35.78, p<0.05 for CA CA 125 and F=4.36, p<0.05 for CA 19-9). Probability of no congenital anomaly for babies was: p (Normal)=e4.41-0.13CA125 - 0.05CA19-9/1+e4.41-0.13CA125- 0.05CA19-9 Using CA 125 as a marker, babies with congenital anomalies were determined with 83.3 percent probability (F= 11.33, p<0.05). On the other hand, it was not possible to predict the type of anomaly with these three markers. CEA, CA 125 and CA 19-9 seem to be prognostic variables associated with congenital anomalies. These biological markers provide information that can be incorporated into the diagnosis of anomalies but without doubt results of markers should be supported by clinical findings.

Biomarkers↗

PubMed2001

Preoperative serum levels of sialyl Lewis(a), sialyl Lewis(x), and sialyl Tn antigens as prognostic markers after curative resection for colorectal cancer.

In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer.

Adult↗

PubMed1992

[Serum sialyl Tn antigen as a prognostic marker in patients with epithelial ovarian cancer].

Circulating serum sialyl Tn (STN) antigen levels were measured in 89 patients with epithelial ovarian cancer, 157 benign disease, and in 126 healthy controls. Serum antigen levels were increased in 48.3% of patients with ovarian cancer. The false positive rate is significantly low (4.0% in healthy controls and 9.6% in benign disease). The levels of STN antigen were significantly higher in sera of patients with cancer than in those in benign and healthy controls (p less than 0.05). The rise in serum STN antigen levels correlated to the size of the primary tumors. Of the histological type, it is interesting to note the high sensitivity in mucinous-type ovarian cancer. Survival at 1, 2, 3, 4 and 5 years for patients with STN-negative (serum STN levels less than 50 U/ml) versus STN-positive (serum STN levels greater than or equal to 50 U/mol) was 96.2, 92.3, 86.5, 82.7, and 76.9% versus 59.5, 29.7, 18.9, 10.8, and 10.8%, respectively (p less than 0.05). The overall survival probability was worse in patients with STN-positive sera. Percent progression-free survival at 1, 2, 3, 4 and 5 years for patients with STN-negative versus STN-positive was 90.4, 86.5, 76.9, 59.6, and 51.9% versus 35.1, 16.2, 8.1, 8.1, and 5.4%, respectively (p less than 0.05). The overall progression-free period of survival was shorter in patients with STN-positive sera. Multivariate regression analysis revealed that positive STN, stage, PS and histologic grade were the four variables of most importance in predicting survival. These results indicate that a positive STN antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.

Antigens, Neoplasm↗

PubMed1992

Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease.

Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease.

Adult↗

PubMed2006

[Angiotensin converting enzyme activity in the clinical course and forming of cor pulmonale in patients with chronic obstructive pulmonary diseases].

The aim of the study was to evaluate the influence of ACE in various biological media (blood, sputum, and lung tissue) on the clinical manifestations and morphofunctional cardiac variables in 137 patients with chronic obstructive pulmonary disease (COPD), of whom 17% had mild, 70% had medium, and 13% had severe degree of the disease according to Federal program, 1999. Seventy percent of the patients had stage II pulmonary hypertension according to Paleyev, 1986, while the number of patients with stage I and III was 14 and 16%, respectively. Circulatory insufficiency was mild (NYHA I to II) in 124 patients, and medium (NYHA III) in 13 patients only. The results of the study demonstrate that COPD exacerbation is accompanied by an increase in ACE activity, mostly in the lung tissue, induced sputum (IS), and, to a lesser degree, in blood serum; ISA CE activity is almost the same as that in the lung tissue. The study established a direct correlation between IS ACE activity and the level of C-reactive protein, an inflammatory process activity marker, and a reverse correlation between IS ACE activity and respiratory function variables, the latter characterizing bronchial obstruction. The study shows a strong direct correlation between IS ACE activity and the degree of right ventricular (RV) and left ventricular (LV) hypertrophy, as well as diastolic function disturbances according to RV isovolumetric relaxation time and LV early diastolic filling delay time. There is a strong reverse correlation between IS ACE activity and the disbalance of the ratio of blood flow velocities during early and late diastolic ventricular filling. The study found no significant correlations between ACE activity and the variables of ventricular systolic function. The study demonstrates a significant role of ACE activity changes in the progression of obstruction, inflammation, and myocardial remodeling.

Adult↗

PubMed1990

Quality control test for immunoreactivity of radiolabeled antibody.

A rapid method for the measurement of the immunoreactive fraction of a radiolabeled monoclonal antibody or antibody fragment has been developed. This may be used as a quality control test prior to patient administration of the radiolabeled antibody preparation. The test employs solid phase antigens and the assay is conducted under conditions of antigen excess. Assay parameters have been evaluated and a standardized procedure has been developed. The assay has been compared to a standard extrapolation method and found to give approximately the same result. The test has been used on four different radiolabeled antibodies currently in clinical trials in patients with colorectal cancer. Mean immunoreactive fractions for these radiolabeled antibodies ranged from 35 to 65% and the variability of the immunoreactive fraction ranged from 140 to 240% for different antibodies. We conclude that the quality, defined as the immunoreactive fraction, of radiolabeled antibodies is both low and highly variable, indicating the need for a quality control test of these radiopharmaceuticals in the clinic prior to patient administration.

Animals↗

PubMed1997

Second-trimester maternal urinary gonadotrophin peptide screening for fetal Down syndrome in Asian women.

Maternal urinary gonadotrophin peptide (UGP) was recently found to be elevated in second-trimester Down syndrome pregnancies. There is controversy about its screening efficacy. Data in the Asian population are scanty. We measured the UGP levels in 29 Down syndrome pregnancies and 297 controls and expressed them as a ratio of the urine creatinine concentration. Median UGP MOM was elevated to 3.44 (95 per cent confidence interval 1.99-5.13) in cases, compared with controls. UGP values were widely scattered in cases and controls with extensive overlap such that only 35 per cent of Down syndrome cases were expected to be detected at a 5 per cent false-positive rate. The data of the present study and previous reports show that there is a wide variability of gestation-specific UGP median values. UGP alone does not appear to be an effective screening marker for fetal Down syndrome.

Adult↗