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PubMed2004

Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits.

We investigated the anticoagulant effects of argatroban, a direct thrombin inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits. Three sham circuits were prepared according to our hospital's standard practice and run for six hours simultaneously. Two circuits were anticoagulated with argatroban (one with heparin in the wet prime and one without). One circuit had heparin in the initial prime and was then anticoagulated with heparin. We measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes), activated clotting times (ACTs) and partial thromboplastin times (aPTTs), and monitored thrombus formation using thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No clot initiation was detected by thromboelastography. Thrombin generation was decreased in circuits anticoagulated with argatroban versus heparin, despite aPTTs being less prolonged. These results suggest that argatroban may be more efficacious than heparin for anticoagulation in ECMO. Additional studies are warranted to further evaluate argatroban in this setting.

Arginine↗
PubMed1996

Elevated serum levels of manganese superoxide dismutase in polymyositis and dermatomyositis.

We studied serum concentrations of manganese superoxide dismutase (Mn SOD) and copper-zinc superoxide dismutase (Cu/Zn SOD) in 22 patients with polymyositis and dermatomyositis (PM/DM), 87 patients with four types of muscular dystrophy, 20 patients with amyotrophic lateral sclerosis, and 15 patients with collagen vascular diseases (CVD). Serum levels of Mn SOD were increased only in the patients with PM/DM and CVD, and the elevation was more prominent in those with PM/DM. Levels of Cu/Zn SOD were slightly elevated in some patients with PM/DM and Duchenne muscular dystrophy. In patients with PM/DM, the change in Mn SOD levels corresponded to disease activity as closely as or more closely than those of creatine kinase. The results indicate that serum Mn SOD may be a useful clinical marker for PM/DM.

Adolescent↗
PubMed2005

First clinical experience with beta-trace protein (prostaglandin D synthase) as a marker for perilymphatic fistula.

A diagnosis of perilymphatic fistula is still controversial. Recently, a case report indicated that beta-trace protein (prostaglandin D synthase) might be a potential marker for perilymphatic fluid. In this multicentre clinical case series study beta-trace protein was used as a marker for perilymphatic fluid fistula. Fifteen fluid samples were collected during diagnostic tympanoscopy. In addition, five samples were collected from patients with tympanic membrane perforation for use as as negative controls. Samples were obtained using precision glass capillaries and were analysed for beta-trace protein using laser nephelometry. The diagnosis of perilymphatic fistula was defined by the patient's history, the audiological and vestibular investigation and the findings at tympanoscopy. The cut-off level of beta-trace protein for perilymph-positive samples was chosen at 1.11 mg/l. The sensitivity and specificity were calculated using a 2 x 2 contingency table. There was no false positive result, but in two cases a false negative result was found. The specificity was 1 and the sensitivity was 0.81. The material of this first clinical study is small owing to the rarity of patients undergoing diagnostic tympanoscopy for perilymphatic fluid fistula. However, according to these preliminary results beta-trace protein might be a promising marker in the diagnosis of perilymphatic fluid fistulas.

Biomarkers↗
PubMed1996

Future research directions for evaluating human genetic and cancer risk from environmental exposures.

The utility of biomarkers for evaluating the genotoxicity of environmental exposures is well documented. Biomarkers of both exposure and effect provide bases for assessing human-genotoxicant interactions and may be indicative of future disease risk. At present, there is little information on the predictive value of these assays for either a population or the individuals tested. This paper describes some aspects of biomarker assays, the possible use of susceptibility measures in biomonitoring protocols, and the need for evaluation of disease relevance. A population study involving epidemiologists, geneticists, toxicologists, statisticians, and physicians is proposed to determine the disease relevance of these biomarkers.

Biomarkers↗
PubMed1998

Medium-term bioassays for carcinogenicity of chemical mixtures.

Carcinogenic effects of chemical mixtures were examined with a medium-term liver bioassay for carcinogens or a multiorgan medium-term bioassay using male F344 rats. In the medium-term liver bioassay, rats were initially treated with diethylnitrosamine (DEN) at 200 mg/kg body weight, i.p.; after 2 weeks they received chemical mixtures such as 10 different heterocyclic amines at one-tenth or one-hundredth the dose levels used in carcinogenicity studies and the mixtures of 20 different pesticides, each at acceptable daily intake (ADI) levels or a mixture of 100 times ADI levels. All animals were subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. The number and areas of glutathione S-transferase placental form (GST-P) positive foci (preneoplastic lesions in the liver) were compared between respective groups. When 10 heterocyclic amines were mixed in the diet at one-tenth dose level, clear synergism was observed, but no combined effects were evident with the one-hundredth dose levels. In the pesticide experiment, treatment of rats with the 20-pesticide mixture at the ADI dose level did not enhance GST-P-positive foci. In contrast, a mixture of 100 times the ADI significantly increased those values. In a multiorgan bioassay of 28 weeks, mixtures of 40 high-volume compounds and 20 pesticides (suspected carcinogens) added together at their respective ADI levels did not enhance carcinogenesis in any organs initiated by five different carcinogens (DEN, N-methylnitrosourea, dimethylhydrazine, N-butyl-N-(4-hydroxybutyl)nitrosamine, and dihydroxy-di-n-propylnitrosamine) in combination. The combination effect of low dietary levels of five antioxidants, butylated hydroxyanisole, caffeic acid, sesamol, 4-methoxyphenol, and catechol, were also examined using the multiorgan bioassay. The incidence of forestomach papillomas was significantly increased only in the combination group and the results indicate that combination of the five antioxidants can exert additive/synergistic effects on tumorigenesis in the multiorgan bioassay. These results indicate that chemical mixtures at very low doses did not enhance preneoplastic lesions synergistically but the mixtures at certain doses show synergism in the target organ. The medium-term bioassays are particularly useful tools for this purpose.

Animals↗
PubMed2004

More fibrosis and thrombotic complications but similar expression patterns of markers for coagulation and inflammation in symptomatic plaques from DM2 patients.

OBJECTIVE: One of the possible pathological mechanisms behind the increased vascular injury in diabetes mellitus type 2 (DM2) is the formation of advanced glycation end products (AGEs). The aim of this study was to investigate whether the presence of AGEs and specific markers for coagulation and inflammation in symptomatic atherosclerotic plaques from DM2 patients differs from plaques from nondiabetics. METHODS AND RESULTS: Carotid atherectomies were obtained from DM2 patients (n=11) and controls without DM2 matched for age and other cardiovascular risk factors (n=12) who were treated for symptomatic carotid artery stenosis. Plaques were graded according to the American Heart Association classification of lesions. More fibrosis and more thrombotic complications (p=0.007) were observed in carotid atherectomies from DM2 patients. Percentages of immunostained smooth muscle cells and macrophages in the lesions, quantified planimetrically, did not differ between the two groups. No differences were found in the immunostaining for T cells, tissue factor (TF), endothelial protein C receptor (EPCR), nuclear factor kappaB, and the AGE carboxymethyllysine. CONCLUSIONS: These findings demonstrate that DM2 is associated with increased plaque complications; however, a local changed presence of AGEs, TF, and EPCR seems not to be involved in this end stage of atherosclerosis.

Aged↗
PubMed2006

Immunochemistry of lysosomal storage disorders.

BACKGROUND: Lysosomal storage disorders are a group of genetic diseases, each with a broad spectrum of clinical presentation that ranges from attenuated to severe. The immunochemical analysis of patient samples is aimed at several key aspects of patient management, including early detection of the disorder, prediction of clinical severity, determining the most appropriate therapeutic regimen, and monitoring of patients on therapy. METHODS: In this study, we review the current and emerging technology available to achieve these assessments. RESULTS: Immune assays have direct practical application for the early detection, diagnosis and prognosis of lysosomal storage disorder patients. Multiplexing of these assays may provide a platform to allow newborn screening for multiple lysosomal storage disorders. CONCLUSIONS: We have reviewed the immunochemical techniques available for the analysis of lysosomal storage disorder patient samples and advise that these may be used in conjunction with other technologies for effective patient management.

Biomarkers↗
PubMed2006

gamma-Glutamyltransferase as a predictor of chronic kidney disease in nonhypertensive and nondiabetic Korean men.

BACKGROUND: Little research has been done to examine whether gamma-glutamyltransferase (GGT) is prospectively associated with the development of chronic kidney disease (CKD). We performed a prospective study to examine the association between GGT and the risk for the development of CKD. METHODS: The study cohort included a total of 10 337 healthy males with normal baseline kidney functions and no proteinuria. Participants were workers in a semiconductor manufacturing company and its 13 affiliates. CKD was defined as either the presence of proteinuria or a glomerular filtration rate (GFR) of < 60 mL x min(-1) x (1.73(2))(-1). Cox proportional hazards models were used to calculate the adjusted hazard ratios in separate models for CKD. RESULTS: During a follow-up period of 25,774.4 person-years, 366 men developed CKD. After adjustments were made for age, baseline GFR, triglyceride, and HDL-C, the risk for CKD increased with an increasing quartile of serum GGT (p for trend <0.001). The top one fourth of serum GGT vs the bottom one fourth of relative risks for CKD was 1.90 (95% confidence interval, 1.37-2.63). These associations were also apparent in participants who consumed < or = 20 g/day of alcohol and those with normal weight, with values of alanine aminotransferase within reference intervals, or with C-reactive protein < 3.0 mg/L, and participants without metabolic syndrome. CONCLUSIONS: Our findings, which were obtained from a large work-site cohort and excluded individuals with diabetes and hypertension, indicated that serum GGT may be an early predictor for the development of CKD, independent of baseline confounding factors.

Adult↗
PubMed1993

Serum concentration of soluble interleukin 2 receptors in asthma. Correlation with disease activity.

We evaluated whether serum soluble interleukin 2 receptor (sIL-2R), a marker of T lymphocyte activation in vivo, could be useful to monitor disease activity in asthma. Venous blood was collected from 26 patients with acute severe asthma prior to the commencement of systemic corticosteroid therapy (day 1), 15 with stable disease, and 13 normal control subjects. Serum sIL-2R level was significantly higher in acute asthma (462.7 +/- 36.1 U/ml; mean +/- SEM) than stable disease (328.5 +/- 30.4 U/ml, p = 0.013) which in turn, was significantly raised when compared with control subjects (239.0 +/- 22.9 U/ml; p = 0.0003 vs acute; p = 0.036 vs stable). Nevertheless, sIL-2R concentrations in 11 patients with acute and 11 with stable disease did not exceed the upper limit of normal, ie, mean +.2 SD of the value in control subjects = 404.4 U/ml. Repeated measurements of sIL-2R in 24 acute asthmatics on day 3 revealed no significant fall (464.6 +/- 37.2 U/ml, NS), although the reduction in sIL-2R was significantly correlated with the corresponding improvement in peak expiratory flow (r = -0.52, p = 0.005). Following resolution of the acute attack, further measurements performed in 11 of these subjects on day 28 showed a significant fall in sIL-2R (p = 0.016). Our data showed that although serum sIL-2R was raised in asthma and, to a certain extent, might reflect disease activity, the considerable overlap of values between asthma of differing severity and normal control subjects precludes its clinical use as an index of asthma severity.

Acute Disease↗
PubMed1995

Serum class I and II alcohol dehydrogenase activity during the course of viral hepatitis.

We examined the activities of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with viral hepatitis using the fluorogenic substrates 4-methoxy-1-naphthaldehyde for class I and 6-methoxy-2-naphthaldehyde for class II. It was found that serum activities of class I and II alcohol dehydrogenase isoenzymes over the course of five weeks of hospitalisation were higher than those of controls. The greatest increase in activities was found at the onset of disease, exceeding the mean control value by about 30 fold for class I and 4 fold for class II. These activities were lower than that of aminotransferase but higher than those for lactate dehydrogenase, alkaline phosphatase and gamma-glutamyltransferase. Thereafter, the activity of alcohol dehydrogenase isoenzymes gradually decreased, but did not reach the values of the control groups in the last period of the study. Activities of class I and II alcohol dehydrogenase isoenzymes correlated well with those of alanine and aspartate aminotransferase and lactate dehydrogenase in the first weeks of illness. These results clearly demonstrate that especially the activity of class I alcohol dehydrogenase isoenzyme measured by a fluorimetric method can be a useful marker of liver cell damage in the course of viral hepatitis.

Adolescent↗
PubMed1999

Cardiac troponin I and troponin T: recent players in the field of myocardial markers.

The troponin (Tn) complex consists of three subunits referred to as TnT, TnI and TnC. Myocardium contains TnT and TnI isoforms which are not present in skeletal muscles and which can be separated from the muscular isoforms by immunological techniques. Using commercially available immunoassays, clinical laboratories are able to determine cardiac TnT and TnI (cTnT and cTnI) quickly and reliably as classical cardiac markers. After acute myocardial infarction, cTnT and cTnI concentrations start to increase in serum in a rather similar way than CK-MB, but return to normal after longer periods of time (approximately one week). Because of their excellent cardiac specificity, Tn subunits appear ideally suited for the differential diagnosis of myocardial and muscular damage, for example in noncardiac surgery patients, in patients with muscular trauma or with chronic muscular diseases, or after intense physical exercise. cTnT and cTnI may also be used for detecting evidence of minor myocardial damage: therefore they have found new clinical applications, in particular risk stratification in patients with unstable angina. In spite of the possible reexpression of cTnT in human skeletal muscles, and of the lack of standardization of cTnI assays, Tn subunits are not far to meet the criteria of ideal markers for acute myocardial injury. Only an insufficient sensitivity in the first hours following the acute coronary syndroms requiries to maintain an early myocardial marker in the cardiac panel for routine laboratory testing.

Biomarkers↗
PubMed1998

Low incidence of minor myocardial damage associated with coronary stenting detected by serum troponin T comparable to that with balloon coronary angioplasty.

The use of the serum troponin T (TnT) level as a means of assessing minor myocardial injury, which affects the long-term prognosis, has not been fully clarified in patients with coronary artery disease in whom a coronary stent has been implanted. We measured the TnT level to determine the incidence of myocardial damage associated with stent implantation. A total of 29 patients who underwent successful stent implantation (stenting group) were studied and compared with 45 patients who underwent successful coronary balloon angioplasty during the same period (balloon angioplasty group). The serum TnT level was measured by enzyme immunoassay 36 hours after the stenting or balloon angioplasty. The activities of serum creatine kinase (CK) and its isoenzyme MB (CK-MB) were measured by a modified Rosalski method and an immunoinhibition method, respectively, before, immediately after, and 6, 12, and 24 hours after the procedure. Elevation of the TnT level was found in 3.4% (1/29; 0.35 ng/ml) of the patients in the stenting group and in 8.9% (4/45; 0.75 +/- 0.21 ng/ml) of those in the balloon angioplasty group. Elevation of the CK and CK-MB activities was found in 3.4% (1/29; 163 IU/l) and 0%, respectively in the stenting group, and 15.5% (7/45; 375 +/- 143 IU/l) and 4.4% (2/45; 24 and 49 IU/l), respectively, in the balloon angioplasty group. TnT elevation was not invariably accompanied by CK or CK-MB elevation, or by angiographically visible side branch occlusion. For TnT, CK-MB activity and CK activity, there was no significant difference between in the incidence of elevation in the balloon angioplasty group and that in the stenting group. In summary, the incidence of myocardial damage associated with stent implantation seems to be low and comparable to that associated with balloon angioplasty. Despite the low incidence, measurement of the serum TnT level in addition to CK-MB measurement is essential in assessing minor myocardial damage.

Aged↗
PubMed2002

Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats.

Aberrant crypt foci (ACF) in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks) and medium-term (30 weeks) assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH) in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg) twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks) assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks) assay.

Adenocarcinoma↗
PubMedDate not supplied

Adult-onset Still's disease: hepatic involvement and various serum markers relating to the disease activity.

A 53-year-old woman was admitted to our hospital due to high fever, arthralgia and skin rash. Main laboratory data included the following: WBC 17,100/mm, GOT 58 U, GPT 47 U, LDH 1,510 U, ferritin 19,000 ng/ml, adenosine deaminase 79.1 U/l. She was diagnosed as having adult-onset Still's disease. Aspirin (3.0 g/day) and prednisolone (40 mg/day) were administered. All the symptoms and laboratory data improved rapidly. Adenosine deaminase, ferritin, and LDH are considered to originate mainly from the liver. Liver injury in this disease may be a primary lesion, and various serum markers may be associated with the liver abnormalities.

Adenosine Deaminase↗
PubMedDate not supplied

Enzyme and hormonal markers in the differential diagnosis of human azoospermia.

The serum concentrations of FSH, LH, prolactin, testosterone, and estradiol and the enzymatic activities of hyaluronidase, glucosidases (alpha-glucosidase, beta-glucosidase, alpha-mannosidase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and beta-galactosidase), lactate dehydrogenase and its isoenzymes (LDH1, LDH2, LDH3, LDH-X, LDH4), and total proteins were measured in the semen of 69 subjects (8 normozoospermic controls, 7 secretory, and 54 excretory azoospermic subjects). FSH levels rose with the deterioration in spermatogenesis and served to differentiate the secretory from the excretory azoospermias. The only source of hyaluronidase and LDH-X in the ejaculate is the spermatozoa. alpha-Glucosidase activity essentially originates in the epididymis. The seminal determination of alpha-glucosidase and, to a lesser extent, alpha-mannosidase and N-acetyl-beta-D-glucosaminidase helps rapidly, sensitivity, reliably, and noninvasively to differentiate secretory azoospermias (with higher enzymatic activity) from the excretory type (less enzymatic activity) and may be of use in identifying with a certain degree of reliability the site of obstruction in the male genital tract.

Biomarkers↗