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At least 1,189 records · Page 66Linked to original sources
PubMed2002

Stability of B-type natriuretic peptide levels during exercise in patients with congestive heart failure: implications for outpatient monitoring with B-type natriuretic peptide.

BACKGROUND: B-natriuretic peptide (BNP), a neurohormone secreted from the cardiac ventricles, reflects left ventricular pressure and correlates to disease severity and prognosis. The fact that BNP levels can now be measured by a rapid assay suggests its potential usefulness in the outpatient clinic. However, if patient activity were to markedly alter BNP levels, its use would be less attractive for monitoring patients in the outpatient clinical setting. METHODS: A total of 30 patients (10 normal, 10 New York Heart Association [NYHA] class I-II, 10 NYHA class III-IV) exercised with an upright bicycle protocol. Exercise was carried out to 75% of maximum heart rate, and venous blood was sampled before, immediately after, and 1 hour after completion of exercise. Plasma levels of BNP, epinephrine, and norepinephrine were measured. RESULTS: BNP levels at baseline were 29 +/- 11 pg/mL for normal subjects, 126 +/- 26 pg/mL for NYHA I-II subjects, and 1712 +/- 356 pg/mL for NYHA III-IV subjects. The change in BNP levels with exercise was significantly lower than the change in epinephrine and norepinephrine (P <.001). In normal subjects, BNP increased from 29 pg/mL to 44 pg/mL with peak exercise, still within the range of normal (<100 pg/mL). This is compared with larger increases of norepinephrine (716 pg/mL to 1278 pg/mL) and epinephrine (52 pg/mL to 86 pg/mL) with exercise in normal subjects. There were also only small increases in BNP with exercise in patients with congestive heart failure (NYHA I-II, 30%; NYHA III-IV, 18%). For the same groups, epinephrine levels increased by 218% and 312%, respectively, and norepinephrine levels increased by 232% and 163%, respectively. One hour after completion of exercise, there were only minimal changes in BNP levels from baseline state in normal subjects (+0.9%) and patients with NYHA I-II (3.8%). In patients with NYHA III-IV, there was a 15% increase from baseline 1 hour after exercise. CONCLUSIONS: BNP levels show only minor changes with vigorous exercise, making it unlikely that a normal patient would be classified as having congestive heart failure based on a BNP level obtained after activity. Prior activity should not influence BNP levels in patients with congestive heart failure. Therefore, when a patient presents to clinic with a marked change in their BNP level, it may reflect a real change in their condition.

Atrial Natriuretic Factor↗
PubMed2003

Health technology assessment in clinical biochemistry. Methylmalonic acid: a Danish showcase.

In 1992 plasma methylmalonic acid (MMA) was introduced in Denmark for diagnosing vitamin B-12 deficiency. Now, 10 years later, we report on a health technology assessment (HTA) suggesting that the clinical usefulness of MMA is uncertain. MMA is an obvious component for measurement in the diagnosis of vitamin B-12 deficiency because MMA accumulates when there is a lack of vitamin B-12, and technologically the analysis is of high quality. The diagnostic sensitivity of MMA is high, whereas the diagnostic specificity is debatable, and our results suggest it to be relatively low. The organizational aspect implies that both MMA and P-cobalamins have been increasingly employed, though no consensus on the use of the analyses has emerged. The benefit to the patient is not obvious. An increased level of MMA does not predict further increases over time, and vitamin B-12 treatment shows limited clinical benefit in individuals with a moderately increased MMA. The economic consequences of introducing MMA were an increase in the costs of MMA and P-cobalamins of 12% per year during 1992-2000 and an increase in the turnover of vitamin B-12 preparations of 9% per year. In conclusion, MMA was introduced on sound grounds for both pathophysiological considerations and analytical quality. Our HTA shows that the resources employed to diagnose and to treat vitamin B-12 deficiency have increased considerably, but yet we have no evidence to suggest the clinical benefit.

Biomarkers↗
PubMed1999

Severe liver failure in exertional heat stroke.

Exertional heat stroke usually occurs in warm climates. Increased serum levels of liver enzymes is a common finding in this condition, whereas liver failure is a more rare event that carries a poor prognosis. Liver transplantation has been recommended as treatment in cases of severe liver failure, but no long-term survival after this procedure in exertional heat stroke has been described. We report the case of a 31-year-old man who had a heat stroke after running 5 km at 21 degrees C. He developed severe liver damage, with serum alanine aminotransferase (ALAT) activities increasing to 16,410 U/l (reference values, 10-50 U/l) after 48 h, concomitantly with a pronounced coagulation disturbance, with Normotest (NT) decreasing to 12% (international normalized ratio (INR) = 4.2) (reference values, 70%-130% for NT and 0.8-1.2 for INR). A liver biopsy on the 5th day after the incident showed extensive liver cell necrosis. The patient was referred to be considered for liver transplantation but recovered completely on conservative treatment. We conclude that exertional heat stroke is a diagnostic possibility also in temperate climates and that severe liver failure may ensue. The liver injury is reversible, and the indications for liver transplantation in this situation have not been clarified.

Adult↗
PubMed2006

Role of vascular endothelial growth factor in pulmonary endothelial cell injury by exercise challenge in asthmatic patients.

This study was designed to examine the role of vascular endothelial growth factor (VEGF) in pulmonary endothelial cell injury by exercise in asthmatics. Post-exercise circulating thrombomodulin (TM) levels were significantly increased in asthmatics. Moreover, the increase in TM levels with exercise was significantly correlated with VEGF level in induced sputum from asthmatics (r = 0.80, p = 0.0007). After inhaled steroid therapy, post-exercise TM levels were significantly decreased, but the increase in TM levels with exercise was also correlated with VEGF level (r = 0.60, p = 0.01). Thus, pulmonary endothelial cells stimulated by VEGF in asthmatic airways may be sensitive to exercise challenge.

Adult↗
PubMed2006

Increased serum lactate dehydrogenase isoenzymes in Ph-negative chronic myeloproliferative diseases: a metabolic adaptation?

We evaluated the significance of lactate dehydrogenase (LDH) isoenzymes in chronic myeloproliferative disorders (CMDs) by studying LDH isoenzymes in the serum of patients with secondary polycythemia (SP), polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) in different disease status. LDH activity and isoenzymes were evaluated retrospectively in serum samples from four groups of patients and compared with a control group. LDH activity and isoenzyme distributions of patients with SP and PV did not reveal significant variations with respect to controls. In the ET and IMF group LDH isoenzyme revealed significant variations: IMF showed significant increase of LDH2 and significant reduction of LDH5 isoenzyme, whereas ET showed significant decrease in LDH1 and increase of LDH3. These data suggest that LDH isoenzyme patterns may be a useful marker of CMDs, but this enzymatic pattern could be expression of a metabolic adaptation.

Adaptation, Physiological↗
PubMed2003

A factor analysis of the Fagerström Test for Nicotine Dependence (FTND).

Psychometric study of the Fagerström Test for Nicotine Dependence (FTND) provides insight into its structure and the dimensions of nicotine addiction it assesses. We evaluated the factor structure of the FTND in 541 research volunteers, most with histories of polysubstance use. Tetrachoric and phi correlation techniques were utilized and promax- and varimax-rotated solutions are reported. Two factors were found. Factor 1 was defined by questions regarding time to first cigarette in after waking, which cigarette is most preferred, and prominence of morning smoking. Factor 2 was defined by questions regarding difficulty refraining from smoking, amount smoked, and smoking while ill. The question "How soon on waking do you smoke your first cigarette?" loaded substantially on both Factor 2 and Factor 1. Repeating the analyses after stratification by gender did not change the results. The factor structure from our sample population was similar to results reported by previous studies with different types of populations. We propose that Factor 1 assesses the degree of urgency to restore nicotine levels to a given threshold after nighttime abstinence, whereas Factor 2 reflects the persistence with which nicotine levels are maintained at about that threshold during waking hours. Thus, the FTND may assess distinguishable self-reportable pharmacological dimensions of nicotine addiction. These two dimensions may provide indirect assessment of a smoker's daily nicotine intake. Testing this hypothesis requires correlation of biomarkers and responses to specific items of the FTND.

Adolescent↗
PubMed2026

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

Humans↗
PubMed2004

Correlation between interferon- gamma secretion and cytotoxicity, in virus-specific memory T cells.

ELISpot and intracellular cytokine staining are replacing the traditional cytolytic ((51)Cr release) assay method in vaccine trials using human immunodeficiency virus (HIV)-1, and it is widely assumed that the number of interferon (IFN)- gamma -secreting T cells is a surrogate for the level of cytolytic activity. Thus, we sought to determine whether the detection of IFN- gamma in CD8(+) T cells correlates with cytolytic ability in vitro. In 29 (69.0%) of 42 HIV-1-seronegative immunocompetent individuals (22 unvaccinated and 20 vaccinated), virus-specific T cell responses recognizing cytomegalovirus, Epstein-Barr virus, and influenza and HIV-1 Gag epitopes were detected by at least 1 assay method (ELISpot, intracellular cytokine staining, and/or (51)Cr release), and 18 (62.1%) of these 29 demonstrated both IFN- gamma secretion and cytolysis. There was strong correlation between the results of IFN- gamma ELISpot and those of IFN- gamma intracellular cytokine staining ( rho =0.88) and between the results of (51)Cr release and those of intracellular cytokine staining ( rho =0.81); although the correlation is not absolute, intracellular cytokine staining can be used--and is superior to ELISpot--as a surrogate for cytolytic assays.

Antigens, Viral↗
PubMed1996

Clinical significance of measurements of antithyroid antibodies in the diagnosis of Hashimoto's thyroiditis: comparison with histological findings.

Measurements of antithyroglobulin and antimicrosomal (antiperoxidase) antibodies have been performed widely for the clinical diagnosis of autoimmune thyroid diseases. The present study was designed to compare these antibody titers with histological findings of the thyroid in patients with diffuse goiter who were suspected of having Hashimoto's thyroiditis. One hundred and ten euthyroid or hypothyroid patients (10 males and 100 females; age 48 +/- 15 (SD) years old) with diffuse goiter were studied for the measurement of antithyroglobulin and antimicrosomal or antiperoxidase antibodies by a hemagglutination technique (TGHA and MCHA, respectively) and by a newly developed radioassay (TgAb and TPOAb, respectively). The antibody titers were compared with the histological findings obtained by needle biopsy. TgAb, TPOAb, TGHA, and MCHA were detected in 80 (96.4%), 61 (73.5%), 37 (44.6%), and 54 (65.1%) of 83 patients with histologically proven Hashimoto's thyroiditis, respectively, but in only one (3.7%) of 27 patients without any inflammatory changes in the biopsy specimen. In 55 patients with negative TGHA and MCHA, the TgAb positivity was more closely associated with the histological diagnosis of Hashimoto's thyroiditis than the TPOAb positivity was, the incidence of each antibody in Hashimoto's thyroiditis being 89.7% (26/29) and 27.6% (8/29), respectively. In conclusion, the histological diagnosis of Hashimoto's thyroiditis can most precisely be predicted by the newly developed radioassay for TgAb.

Adolescent↗
PubMed2005

Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial.

BACKGROUND: Soy isoflavones have numerous biological properties that suggest that they may protect against colorectal cancer. Colorectal epithelial cell proliferation has been used extensively as an intermediate endpoint biomarker for colorectal neoplasia. OBJECTIVE: We tested the hypothesis that supplementation with soy protein containing isoflavones decreases colorectal epithelial cell proliferation. DESIGN: A 12-mo randomized intervention was conducted in men and women aged 50-80 y with recently diagnosed adenomatous polyps. One hundred fifty participants were enrolled and randomly assigned to an active treatment group (58 g protein powder/d containing 83 mg isoflavones/d; +ISO) or a control group (ethanol-extracted soy-protein powder containing 3 mg isoflavones; -ISO). Biopsy specimens from the cecum, sigmoid colon, and rectum were collected at baseline and at the 12-mo follow-up. Ki-67 antibody immunohistostaining was used to detect cell proliferation. One hundred twenty-five participants completed the study, and proliferation was measured in the first 91 who completed the study. RESULTS: In the sigmoid colon, cell proliferation increased by 0.9 (95% CI: 0.09, 1.9) labeled nuclei per crypt more (11%) in the +ISO group than in the -ISO group over the 12-mo intervention, which was opposite the direction predicted. The number of labeled nuclei per 100 mum crypt height also increased more in the +ISO than in the -ISO group. In the cecum and sigmoid colon, but not in the rectum, the proliferation count increased as the serum genistein concentration increased. Proliferation distribution and crypt height were not changed by treatment at any site. CONCLUSIONS: Supplementation with soy protein containing isoflavones does not reduce colorectal epithelial cell proliferation or the average height of proliferating cells in the cecum, sigmoid colon, and rectum and increases cell proliferation measures in the sigmoid colon.

Adenomatous Polyps↗
PubMed1999

Effect of transgalactooligosaccharides on the composition of the human intestinal microflora and on putative risk markers for colon cancer.

BACKGROUND: Nondigestible oligosaccharides have been claimed to benefit the health of the colon by selectively stimulating the growth of bifidobacteria and by decreasing the toxicity of the colon contents. OBJECTIVE: We compared the effect of 2 doses of transgalactooligosaccharides and a placebo on the composition and activity of the intestinal microflora in 18 women and 22 men. DESIGN: Strictly controlled experimental diets were supplied to 3 intervention groups in a parallel design. The study was divided into 2 consecutive 3-wk periods during which each participant consumed a run-in diet followed by an intervention diet that differed only in the amount of transgalactooligosaccharides: 0 (placebo), 7.5, and 15 g/d. Breath samples and fecal samples were collected at the end of both the run-in and intervention periods. RESULTS: Apparent fermentability of transgalactooligosaccharides was 100%. The highest dose of transgalactooligosaccharides significantly increased the concentration of breath hydrogen by 130% (P < 0.01) and the nitrogen density of the feces by 8.5% (P < 0.05). The number of bifidobacteria increased after both placebo and transgalactooligosaccharides ingestion, but the differences between these increases were not significantly different. Transgalactooligosaccharides did not significantly affect bowel habits; stool composition; the concentration of short-chain fatty acids or bile acids in fecal water; the concentration of ammonia, indoles, or skatoles in feces; fecal pH; or the composition of the intestinal microflora. CONCLUSION: We conclude that transgalactooligosaccharides are completely fermented in the human colon, but do not beneficially change the composition of the intestinal microflora, the amount of protein fermentation products in feces, or the profile of bile acids in fecal water.

Adolescent↗
PubMedDate not supplied

Limitations in the use of gamma-glutamyl transferase estimations in alcohol-dependent subjects.

This paper studies a cohort of randomly selected attenders at a district alcohol treatment service and examines the relationship between clinical assessments and laboratory markers currently in use in the unit. It measures in particular the rate of change of serial gamma-glutamyl transferase (GGT) during abstinence throughout an alcohol treatment programme in alcohol-dependent subjects. The results show that GGT is less often elevated in alcohol-dependent patients than was previously thought. Its predictive value changes little with respect to the age of the subject and length of drinking history. Measurement of GGT adds little to the diagnostic sensitivity of careful history taking. In the alcohol-dependent population, GGT estimation is of little value and a normal GGT does not exclude chronic alcohol dependence.

Adult↗
PubMed2000

Metabolism of chemical carcinogens.

The transformation of chemicals is important in carcinogenesis, both in bioactivation and detoxification. Major advances in the past 20 years include appreciation of the migration of reactive electrophiles, the ability of Phase II conjugating enzymes to activate chemicals, understanding of the human enzymes, the realization that DNA modification can result from endogenous chemicals, and the demonstration that cancers can result from the metabolism of chemicals to non-covalently bound products. Pathways of transformation in which major insight was gained during the past 20 years include nitropolycyclic hydrocarbons, polycyclic hydrocarbons and their diols, vinyl halides and dihaloalkanes. Advances in analytical methods and recombinant DNA technology contributed greatly to the study of metabolism of chemical carcinogens. Major advances have been made in the assignment of roles of individual enzymes in reactions. The knowledge developed in this field has contributed to growth in the areas of chemoprevention, molecular epidemiology and species comparisons of risk. Some of the areas in which future development relevant to carcinogen metabolism is expected involve pathways of transformation of certain chemicals, regulation of genes coding for many of the enzymes under consideration and genomics.

Animals↗
PubMed1994

Troponin T and myoglobin at admission: value of early diagnosis of acute myocardial infarction.

We studied the predictive power at admission of troponin T and myoglobin and compared them with that of CK and CK-MB activity and ECG in 290 consecutive patients admitted for evaluation of a suspected AMI. The likelihood ratio for an ischaemic ECG at admission < 4 h (between 4 and 12 h) after onset of chest pain was 2.85 (1.92), for a inconclusive ECG 1.53 (1.98) and for a normal ECG 0.27 (0.35). In patients admitted < 4 h after onset of chest pain, the likelihood ratio for abnormal and normal myoglobin concentrations (8.06 and 0.67) was considerably better for detection of AMI as defined by the WHO criteria than for the other markers, including the ECG. In patients admitted 4-12 h after onset of chest pain, the likelihood ratios for abnormal and normal myoglobin concentrations were 4.88 and 0.42; for troponin T 3.11 and 0.31; for CK activity 3.44 and 0.49 and for CK-MB activity 4.08 and 0.54 respectively. The sensitivity for troponin T (64%) was better than that of the other markers but its specificity (74%) was worse, because in patients with unstable angina troponin T was frequently elevated (37%). Stepwise logistic regression analysis showed that the best predictors of AMI within 4 h after onset of chest pain were the ECG and myoglobin and between 4-12 h after onset of chest pain the ECG, CK-MB activity and myoglobin.

Angina, Unstable↗
PubMed2005

Interactions of contact allergens with dendritic cells: opportunities and challenges for the development of novel approaches to hazard assessment.

The identification of potential skin sensitizing chemicals is a key step in the overall skin safety risk assessment process. Traditionally, predictive testing has been conducted in guinea pigs. More recently, the murine local lymph node assay (LLNA) has become the preferred test method for assessing skin sensitization potential. However, even with the significant animal welfare benefits provided by the LLNA, there is a need to develop non-animal test methods for skin sensitization. Mechanistic understanding of allergic contact dermatitis has increased substantially in recent years. For example, a number of changes are known to occur in epidermal Langerhans cells, the principal antigen-presenting dendritic cell in the skin, as a result of exposure to chemical allergens, including the internalization of surface major histocompatibility complex (MHC) class II molecules via endocytosis, the induction of tyrosine phosphorylation, the modulation of cell surface markers, and cytokine expression. The application of this knowledge to the design of predictive in vitro alternative tests provides both unique opportunities and challenges. In this review, we have focused specifically on the impact of chemical exposure on dendritic cells and the potential use of that information in the development of cell-based assays for assessing skin sensitization potential of chemicals in vitro.

Allergens↗