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Results for “Biomarker variability”

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PubMed2004

Comparative analysis of passive dosimetry and biomonitoring for assessing chlorpyrifos exposure in pesticide workers.

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the US Environmental Protection Agency (EPA) has the authority to regulate the use of pesticides to prevent unreasonable adverse human health effects associated with pesticide exposure. Accordingly, the EPA requires pesticide registrants to perform studies evaluating the potential for pesticide handler exposure. Data from five such studies that included exposure measurements based on both external measurements and biological monitoring were used to examine methods of assessment, routes and determinants of exposure and dose to the pesticide chlorpyrifos. Eighty workers across four job classes were included: mixer/loaders (M/L, n = 24), mixer/loader/applicators (M/L/A, n = 37), applicators (A, n = 9) and re-entry scouts (RS, n = 10). Results showed that doses were highly variable and differed by job class (P < 0.05) with median total (inhalation and dermal combined) exposure-derived absorbed doses (EDADtot) of 129, 88, 85 and 45 microg/application for A, M/L/A, M/L and RS, respectively. Doses derived from the measurement of 3,5,6-trichloro- 2-pyridinol (3,5,6-TCP) in urine were similar in magnitude but differed in rank with median values of 275, 189, 122 and 97 microg/application for A, M/L, RS, and M/L/A, respectively. The relative contribution of dermal to inhalation exposure was examined by their ratio. The median ratios of exposure-derived absorbed dermal dose (EDADderm) (assuming 3% absorption) to exposure-derived absorbed inhalation dose (EDADinh) (assuming 100% absorption) across job classes were 1.7, 1.5, 0.44 and 0.18 for RS, M/L, A and M/L/A, respectively, with an overall median of 0.6. For 34 of 77 workers (44%), this ratio exceeded 1.0, indicating the significance of the dermal exposure pathway. Different dermal absorption factor (DAF) assumptions were examined by comparing EDADtot to the biomarker-derived absorbed dose (BDAD) as a ratio where EDADtot was calculated assuming a DAF of 1, 3 and 10%. Median ratios of 0.45, 0.71 and 1.28, respectively, were determined suggesting the DAF is within the range of 3-10%. A simple linear regression of urinary 3,5,6-TCP against EDADtot indicates a positive association explaining 29% of the variability in the 3,5,6-TCP derived estimate of dose. A multiple linear regression model including the variables EDADderm, EDADinh and application type explained 46% of the variability (R2 = 0.46) in the urinary dose estimate. EDADderm was marginally significant (P = 0.066) while EDADinh was not (P = 0.57). The EDADderm regression coefficient (0.0007) exceeded the coefficient for EDADinh (0.00002) by a factor of 35. This study demonstrates the value of the pesticide registrant database for the purpose of evaluating pesticide worker exposure. It highlights the significance of the dermal exposure pathway, and identifies the need for methods and research to close the gap between external and internal exposure measures.

Agriculture↗

PubMed2005

Progression of age-related macular degeneration: prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers.

BACKGROUND: Age-related macular degeneration (AMD) and cardiovascular disease share common risk factors. Inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor alpha receptor 2, soluble intercellular and vascular adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and lipid biomarkers, including lipoprotein(a) and apolipoprotein B, have all been associated with cardiovascular disease. We previously found an association between AMD and CRP in a cross-sectional analysis, but the prospective relationships between AMD, CRP, and the other cardiovascular disease markers are unknown. OBJECTIVE: To test the hypothesis that baseline cardiovascular disease biomarkers are associated with subsequent increased risk for progression of AMD. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study involved 251 participants aged 60 years and older who had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least one eye at baseline. The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens obtained at baseline were analyzed for levels of the various biomarkers. The average follow-up time was 4.6 years. MAIN OUTCOME MEASURES: Relationship between biomarkers and incidence rates of progression of AMD. RESULTS: Comparing the highest quartile with the lowest quartile, CRP was associated with progression of AMD, with a multivariate adjusted relative risk (RR) of 2.10 (95% confidence interval [CI], 1.06-4.18; P for trend, .046) controlling for body mass index, smoking, and other cardiovascular variables and a multivariate adjusted RR of 2.02 (95% CI, 1.00-4.04; P for trend, .06) controlling additionally for antioxidant nutrients. Interleukin 6 was also related to progression of AMD, with a multivariate adjusted RR of 1.81 (95% CI, 0.97-3.36; P for trend, .03). Comparing the highest quartile with the lowest quartile, the effect estimates for vascular cell adhesion molecule 1 (multivariate adjusted RR, 1.94) and apolipoprotein B (adjusted RR, 1.39) were in the positive direction but were not statistically significant (P for trend, .08 and .24, respectively). The CRP and IL-6 levels were both significantly related to higher body mass index and current smoking. CONCLUSIONS: Higher levels of the systemic inflammatory markers CRP and IL-6 are independently associated with progression of AMD.

Aged↗

PubMed2026

Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32°C during daytime; 30°C during nighttime) and thermoneutral conditions (26°C) for 8 h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans↗

PubMed2005

Cellular alterations in Mytilus galloprovincialis (LMK) and Tapes philippinarum (Adams and Reeve, 1850) as biomarkers of environmental stress: field studies in the Lagoon of Venice (Italy).

A long-term biomonitoring study was carried out in the Lagoon of Venice (North-East Italy) with the aim of evaluating variations in biological responses to environmental stress in estuarine bivalves. Two different species, the mussel Mytilus galloprovincialis and the clam Tapes philippinarum, both widespread in the Lagoon, were studied in several sites. Two cellular biomarkers: lysosomal membrane stability in digestive cells and thickness of digestive epithelia, were evaluated in native organisms (on a seasonal basis), and in organisms which have been transferred from a reference site to several differently influenced ones. Results indicate that, to some extent, both test and organisms were able to highlight site-specific differences, but the effects of pollution were generally more easily detected by reduction in lysosomal stability than by reduction in digestive tubule epithelium. Further findings show that the inherent variability of a number of natural parameters, particularly in the reference sites, produced less effective results when biological responses in the reference organisms were compared with the polluted ones. The assessment of the two conditions was most valuable when they referred to the 25-75% range of values comprised within the seasonal medians, recorded respectively in control and polluted sites. Impaired from steady states were most effectively distinguished when the control values were medians from two reference locations. Lately, the overall results indicate that both biomarkers are more suitably deployed through the translocation approach, revealing it to be more sensitive than traditional biomonitoring, at least in the sense that it may overcome problems related to the adaptation of native organisms to sub lethal chronic pollution levels.

Animals↗

PubMed1996

Tumor markers in patients with pancreatic carcinoma.

BACKGROUND: Tumor markers are putative prognostic indicators for patients with carcinoma, but have not heretofore been evaluated in patients with Stage II and III pancreatic carcinoma. METHODS: Patients with Stage II (n=9) and Stage III (n=25) unresectable regional adenocarcinoma of the pancreas were treated with combined modality therapy. Treatment consisted of split course radiotherapy and simultaneous combination chemotherapy with fluorouracil infusion, streptozotocin, and cisplatin. Prior to treatment, patients free of both infection and jaundice provided blood for CA 19-9, carcinoembryonic antigen (CEA) and CA 125 assays. RESULTS: The overall median survival of Stage II patients was 21.1 months. Due to the small number of Stage II patients with markedly abnormal assays, it was not possible to test for a statistically significant association between pretreatment tumor assays and survival. Among patients with Stage III pancreatic carcinoma, a CA 19-9 assay of 2000 u/ML or less identified a group of 16 patients with a median survival of 12.8 months. In contrast, 8 Stage III patients with a CA 19-9 assay of greater than 2000 u/mL had a median survival of 8 months and only 1 patient survived for 1 year (P=0.020, log rank test; P=0.010, Wilcoxon test). Among Stage III patients, a comparison of those with a normal assay versus any degree of abnormal assay failed to provide prognostic information. Analyses based on a combination of CA 19-9 and CA 125 assays provided additional powerful prognostic information: (P=0.002, log rank test; P=0.005, Wilcoxon test). CEA assays failed to provide information alone or in combination with the CA 19-9 assay. After adjusting for the CA 19-9 assay in multivariate analyses, neither performance status nor tumor size were significant prognostic variables for patients with Stage III cancers. CONCLUSIONS: Pretreatment CA 19-9 assays provide powerful independent and objective prognostic information.

Biomarkers, Tumor↗

PubMed1989

Preoperative prediction of outcome in patients with rectal and rectosigmoid cancer.

This study evaluated the possibility of dividing patients with primary rectal carcinoma into prognostic groups before surgery based on preoperative serum levels of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and an antigen defined by the monoclonal antibody C-50 (CA-50), as well as on some easily available clinical characteristics providing prognostic information. The evaluation was made both for patients who were "potentially curable" by surgery and, among those, for patients who were "potentially cured." Using the Cox regression model, the serum levels of the three tumor markers, together with the knowledge of whether or not the tumor was polypoid were combined to make up the set of variables that best predicted patient outcome. These variables and their associated regression coefficients were used to classify the patients according to prognosis. The cancer-specific mortality rate for the 24% of potentially curable patients with the best prognosis was 15%; for the 26% of potentially curable patients with the worst prognosis, the cancer-specific mortality rate was 57%. For potentially cured patients among those who were potentially curable, the cancer-specific mortality rates for patients with the best and worst prognoses were 14% and 47%, respectively. The information provided by these preoperatively available variables together was comparable with that given by Dukes' staging system, but the latter system was more informative. On the other hand, some of the preoperative variables provided information not provided by Dukes' staging system.

Adult↗

PubMed2001

The value of capillary whole blood lactate for blood transfusion requirements in anaemia of prematurity.

OBJECTIVE: To evaluate the usefulness of blood lactate as an indication for blood transfusion in anaemia of prematurity by means of a study protocol which considers the site of blood sampling and the repeatability of lactate measurements. DESIGN: Prospective clinical study. SETTING: Multidisciplinary, neonatalpaediatric intensive care unit of a non-university, teaching children's hospital. PATIENTS AND METHODS: Comparison of pre- and 48-h post-transfusion capillary whole blood lactate in 18 anaemic premature babies. In 30 neonates the agreement between capillary and arterial lactate was analysed by using the Bland Altman plot. In 30 stable premature infants four capillary lactate measurements were carried out within 24 h and analysed with regard to variability (coefficient of variation (CV); association between SD and mean) and to establish normal values. RESULTS: In the transfused infants, haematocrit increased from 23 (SD 3)% to 37 (SD 3)%. Mean lactate decreased from 2.5 (SD 1.0) to 1.7 (SD 0.5) mmol/l (p = 0.003). Pretransfusion lactate did not correlate with pre-transfusion haematocrit, heart rate, respiratory rate, number of apnoeas/bradycardias and weight gain (multiple regression). The mean difference between capillary and arterial lactate was 0.17 (SD 0.24) mmol/l and the 95 % confidence interval (CI) was -0.31 to 0.65 mmol/l. The CV of repetitive measurements was 19.8 (SD 9.8)% and SD correlated positively with mean lactate values (p = 0.001); the 95 % CI (normal range for premature infants) was 1.56-1.90 mmol/l. CONCLUSIONS: Capillary whole blood lactate measurements in newborn babies agree excellently with arterial values. Lactate measurements add little information to the decision whether to transfuse or not, considering the variability of this parameter in stable premature infants and the lack of correlation with other possible clinical indicators of compromised oxygen delivery.

Anemia, Neonatal↗

PubMed1995

The detection of subchronic testicular damage using urinary creatine: studies with 2-methoxyethanol.

We have previously shown that a number of testicular toxicants administered acutely to rats raise urinary creatine. The aim of this study was to determine if this creatinuria was maintained during subchronic testicular damage. Repeated exposure of rats to 2-methoxyethanol for 10 days administered in the drinking water caused significant testicular damage at the highest dose. The urinary creatine:creatine ratio was significantly increased in the animals receiving the highest dose (220 mg/kg per day) and also those receiving doses of 87 mg/kg per day. Increases in the ratio seen after the lowest dose (43 mg/kg per day) were significant in some cases, but showed more variability. Relative testicular weight was only significantly reduced after the highest dose. Increases in body weight over the time of exposure were only significantly lower after the highest dose of 2-methoxyethanol. The results indicate that urinary creatine may be a useful biomarker for chronic testicular damage.

Animals↗

PubMed1999

Maximum grip strength is not related to bone mineral density of the proximal femur in older adults.

In the past decade there have been numerous publications reporting a significant and direct relationship between handgrip strength and bone mineral density (BMD) of the proximal femur in older adults. The present report challenges the appropriateness of the methods, and thus the conclusions used in these studies. Specifically, these studies failed to control for the concomitant influence of body weight on both BMD and muscle strength. In the present study, maximum handgrip strength was measured using a conventional hand-held hydraulic dynamometer. Bone mineral density of the proximal femur was measured using dual-energy X-ray absorptiometry (DXA). Using allometric scaling, the influence of body weight on the value of maximum handgrip strength was removed for the data of the women. A small, but significant relationship between BMD of the proximal femur and maximum handgrip strength was found that accounted for about 6% of the total variation. The relationship between BMD of the proximal femur and unscaled maximum handgrip strength was not significant for the men. The findings diminish the confidence in a protective effect of skeletal muscle on some nonadjacent skeletal structures and suggest that these relationships may benefit from being revisited. The results highlight the utility of allometric scaling in analyses in which the relationship between a physiological variable and a body dimension variable can be nonlinearly and simultaneously influenced by other body dimension variables that are not considered in the analysis and therefore are statistically uncontrolled.

Absorptiometry, Photon↗

PubMed2004

Dexamethasone as a probe for docetaxel clearance.

PURPOSE: A pilot study was conducted in 23 patients in order to assess the correlation between docetaxel clearance (CL) and pharmacokinetics of dexamethasone. Dexamethasone is mainly 6-beta hydroxylated by CYP3A4, and is regularly used as standard docetaxel premedication. Genotyping of known functional single nucleotide polymorphism (SNP) of CYP3A5 (G22893A) and mdr-1 (G2677T, G2677A, and C3435T) have been performed in order to tentatively correlate genotype with docetaxel and dexamethasone pharmacokinetics. PATIENTS AND METHODS: To be eligible for this study, patients were required to have a solid malignancy for which docetaxel was indicated. A population pharmacokinetic approach was used to determine individual pharmacokinetic parameters of both docetaxel and dexamethasone by Bayesian analysis, and to screen relationships between docetaxel CL and patients' demographic, phenotype and genotype covariates. RESULTS: Three different pharmacokinetic parameters of dexamethasone were significantly correlated with docetaxel CL: dexamethasone plasma clearance (DPC) that ranged between 7.7 and 27.2 l/h, urinary amount of 6beta-hydroxydexamethasone, and the ratio between urinary amount of 6beta-hydroxydexamethasone and unchanged dexamethasone. The best covariate model was docetaxel CL (l/h) = 356 x fu(alpha1-AG) x (1-0.17 x HPMT)(1+0.126 x DPC) where fu(alpha1-AG) is the unbound plasma fraction of docetaxel calculated from alpha1-acid glycoprotein plasma level, and HPMT is hepatic metastasis coded as 1 if present or 0 if absent. No significant difference in docetaxel CL was observed between the several genotypes. CONCLUSIONS: Dexamethasone may be used as a probe to predict docetaxel clearances, hence reducing interindividual variability.

Adult↗

PubMed2004

Antibodies to platelet factor 4/heparin are associated with elevated endothelial cell activation markers in patients with acute coronary ischemic syndromes.

BACKGROUND: We postulated that antibodies to platelet factor 4/heparin complex lead to a heightened inflammatory state, contributing to an increased risk of recurrent thrombotic events. METHODS: We analyzed serum from a subset of patients in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had prior heparin exposure. We selected 109 patients with the 30 day primary endpoint (death, MI or revascularization) and an equal number of controls, excluding patients with thrombocytopenia. Anti-platelet factor 4/heparin antibodies and inflammatory markers (sVCAM-1, sICAM-1, sE-selectin, sP-selectin, us-CRP, IL-6) were measured on serum samples. RESULTS: Patients with anti-PF4/heparin antibodies were more likely to have death or MI (30.4% vs. 11.3%, p = 0.01), or MI (21.7% vs. 6.2%, p = 0.01) than patients who were antibody negative. In a multiple logistic regression model that included inflammatory markers and clinical risk factors, antibody to PF4/heparin was a strong predictor of 30 day MI (odds ratio: 9.0; 95% confidence intervals 2.1-38.6; p < 0.01), with IL-6 being the only other predictor (odds ratio: 1.1; 95% confidence intervals 1.0-1.2; p = 0.03). Antibody positive patients had higher levels of sVCAM-1 (892 +/- 263 microg/l versus 780 +/- 228 microg/l; p = 0.04) and sICAM-1(246 +/- 50 microg/l versus 222 +/- 71microg/l; p = 0.02) than antibody-negative patients. CONCLUSIONS: Antibodies to the platelet factor 4/heparin complex were associated with elevated levels of endothelial but not platelet activation markers, or markers of a systemic inflammatory state. Anti-PF4/heparin antibodies were associated with a 9-fold increased risk of recurrent MI at 30 days. We measured soluble cell adhesion molecules, CRP and IL-6 from 218 non-thrombocytopenic patients, 23 of whom had antibodies to PF4/heparin. Antibody positive patients had higher levels of sVCAM-1 (892 +/- 263 microg/l versus 780 +/- 228 microg/l; p = 0.04) and sICAM-1(246 +/- 50 microg/l versus 222 +/- 71 microg/l; p = 0.02). In a multiple logistic regression model, antibody to PF4/heparin was a predictor of 30 day MI (odds ratio: 9.0; 95% CI: 2.1-38.6; p < 0.01). The presence of antibodies to PF4/heparin, even in the absence of thrombocytopenia, is a stronger predictor of 30 day MI than clinical variables or inflammatory markers.

Acute Disease↗

PubMed1996

Clinical and biological markers for outcome in schizophrenia: a review of a longitudinal follow-up study in Uppsala schizophrenia research project.

During a 10-year period, 120 drugfree DSM-III-R schizophrenic patients were consecutively and unselectively admitted to a ward for young psychotic patients and subjected to a battery of examinations including symptomatology, cerebrospinal fluid (CSF)-biochemistry, computed tomography (CT)-scan, neurophysiologic and psychophysiologic (Electrodermal activity, EDA) parameters before antipsychotic treatment was initiated. After discharge, the patients were longitudinally followed with ratings of outcome (Strauss-Carpenters outcome scale) at years 1, 3, and 5 after index admission. The aim of the study was to find possible early markers for outcome in schizophrenia. At 5 years, 30% of the patients had a good outcome (total score > 13) and 15% a poor outcome (total score < 8). Poor premorbid adjustment and low level of education as well as negative schizophrenic symptomatology at index admission were associated with a poor outcome 5 years later. Positive symptomatology and a family history of schizophrenia did not predict outcome. Patients with a poor outcome (total score < 8) had a significantly more deviant CSF HVA/5-HIAA quotient than those with a very good outcome (total score > 15) as compared with healthy controls. Further, the CSF-peptides neuropeptide Y, dynorphin A, and CRF were predictable for outcome at the 5-year follow-up evaluation. Male schizophrenics who were "nonresponders" on the EDA test showed an almost 100% poor outcome, which was not found in females. In summary, several clinical and biological variables seem to have a predictable value for outcome in schizophrenia and, early identification of them might be a challenge for our future treatment strategies.

Biomarkers↗

PubMed2026

Global inequalities in cardiometabolic care and achievable cardiovascular risk reduction by wealth, region, and sex: a pooled analysis of individual participant data from 76 countries.

BACKGROUND: Wealth-related inequalities affect cardiometabolic health worldwide, but their implications for cardiometabolic care and potentially preventable cardiovascular disease remain poorly understood. We aimed to quantify wealth-related inequalities in the care cascade for hypertension, diabetes, and hypercholesterolaemia by wealth quintile, region, and sex. METHODS: In this cross-sectional, individual-level analysis, we analysed harmonised, nationally representative health examination surveys conducted in five WHO regions. Adults aged 18 years or older with data on age, sex, wealth, and at least one cardiometabolic outcome were eligible. All variables in the surveys were obtained from standardised in-person examinations. We evaluated hypertension, diabetes, and hypercholesterolaemia and applied a care cascade of disease awareness, treatment, and control for each condition uniformly across all surveys. Disease status was defined from measured biomarkers, self-reported diagnosis, or current medication; awareness and treatment were based on self-reported information, and control on measured biomarkers. Each indicator was expressed as the proportion of all individuals with the corresponding condition. Socioeconomic position was assessed using household wealth indices derived within each survey, and participants were ranked within each country and categorised into country-specific quintiles (quintile 1 to quintile 5), with quintile 1 including those with the least household wealth. Inequality was quantified by the quintile 5 minus quintile 1 difference, the slope index of inequality (SII), and relative index of inequality (RII). Predicted 10-year cardiovascular risk was estimated with the Globorisk equations, and trial-derived relative risk reductions were applied to estimate achievable absolute risk reduction. The ASANDE consortium is registered with ClinicalTrials.gov (NCT07427355). FINDINGS: We analysed data from 109 surveys conducted in 76 countries between 2002 and 2024. 315 403 (65·9%) of 478 947 survey participants with available data were included in this analysis (median age 40 years [IQR 30-52], 185 209 [58·7%] women, and 130 194 [41·3%] men). Inequalities widened progressively across the care cascade in all regions and were most pronounced for disease control. Pooled across regions, the SII for control was 4·4% (95% CI 2·4-6·4) for hypertension (RII 1·1, 1·1-1·2), 4·8% (0·6-9·0) for diabetes (RII 1·1, 1·0-1·2), and 6·5% (3·8-9·2) for hypercholesterolaemia (RII 1·1, 1·0-1·1). However, regional patterns varied substantially. In the region of the Americas, disease control consistently favoured wealthier individuals (SII 9·2% for hypertension, 4·8-13·5; RII 1·2, 1·1-1·3). In the African region, coverage was uniformly low, and the largest absolute inequality favoured individuals with the least wealth, particularly for hypercholesterolaemia treatment (SII -37·6%, -49·7 to -25·5; RII 0·6, 0·5 to 0·7). Baseline cardiovascular risk was higher in individuals with the least wealth than among the wealthiest (13·6% vs 12·2%), but achievable absolute risk reduction was correlated with baseline risk rather than with treatment coverage: achievable reduction was greatest in the European Region (3·9%) and lowest in the Africa region (2·5%). Across all regions, achievable absolute risk reduction was greater in men than in women (4·6% vs 3·5% in the European region). INTERPRETATION: The populations with the largest treatment gaps are not necessarily those that could achieve the greatest absolute reduction in cardiovascular risk through treating individuals who are currently untreated. In settings where coverage is uniformly low, expanding the supply of care matters more than redistributing access to it. Moreover, because socioeconomic inequalities widen after diagnosis, screening alone is unlikely to reduce disparities unless accompanied by sustained access to treatment. Policy should prioritise overall population health over maximise equity within the population. FUNDING: None.

Journal Article↗

PubMed2001

Molecular markers for gyrodactylids (Gyrodactylidae: Monogenea) from five fish families (Teleostei).

Thirty-one gyrodactylid species from five families of freshwater fish were examined and variable region V4 of the 18S small subunit ribosomal RNA gene and ribosomal RNA internal transcribed spacers ITS1 and ITS2 were sequenced. Both the V4 region and spacers ITS1 and ITS2 proved useful for gyrodactylid diagnosis. Sequences of these fragments exhibited interspecific variations and allowed clear determination at the species level. In some cases, the length of the ITS1 PCR fragment provided useful genetic markers. Species that yielded a short ITS1 fragment also showed distinct groupings in ITS2 and V4 sequences that were markedly different to sequences from species that contain a long ITS1. Repetitive sequences located in the ITS1 of Gyrodactylus gobii and Gyrodactylus vimbi accounted for some of the variations in length of PCR products. There was no evidence for intraspecific variation within these regions and short tandem repeats were not found in the other species studied. The number of polymorphic and intraspecific variations in nucleic acid sequences was low, therefore these variations did not affect species determination of gyrodactylids. Minor differences in the sequences between Western and Eastern European populations were detected for Gyrodactylus salaris/Gyrodactylus thymalli, Gyrodactylus teuchis and Gyrodactylus truttae, but these do not affect species diagnosis based on ribosomal DNA sequence. These results confirm the utility of both variable region V4 and the ITS as molecular markers for Gyrodactylus species.

Animals↗

PubMed2000

Immune alterations in three mouse strains following 2-deoxy-D-glucose administration.

Using 2-deoxy-D-glucose (2-DG)-induced stress, our laboratory has developed studies to define stress effects on immune responses. Here, we report effects of increasing doses of 2-DG on the immune response of BALB/c, C57BL/6 and BDF(1) mice 2 h after three injections of 0 to 2000 mg/kg of 2-DG. Female 4- to 5-week-old mice were euthanized and blood and spleens were collected. A suspension of partially purified mature T splenocytes was obtained by negative selection using J11.d2 antibodies. Glucose and corticosterone levels were measured in the plasma of each mouse. Splenocyte and mature T splenocyte suspensions were tested in in vitro proliferation assays with or without concanavalin A. Splenocytes were analyzed for the following cell-surface markers: CD3, TCR alpha/beta, CD4, CD8 and major histocompatibility complex (MHC) Class II. Significant increases in blood glucose levels were observed in C57BL/6 and BALB/c strains with the highest 2-DG dose (p<0.05). Corticosterone levels were higher in BDF(1) mice and C57BL/6 mice following the administration of 1000 and 2000 mg/kg of 2-DG, respectively (p<0.01). In vitro proliferation of mature T splenocytes in the presence of concanavalin A was decreased in BDF(1) (p<0.05) but not in BALB/c and C57BL/6 mice. In addition, in BDF(1) mice the decrease was highly correlated with an increase of CD3+ and TCR alpha/beta+ cells in the spleen. These results demonstrated high variability in the response of different mouse strains to 2-DG-induced stress.

Animals↗

PubMed1999

The second order autoregressive model in the evaluation of postural stability.

The properties of a new postural stability criterion based on the analysis of the difference between centre of pressure and centre of gravity are discussed. This difference may be regarded as the control variable representing active work of ankle muscles allowing to maintain equilibrium and can be effectively modelled as the second order autoregressive process. The model includes two parameters, which allow us to compute stability margin and respective peak frequency considered here as stability biomarkers characterising the human posture control system. The approach, originally designed for quiet stance, lets us effectively assess the stability changes during performance of postural tasks at different levels of difficulty. The latter feature may indicate that the method can find clinical application in the assessment of postural disorders as a supplementary tool reinforcing traditional measures of postural sway. This is particularly convincing in view of the fact that the correlations between old and new measures are low, what implies that the stability biomarkers contain different information concerning the stability of posture as compared with other indices.

Adult↗

PubMed2005

Progress in clinical neurosciences: cognitive markers of progression in Alzheimer's disease.

The objective of this review is to summarize the literature on Alzheimer's disease progression utilizing cognitive batteries to track change over time. Studies published in English and obtained through PubMed searches (1983-2004) were included (i) if they had a longitudinal design and followed probable Alzheimer's patients diagnosed by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association or Diagnostic and Statistical Manual III/IV criteria, and (ii) if the techniques used for serial assessment were well-established in terms of validity and reliability. Longitudinal studies examining Alzheimer's disease progression report highly variable annual rates of change in decline rate. It remains unclear if this reflects disease subgroups or stage-related rate of decline. In conclusion a combination of stage-appropriate cognitive tests such as the Mattis Dementia Rating Scale and the Severe Impairment Battery, along with appropriate statistical methods to account for individual variability in decline rates, can capture the progression of Alzheimer disease and may be useful in further investigation.

Alzheimer Disease↗

PubMed2001

Serum creatine kinase level is a poor predictor of muscle function after injury.

Serum creatine kinase and dorsiflexion torque levels were measured in New Zealand White rabbits 1, 2, 7, 14, or 28 days after a single bout of eccentric exercise (n=26). No significant correlation was observed between creatine kinase activity and torque across time periods (P>0.15) and the regression relationship described only about 8% of the experimental variability. These data demonstrate that there exists a poor correlation between serum creatine kinase levels and skeletal muscle function after eccentric exercise.

Animals↗