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PubMedDate not supplied

[Toxicological significance of biological markers].

Biological monitoring or, simply, biomonitoring (BM), refers to the periodic measurement of biological markers, or biomarkers (BMKs), in human fluids and tissues to assess the interaction (absorption, early health effects, susceptibility) between physical, chemical or biological agents and the human organism. The primary aim of BM in the workplace is to integrate environmental monitoring data and detect early, reversible biochemical or functional changes in workers exposed to chemicals before they become clinically relevant. BM also contributes to the assessment of chemical risk to workers, as individuals or as a group. Biomarkers are generally divided into three main types: biomarkers of exposure (BME), response/effect (BMR), and susceptibility (BMS). Other, more specific types of biomarkers are those of internal dose (BID), those of biologically effective dose (BED) and early biomarkers of disease (EBD). It is not always easy, however, to allocate a given BMK--such as the measurement of cytochrome P450 phenotype in subjects exposed to organic solvents--to one or the other type. Biomonitoring provides several advantages over environmental monitoring or health surveillance. For example, it allows an estimate of inter- and intra-individual variability in the absorption, distribution and excretion of chemicals. It also allows the detection of reversible changes before the appearance of a clinically relevant occupational impairment or disease. For these reasons, BM has become a routine procedure in occupational health practice throughout the world. Even the widely acknowledged, recently updated Code of Ethics for Occupational Health Professionals, a milestone in occupational health practice, only provides the basic ethical principles associated with biological monitoring. The aim of the present paper is to survey the various types of BMK available today with two main objectives: to discuss their toxicological significance and highlight the substantial differences that exist between their use in the practice of occupational health and in medical research. The development of new, more valid and reliable BMKs is strongly dependent on the understanding not only of the toxicokinetic and toxicodinamic mechanisms of chemicals, but also of the various susceptibility factors involved, whether genetic or environmental. It is hoped that the concurrent use of BMKs of different types may improve chemical risk assessment in workers, both individually and as a group.

Biomarkers↗

PubMed2002

Relationship between physical activity and oxidative stress biomarkers in women.

PURPOSE: To examine the relationship between physical activity and levels of plasma lipid peroxides, superoxide dismutase in erythrocytes (SOD), and glutathione peroxidase (GSH-Px) in whole blood activities. METHODS: Cross-sectional study in 488 Spanish women. Two categories of leisure time physical activity were defined according to their intensity: low ( 6 METs). Energy expenditure in household activities was also recorded. Multivariate linear regression analyses were used to adjust for the effect of physical activity on lipid peroxides and SOD and GSH-Px for confounding variables. RESULTS: The amount of leisure time physical activity was associated with high activity levels of SOD (P = 0.022) and GSH-Px (P = 0.002). Similar results were obtained when physical activity in household activities was added to total leisure physical activity. Physical activity of low intensity was associated with high SOD activity levels (P = 0.002) and that of high intensity with high GSH-Px activity levels (P = 0.001). CONCLUSION: The amount and intensity of leisure physical activity were directly related to both antioxidant enzyme activity levels. The findings of this study suggest a modulatory effect of leisure physical activity intensity on antioxidative balance in the studied female population.

Adult↗

PubMedDate not supplied

1H-Nuclear magnetic resonance pattern recognition studies with N-phenylanthranilic acid in the rat: time- and dose-related metabolic effects.

N-Phenylanthranilic acid (NPAA) causes renal papillary necrosis (RPN) in the rat following repeated oral dosing. Non-invasive early detection of RPN is difficult, but a number of potential biomarkers have been investigated, including phospholipid and uronic acid excretion. This study used 1H-nuclear magnetic resonance (NMR) spectroscopic analysis of urine to investigate urinary metabolic perturbations occurring in the rat following exposure to NPAA. Male Alderley Park rats received NPAA (300, 500 or 700 mg kg(-1) day(-1) orally) for 7 days, and urine was collected on days 7-8, 14-15, 21-22 and 28-29. In a separate study, urine was collected on days 1-2, 3-4, 5-6 and 7-8 from rats receiving 500 mg kg(-1) day(-1). Samples were analysed by 1H NMR spectroscopy combined with multivariate data analysis and clinical chemistry. Histopathology and clinical chemistry analysis of terminal blood samples was carried out following termination on days 4, 6, 8 and 29 (4 week time course) and days 2, 4, 6 and 8 (8 day study). Urine analysis revealed a marked, though variable, excretion of beta-hydroxybutyrate, acetoacetate and acetone (ketone bodies) seen on days 3-4, 5-6 and 7-8 of the study. It is postulated that the ketonuria might be secondary to an alteration in fatty acid metabolism due to inhibition of prostaglandin synthesis. In addition, an elevation in urinary ascorbate was observed during the first 8 days of the study. Ascorbate is considered to be a biomarker of hepatic response, probably reflecting an increased hepatic activity due to glucuronidation of NPAA.

Animals↗

PubMed2003

Gene expression analysis of the acute phase response using a canine microarray.

The safety of pharmaceuticals is typically assessed in the dog and rat prior to investigation in humans. As a result, a greater understanding of adverse effects in these preclinical testing species would improve safety assessment. Despite this need, there is a lack of tools to examine mechanisms and identify biomarkers in the dog. To address this issue, we developed an Affymetrix-based oligonucleotide microarray capable of monitoring the expression of thousands of canine genes in parallel. The custom canine array contains 22,774 probe sets, consisting of 13,729 canine and 9045 human-derived probe sets. To improve cross-species hybridization with human-derived probes, the detection region was moved from the variable 3' UTR to the more homologous coding region. Testing of this strategy was accomplished by comparing hybridization of naive dog liver RNA to the canine array (coding region design) and human U133A array (standard 3' design). Although raw signal intensity was greater with canine-specific probe sets, human-derived probes detected the expression of additional liver transcripts. To assess the ability of this tool to detect differential gene expression, the acute phase response was examined in beagle dogs given lipopolysaccharide (LPS). Hepatic gene expression 4 and 24 h post-LPS administration was compared to gene expression profiles of vehicle-treated dogs (n=3/group). Array data was consistent with an acute inflammatory response, with transcripts for multiple cytokines and acute phase proteins markedly induced 4 h after LPS challenge. Robust changes in the expression of transcripts involved with glucose homeostasis, biotransformation, and extracellular matrix remodeling were observed 24 h post-dose. In addition, the canine array identified several potential biomarkers of hepatic inflammation. Strong correlations were found between gene expression data and alterations in clinical chemistry parameters such as serum amyloid A (SAA), albumin, and alkaline phosphatase (ALP). In summary, this new genomic tool successfully detected basal canine gene expression and identified novel aspects of the acute phase response in dog that shed new light on mechanisms underlying inflammatory processes.

Acute-Phase Reaction↗

PubMed2006

CSF biomarkers in frontotemporal lobar degeneration: relations with clinical characteristics, apolipoprotein E genotype, and neuroimaging.

In order to better understand the large variation in cerebrospinal fluid (CSF) tau and amyloid-beta(1-42) (Abeta42) in frontotemporal lobar degeneration (FTLD), relations between these biomarkers and clinical parameters, neuroimaging characteristics, and apolipoprotein E (ApoE) genotype were studied in 31 patients with FTLD, including 16 patients with the frontal variant and 15 with the temporal variant. CSF tau was highest in FTLD with predominant temporal involvement. In the frontal subgroup, CSF tau level was influenced by the number of ApoE epsilon3 alleles. In the temporal subgroup, CSF tau level was dependent on a combination of CSF Abeta42, age, disease duration, and disease severity. No relation with degree of atrophy or asymmetry on neuroimaging could be established. CSF Abeta42 variability remained unexplained. Future research could study the role of ApoE genotype and Abeta42 in FTLD, as well as establish measures for disease intensity.

Age Factors↗

PubMed2002

Urinary p-nitrophenol as a biomarker of household exposure to methyl parathion.

Methyl parathion (MP) is an organophosphate pesticide illegally applied to the interiors of many hundreds of homes throughout the United States by unlicensed pesticide applicators. Public health authorities developed a protocol for investigating contaminated homes and classifying their need for public health interventions. This protocol included environmental screening for MP contamination and 1-day biomonitoring (a.m. and p.m. spot urine samples) of household members for p-nitrophenol (PNP), a metabolite of MP. The variability of urinary PNP excretion under these exposure conditions was unknown. We collected a.m. and p.m. spot urine samples for 7 consecutive days from 75 individuals, who were members of 20 MP-contaminated households in the greater Chicago, Illinois, area, and analyzed them for PNP. We also assessed the ability of the 1-day sampling protocol to correctly classify exposed individuals and households according to their need for public health interventions, assuming that 1 week of sampling (14 urinary PNPs) represented their true exposure condition. The coefficient of variation of log urinary PNPs for individuals over the course of 7 days of a.m. and p.m. sampling averaged about 15%. Adjusting for urinary excretion of creatinine improved reproducibility of urinary PNPs among children but not among adults. The 1-day protocol correctly classified true risk category in 92% of individuals and 85% of households. The data contained in this study can be used to refine what is already a reasonable and effective approach to identifying MP-exposed households and determining the appropriate public health intervention.

Adolescent↗

PubMed2004

CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: ability of inflammatory markers to predict disease in asymptomatic patients: a background paper.

There is great interest in moving beyond established risk factors to consider markers of inflammation for the prediction of initial cardiovascular disease events. Inflammatory markers such as leukocyte count, serum amyloid A, C-reactive protein, and vascular outcomes in individuals free of cardiovascular disease at baseline are the key markers that have been investigated in the population setting. A meta-analysis of 11 prospective studies in asymptomatic individuals compared people in the bottom third of the C-reactive protein distribution with those in the top tertile. The authors reported an odds ratio of 2.0 (95% CI 1.6 to 2.5) for coronary heart disease among people in the top tertile. These results are among the strongest assembled thus far to recommend incorporating newer biomarkers into coronary heart disease risk estimation algorithms. A variety of issues should be considered and conditions satisfied before vascular disease risk factors are adopted into regular use. The type of vascular event and the follow-up interval are important features because results for short-, intermediate-, and long-term intervals may yield different results. The factors under consideration should have been standardized, and characteristics such as the variability of the measurements, correlations with established factors, evidence from observational studies and clinical trials, type of effect (linear, nonlinear, dichotomous), improvement in overall prediction (discrimination), generalization of results (calibration), and cost can affect the utility. Each of these issues needs to be considered and the effects on relative, absolute, and population-attributable risks described. In particular, we need to (1) develop sound strategies for implementing new testing and (2) demonstrate the benefit of testing by using the current foundation of prior probabilities developed from already-published risk factor assessments based on large population studies.

Biomarkers↗

PubMed1997

Aspiration and imprint cytopathology of salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a highly malignant primary epithelial neoplasm of the salivary glands. The histology of this lesion resembles that of cribriform and comedo-type intraductal carcinoma of the breast, yet the cytopathology of salivary duct carcinoma has been described in only a few instances in the past. METHODS: The authors report two cases of SDC diagnosed by fine-needle aspiration biopsy and one case imprinted after resection. The cytologic features that may permit diagnosis of this entity are described. RESULTS: Cytologic features include variably cellular smears containing loose clusters of cribriform and glandlike aggregates; monomorphic polygonal cells with round-to-oval nuclei; abundant, finely granular cytoplasm; indistinct nucleoli; and variable necrosis. CONCLUSIONS: The cytologic findings for SDC are relatively unique and may allow for its specific diagnosis on aspiration cytopathology.

Aged↗

PubMed1987

Tumor markers in bronchogenic carcinoma. Superiority of tissue polypeptide antigen to carcinoembryonic antigen and carbohydrate antigenic determinant 19-9.

One hundred six patients with histologically proven bronchogenic carcinoma were tested for carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and carbohydrate antigenic determinant 19-9 (CA19-9). A total of 349 CEAs, 350 TPAs, and 317 CA19-9s were measured. In addition, sera were assayed from 57 patients with pulmonary benign diseases and their CEA, TPA, and CA19-9 levels were used as negative controls for specificity and accuracy. One hundred twenty healthy subjects provided our normal CA19-9 reference value. Sensitivity, specificity, and accuracy were obtained for CEA, TPA, and CA19-9, respectively. Significant intermarker correlations were found both at diagnosis and during follow-up, CEA and CA19-9 being the most closely related substances. The percentage of patients with elevated levels of TPA increased significantly according to tumor load. Individual values of TPA related significantly to the stage of disease. Concentrations of CEA, TPA, and CA19-9 varied significantly during the course of the illness in relation to treatment response; however, TPA showed the closest relationship to the clinical status assessments of the follow-up period. Abnormal pretreatment levels of TPA were significantly associated with a poor outcome. Biomarker combinations were clinically evaluated by calculating the mean of the percentage of the reference value for each combined marker. Using this method, any association of TPA with CEA and/or CA19-9 revealed neither a greater diagnostic accuracy nor a more reliable predictive capacity for the above clinical variables than TPA evaluated on its own. The authors believe that a single TPA assay should be added to the initial and subsequent clinical assessments of patients with bronchogenic carcinoma.

Antigens, Neoplasm↗

PubMed1998

Pronounced skin capillary ischemia in the feet of diabetic patients with bad metabolic control.

Skin capillary circulation is impaired during postocclusive reactive hyperaemia (PRH) in toes of diabetic patients independent of diabetes duration and macrocirculation. The aim of this study was to examine its relation to metabolic control. The skin microcirculation was investigated in 20 patients with insulin-dependent diabetes mellitus: 10 patients with bad [HbA1c > 7.5 (8.7 +/- 0.8) %], and 10 patients with good metabolic control [HbA1c < 7.5 (6.3 +/- 1.0) %]. The diabetes duration was similar in both groups (16 +/- 9 and 16 +/- 6 years, respectively). None had macroangiopathy. Thirteen healthy subjects served as controls. The capillary blood cell velocity (CBV) in the nailfold of the great toe was investigated by videophotometric capillaroscopy, and the total skin microcirculation by laser Doppler fluxmetry (LDF). CBV and LDF were studied during rest and after 1-min arterial occlusion. The vibration perception thresholds (VPT) of the feet were higher (p < 0.05) in the patients with bad (34 +/- 12 V), as compared to patients with good metabolic control (18 +/- 10 V) and to healthy subjects (13 +/- 3 V). Peak CBV during PRH was reduced in both patient groups (p < 0.01), and lowest in the patients with bad metabolic control (p < 0.05). Time to peak CBV was prolonged (p < 0.01) in the patients with bad, while normal in the patients with good metabolic control. LDF was similar in all groups. An inverse correlation was found between HbA1c and peak CBV during PRH (r = 0.60; p = 0.008), while positive correlations were found to time to peak CBV (r = 0.62; p = 0.004) and VPT (r = 0.60; p = 0.01). No associations were seen between VPT and the microcirculatory variables. The results indicate that the metabolic control is of importance for the nutritive capillary circulation and the peripheral nerve function in the diabetic foot.

Adult↗

PubMed2004

Variability of collagen crosslinks: impact of sample collection period.

Because of the variability of collagen crosslinks, their use as markers for bone resorption is often criticized. We hypothesized that the variability could be reduced by collecting urine for 24 hours (or longer) instead of using single voids, and by not normalizing to creatinine. Urine samples were collected from 22 healthy subjects during two or more 24-hour periods. Each 24-hour pool and each 2nd void of the day were analyzed for N-telopeptide (NTX), pyridinium (PYD), and deoxypyridinoline (DPD) crosslinks. Data were analyzed by using linear regression. For NTX, R2 for the two, 2nd-void samples (n = 38) was 0.55, whereas R2 for the two 24-hour pools was 0.51 or 0.52, expressed per day or per creatinine. For PYD and DPD, R2 for the 2nd-void samples was 0.26 and 0.18, R2 for the 24-hour pools expressed per day was 0.58 and 0.74, and R2 for the 24-hour pools expressed per creatinine was 0.65 and 0.76, respectively. Regression of the 2nd void and the corresponding 24-hour pool, expressed per day, yielded R2 = 0.19, 0.19, and 0.08, for NTX, PYD, and DPD, respectively (n = 76 each). For the 2nd-void sample and its corresponding 24-hour pool, expressed per creatinine, R2 = 0.24, 0.33, and 0.08, respectively. In a separate study, the coefficient of variation for NTX was reduced (P < 0.05) when data from more than one 24-hour collection were combined. Thus, the variability inherent in crosslink determinations can be reduced by collecting urine for longer periods. In research studies, the high variability of single-void collections, compounded by creatinine normalization, may alter or obscure findings.

Adult↗

PubMed1998

[Myofibroblastic tumors. Brief review of clinical aspects, diagnosis and differential diagnosis].

This review summarizes myofibroblastic tumours that have been characterized in the last years. These lesions include: fibromatoses in adults and infants (infantile digital fibromatosis and infantile myofibromatosis); myofibroma of adults, an almost exclusively solitary lesion in the skin which is characterized morphologically as a biphasic lesion composed of spindle-shaped eosinophilic tumour cells and more primitive mesenchymal tumour cells associated with a haemangiopericytoma-like vasculature; dermatomyofibroma (plaque-like dermal fibromatosis), a band-like myofibroblastic proliferation in young female patients, which is mainly located in the periaxillar region and in which distinction from more aggressive, plaque-like variant of dermatofibrosarcoma protuberans is mandatory; myofibroblastoma of the breast, a well-circumscribed lesion composed of spindle shaped, desmin-positive tumour cells, which is seen mainly in elderly male patients and has to be distinguished from other spindle cell lesions of the breast; angiomyofibroblastoma, a well-circumscribed myofibroblastic neoplasm of the vulva and vagina composed of avoid to round myoid tumour cells with scattered multinucleated cells, which forms a continuous morphological spectrum with the clinically more aggressive angiomyxoma in this location; intranodal myofibroblastoma, a distinctive proliferation of myofibroblastic cells associated with so-called amianthoid fibres, which is seen most commonly in inguinal lymph nodes; myofibroblastoma/myofibroblastic tumour of soft tissues, a variably well-circumscribed myofibroblastic lesion which lacks atypia and is composed of actin and/or desmin positive tumour cells, and poorly delineated sarcomas with myofibroblastic differentiation (myofibrosarcoma).

Adult↗

PubMed2006

Prognostic factors for anaplastic astrocytomas.

Anaplastic astrocytomas (WHO grade III) constitute about 10% of all gliomas. Definitive data on predictive and prognostic factors are lacking for these neoplasms that are considered the most enigmatic entity among the whole spectrum of astrocytic tumors because of their unclear biologic behavior and variable clinical outcome. Currently, only few factors have been identified as useful for prognosis of anaplastic astrocytoma: age and Karnofsky Performance Status. Attempts have been made to identify biological prognostic factors for response to therapy and clinical outcome, as well as potential targets for new therapies. Potential prognostic biomarkers concern tumor suppressor genes on chromosome 9q that are involved in the RB1 pathway; PTEN, the PI3k/Akt/p70s6k cascade, survivin gene, Formylpeptide receptor, minichromosome maintenance protein 3 and genes on chromosome 7. Furthermore, some angiogenic factors (e.g. hypoxia-inducible factor-1alpha, vascular endothelial growth factor and scatter factor/hepatocyte growth factor) and the methylation status of O6-methylguanine-DNA methyltransferase gene (one of the main effectors of DNA repair system) are emerging novel putative determinants of prognosis. Moreover, recent studies on magnetic resonance imaging characteristics give prognostic significance to the presence of necrosis and enhancement. The state of the art pictured here underlie the recent interest on gene expression profile to identify aberrations useful to understand the biologic behavior of astrocytic tumors. Our knowledge in this field is still limited, and remains an issue of great concern.

Adult↗

PubMed2006

Nutritional and inflammatory status influence darbepoetin dose in pre-dialysis elderly patients.

Anaemia is a common finding in elderly patients particularly in those with chronic kidney disease. Effective correction of anaemia improves survival and quality of life. The association between anaemia and a poor nutritional status as well as the presence of inflammation has already been documented. The aim of our study was to assess the impact of the nutritional and inflammatory status on darbepoetin dose requirements of elderly patients followed in a "Chronic Kidney Disease" outpatient clinic. We included 71 elderly patients (age>or=65 years) in a "Chronic Kidney Disease" outpatient clinic. Creatinine Clearance (CrCl) was estimated according to the Cockroft-Gault equation. Nutritional status was evaluated by biochemical and anthropometric parameters. Tumour Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were used as biomarkers of inflammation. Our patients (56% males) with a mean age of 76.2+/-6.6 years were followed for 33.1+/-43.6 months. Mean eCrCl was 13.5+/-7.2 ml/mn/1.73 m2. All patients were under supplemental iron therapy and 74.7% needed darbepoietin (0.762+/-0.6 (microg/kg/week) to correct anaemia. Among the several variables regressed on darbepoietin dose, in a multiple regression model, only Hb, IL-6 and TNF-alpha levels and SGA score predicted the need for higher doses of darbepoietin. (r=0.677; r2=0.459). In Conclusion, in our pre-dialysis elderly patients, markers of a poor nutritional status (SGA and albumin) and inflammation (IL-6 and TNF-alpha) independently predicted the use of higher doses of darbepoietin to correct anaemia.

Aged↗

PubMed2004

Human kallikrein 11: an indicator of favorable prognosis in ovarian cancer patients.

OBJECTIVES: Human kallikrein 11 (hK11) is a secreted serine protease, highly expressed in hormonally regulated tissues, including the prostate and the ovary. Our preliminary studies indicate that hK11 may represent a diagnostic and prognostic biomarker for ovarian cancer. The aim of the present study was to examine the prognostic value of hK11 expression in ovarian tumors. METHODS: Using our established immunofluorometric assay, hK11 levels were quantified (ng per mg of total protein) in 134 ovarian tumor extracts and correlated with various clinicopathological variables and outcome [progression-free survival (PFS), overall survival (OS)], over a median follow-up period of 42 months. RESULTS: hK11 concentration in ovarian tumor cytosols ranged from 0 to 155 ng/mg of total protein, with a median of 1.45 ng/mg. An optimal cutoff value of 6.3 ng/mg was selected to categorize tumors as hK11-positive or negative. hK11-positive tumors were most often of early stage (Stage I/II) and grade (G1/G2) (P < 0.05). Univariate analysis revealed that patients with hK11-positive tumors had a significantly longer PFS (HR of 0.39, P = 0.005) and OS (HR of 0.44, P = 0.033). Cox multivariate analysis indicated that hK11 was an independent prognostic indicator of PFS (HR of 0.47, P = 0.042). Kaplan-Meier survival curves further confirmed that women with hK11-positive tumors have longer PFS and OS (P = 0.003 and P = 0.028, respectively). Also, a weak positive correlation was found between the expression levels of tissue hK11 and tissue CA125 (rs = 0.508; P < 0.001). CONCLUSIONS: These results further validate our initial findings that hK11 is an independent marker of favorable prognosis in ovarian cancer patients.

Adult↗

PubMed2005

Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis.

Antiresorptive agents are effective in preventing and treating postmenopausal osteoporosis, provided they are taken as directed. Regular physical examinations including height measurements may fail to ensure optimal compliance. Bone mineral density (BMD) measurement is indispensable for determining whether treatment is warranted. The measurement can be repeated after 2 years at least, provided quality-control procedures are adequate. BMD changes over time should be compared to the least significant change calculated from the in vivo BMD reproducibility at the measurement center. However, BMD changes are not correlated with the fracture risk reduction induced by antiresorptive treatment. Biochemical markers for bone turnover can be monitored after only 3-6 months provided steps are taken to control for intraindividual variability. They are useful when patient compliance is poor or the treatment response inadequate.

Biomarkers↗

PubMed1997

LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I.

Acromegaly is associated with changes in lipoprotein metabolism and an excess in cardiovascular mortality. We have examined low density lipoprotein (LDL) subfraction distribution in 24 patients with active acromegaly and in controls matched for age, sex and body mass index. LDL was subfractionated by density gradient ultracentrifugation. The concentration of small dense LDL-III was significantly higher in the acromegalic patients compared to the controls (94.2 +/- 44.9 versus 67.2 +/- 30.4 mg/dl, P < 0.05) and there was a concomitant reduction in the intermediate subfraction LDL-II (124.8 +/- 31.3 versus 149.9 +/- 30.0 mg/dl, P < 0.05). Univariate analysis showed that both growth hormone (GH) and insulin-like growth factor (IGF)-I correlated with LDL-III and inversely with LDL-II. Acromegalic patients were found to have lower hepatic lipase (HL) and lipoprotein lipase (LPL) activities than controls (HL: 13.29 +/- 6.56 versus 21.58 +/- 7.27 micromol FFA released/ml/h, P < 0.001: LPL: 7.22 +/- 3.04 versus 11.53 +/- 7.85 micromol FFA released/ml/h, P < 0.05) whereas plasma cholesteryl ester transfer protein (CETP) activity was significantly increased (8.15 +/- 1.81 versus 5.54 +/- 1.86 pmol/microl/h, P < 0.001). Both GH and IGF-I were significantly associated with HL, LPL and CETP activities. Multivariate analysis on this relatively small sample size showed that in normal subjects, triglyceride and HL activity were the major determinants of LDL-III. In contrast, GH and HDL were the main determinants in acromegaly, accounting for 32 and 24% in the variability of LDL-III respectively. In conclusion, GH excess has a direct effect on LDL subfraction distribution.

Acromegaly↗

PubMed2000

Population studies of diet and obesity.

Population-based research on diet, obesity and the metabolic syndrome is faced with accumulating evidence of biases that may profoundly affect results. One potential source of bias, which is often neglected in nutritional epidemiology, arises from self-selected study populations. Subjects who agree to participate in surveys may be at less risk of metabolic syndrome than those who refuse. Analogous to observations in adult populations, studies of schoolchildren have also yielded clear evidence of self-selection. Whether such selection patterns influence analytical results depends on how the biases relate to the dependent and independent variables being studied. Systematic dietary reporting error is another source of bias in studies of nutritional risk factors for disease. While obesity-related under-reporting bias is now well documented, less is known about whether specific foods and nutrients are disproportionately affected. However, two studies employing biomarkers for protein have suggested that obese subjects under-reported the proportion of energy from fat plus carbohydrate. This should alert epidemiologists to the possibility that a dual reporting bias may be present in studies of diet and disease: general under-reporting among obese subjects compounded by food-specific errors. In summary, biases due to self-selection and selective dietary under-reporting may produce consequences in epidemiological studies that are both unpredictable and complex. We conclude this review with recent findings involving dietary fat intake and regional adiposity in a population-based study of women. These preliminary results may have etiological relevance to the development of metabolic syndrome, but multiple biases of the type described previously may also be operating.

Anthropometry↗