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PubMed1979

Modifications of the pattern-evoked potential (PEP) in relation to the stimulated part of the visual field (clues for the most probable origin of each component).

A spatio-temporal analysis of the successive and simultaneous components of the pattern-evoked potential recorded on the scalp, and of their modifications according to which part of the visual field is stimulated, was carried out with 20 'normal' subjects, in order to shed some light on their most probable sites of origin. The stimulus consisted in the onset of a 20 degree checkerboard presented in runs of 75 stimuli each. Its duration was 750 msec and its frequency of occurrence was random (about 1 every 1500 msec). Twelve different visual field situations were recorded: whole field, half fields and quadrants and stimuli limited to the fovea, to the macula and to extramacular areas. Data were collected from 9 active electrodes (in line, forming a cross montage), and various reference electrodes (ear lobes, Fz, non-cephalic). Eye movements were simultaneously recorded. The electrophysiological data were digitized on line and processed by computer in the form of averaged spatio-temporal maps. In addition to the classical posterior components which peak on the midline (N 60, N 140, and P 200) or less than 4 cm away on both sides (P 90), a late negative wave (LN 210) was differentiated which peaked lower than the inion and more than 8 cm away from the midline on both hemispheres. The large inter-individual variability of the spatio-temporal organization of these components under the same conditions, as well as its very good intra-individual reproducibility, were emphasized. Interpreted on the basis of a simple dipole sheet model of the visual cortex, the changes observed for each component in the 12 experimental situations led to the following suggestions: only the first component N 60 could reflect the activity of the part of area 17 emerging on the convexity, whereas P 90 (Jeffreys' CI) is more likely to originate in area 19 and the midline components N 140 and P 200 in area 18. The topography and reactivity of LN 210 could fit with the hypothesis that it reflects activity of the infero-temporal cortex.

Adult↗

PubMed1991

Coping style, trait anxiety and cortisol reactivity during mental stress.

The present study examined whether salivary cortisol secretion as an index of stress reactivity to continuous mental task performance reflected individual differences in coping styles. During 4 hr of continuous mental tasks significantly higher cortisol levels were found in comparison with a control session. However, individual variability in the cortisol response was high. Correlational data indicate a significant negative relationship between the coping style 'comforting cognitions' and the individual cortisol response during mental stress. During this particular type of cognitive stress, where the subject has no control over the experimental situation, comforting and emotion-focused coping may be effective because of the subject's efforts of trying to reframe the inevitable situation in a positive and self-encouraging way. In contrast, there was no significant relationship between trait anxiety and individual glucocorticoid susceptibility to mental stress.

Adaptation, Psychological↗

PubMed1999

Cytomegalovirus in the pathogenesis of atherosclerosis: the role of inflammation as reflected by elevated C-reactive protein levels.

OBJECTIVES: We hypothesized that cytomegalovirus (CMV) infection: 1) stimulates an inflammatory response, reflected by elevated C-reactive protein (CRP) levels, and 2) predisposes to coronary artery disease (CAD), in part, through CMV-induced inflammation. BACKGROUND: Although some studies show an association between CMV and atherosclerosis, others do not. We believed that CMV exerted an atherogenic effect by inducing inflammation, and the disparate results may derive partly from individual variability in the capacity to control CMV inflammatory activity. METHODS: Blood samples were tested for CMV seropositivity and CRP levels from 238 individuals being evaluated for CAD by coronary angiography. RESULTS: An elevated CRP level (>0.5 mg/dl) was a significant CAD determinant even after adjustment for traditional CAD risk factors (odds ratio [OR] = 2.4; p = 0.02). Moreover, CMV seropositivity was significantly associated with increased CRP levels (p = 0.04 after adjustment for CAD risk factors), suggesting that CMV could evoke a subclinical inflammatory response. However, considerable host variation existed in this response to CMV. When adjusted for CAD risk factors, the OR for CAD were 1.3 in the subgroup with CMV seropositivity alone (p = 0.7), 2.3 in the subgroup with elevated CRP levels alone (p = 0.2), and 4.3 in the subgroup with combined CMV seropositivity and elevated CRP levels (p = 0.01). CONCLUSIONS: Our results suggest that 1) CMV elicits a subclinical inflammatory response, but only in certain individuals, and 2) individuals with an inflammatory response appear susceptible to the atherogenic effects of CMV, whereas those without appear resistant. These results may partly explain the disparate results of studies attempting to relate CMV to atherogenesis.

Adult↗

PubMed2003

Gene expression for carbonic anhydrase isoenzymes in human nasal mucosa.

Carbonic anhydrase (CA) is physiologically important in the reversible hydration reaction of CO(2); it is expressed in a number of isoforms (CA I-XIV) with varying degrees of enzymatic activity. In nasal chemesthesis, CA inhibition decreases the electrophysiologic response to CO(2), a common irritant test compound. CA enzymatic activity has been demonstrated in the human nasal mucosa using enzyme histochemical methods, but no systematic study of nasal mucosal CA isoenzyme gene expression has been published. We examined CA gene expression in superficial nasal mucosal scrapings from 15 subjects (6 females; 6 allergic rhinitics; age range, 21-56 years). Both non-quantitative and quantitative reverse transcription polymerase chain reaction (RT-PCR) were performed using primers for each gene coding for the 11 catalytically active CA isoenzymes and the housekeeping gene GADPH. Amplification products of GADPH and 10 of the 11 CA genes were detected in the specimens (CA VA was not detected). Relative expression of the CA genes was quantified using real-time PCR. Averaged across subjects, the relative abundance of the CA isoenzyme transcripts is as follows: CA XII > CA II > CA VB > CA IV > CA IX > CA III > CA XIV > CA I > CA VI > CA VII. Limited qualitative validation of gene expression was obtained by immunohistochemistry for CA I, CA II and CA IV. We also observed inter-individual variability in the expression of CA isoenzymes in human nasal mucosa, potentially contributing to differences in nasal chemosensitivity to CO(2) between individuals

Adolescent↗

PubMed1991

P450 and human cancer.

Most of the chemical carcinogens in our environment are activated mainly by a restricted number of cytochrome P450 species, P450 1A1, 1A2, 2E1, and 3A. This metabolic activation of procarcinogens is a crucial part of the initial host response to the environmental exposure, since most chemical carcinogens do not show any carcinogenicity by themselves. Inter-individual variability in the metabolic activity may thus be a key host factor to explain the differences in susceptibility to chemical carcinogenesis among individuals. Recent studies on P450s in cancer etiology have provided some valuable insights into this problem.

Animals↗

PubMed1983

Acebutolol pharmacokinetics in renal failure.

Acebutolol was administered orally in a single dose of 200 mg to 17 individuals whose renal function varied markedly. The plasma half-life and elimination rate constant for acebutolol showed a four-fold variation but these did not correlate with the degree of renal impairment. However, there was a good correlation between the renal clearance of creatinine and that of acebutolol (P less than 0.001). The half-life and elimination rate of the acetyl metabolite, diacetolol, were subject to 10-fold inter-individual variability which correlated significantly with the creatinine clearance and serum creatinine concentration. The AUC for the acetyl metabolite showed a 40-fold individual variation which also correlated with renal function. It is concluded that renal elimination is the principal route of excretion for diacetolol but not the parent compound, acebutolol.

Acebutolol↗

PubMed1993

Age-related morphine kinetics in infants.

The pharmacokinetics of morphine was studied in 27 infants receiving a single intravenous dose of 0.1 mg/kg morphine after surgery (n = 23) or during mechanical ventilation (n = 4). The pharmacokinetics of morphine varied greatly between the subjects, especially in the neonates. The clearance and half-life varied distinctly with postnatal age. The mean (+/- SD) half-life was 8.1 +/- 8.1 h in 10 neonates younger than 1 week, 5.4 +/- 3.4 h in 10 infants aged from 1 week to 2 months and 2.6 +/- 1.7 h in 7 infants aged from 2 to 6 months. Mean clearance increased significantly with age, being 8.7 +/- 5.8 ml/min/kg in the youngest age group, 11.9 +/- 5.1 ml/min/kg in those aged 1 week to 2 months and 28.0 +/- 8.9 ml/min/kg in those aged 2-6 months, and was also significantly lower in the critically ill infants. The clearance and half-life of morphine begin to approach adult values after the age of 1 month, but great individual variability exists even after that. In order to reduce the risk of overdosing or underdosing, the dose of morphine should be titrated individually.

Aging↗

PubMed2004

Coronary age as a risk factor in the modified Framingham risk score.

BACKGROUND: Clinical guidelines emphasize risk assessment as vital to patient selection for medical primary intervention. However, risk assessment methods are restricted in their ability to predict further coronary events. The most widely accepted tool in the United States is the Framingham risk score. In these equations age is a powerful risk factor. Although the extent of coronary atherosclerosis increases with age, there is large inter-individual variability in the rate of development and progression of this disease. This fact limits the utility of Framingham scoring when applied to individuals. Electron beam tomography (EBT), which measures coronary calcium, provides a non-invasive method for assessing coronary plaque burden, thus offering the possibility of providing a more accurate estimate of an individual's "arterial age" than from chronological age alone. METHODS: In this paper we discuss a new and simple method for incorporating the coronary calcium score (CCS) to modify the Framingham Risk Assessment (FRA). Using this method, a coronary artery calcium (CAC) age equivalent is generated that replaces chronological age in Framingham scoring. RESULTS AND DISCUSSION: Using a percentile table of CCS scores by age group and sex, individuals are matched to the age group whose calcium score most closely approximates their own individual score. The original 10-year absolute risk score of a 65-year old man with a CCS of 6 based on chronological age is 10%, whereas the modified absolute risk score based on CAC age equivalents is 2%. CONCLUSION: Our approach of replacing chronological age with CAC age equivalents in the Framingham equations possesses simplicity of application combined with precision. Physicians can easily derive adjusted Framingham risk scores and prescribe intervention methods based on patients' ten-year risks. The adjusted ten-year risks are likely to be more accurate than unadjusted risks since they are based on coronary calcium score information. The modified FRA approach not only may increase the predicted risk for some patients, but also may decrease the predicted risk for others, making it a more precise adjustment than other methods.

Journal Article↗

PubMedDate not supplied

Octreotide.

The use of SC or IV octreotide, a long-acting synthetic analog of somatostatin, provides a promising pharmacologic approach to reducing drainage in selected patients with a congenital or postoperative chylothorax, who do not respond to conservative treatment strategies. Prompt institution of octreotide therapy after surgery in patients with significant drainage or the formation of chyle may reduce the expense and morbidity associated with a prolonged hospital stay. Given the individual variability in patient response to octreotide and the limited clinical data regarding its use in the pediatric population, octreotide therapy must be individualized with careful consideration being given to possible benefits versus inherent risks.

Chylothorax↗

PubMed1982

The pattern of interhemispheric connections and its relationship to extrastriate visual areas in the macaque monkey.

The distribution of interhemispheric connections was studied in extrastriate visual cortex of the macaque monkey. Callosal fiber terminations were identified by staining for anterograde degeneration following transection of the splenium of the corpus callosum. Retrogradely labeled cell bodies of callosal projection neurons were identified histochemically following application of horseradish peroxidase to the cut surface of the callosum. Results were displayed on unfolded, two-dimensional representations of the cortex, which permitted spatial and topological relationships between callosal recipient and callosal free cortical regions to be discerned readily. The overall pattern of callosal inputs to visual cortex can be subdivided into nine callosal recipient zones which surround seven callosal free regions in the occipital, temporal, and parietal lobes. This pattern provides reliable and useful landmarks for identifying the borders of at least five topographically organized extrastriate visual areas. There is a pronounced dorsoventral asymmetry in callosal projections, not recognized in previous studies, which reflects an asymmetry in the organization of visual areas in dorsal versus ventral halves of the occipital lobe. The pattern of callosal fiber terminations is mirrored by a very similar distribution of callosal projection neurons. There are significant regional differences in the laminar distribution of callosal projection cells, and these differences may reflect functionally distinct cortical subdivisions. A considerable degree of individual variability was found in the relationship of callosal connections to gyral and sulcal landmarks as well as in the fine structure of individual callosal recipient strips, suggesting that each animal has a unique "callosal fingerprint." These findings emphasize the usefulness of the callosal pathway in elucidating the functional organization of extrastriate visual cortex.

Animals↗

PubMed2005

[DNA adducts as biological markers for human exposure to polycyclic aromatic compounds].

Polycyclic Aromatic Hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention or preventive study. The successful applicability of DNA adducts as early endpoints depends on several criteria: (1) Adduct levels in easily accessible surrogate tissues should reflect adduct levels in target tissues (2) Toxic-kinetics and the temporal relevance should be properly defined (3) Sources of inter and intra individual variability must be know and controllable (4) Adduct analysis must have advantages as compared to other markers of PAH exposure. Higher proportions of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposure. Furthermore, DNA adducts levels varied according to changes in exposure. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Intra-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH metabolism. DNA adducts measurements have three advantages over traditional exposure assessment: (1) they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over longer periods of time (2) Biological monitoring of DNA adducts accounts for all exposure routes (3) DNA adduct may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. There is a sufficiently large scientific basis to justify the application of DNA adduct measurements as biomarkers in exposure assessment. However, their use in risk assessment requires further investigation.

Biological Transport↗

PubMed2003

Abnormal variability and distribution of functional maps in autism: an FMRI study of visuomotor learning.

OBJECTIVE: Autism is a neurally based psychiatric disorder, but there is no consensus regarding the underlying neurofunctional abnormalities. Previous functional magnetic resonance imaging (fMRI) studies of simple movement suggested individually variable and scattered functional brain organization in autism. The authors examined whether such abnormalities generalize to multimodal processing (visually driven motor sequence learning). METHOD: Eight male autistic patients and eight comparison subjects matched with the patients on age, gender, and handedness were examined by using fMRI while they performed finger press movements prompted by visually presented repeating six-digit sequences. Hemodynamic responses to the six-digit sequences were statistically compared to responses to single-digit stimuli in one experiment and to regular six-digit sequences in another experiment. RESULTS: Both groups showed activations in bilateral premotor, superior parietal, and occipital cortices in both experiments. Task-by-group interactions showed that superior parietal activations were less pronounced in the autism group, whereas prefrontal cortex and more posterior parietal loci showed greater activation in the autism group than in the comparison group. The distances between Individual subjects' activation peaks and the groupwise peak were greater in the autism group than in the comparison group. CONCLUSIONS: The results support earlier findings of abnormal variability and scatter of functional maps in autism. They are consistent with evidence from other studies suggesting early-onset disturbances in the development of cerebello-thalamo-cortical pathways in autism.

Adolescent↗

PubMed1996

Autoregulation of body composition during weight recovery in human: the Minnesota Experiment revisited.

OBJECTIVES: To gain insights into the control systems underlying human variability in the regulation of body composition during weight recovery, as well as the disproportionate recovery of fat relative to lean tissue, the classical Minnesota Experiment conducted on 32 men subjected to long-term semi-starvation and refeeding was revisited with the following objectives: (1) to determine whether the control of energy-partitioning between lean and fat tissues during weight loss and weight recovery is an individual characteristic, and if a predictor can be statistically identified, (2) to determine whether the reduction in thermogenesis during weight loss persists during weight recovery, and underlies the disproportionate recovery of fat tissue and (3) to integrate the control of energy-partitioning and that of thermogenesis in order to explain the pattern of lean and fat tissue mobilisation and deposition during weight loss and weight recovery. METHODS: Individual data on body weight, body fat, fat-free-mass (FFM), and basal metabolic rate (BMR), assessed during the control baseline period (i.e. prior to weight loss), at the end of 24 weeks of semi-starvation, and at the end of a 12 week period of restricted refeeding, were used to calculate the following parameters: (i) a quantitative index of energy-partitioning, the P-ratio, defined as the proportion of body energy mobilised as protein during weight loss, or as the proportion of body energy deposited as protein during weight recovery, (ii) a quantitative index of changes in thermogenesis, defined as the change in BMR adjusted for FFM (or for both FFM and fat mass) and (iii) the degree of replenishment of fat and FFM compartments, defined as the recovery of body fat and FFM (during refeeding) as a percentage of that lost during semi-starvation. RESULTS: This re-analysis indicates the following: (i) a large inter-individual variability in P-ratio during both weight loss and weight recovery, but for a given individual, the P-ratio during refeeding is strongly correlated with the P-ratio during semi-starvation, (ii) body composition during the control period is the most important predictor of variability in P-ratio, such that the higher the initial % body fat, the lower the proportion of energy mobilised as protein, and hence the greater the propensity to mobilise fat during semi-starvation and to subsequently deposit fat during refeeding and (iii) at week 12 of refeeding, the change in adjusted BMR is found to be reduced by a magnitude which is inversely proportional to the degree of fat recovery, but is unrelated to the degree of FFM recovery. A quantitative relationship is derived between the P-ratio during refeeding, the % fat recovery, and the P-ratio during semi-starvation. CONCLUSIONS: Evidence is presented here suggesting that (i) human variability in the pattern of lean and fat tissue deposition during weight recovery is to a large extent determined by individual variations in the control of energy-partitioning, for which the initial % body fat is the most important predictor and (ii) the disproportionate gain in fat relative to lean tissue during weight recovery is contributed by a reduction in thermogenesis (i.e. increased efficiency of food utilization) for accelerating specifically the replenishment of the fat stores. These control systems, operating via energy-partitioning and thermogenesis, have been integrated into a compartmental model for the regulation of body composition during underfeeding/refeeding, and can be used to explain the individual pattern of lean and fat tissue deposition during weight recovery in situations ranging from the rehabilitation after malnutrition to the relapse of obesity.

Adipose Tissue↗

PubMedDate not supplied

Detection of intrauterine growth retardation in twins using individualized growth assessment. II. Evaluation of third-trimester growth and prediction of growth outcome at birth.

Second- and third-trimester growth in 34 twin fetuses was evaluated with ultrasonography by measurement of five anatomic parameters. Rossavik growth models, derived from second-trimester measurements, were used to specify expected third-trimester growth curves. Actual measurements were compared to predicted measurements by calculation of the percent deviations. Growth outcome at birth [normal, intrauterine growth retardation (IUGR)] was determined from Neonatal Growth Assessment Scores. Growth in the second trimester was similar in normal and IUGR twins. In the third trimester, abnormal negative deviations were larger and more numerous in IUGR twins. However, there was considerable individual variability and normal twins also had abnormal negative deviations. In IUGR twins, the first appearance of an abnormal negative deviation was quite variable (range: 28.6 weeks to 35.1 weeks), as was the parameter to show such a deviation. Prediction of neonatal outcome was poor using individual anatomic parameters but improved considerably with use of all five parameters. However, some fetuses were misclassified when only the number of abnormal negative deviations was used. The Prenatal Growth Assessment Score (PGAS), determined by both the number and magnitude of abnormal negative deviations, predicted neonatal outcomes with a sensitivity of 100% and specificity of 100%. On average, PGAS values were abnormal 5 weeks before delivery. These results indicate that normal and IUGR twins can be separated, using third-trimester growth patterns, if multiple parameter Individualized Fetal Growth Assessment is employed.

Diseases in Twins↗

PubMed1995

Stressful events and individual beliefs as correlates of economic disadvantage and aggression among urban children.

This study examined 3 factors that were hypothesized to increase risk for aggression among urban children: economic disadvantage, stressful events, and individual beliefs. Participants were 1,935 African American, Hispanic, and White elementary-school boys and girls assessed over a 2-year period. The relation between individual poverty and aggression was only significant for the White children, with significant interactions between individual and community poverty for the other 2 ethnic groups. With a linear structural model to predict aggression from the stress and beliefs variables, individual poverty predicted stress for African American children and predicted beliefs supporting aggression for Hispanic children. For all ethnic groups, both stress and beliefs contributed significantly to the synchronous prediction of aggression, and for the Hispanic children, the longitudinal predictions were also significant. The findings are discussed in terms of their implications for preventive interventions in multiethnic, inner-city communities.

Black or African American↗

PubMed2003

Navigating disrupted transitions: getting back on track after dropping out of high school.

Using ecological-developmental and resilience perspectives, this study utilizes quantitative and qualitative methods to examine the role of family, community, and individual variables in reestablishing school and work pathways for a diverse sample of 182 Boston-area high school dropouts. Extra familial involvement and individual coping style prove the best predictors of on-track status.

Adolescent↗

PubMed2000

Inositol 1,4,5-trisphosphate synthesis in mononuclear white blood cells of malignant hyperthermia-susceptible and normal human beings, following in vitro exposure to halothane, caffeine and ryanodine.

Despite a plethora of findings associated with the pathophysiology of malignant hyperthermia (MH), the in vitro contracture test (IVCT) is the only reliable test for diagnosis of this heterogeneous syndrome in man. An increase of 1,4,5-IP3 (inositol 1,4,5-trisphosphate), a second messenger involved in cellular calcium homeostasis, has been observed in muscle tissue of MH susceptible (MHS) patients. The aim of this study was to evaluate if the known differences of 1,4,5-IP3 content in muscle tissue might be reproduced in mononucleated white blood cells (MWBCs). Subsequently, MWBCs of 23 healthy controls and 12 patients with a clinical suspicion for MH disposition were isolated and screened for 1,4,5-IP3 content. An IVCT according to the protocol of the European Malignant Hyperpyrexia Group (EMHG) was performed on muscle specimens of 12 patients. Eight MHN and four MHS individuals were diagnosed. Additionally, 1,4,5-IP3 synthesis in MWBCs was detected following in vitro exposure to IVCT test substances halothane (2%), caffeine (1-30mM), and ryanodine (1-5 microM). A broad inter-individual variability of 1,4,5-IP3 content was observed in MWBCs of all volunteers, but no differences were detected between MHS and MHN individuals. These findings are in strong contrast to those observed in muscle tissue. In vitro exposure of isolated MWBCs to halothane, caffeine and ryanodine yielded no statistically significant differences between groups. A time- and concentration-dependent increase in cellular 1,4,5-IP3 content could be induced in some but not all individuals of both groups. Since no correlation was obtained between induction of 1,4,5-IP3-synthesis following in vitro exposure of MWBCs to MH test substances and MH disposition, this study was terminated. We conclude from our data that the detection of 1,4,5-IP3 synthesis in MWBCs is not suitable for diagnosis of MH disposition. It remains questionable whether an altered 1,4,5-IP3 metabolism in MWBCs is involved in pathologic cascades of MH. Therefore, other cell tissues should be evaluated in further studies to clarify the role of the 1,4,5-IP3 metabolism in MH.

Anesthetics, Inhalation↗

PubMed2006

Clinical performance of original and revised Bethesda guidelines for the identification of MSH2/MLH1 gene carriers in patients with newly diagnosed colorectal cancer: proposal of a new and simpler set of recommendations.

UNLABELLED: Identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is a critical and difficult issue. For this purpose, the National Cancer Institute outlined a set of recommendations, the Bethesda guidelines, which have recently been revised. OBJECTIVE: To compare the clinical performance of original and revised Bethesda guidelines for the detection of MSH2/MLH1 gene carriers in patients with colorectal cancer. METHODS: A total of 1,222 patients with newly diagnosed colorectal cancer were included in the EPICOLON study, a prospective, multicenter, nationwide epidemiology survey aimed at establishing the incidence of HNPCC in Spain (JAMA 2005; 293:1986-1994). Performance characteristics of the original and revised Bethesda guidelines were assessed with respect to the presence of MSH2/MLH1 germline mutations. Logistic regression analysis was performed to establish the most effective strategy. RESULTS: Original or revised Bethesda guidelines were equivalent strategies in terms of sensitivity (100%vs 100%; ns), specificity (98.1%vs 97.9%; ns), and overall accuracy (98.1%vs 97.9%; ns), as well as positive (25.8%vs 24.2%) and negative predictive values (100%vs 100%). The most discriminating individual variables were criteria number 1 (i.e., fulfillment of the Amsterdam criteria; RR = 34.14; 95% CI = 6.85-170.16; p < 0.001) and number 2 (i.e., individuals with two HNPCC-related neoplasms; RR = 35.63; 95% CI = 4.83-262.6; p < 0.001) of the original guidelines, and criterion number 1 of the revised guidelines (i.e., colorectal cancer diagnosed under 50 yr of age; RR = 29.34; 95% CI = 3.81-225.96; p= 0.001). The aggregation of these three criteria was equivalent to both Bethesda guidelines in terms of sensitivity (100%) and negative predictive value (100%), but superior to the revised criteria regarding specificity (98.5%; p < 0.05), overall accuracy (98.5%; p < 0.05), and positive predictive value (30.8%). CONCLUSIONS: Original and revised Bethesda guidelines are equivalent, highly effective criteria for the identification of MSH2/MLH1 gene mutation carriers in patients with newly diagnosed colorectal cancer. A new set of recommendations, based on a combination of some of their individual criteria, may provide additional advantages in terms of effectiveness.

Adaptor Proteins, Signal Transducing↗