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PubMed2001

Relationship between run times to exhaustion at 90, 100, 120, and 140% of vVO2max and velocity expressed relatively to critical velocity and maximal velocity.

The aim of the present study was to explain the inter-individual variability in running time to exhaustion (tlim) when running speed was expressed as a percentage of the velocity, associated with maximal oxygen uptake (vVO2max). Indeed for the same percentage of vVO2max the anaerobic contribution to energy supply is different and could be dependent on the critical velocity (Cv) and also on the maximal running velocity (vmax). Ten subjects ran four tlim at 90, 100, 120, and 140% of vVO2max; mean and standard deviation for tlim were 839 +/- 236 s, 357 +/- 110 s, 122 +/- 27 s, and 65 +/- 17s, respectively. Each velocity was then expressed 1) as a percentage of the difference between vVO2max and Cv (%AeSR); 2) as a percentage of the difference between vmax and Cv (%MSR); 3) as a percentage of the difference between vmax and vVO2max (%AnSR). Highest correlations were found between tlim90 and tlim100 and velocity expressed as %MSR (r = -0.82, p < 0.01 and r = -0.75, p < 0.01), and between tlim120 and tlim140 and velocity expressed as %AnSR (r = -0.83, p < 0.01 and r = -0.94, p < 0.001). These results show that the same intensity relative to aerobic contribution did not represent the same absolute intensity for all and could partly explain variability in tlim. Therefore expressing intensity as a percentage of MSR for sub-maximal and maximal velocities and as a percentage of AnSR for supra-maximal velocities allows individual differences in anaerobic work capacity to be taken into account and running times to exhaustion to be predicted accurately.

Adult↗
PubMed1987

[Psychophysiology of schizophrenic disorders of attention--concepts, findings and working hypotheses].

Starting from early clinical descriptions according to which there exists a polarity of attentional behavior in schizophrenia, we compare a number of pertinent theoretical concepts put forward up to now. Special attention is given to the question of functional hemispherical asymmetries, and here especially to a working hypothesis according to which the neuropsychological deficits in schizophrenics result from a coordination deficit of two differently lateralized attention systems. Taking into consideration certain neurophysiological (especially electro-encephalographical) findings, we discuss a model which places in opposition sensory intake behaviors and sensory rejection behaviors. Then we give a condensed presentation of relevant findings of our own. In particular, it could be shown that clinical improvement goes along with a certain change of the topographical distribution of absolute alpha-power, and that the intensity of some psychopathological symptoms correlates with the lateralization of posterior absolute alpha-power. Relationships also occurred between psychopathology on the one hand and the performance level in a visuo-motor tracking task or the eye movement behavior recorded during a picture viewing task, on the other. A concluding synopsis, comprising both empirically proven and theoretically postulated relationships, serves to formulate working hypotheses for clinical-psychophysiological correlation studies to be done in the future. In contrast to the current practice of assigning patients to the usual diagnostic subgroups, we advocate from a research-oriented point of view the grouping of those patients who show certain combinations of clinical and psychophysiological signs at a certain moment. Such a procedure holds out a prospect of solving a central problem of schizophrenia research consisting of the considerable intra- and individual variability of findings. Instead of changeable sick persons, defined systems states would be classified. Knowledge of the dynamics of such systems states could contribute to a rational therapy in the individual patient.

Attention↗
PubMed2000

Underestimation of Mycobacterium tuberculosis infection in HIV-infected subjects using reactivity to tuberculin and anergy panel.

BACKGROUND: This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment. METHODS: Clients of four Mexico City HIV detection centres were screened for HIV-1 antibodies (ELISA or haemagglutination, Western Blot); reactivity to PPD (Mantoux PPD, 5TU RT-23), Candida (1:1000, 0.1 ml), and tetanus toxoid (10Lf, 0.1 ml); and CD4+ T cells. Active tuberculosis was excluded. Informed consent was obtained. RESULTS: From 5130 clients 1168 subjects were enrolled; of these 801 (68.6%) were HIV positive. Reactivity to PPD among HIV-positive subjects was found in 174 (22%), 261 (32.6%), and 296 (37%), at PPD cutoff levels of > or =10 mm, > or =5 mm, and > or =2 mm as compared to 224 (61%) of 367 HIV-negative individuals' reactors to PPD (> or =10 mm) (P < 0.001). After exclusion of anergic individuals using two cutoff levels for cutaneous allergens (< or =2 mm and < or =5 mm), PPD reactivity between HIV-infected and uninfected individuals continued to be significantly different. Only HIV-infected individuals with CD4+ T cells > or =500 cells/mm3 had similar reactivity to PPD as HIV-uninfected individuals. Variables associated with PPD reactivity were CD4+ T cell counts, BCG scar, HIV infection and age. CONCLUSIONS: PPD reactivity was useful to diagnose tuberculosis infection only among HIV-infected individuals with CD4+ counts > or =500 cells/mm3. Among individuals with lower counts, lowering cutoff levels or using anergy panel did not permit comparable reactivity as that observed among HIV-uninfected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1993

Variability of human sperm response to immediate and prolonged exposure to pentoxifylline.

Pentoxifylline improves some motility characteristics of human spermatozoa, but the variability of response to this drug has not been clearly defined. We used computer-assisted sperm motion analysis to examine the in-vitro response of spermatozoa to pentoxifylline. Individuals (n = 31) with normal sperm counts were randomly selected and their spermatozoa exposed to different concentrations of pentoxifylline. Further tests on a subgroup of individuals examined the longevity of spermatozoa in response to this agent. Straight line velocity (VSL) was only improved at 0.1 mM and the major effect of the drug was on curvilinear velocity (VCL) and lateral head displacement (ALH). Prolonged exposure to pentoxifylline enhanced sperm motion only at 0.1 mM. Higher concentrations produced dose-dependent detrimental effects on all the motion characteristics. There was considerable inter-individual variability in both VCL and ALH response ranging from little or no detectable response to a 40% increase above control value. The maximum response was most commonly seen at a concentration of 2 mM pentoxifylline.

Humans↗
PubMed2003

Pharmacogenomics of hypertension.

PURPOSE OF REVIEW: The emerging field of pharmacogenomics has the potential to fundamentally change the management of essential hypertension, a common, perhaps polygenic syndrome characterized by substantial inter-individual variability in drug responsiveness. As understanding of sequence diversity in the human genome progresses, the prospect grows for tailoring the prescription of antihypertensive drugs to complement common genetic variations among individual patients, allowing optimization of blood pressure control and improved avoidance of drug side effects. Some principles of pharmacogenomics are presented here, along with a review of the most recent literature on genetic determinants of antihypertensive drug responses, with a preview of likely developments to come. RECENT FINDINGS: Polymorphisms at candidate pharmacodynamic loci (such as angiotensinogen, angiotensin converting enzyme, and the angiotensin II receptor) have already been shown to predict responses to such specific treatments as angiotensin converting enzyme inhibition and angiotensin II blockade. The National Institutes of Health have established a multi-institutional pharmacogenetics network and knowledge base, whose goals include understanding how common polymorphisms influence therapeutic responses to a variety of drugs, including antihypertensive agents. SUMMARY: The study of genetic determinants of drug responses, particularly at the pharmacodynamic (drug target/receptor and post-receptor) level, is likely to allow us to more precisely tailor therapy to the individual patient, as well as to promote the creation of novel therapies.

Animals↗
PubMedDate not supplied

Assessing quality of life in older persons with schizophrenia.

OBJECTIVE: There have been few studies of quality of life (QOL) indicators in older schizophrenic persons, and these studies have used narrow measures of QOL. The authors sought to demonstrate that self-appraisals of QOL are useful and valid in older schizophrenic persons. A second aim was to provide provisional support for a model of QOL in this population. METHODS: The sample was 99 community-dwelling schizophrenic persons age 55+ and a community-comparison group (N=84). Using the Quality of Life Index (QLI), they compared the variable sets of their model (Objective, Subjective, and Psychiatric domains) for the schizophrenic and the community samples to determine whether the explained variance in the QLI was equivalent between groups for each of the three variable sets. To assess the model of QOL, for the entire sample, the global scale score of the QLI was regressed on three predictor variable sets, the three demographic covariates, and group membership. RESULTS: All of the group differences were considered "small effect sizes." There were no significant differences between groups in the individual-variable regression coefficients. For the entire sample, when the QLI was regressed on the three predictor variable sets simultaneously, the model explained 61% of the variance in the QLI, and group membership was not significant. CONCLUSIONS: The analyses demonstrated the reliability and validity of the QLI in older schizophrenic persons and supported its validity by producing results comparable to general-community residents. The overall model was highly significant and should serve as basis for future studies of QOL.

Aged↗
PubMed1990

Characteristics of volunteers who deliver health education and promotion: a comparison with organization members and program participants.

The use of volunteers in this culture for community health endeavors is an understudied area. Yet, there may be many potential benefits for utilizing volunteers in the delivery of community health education and promotion. Volunteers may have more immediate access to their peers, credibility, and familiarity with the cultural environment and organization elements. An assumption of volunteer use is that persons drawn from a targeted organization (or community subgroup) will be like other members. Such an assumption, however, should be confirmed or disproved. This article compares a sample of volunteers to a sample of members from organizations from which the volunteers were recruited. The paper also compares the volunteers to a sample of program participants. The participants were persons to whom the volunteers delivered CVD prevention programming and, in most cases, were also organization members. Collectively using the variables under investigation, multivariate analyses of variance found that the volunteers were different from the organization members, and different from program participants. To assess differences between the samples on each individual variable, univariate tests were conducted stratifying the samples by age. Statistically significant differences were found regarding organization activity, formal education level, success with past health habit change, health self-assessment, occupation, gender, and marital status.

Adult↗
PubMed1999

Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm.

BACKGROUND: A child who has an acutely irritable hip can pose a diagnostic challenge. The purposes of this study were to determine the diagnostic value of presenting variables for differentiating between septic arthritis and transient synovitis of the hip in children and to develop an evidence-based clinical prediction algorithm for this differentiation. METHODS: We retrospectively reviewed the cases of children who were evaluated at a major tertiary-care children's hospital between 1979 and 1996 because of an acutely irritable hip. Diagnoses of true septic arthritis, presumed septic arthritis, and transient synovitis were explicitly defined on the basis of the white blood-cell count in the joint fluid, the results of cultures of joint fluid and blood, and the clinical course. Univariate analysis and multiple logistic regression analysis were used to compare groups. A probability algorithm for differentiation between septic arthritis and transient synovitis on the basis of independent multivariate predictors was constructed and tested. RESULTS: Patients who had septic arthritis differed significantly (p < 0.05) from those who had transient synovitis with regard to the erythrocyte sedimentation rate, serum white blood-cell count and differential, weight-bearing status, history of fever, temperature, evidence of effusion on radiographs, history of chills, history of recent antibiotic use, hematocrit, and gender. Patients who had true septic arthritis differed significantly (p < 0.05) from those who had presumed septic arthritis with regard to history of recent antibiotic use, history of chills, temperature, erythrocyte sedimentation rate, history of fever, gender, and serum white blood-cell differential. Four independent multivariate clinical predictors were identified to differentiate between septic arthritis and transient synovitis: history of fever, non-weight-bearing, erythrocyte sedimentation rate of at least forty millimeters per hour, and serum white blood-cell count of more than 12,000 cells per cubic millimeter (12.0 x 10(9) cells per liter). The predicted probability of septic arthritis was determined for all sixteen combinations of these four predictors and is summarized as less than 0.2 percent for zero predictors, 3.0 percent for one predictor, 40.0 percent for two predictors, 93.1 percent for three predictors, and 99.6 percent for four predictors. The chi-square test for trend and the area under the receiver operating characteristic curve indicated excellent diagnostic performance of this group of multivariate predictors in identifying septic arthritis. CONCLUSIONS: Although several variables differed significantly between the group that had septic arthritis and the group that had transient synovitis, substantial overlap in the intermediate ranges made differentiation difficult on the basis of individual variables alone. However, by combining variables, we were able to construct a set of independent multivariate predictors that, together, had excellent diagnostic performance in differentiating between septic arthritis and transient synovitis of the hip in children.

Acute Disease↗
PubMed1975

[Variability of heat resistance of frog muscle tissue in Ringer's solution].

The variability in the initial level of heat resistance of muscles was found to decrease with increase in the duration of keeping the frogs in vivarium. However, the variability in the resistance of isolated muscles kept in Ringer's solution during 90 min. is independent of this factor and lesser than the initial one. The data obtained suggest that the narrowing of the variability in the resistance of muscles kept in Ringer's solution is determined by the dispersion of the initial level of the resistance. This phenomenon is only observed when the individual variability in the resistance of muscles is sufficiently high immediately after their isolation.

Acclimatization↗
PubMed1981

[Changes in blood prolactin in relation to the menstrual cycle].

Scientists are in general agreement on the hypothesis of a prolactin surge at midcycle. In order to test this hypothesis the Authors measured radioimmunoassayable circulating prolactin in the follicular phase and at midcycle in 15 normally menstruating health women. Due to the well known individual variability, mean prolactin values showed statistically poor differences in the two phases of the cycle. Though, a very good positive correlation (r = 0.72, p less than 0.01) was shown when individual follicular values were plotted against the corresponding midcycle values. The Authors conclude that at midcycle prolactin increases significantly and discuss physiological significance of this phenomenon.

Adult↗
PubMed2005

Variability in response to aspirin: do we understand the clinical relevance?

Aspirin, an irreversible inhibitor of platelet prostaglandin synthase activity, is the cornerstone of therapy for acute coronary syndromes. In recent years, laboratory and clinical data have accumulated that suggest there may be significant individual variability in the response to aspirin and that the effects of aspirin therapy vary significantly over time. There is, as of yet, no cohesive explanation for this variability. The term 'aspirin resistance' has been loosely applied to situations in which the clinical or ex vivo effects of aspirin are less than expected. In this review we discuss the clinical data regarding this phenomenon and the need for prospective evaluation of aspirin non-responders.

Acute Disease↗
PubMed1992

Assessment of changes in body water by bioimpedance in acutely ill surgical patients.

OBJECTIVE: To evaluate the relationship between changes in body bioelectrical impedance (BI) at 0.5, 50 and kHz and the changes in body weight, as an index of total body water changes, in acutely ill surgical patients during the rapid infusion of isotonic saline solution. DESIGN: Prospective clinical study. SETTING: Multidisciplinary surgical ICU in a university hospital. PATIENTS: Twelve male patients treated for acute surgical illness (multiple trauma n = 5, major surgery n = 7). SELECTION CRITERIA: stable cardiovascular parameters, normal cardiac function, signs of hypovolemia (CVP < or = 5 mmHg, urine output < 1 ml/kg x h). INTERVENTIONS: After baseline measurements, a 60 min fluid challenge test was performed with normal saline solution, 0.25 ml/kg/min [corrected]. MEASUREMENTS AND RESULTS: Body weight (platform digital scale), total body impedance (four-surface electrode technique; measurements at 0.5, 50 and 100 kHz) and urine output. Fluid retention induced a progressive decrease in BI at 0.5, 50 and 100 kHz, but the changes were significant for BI 0.5 and BI 100 only, from 40 min after the beginning of the fluid therapy onwards. There was a significant negative correlation between changes in water retention and BI 0.5, with individual correlation coefficients ranging from -0.72 to 0.95 (p < 0.01-0.0001). The slopes of the regression lines indicated that for each kg of water change, there was a mean decrease in BI of 18 ohm, but a substantial inter-individual variability was noted. CONCLUSION: BI measured at low frequency can represent a valuable index of acute changes in body water in a group of surgical patients but not in a given individual.

Acute Disease↗
PubMed1994

The role of coenzyme A in the biotransformation of 2-arylpropionic acids.

A number of 2-arylpropionic acid non-steroidal anti-inflammatory drugs ('profens') undergo highly enantioselective inversion from the (R)- to (S)-enantiomer. The mechanism of this inversion reaction involves the initial enantioselective formation of a coenzyme A thioester followed by epimerization and finally hydrolysis to regenerate free acids. Long-chain fatty acyl-CoA synthetase appears to mediate the initial thioester formation and an epimerase of an unknown physiologic function effects the second step. The hydrolases mediating the final step are poorly defined. Available evidence suggests that the liver is quantitatively the most important tissue site of inversion but local tissue inversion may influence the pharmacological and toxicological response of a given organ. Data from isolated rat hepatocytes indicate that other xenobiotics can modulate the formation and hydrolysis of ibuprofenyl-CoA by influencing inversion pathways, non-inversion pathways or both. Interactions between xenobiotics may therefore accentuate inter-individual variability in response to 2-aryl-propionic acids. The formation of 2-arylpropionyl-CoA thioesters in vivo has the potential to disrupt numerous biochemical pathways in addition to enhancing individual exposure to the potent anti-inflammatory (S)-enantiomers.

Acyl Coenzyme A↗
PubMed2003

Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation.

The antiepileptic drug lamotrigine (LTG) is known to reduce cortical excitability evaluated by transcranial magnetic stimulation (TMS). We investigated the relationship between LTG oral dosages, serum levels and inhibitory effects on resting motor threshold (RMT), a parameter of motor system excitability assessed by TMS. In a randomized, placebo-controlled crossover study 16 male volunteers received 325 mg LTG as a single dose, as bi-hourly graded cumulative dose, or placebo. RMT and serum levels were measured before and after 2-8 h. With single dose, RMT elevation showed a poor but significant correlation to serum levels. With graded dose, serum levels as well as RMT increased dose-dependently with significant (P<0.0001) linear correlation. However, detailed comparison showed a high inter-individual variability in the relationship resembling a sigmoid correlation. Different mechanisms besides the sodium-channel blockage as the main mode of action of LTG are discussed to explain the diversity of individual dose-response relationships. Provided that the RMT elevation reflects the antiepileptic potential of LTG, TMS may be developed as a tool to monitor interindividual response of epilepsy patients to LTG treatment as well as to explore efficacy of other antiepileptic drugs with similar mode of action.

Administration, Oral↗
PubMed2004

Spatial learning impairment induced by chronic stress is related to individual differences in novelty reactivity: search for neurobiological correlates.

Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothesized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find a neurobiological substrate that specifically correlated with the differential cognitive vulnerability to chronic stress shown by animals with a different novelty reactivity, this study confirms the hypothesis that rats differ in their susceptibility to display stress-induced impairments in hippocampus-dependent spatial learning tasks. In addition, it provides a model to further search for the neurobiological substrate(s) involved in the differential susceptibility to develop stress-induced cognitive impairments.

Analysis of Variance↗
PubMed2004

Elevated sialic acid, but not CRP, predicts features of the metabolic syndrome independently of BMI in women.

AIMS: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome. SUBJECTS: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m2 (geometric mean 33.1+/-5.8 kg/m2) and aged 19-71 y (mean 45.6+/-12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy. RESULTS: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant (P<0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P<0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 (P<0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P<0.0001). CONCLUSIONS: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.

Adult↗
PubMed1988

Digestion and passage kinetics of chimpanzees fed high and low fiber diets and comparison with human data.

To investigate the digestive kinetics and fiber digestion of great apes, we conducted digestion trials on chimpanzees (Pan troglodytes) with diets of two fiber levels, one containing 34% neutral detergent fiber (NDF) and the other 14% NDF. Chimpanzees exhibited a response to fiber similar to that of humans. First, increases in the fiber concentration of the diet decreased mean transit time (MTT), hindgut turnover time (T) and the digestibility of fiber. Second, differences in MTT and T between the treatments and animals explained most of the variability in the digestibility of fiber components. Third, consistent with human data, the fiber marker passed more slowly than the liquid marker only when the high fiber diet was consumed. Fourth, individual variability, as in humans, was a significant factor affecting digestion and passage. Fifth, the MTT of chimpanzees was longer than that of humans. This result may be due to the apes' larger hindgut. In comparison with other hominoids, humans have smaller volumes in the gastrointestinal tract and hindgut. The gut proportions of modern humans, in combination with evidence from the fossil record, indicate that during its evolution the human lineage was able to overcome nutritional constraints imposed on body size increases in the great apes. We suggest that this advance was achieved through technological and social innovations that permitted early humans to achieve larger body size without lowering dietary quality.

Animals↗
PubMed2000

Molecular epidemiology of genetic polymorphisms in estrogen metabolizing enzymes in human breast cancer.

Epidemiologic studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. For a number of years, the mechanism for estrogens in carcinogenesis was thought to be that of mitotic stimulation, with the growth promotion of ductal epithelial cells harboring precursor mutations in the breast. However, evidence is now available that estrogens may act as initiators of cellular alterations and tumorigenesis. Investigation and measurement of serum levels of estrogens in epidemiologic studies may, therefore, be misleading, because they may reflect levels quite different from those of hormone metabolites to which the target tissue is exposed. Proportions of hormone metabolites may be estimated by evaluation of associations between breast cancer risk and genetic polymorphisms in enzymes involved in hormone metabolism. A number of molecular epidemiologic studies have been conducted to evaluate associations between polymorphic genes involved in steroid hormone metabolism (i.e., CYP17, COMT, CYP1A1, CYP19, GST, and MnSOD) that may account for a proportion of enzymatic variability, and results are discussed in this review. There are strengths and limitations to such an approach, foremost of which may be the lack of insight into the extent to which individual variability in estrogen exposure may be explained by allelic variation. Variability in other endogenous and exogenous factors that impact parent hormones and their metabolites along activation and conjugation pathways may also affect associations in case-control comparisons. This and other possible reasons for inconsistencies in results of molecular epidemiologic studies are discussed. Contributions from population-based studies and those from the laboratory may together move this field ahead and more clearly elucidate the basis of hormonally related cancers, identifying etiologic factors and susceptible populations for preventive strategies.

Breast Neoplasms↗