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At least 883 records · Page 49Linked to original sources
PubMed2003

Conditioning and residual emotionality effects of predator stimuli: some reflections on stress and emotion.

The advantages of using predator-related odor stimuli to study emotional responses in laboratory tests depend on whether such stimuli do elicit a relatively complete pattern of emotionality. This has been confirmed for cat fur/skin odor stimuli, which elicit a range of defensive behaviors in rats that may be reduced by anxiolytic drugs, produce residual anxiety-like behavior in the elevated plus maze and support rapid aversive conditioning to the context in which they were encountered. Although the synthetic fox fecal odor, trimethylthiazoline (TMT), elicits avoidance similar to that seen in response to cat fur/skin odor, this avoidance does not respond to anxiolytic drugs. In addition, TMT does not produce residual anxiety-like behaviors in the elevated plus maze, nor does it support conditioning. As natural cat feces also elicit avoidance but fail to support conditioning, it is possible that the ability of a predator-related odor to serve as an effective unconditioned stimulus (US) relates to its predictive status with reference to the actual presence of the predator. Avoidance per se may reflect that a stimulus is aversive but not necessarily capable of eliciting an emotional response. This view is consonant with findings in a Mouse Defense Test Battery (MDTB) measuring a wide range of defensive responses to predator exposure. A contextual defense measure that may reflect either conditioned or residual but unconditioned emotional responses was almost never reduced by drug effects unless these also reduced risk assessment or defensive threat/attack measures. However, reductions in contextual defense without changes in flight/avoidance measures were much more common. These findings suggest that flight/avoidance, although it obviously may occur as one component of a full pattern of defensive and emotional behaviors, is also somewhat separable from the others. When-as appears to be the case with TMT-it is the major or perhaps only consistent defensive behavior elicited, this may reflect a stimulus that is aversive or noxious but with little ability to predict the presence of threat or danger. That such stimuli fail to support rapid aversive conditioning suggests the need for a reanalysis of the characteristics required for an effective aversive US.

Animals↗
PubMed2006

A magnetic resonance spectroscopy investigation of obsessive-compulsive disorder and anxiety.

The aim of the current study was to use proton magnetic resonance spectroscopy (MRS) to investigate potential irregularities in neurochemical compounds in obsessive-compulsive disorder (OCD) and the extent to which these irregularities are related to state anxiety. Single voxel MRS was used to image the head of the caudate nucleus (HOC) and orbitofrontal white matter (OFWM) bilaterally in adult patients with OCD and a control group. The results indicated that patients with OCD had increased levels of a combined measure of glutamate and glutamine (Glx/Cr) and N-acetyl-l-aspartic acid (NAA/Cr) relative to creatine in the right OFWM and reduced levels of myo-inositol relative to creatine (mI/Cr) in the HOC bilaterally. Correlational analyses indicated that Glx/Cr in the OFWM was related to OCD symptoms, while mI/Cr in the HOC was related to trait and/or state anxiety. Reanalysis of the significant group differences controlling for state anxiety symptoms erased three of the four group differences. These results are discussed in context of the methodological difficulties facing this area of research.

Adult↗
PubMed2004

Acute HPA axis responses, heart rate, and mood changes to psychosocial stress (TSST) in humans at different times of day.

There is evidence showing that HPA axis responses to pharmacological provocation depend on time of day with larger cortisol responses in the afternoon and evening compared to the morning hours. However, it is still unknown whether HPA axis responses to psychological stress are affected by time of day and whether they can be assessed with equal reliability in the morning and afternoon, respectively. The present reanalysis is based on five independent studies conducted in the same laboratory by and. All subjects were confronted with the Trier Social Stress Test (TSST) either in the morning or in the afternoon. The total sample consisted of 180 adults with 115 younger (49 females, 66 males) and 65 older adults (32 females, 33 males). All ANCOVA results controlled for possible age and gender effects. Stress-related free salivary cortisol, total plasma cortisol and ACTH net increases did not differ according to time of day (all p = n.s.). However, as expected pre-stress free salivary and total plasma cortisol levels differed significantly between the morning and afternoon group (both p < 0.005), leading to a significantly higher free cortisol area under the curve (AUC) in the morning (p = 0.02). Taken together, these observations suggest that the adrenal glands may be more sensitive to ACTH in the morning. Additionally, higher basal salivary cortisol levels were related to a lower stress-related net increase in salivary cortisol (p = 0.02), total plasma cortisol (p < 0.0001), and marginally ACTH (p = 0.09). Stress-related heart rate increases did not differ between groups (p = n.s.). The finding that the TSST-induced mood change was differentially affected by time of day requires further exploration. We conclude that comparable HPA axis and heart rate stress responses to psychosocial stress can be measured in the morning and afternoon.

Adrenocorticotropic Hormone↗
PubMed2006

Optimization of a multinomial model for investigating hallucinations and delusions with source monitoring.

Studies of source monitoring have played an important role in cognitive investigations of the inner/outer confusions that characterize hallucinations and delusions in schizophrenia, and multinomial modelling is a statistical/cognitive modelling technique that provides a powerful method for analyzing source monitoring data. The purpose of the current work is to describe how multinomial models can be optimized to answer direct questions about hallucinations and delusions in schizophrenia research. To demonstrate this, we present a reanalysis of previously published source monitoring data, comparing a group of patients with schneiderian first rank symptoms to a group without schneiderian first rank symptoms. The main findings of this analysis were (1) impaired recognition of self-generated items and (2) evidence that impaired source discrimination of perceived items is accompanied by an internalization bias in the target symptom group. Statistical and cognitive interpretations of the findings are discussed.

Cognition Disorders↗
PubMed2006

Sex ratio determination in bovine semen: a new approach by quantitative real time PCR.

Sex preselection of livestock offspring in cattle represents, nowadays, a big potential for genetic improvement and market demand satisfaction. Sperm sorting by flow cytometer provides a powerful tool for artificial insemination and production of predefined sexed embryos but, an accurate verification of the yield of sperm separation remains essential for a field application of this technique or for improvement and validation of other related semen sexing technologies. In this work a new method for the determination of the proportion of X- and Y-bearing spermatozoa in bovine semen sample was developed by real time PCR. Two sets of primers and internal TaqMan probes were designed on specific X- and Y-chromosome genes. To allow a direct quantification, a standard reference was established using two plasmid cDNA clones (ratio 1:1) for the specific gene targets. The method was validated by a series of accuracy, repeatability and reproducibility assays and by testing two sets of sorted and unsorted semen samples. A high degree of accuracy (98.9%), repeatability (CV=2.58%) and reproducibility (CV=2.57%) was shown. The results of X- and Y-sorted semen samples analysed by real time PCR and by flow cytometric reanalysis showed no significant difference (P>0.05). The evaluation of X-chromosome bearing sperms content in unsorted samples showed an average of 51.11+/-0.56% for ejaculates and 50.17+/-0.58% for the commercial semen. This new method for quantification of the sexual chromosome content in spermatozoa demonstrated to be rapid and reliable, providing a valid support to the sperm sexing technologies.

Animals↗
PubMed2006

Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication.

The purpose of the analysis described here was to assess reproductive endocrine disorders in 148 women with epilepsy (WWE) by epilepsy type and antiepileptic drug use. Women with idiopathic generalized epilepsy had a higher prevalence of reproductive endocrine disorders than control subjects. In addition, hyperandrogenism, polycystic ovaries, and polycystic ovary syndrome were more prevalent in WWE on valproate than in WWE taking other drugs or control women. The use of VPA was a predictor of the development of polycystic ovaries and polycystic ovary syndrome, and the use of valproate and younger age predicted the development of hyperandrogenism. In conclusion, both idiopathic generalized epilepsy and valproate were associated with an increased risk of reproductive endocrine disorders in WWE in this post hoc reanalysis of data on a large number of WWE. This was especially evident if the epilepsy was active and required treatment early in life.

Adolescent↗
PubMed2006

Analyzing chromatin remodeling complexes using shotgun proteomics and normalized spectral abundance factors.

Mass spectrometry-based approaches are commonly used to identify proteins from multiprotein complexes, typically with the goal of identifying new complex members or identifying post-translational modifications. However, with the recent demonstration that spectral counting is a powerful quantitative proteomic approach, the analysis of multiprotein complexes by mass spectrometry can be reconsidered in certain cases. Using the chromatography-based approach named multidimensional protein identification technology, multiprotein complexes may be analyzed quantitatively using the normalized spectral abundance factor that allows comparison of multiple independent analyses of samples. This study describes an approach to visualize multiprotein complex datasets that provides structure function information that is superior to tabular lists of data. In this method review, we describe a reanalysis of the Rpd3/Sin3 small and large histone deacetylase complexes previously described in a tabular form to demonstrate the normalized spectral abundance factor approach.

Chromatin Assembly and Disassembly↗
PubMed2003

Characterization of angiosperm nrDNA polymorphism, paralogy, and pseudogenes.

Many early reports of ITS region (ITS 1, 5.8S, and ITS 2) variation in flowering plants indicated that nrDNA arrays within individuals are homogeneous. However, both older and more recent studies have found intra-individual nrDNA polymorphism across a range of plant taxa including presumed non-hybrid diploids. In addition, polymorphic individuals often contain potentially non-functional nrDNA copies (pseudogenes). These findings suggest that complete concerted evolution should not be assumed when embarking on phylogenetic studies using nrDNA sequences. Here we (1). discuss paralogy in relation to species tree reconstruction and conclude that a priori determinations of orthology and paralogy of nrDNA sequences should not be made based on the functionality or lack of functionality of those sequences; (2). discuss why systematists might be particularly interested in identifying and including pseudogene sequences as a test of gene tree sampling; (3). examine the various definitions and characterizations of nrDNA pseudogenes as well as the relative merits and limitations of a subset of pseudogene detection methods and conclude that nucleotide substitution patterns are particularly appropriate for the identification of putative nrDNA pseudogenes; and (4). present and discuss the advantages of a tree-based approach to identifying pseudogenes based on comparisons of sequence substitution patterns from putatively conserved (e.g., 5.8S) and less constrained (e.g., ITS 1 and ITS 2) regions. Application of this approach, through a method employing bootstrap hypothesis testing, and the issues discussed in the paper are illustrated through reanalysis of two previously published matrices. Given the apparent robustness of the test developed and the ease of carrying out percentile bootstrap hypothesis tests, we urge researchers to employ this statistical tool. While our discussion and examples concern the literature on plant systematics, the issues addressed are relevant to studies of nrDNA and other multicopy genes in other taxa.

DNA, Ribosomal↗
PubMed2004

Phylogeny of the Falconidae (Aves): a comparison of the efficacy of morphological, mitochondrial, and nuclear data.

We sequenced 2800+ bp of the RAG-1 exon for representatives of all the currently recognized genera in the avian family Falconidae. A phylogenetic analysis of these data was compared to prior analyses of mitochondrial (cytochrome-b) and morphological (syringeal) data. The nuclear RAG-1 sequences produced results that were in agreement with the morphological results, but differed from the mitochondrial results with regard to monophyly of the genus Micrastur. A reanalysis of the cytochrome-b (cyt-b) data suggested that this result was due to heterogeneity in base composition. Comparisons of data quality and quantity across the three data sets indicate that the nuclear DNA sequences and the morphological data have similar consistency and retention indices as well as noise distributions that are superior to those of cyt-b. However, the RAG-1 data identify more nodes with high bootstrap support indices than do either morphology or mitochondrial sequences. In the final assessment, RAG-1 sequences were superior in phylogenetic utility both to syringeal morphology (because of sheer number of characters) and to cyt-b sequences (because of reduced noise and homogeneity of base composition, but in spite of having many fewer characters).

Animals↗
PubMed2004

Molecular systematics and time-scale for the evolution of Timarcha, a leaf-beetle genus with a disjunct Holarctic distribution.

In recent years we have investigated the evolution of the Holarctic leaf-beetle genus Timarcha using molecular approaches, but to date several important questions remained unanswered, including its systematic arrangement in a temporal context, or the phylogenetic placement of the Nearctic taxa. Here I present a reanalysis of available genetic data together with newly generated data for key taxa (markers 16S rDNA, CO2, ITS-2, and 18S rDNA), including the Nearctic species (subgenus Americanotimarcha), using direct optimization-based phylogenetic reconstructions. Lineage ages are estimated using maximum likelihood branch-length estimates and the molecular clock calibration derived from several presumed vicariance events in the Mediterranean. Phylogenetic analyses and 18S rDNA divergences suggest the ancient divergence of the Nearctic and Palaearctic lineages, related to the North Atlantic opening in the middle Eocene. The diversification of the Palaearctic Timarcha seems closely related to the geological evolution of the Mediterranean area during the Tertiary, with Pleistocenic climate changes affecting species ranges and lineage extinction, but not resulting in extensive speciation.

Animals↗
PubMed2005

Cytochrome b and Bayesian inference of whale phylogeny.

In the mid 1990s cytochrome b and other mitochondrial DNA data reinvigorated cetacean phylogenetics by proposing many novel and provocative hypotheses of cetacean relationships. These results sparked a revision and reanalysis of morphological datasets, and the collection of new nuclear DNA data from numerous loci. Some of the most controversial mitochondrial hypotheses have now become benchmark clades, corroborated with nuclear DNA and morphological data; others have been resolved in favor of more traditional views. That major conflicts in cetacean phylogeny are disappearing is encouraging. However, most recent papers aim specifically to resolve higher-level conflicts by adding characters, at the cost of densely sampling taxa to resolve lower-level relationships. No molecular study to date has included more than 33 cetaceans. More detailed molecular phylogenies will provide better tools for evolutionary studies. Until more genes are available for a high number of taxa, can we rely on readily available single gene mitochondrial data? Here, we estimate the phylogeny of 66 cetacean taxa and 24 outgroups based on Cytb sequences. We judge the reliability of our phylogeny based on the recovery of several deep-level benchmark clades. A Bayesian phylogenetic analysis recovered all benchmark clades and for the first time supported Odontoceti monophyly based exclusively on analysis of a single mitochondrial gene. The results recover the monophyly of all but one family level taxa within Cetacea, and most recently proposed super- and subfamilies. In contrast, parsimony never recovered all benchmark clades and was sensitive to a priori weighting decisions. These results provide the most detailed phylogeny of Cetacea to date and highlight the utility of both Bayesian methodology in general, and of Cytb in cetacean phylogenetics. They furthermore suggest that dense taxon sampling, like dense character sampling, can overcome problems in phylogenetic reconstruction.

Animals↗
PubMed2004

Reevaluation of mortality risks from leukemia in the formaldehyde cohort study of the National Cancer Institute.

OBJECTIVE: To determine whether the National Cancer Institute's (NCI) recent suggestion of a causal association between formaldehyde exposure and mortality from leukemia and myeloid leukemia (ML) is robust with respect to alternative characterizations and categorizations of formaldehyde exposure and to alternative methods of data analysis. METHODS: The original authors provided the cohort data. We computed US and local county rate-based standardized mortality ratios (SMRs) and internal cohort rate-based relative risks (RR) by categories of four formaldehyde exposure metrics (highest peak, average intensity (AIE), cumulative, and duration), using both NCI categories and an alternative categorization based on tertiles of deaths from all leukemia among exposed subjects. For highest peak exposure, we computed RRs by the duration of time worked in the highest peak category and the time since highest peak exposure. For AIE, we computed RRs by the duration of exposure and the time since first exposure. RESULTS: Our external comparisons revealed that the elevated leukemia and ML RRs and associated trends reported by NCI for highest peak and AIE occurred because null (or slight) to moderate mortality excesses were compared with statistically significant baseline category deficits in deaths. Our alternative categorization of AIE yielded leukemia and ML SMRs close to 1.0 in the highest exposure category, and revealed weaker evidence of a trend in RRs for leukemia and ML. We corroborated NCI's finding of no association for cumulative and duration of formaldehyde exposure. We found no consistent evidence that leukemia or ML risks increased with increasing duration of time spent in a given highest peak exposure (or for AIE, duration of exposure in a given AIE category). We also found no consistent evidence that leukemia or ML risks were greater in the more relevant shorter (less than 20 years) versus longer (20+ years) periods of time from the first highest peak exposure (or for AIE, first exposure). CONCLUSIONS: Our reanalysis provided little evidence to support NCI's suggestion of a causal association between formaldehyde exposure and mortality from leukemia and ML. NCI's key findings for highest peak exposure and AIE do not adequately account for the inordinately large deficits in deaths in the categories used as the baselines for internal rate-based RRs. The NCI findings also do not adequately account for the duration of time subjects spent in the highest peak category (or for AIE, duration of exposure) or the time since their first peak exposure (or for AIE, time since first exposure). Our finding that NCI's suggestion of a causal association is not robust with respect to alternative categorizations of formaldehyde exposure and methods of data analysis casts considerable additional uncertainty regarding the validity of this suggested association.

Cohort Studies↗
PubMed2005

Reevaluation of mortality risks from nasopharyngeal cancer in the formaldehyde cohort study of the National Cancer Institute.

OBJECTIVE: To determine whether the National Cancer Institute's (NCI) recent suggestion of a causal association between formaldehyde exposure and mortality from nasopharyngeal cancer (NPC) is robust with respect to alternative methods of data analysis and alternative categorizations of formaldehyde exposure. METHODS: The original authors provided the cohort data. We computed U.S. and local county (regional) rate-based standardized mortality ratios (SMRs) and internal cohort rate-based relative risks (RR) by categories of four formaldehyde exposure metrics (highest peak, average intensity, cumulative, and duration of exposure), using both NCI categories and an alternative categorization based on tertiles of all NPC deaths among exposed subjects. We computed SMRs and RRs for each of 10 study plants and by plant group (Plant 1 (n = 4261) vs. Plants 2-10 (n = 21,358)). RESULTS: Six of 10 NPC deaths observed in the NCI study occurred in only one plant (Plant 1) and the remaining four cases occurred individually in four of the other nine plants studied. A large, statistically significant, regional rate-based NPC SMR of 10.32 (95% CI = 3.79-22.47) among formaldehyde-exposed workers in Plant 1 contrasted sharply with a 35% deficit in NPC deaths (SMR = .65, 95% CI = .08-2.33) among exposed workers in Plants 2-10 combined. The statistically significant exposure-response relationship with formaldehyde and NPC reported in the NCI study for highest peak exposure was driven entirely by a large, statistically significant excess NPC risk in Plant 1 for the highest peak exposure category (4+ ppm). For the remaining nine plants, RRs for all non-baseline highest peak exposure categories were less than 1.0, and we observed no evidence of an exposure-response relationship. Most of the observed NPC excesses for the non-baseline categories of the other exposure metrics (average intensity, cumulative, and duration of formaldehyde exposure) were concentrated in Plant 1, and by contrast to the NCI findings, none of the corresponding exposure-response relationships was statistically significant. CONCLUSIONS: Overall, our reanalysis provided little evidence to support NCI's suggestion of a causal association between formaldehyde exposure and mortality from NPC. NCI's conclusion of a possible causal association was driven heavily by anomalous findings in one study plant (Plant 1). An independent and larger study of Plant 1 by the current authors concluded the NPC excess was not associated with formaldehyde exposure. Our findings cast considerable additional uncertainty regarding the validity of NCI's suggested causal association.

Academies and Institutes↗
PubMed2005

Weighing the results of differing 'low dose' studies of the mouse prostate by Nagel, Cagen, and Ashby: quantification of experimental power and statistical results.

Differing experimental findings with respect to "low dose" responses in the mouse prostate after in utero exposure have generated considerable controversy. An analysis of such controversies requires a broad strength and weight of the evidence approach. For example, a National Toxicology Program review panel acquired the raw data from nearly 50 studies and then statistically reanalyzed these data in a common and comparable approach. However, the statistical power of the various studies was not calculated and the quantitative p values were not reported in this reanalysis. Such calculations and values address vital strength- and weight-of-the-evidence questions: (1) how sensitive were the various studies to detect changes in prostate weight, particularly the negative replicate studies and (2) what were the p values; were negative studies robust or only marginal in their inability to find an effect? We first examined the statistical power of the studies to detect a positive effect on prostate weight. Preliminary calculations indicated that the two subsequent replicating studies were indeed more sensitive to changes in prostate weight in comparison to the original study, having reasonable power to detect an effect at only 50% of the response reported in the original study. Additional calculations were performed using the raw data available from one negative replicating study and the methods recommended by the statistics subpanel of the original review. This analysis used Dunnett's multiple comparison procedure for groups with p<0.05 to infer statistical significance, employed an analysis-of-covariance model with body weight as a covariate, and addressed litter as a nested random effect. The quantitated p values for this replicated study, comparing the two Bisphenol A treatment groups (2 and 20 microg/kg/day) to the control, were 0.821 and 0.972, respectively. This indicates this study was indeed robust in finding no treatment-related effect. Thus, the weight and strength of the evidence, based on sensitivity and quantitative p value, was that it is highly unlikely for this negative replicating study to have missed a true effect. In the future, we recommend a similar use of statistical power analysis for those designing experimental studies and for those conducting weight-of-the-evidence reviews, and we also recommend the clear quantitation and reporting of p values to support the review's interpretation and conclusions.

Algorithms↗
PubMed2006

Mis-specified and non-robust mortality risk models for nasopharyngeal cancer in the National Cancer Institute formaldehyde worker cohort study.

An IARC (International Agency for Research on Cancer) working group categorized formaldehyde as a human carcinogen (Group 1) in 2004. A major component of the epidemiologic evidence evaluated by IARC to reach this decision was the analysis published by Hauptmann et al. [Hauptmann, M., Lubin, J. H., Stewart, P. A., Hayes, R. B., Blair, A. 2004. Mortality from solid cancers among workers in formaldehyde industries. Am. J. Epidemiol. 159, 1117-1130.] of the National Cancer Institute (NCI) historical cohort comprising industrial workers exposed to formaldehyde in 10 U.S. plants. The NCI authors emphasized the relationship found between highest formaldehyde peak exposure and death from nasopharyngeal cancer (NPC). We performed two additional types of re-analyses of the NCI cohort data with focus on peak exposure and NPC mortality. The analyses were aimed at (1) investigating whether the model specification chosen by Hauptmann et al. (2004) was appropriate (interaction assessment) and (2) exploring the degree of instability of the risk estimates for NPC in relation to highest peak exposure (sensitivity analysis). Hauptmann et al. (2004) failed to account for an important interaction structure between plant group and the exposure variable that prohibits a generalization of formaldehyde effects within the NCI cohort and, in particular, beyond the NCI cohort. In addition, our sensitivity analysis demonstrates considerable uncertainties in the risk estimates and points convincingly to instability problems particularly related to Plant 1. Even a simple sensitivity model taking only one additional death into account produced a variation of the risk estimates beyond the instability conveyed by standard confidence intervals. The results of our current reanalysis of the NCI study do not support NCI's suggestion of a causal association with formaldehyde exposure and nasopharyngeal cancer. The decision by the IARC working group to reclassify formaldehyde as a Group 1 substance was clearly premature considering: (1) the missing evidence of an NPC excess from the large British and NIOSH cohort studies; (2) the absence of an association with formaldehyde and NPC in the independent and expanded study of Plant 1; and (3) the mis-specified and non-robust internal analysis of the NCI cohort study brought to light in our current re-analysis. Thus, the 2004 IARC decision to reclassify formaldehyde as a Group 1 substance should be reconsidered.

Adenocarcinoma↗
PubMed1991

Further analysis of contraceptive failure of the ovulation method.

Reanalysis of data on the ovulation method of natural family planning collected by the World Health Organization yields the following conclusions. The method is effective during perfect (correct and consistent) use, with a first-year probability of failure of 3.4%. However, it is extremely unforgiving of imperfect use, with a first-year probability of failure of 84.2% if the method is not used correctly. During the initial year, 87% of the cycles were characterized by perfect use. Nevertheless, the 13% of cycles characterized by imperfect use had a tremendous impact on the overall failure rate. During the first year of typical use 22.5% of the women in the clinical trial became accidentally pregnant.

Adult↗
PubMed1996

Use of computerized morphometric analyses of endometrial hyperplasias in the prediction of coexistent cancer.

OBJECTIVE: Our purpose was to determine whether computerized morphometric analysis is predictive of coexistent cancer in uteri that show endometrial hyperplasia in curettings or biopsy specimens. STUDY DESIGN: Forty-five patients with endometrial hyperplasia and 10 patients with well-differentiated cancers diagnosed from curettings or biopsy specimens and treated by hysterectomy at Thomas Jefferson University Hospital between 1989 and 1993 were identified from the pathology department archives. Curettings were analyzed by computerized morphometric analysis at the Free University Hospital in Amsterdam. Pathologists performing the morphometric analyses were blinded to the pathologic diagnoses obtained by examining the hysterectomy specimens. The histopathologic classification of the hysterectomy specimens were used as the end point. RESULTS: Twelve of 45 patients with endometrial hyperplasia (26.7%) by preoperative histopathologic classification showed coexistent carcinoma at hysterectomy. All instances of carcinoma occurred in patients with atypical hyperplasia. Sensitivity of morphometric analysis to predict carcinoma was 100%, with a specificity of 88.5%. The positive predictive value was 83.3%, and the negative predictive value was 100%. A blinded reanalysis of the quantitative analysis in 16 patients showed good reproducibility of this technique (r = 0.93). CONCLUSIONS: Morphometric analysis is useful for predicting which patients with endometrial hyperplasia have coexistent carcinomas. Computerized morphometric analysis may be useful in therapeutic decision making for complex atypical hyperplasia.

Aged↗