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Nonreversible conductive airway ventilation heterogeneity in mild asthma.

A multiple-breath washout technique was used to assess residual ventilation heterogeneity in the conductive and acinar lung zones of asthmatic patients after maximal beta(2)-agonist reversibility. Reversibility was assessed in 13 patients on two separate visits corresponding to a different baseline condition in terms of forced expiratory volume in 1 s [FEV(1); average FEV(1) over 2 visits: 92 +/- 21% of predicted (SE)]. On the visit corresponding to each patient's best baseline, 400 micro g salbutamol led to normal acinar ventilation heterogeneity, normal FEV(1), and normal peak expiratory flow; i.e., none was significantly different from that obtained in 13 matched controls. By contrast, conductive ventilation heterogeneity and forced expiratory flow after exhalation of 75% forced vital capacity remained significantly different from controls (P < or = 0.005 on both indexes). In addition, the degree of postdilation conductive ventilation heterogeneity was similar to what was previously obtained in asthmatic individuals with a 19% lower baseline FEV(1) and twofold larger acinar ventilation heterogeneity (Verbanck S, Schuermans D, Noppen M, Van Muylem A, Paiva M, and Vincken W. Am J Respir Crit Care Med 159: 1545-1550, 1999). We conclude that, even in the mildest forms of asthma, the most consistent pattern of non-beta(2)-agonist-reversible ventilatory heterogeneity is in the conductive lung zone, most probably in the small conductive airways.

Adrenergic beta-Agonists↗

Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice.

We measured the mechanical properties of the respiratory system of C57BL/6 mice using the optimal ventilation waveform method in closed- and open-chest conditions at different positive end-expiratory pressures. The tissue damping (G), tissue elastance (H), airway resistance (Raw), and hysteresivity were obtained by fitting the impedance data to three different models: a constant-phase model by Hantos et al. (Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. J Appl Physiol 72: 168-178, 1992), a heterogeneous Raw model by Suki et al. (Suki B, Yuan H, Zhang Q, Lutchen KR. J Appl Physiol 82: 1349-1359, 1997), and a heterogeneous H model by Ito et al. (Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. J Appl Physiol 97: 204-212, 2004). Both in the closed- and open-chest conditions, G and hysteresivity were the lowest and Raw the highest in the heterogeneous Raw model, and G and H were the largest in the heterogeneous H model. Values of G, Raw, and hysteresivity were significantly higher in the closed-chest than in the open-chest condition. However, H was not affected by the conditions. When the tidal volume of the optimal ventilation waveform was decreased from 8 to 4 ml/kg in the closed-chest condition, G and hysteresivity significantly increased, but there were smaller changes in H or Raw. In summary, values of the obtained mechanical properties varied among these models, primarily due to heterogeneity. Moreover, the mechanical parameters were significantly affected by the chest wall and tidal volume in mice. Contribution of the chest wall and heterogeneity to the mechanical properties should be carefully considered in physiological studies in which partitioning of airway and tissue properties are attempted.

Airway Resistance↗

Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number heterogeneity in Barrett's adenocarcinoma.

Amplification of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c-erbB-2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett's adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n = 5) and dysplastic areas (n = 4). For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoral heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogeneous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoral gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her-2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c-erbB-2 protein overexpression and Her-2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c-erbB-2 status in small biopsies and possibly influence the effectiveness of a potential c-erbB-2 targeting therapy. Figures on http://www.esacp.org/acp/2000/20-1/walch.htm+ ++.

Adenocarcinoma↗

In vivo temperature heterogeneity of atherosclerotic plaques is determined by plaque composition.

BACKGROUND: Temperature heterogeneity of atherosclerotic plaques has been associated with macrophage accumulation in ex vivo studies. We investigated in vivo whether modifying the cell composition of rabbit atherosclerotic plaques by dietary cholesterol lowering can influence temperature heterogeneity. METHODS AND RESULTS: Twenty New Zealand rabbits were randomized to either a normal (n=10) or cholesterol-rich (0.3%) diet (n=10) for 6 months. Thereafter, intravascular ultrasound and intravascular catheter-based thermography of the surface of aortic arch and descending aorta were performed in all animals. Ten control and 5 hypercholesterolemic rabbits were euthanized, and their aortas were analyzed histologically. The 5 remaining rabbits received a normal diet for 3 months and underwent repeat ultrasound and thermography before euthanasia followed by histology. Ex vivo temperature was measured in 3 additional rabbits at 6 months to correlate local temperature with local plaque composition. In control animals, plaque formation and temperature heterogeneity were absent. In hypercholesterolemic rabbits, plaque formation was prominent in the thoracic aorta. Plaques were composed of fibromuscular tissue and contained, underneath endothelial cells, an accumulation of foam cells of macrophage origin. Temperature heterogeneity was markedly elevated and increased with plaque thickness. Importantly, after 3 months of cholesterol lowering, plaque thickness remained unchanged, but temperature heterogeneity was significantly decreased. This paralleled plaque histology, which showed a marked loss of macrophages. The ex vivo experiments demonstrated the relation between local temperature and local total macrophage mass. CONCLUSIONS: In vivo temperature heterogeneity of rabbit atherosclerotic plaques is determined by plaque composition. In vivo thermography may have important clinical implications in the assessment of plaque composition.

Animals↗

Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families.

BACKGROUND: The Romano-Ward long-QT Syndrome (LQTS) is an autosomal dominant inherited trait characterized by prolonged QT interval on ECG, life-threatening arrhythmias, syncope, and sudden death in affected individuals. A gene responsible for this disorder has been shown to be linked to the Harvey ras-1 locus (H-ras-1) DNA marker on the short arm of chromosome 11 (11p) in 7 families. The purpose of this study was to determine, by analyzing 23 families with LQTS for linkage to chromosome 11p, whether evidence exists for more than one gene causing LQTS (ie, locus heterogeneity). METHODS AND RESULTS: Twenty-three families (262 family members) were clinically evaluated using medical histories, ECGs, and Holter recordings. Each corrected QT interval (QTc) were determined using Bazett's formula. Blood for DNA extraction and cell line immortalization was obtained after informed consent. Southern blotting and polymerase chain reaction were performed, and linkage analysis carried out using the LINKAGE computer program (v 5.03). Genetic heterogeneity was determined using the HOMOG 2 (v 2.51) computer program. Twenty-three families were studied for evidence of linkage to chromosome 11p using the H-ras-1 locus probe pTBB-2 and multiple flanking markers, including tyrosine hydroxylase (TH). Two-point linkage analysis using pTBB-2 and TH markers was consistent with linkage in 15 of 23 families, with the maximum single-family LOD score of +3.038 occurring at theta = 0. However, 8 of 23 families had negative LOD scores, with the values in 4 families being less than -2 at theta = 0, consistent with exclusion of linkage. Analysis with the HOMOG program was consistent with genetic heterogeneity (P < .0001). Multipoint linkage data using pTBB-2 and TH were also examined for evidence of heterogeneity. HOMOG analysis of multipoint LOD scores from 100 cM surrounding the H-ras-1 locus also supported heterogeneity (P < .001). CONCLUSIONS: In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage. The remaining 8 of 23 families had negative LOD scores, 4 of which were definitively excluded from linkage. Thus, genetic heterogeneity is definitively (P < .001) demonstrated for this disorder.

Base Sequence↗

Heterogeneity of clara cell glutathione. A possible basis for differences in cellular responses to pulmonary cytotoxicants.

Clara-cell populations show a high degree of variation in susceptibility to injury by bioactivated cytotoxicants. Because glutathione (GSH) is critical for detoxification of electrophilic metabolites, heterogeneity in Clara cell GSH levels may lead to a wide range of cytotoxic responses. This study was designed to define the distinct GSH pools within Clara cells, characterize heterogeneity within the population, and examine whether heterogeneity contributes to susceptibility. Using fluorescent imaging combined with high-performance liquid chromatography analysis, semiquantitative measurements were obtained by evaluation of GSH using monochlorobimane and monobromobimane. In steady-state conditions, the GSH measured in isolated cells was in the femtomole range, but varied 4-fold between individual cells. Clara cells analyzed in situ and in vitro confirmed this heterogeneity. The response of these cells to compounds that modulate GSH was also variable. Diethylmaleate depleted GSH, whereas GSH monoethylester augmented it. However, both acted nonuniformly in isolated Clara cells. The depletion of intracellular GSH caused a striking decrease in cell viability upon incubation with naphthalene (NA). The sulfhydryl-binding fluorochrome BODIPY, which colocalized with tetramethylrosamine, a mitochondrial dye, demonstrated by confocal microscopy that cellular sulfhydryls are highest in the mitochondria, next-highest in cytoplasm, and lowest in the nucleus. These pools responded differently to modulators of GSH. We concluded that the steady-state intracellular GSH of Clara cells exists in distinct pools and is highly heterogeneous within the population, and that the heterogeneity of GSH levels corresponds closely to the response of Clara cells to injury by NA.

Acetylcysteine↗

A hierarchical Naïve Bayes Model for handling sample heterogeneity in classification problems: an application to tissue microarrays.

BACKGROUND: Uncertainty often affects molecular biology experiments and data for different reasons. Heterogeneity of gene or protein expression within the same tumor tissue is an example of biological uncertainty which should be taken into account when molecular markers are used in decision making. Tissue Microarray (TMA) experiments allow for large scale profiling of tissue biopsies, investigating protein patterns characterizing specific disease states. TMA studies deal with multiple sampling of the same patient, and therefore with multiple measurements of same protein target, to account for possible biological heterogeneity. The aim of this paper is to provide and validate a classification model taking into consideration the uncertainty associated with measuring replicate samples. RESULTS: We propose an extension of the well-known Naïve Bayes classifier, which accounts for biological heterogeneity in a probabilistic framework, relying on Bayesian hierarchical models. The model, which can be efficiently learned from the training dataset, exploits a closed-form of classification equation, thus providing no additional computational cost with respect to the standard Naïve Bayes classifier. We validated the approach on several simulated datasets comparing its performances with the Naïve Bayes classifier. Moreover, we demonstrated that explicitly dealing with heterogeneity can improve classification accuracy on a TMA prostate cancer dataset. CONCLUSION: The proposed Hierarchical Naïve Bayes classifier can be conveniently applied in problems where within sample heterogeneity must be taken into account, such as TMA experiments and biological contexts where several measurements (replicates) are available for the same biological sample. The performance of the new approach is better than the standard Naïve Bayes model, in particular when the within sample heterogeneity is different in the different classes.

Algorithms↗

Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice.

OBJECTIVE: Heterogeneity between study results can be a problem in any systematic review or meta-analysis of clinical trials. Identifying its presence, investigating its cause and correctly accounting for it in analyses all involve difficult decisions for the researcher. Our objectives were: to collate recommendations on the subject of dealing with heterogeneity in systematic reviews of clinical trials; to investigate current practice in addressing heterogeneity in Cochrane reviews; and to compare current practice with recommendations. METHODS: We review guidelines for those undertaking systematic reviews and examine how heterogeneity is addressed in practice in a sample of systematic reviews, and their protocols, from the Cochrane Database of Systematic Reviews. RESULTS: Advice to reviewers is on the whole consistent and sensible. However, examination of a sample of Cochrane protocols and reviews demonstrates that the advice is difficult to follow given the small numbers of studies identified in many systematic reviews, the difficulty of pre-specifying important effect modifiers for subgroup analysis or meta-regression and the unresolved debate concerning fixed versus random effects meta-analyses. There was disagreement between protocols and reviews, often either regarding choice of important potential effect modifiers or due to the review identifying too few studies to perform planned analyses. CONCLUSION: Guidelines that address practical issues are required to reduce the risk of spurious findings from investigations of heterogeneity. This may involve discouraging statistical investigations such as subgroup analyses and meta-regression, rather than simply adopting a cautious approach to their interpretation, unless a large number of studies is available. The notion of a priori specification of potential effect modifiers for a retrospective review of studies is ill-defined, and the appropriateness of using a statistical test for heterogeneity to decide between analysis strategies is suspect.

Clinical Protocols↗

Assessing, accommodating, and interpreting the influences of heterogeneity.

Heterogeneity, ranging from measurement error to variation among individuals or regions, influences all levels of data collected for risk assessment. In its role as a nemesis, heterogeneity can reduce the precision of estimates, change the shape of a population model, or reduce the generalizability of study results. In many contexts, however, heterogeneity is the primary object of inference. Indeed, some degree of heterogeneity in excess of a baseline amount associated with a statistical model is necessary in order to identify important determinants of response. This report outlines the causes and influences of heterogeneity, develops statistical methods used to estimate and account for it, discusses interpretations of heterogeneity, and shows how it should influence study design. Examples from dose-response modeling, identification of sensitive individuals, assessment of small area variations and meta analysis provide applied contexts.

Animals↗

Classification of emphysema in candidates for lung volume reduction surgery: a new objective and surgically oriented model for describing CT severity and heterogeneity.

OBJECTIVE: To elaborate a surgically oriented and objective model for classification of emphysema heterogeneity. PATIENTS AND INTERVENTIONS: CT examinations of 66 candidates for lung volume reduction surgery. DESIGN: Emphysema severity was calculated by computer as the emphysema index (EI), a commonly used computer-based quantification that accurately assesses the extent of emphysema of a CT image. The distribution of the EI in different parts of each lung was illustrated in a diagram with the position in the lung (from cranial to caudal) on the x-axis and the EI on the y-axis. The slope of the fitted line was calculated. As a measure of the variation of the EI within each lung, the EI difference was calculated. RESULTS: A diagram was constructed with the absolute value of slope, k, on the x-axis and EI difference on the y-axis. This resulted in a diagram differentiating markedly heterogeneous, intermediately heterogeneous, and homogeneous emphysema. Nineteen patients fulfilled the criteria of bilateral markedly heterogeneous emphysema, 3 patients filled the criteria of bilateral intermediately heterogeneous emphysema, and 18 patients filled the criteria of bilateral homogeneous emphysema. Twenty-six patients had different types of emphysema in the right and left lung. CONCLUSION: We present a method for classification of emphysema heterogeneity that is (1) objective, (2) surgically oriented, and (3) classifies both lungs separately.

Aged↗

Heterogeneity of human luteinizing hormone. Hydrophobic interaction chromatographic fractionation of some preparations.

The heterogeneity of human luteinizing hormone was investigated with high performance hydrophobic interaction chromatography on a TSK phenyl-5PW column using an ammonium sulphate gradient. Recovery of individual subunits, expressed as immunochemical activity, was in the order of 90%. Recovery of the intact hormone was less, approximately 25%. The technique appeared to be independent of the charge heterogeneity of the individual subunits. Each component as obtained by hydrophobic interaction chromatography showed considerable charge heterogeneity when studied by subsequent isoelectric focusing. Nonetheless, all chromatography fractions derived from either subunit showed the same collection of isoelectric values, quantitatively only differences for the beta-subunits could be detected. Heterogeneity of the individual subunits was clearly demonstrated after incubation of the preparations at 37 or 56 degrees C. The heterogeneity of the beta-subunit observed after incubation at 56 degrees C was different to the heterogeneity after incubation at 37 degrees C. After incubation at 56 degrees C, an additional component, with a longer retention time, developed directly from the intact molecule. The component is unstable and is transformed to one of the components detected also after incubation at 37 degrees C. Based on these results the existence of two populations of intact LH molecules with respect to their thermal stability is hypothesized.

Chemical Fractionation↗

Heterogeneity shapes invasion: host size and environment influence susceptibility to a nonnative pathogen.

Theoretical study of invasion dynamics has suggested that spatial heterogeneity should strongly influence the rate and extent of spreading organisms. However, empirical support for this prediction is scant, and the importance of understanding heterogeneity for real-world systems has remained ambiguous. This study quantified the influence of host and environmental heterogeneity on the dynamics of a 19-year disease invasion by the exotic and fatal pathogen, Phytophthora lateralis, within a stream population of its host tree, Port Orford cedar (Chamaecyparis lawsoniana). Using dendrochronology, we reconstructed the invasion history along a 1350-m length of infected stream, which serves as the only route of pathogen dispersal. Contrary to theoretical predictions, the temporal progression of the disease invasion was not related to a host's downstream spatial position, but instead was determined by two sources of heterogeneity: host size and proximity to the stream channel. These sources of heterogeneity influenced both the epidemic and endemic dynamics of this pathogen invasion. This analysis provides empirical support for the influence of heterogeneity on the invasion dynamics of a commercially important forest pathogen and highlights the need to incorporate such natural variability into both invasion theory and methods aimed at controlling future spread.

Animals↗

Nitrogen spatial heterogeneity influences diversity following restoration in a ponderosa pine forest, Montana.

The resource heterogeneity hypothesis (RHH) is frequently cited in the ecological literature as an important mechanism for maintaining species diversity. The RHH has rarely been evaluated in the context of restoration ecology in which a commonly cited goal is to restore diversity. In this study we focused on the spatial heterogeneity of total inorganic nitrogen (TIN) following restoration treatments in a ponderosa pine (Pinus ponderosa)/Douglas-fir (Pseudotsuga menziesii) forest in western Montana, USA. Our objective was to evaluate relationships between understory species richness and TIN heterogeneity following mechanical thinning (thin-only), prescribed burning (burn-only), and mechanical thinning with prescribed burning (thin/burn) to discern the ecological and management implications of these restoration approaches. We employed a randomized block design, with three 9-ha replicates of each treatment and an untreated control. Within each treatment, we randomly established a 20 x 50 m (1000 m2) plot in which we measured species richness across the entire plot and in 12 1-m(2) quadrats randomly placed within each larger plot. Additionally, we measured TIN from a grid consisting of 112 soil samples (0-5 cm) in each plot and computed standard deviations as a measure of heterogeneity. We found a correlation between the net increase in species richness and the TIN standard deviations one and two years following restoration treatments, supporting RHH. Using nonmetric multidimensional scaling ordination and chi-squared analysis, we found that high and low TIN quadrats contained different understory communities in 2003 and 2004, further supporting RHH. A comparison of restoration treatments demonstrated that thin/burn and burn-only treatments created higher N heterogeneity relative to the control. We also found that within prescribed burn treatments, TIN heterogeneity was positively correlated with fine-fuel consumption, a variable reflecting burn severity. These findings may lead to more informed restoration decisions that consider treatment effects on understory diversity in ponderosa pine/Douglas-fir ecosystems.

Biodiversity↗

Should heterogeneity be the basis for conservation? Grassland bird response to fire and grazing.

In tallgrass prairie, disturbances such as grazing and fire can generate patchiness across the landscape, contributing to a shifting mosaic that presumably enhances biodiversity. Grassland birds evolved within the context of this shifting mosaic, with some species restricted to one or two patch types created under spatially and temporally distinct disturbance regimes. Thus, management-driven reductions in heterogeneity may be partly responsible for declines in numbers of grassland birds. We experimentally altered spatial heterogeneity of vegetation structure within a tallgrass prairie by varying the spatial and temporal extent of fire and by allowing grazing animals to move freely among burned and unburned patches (patch treatment). We contrasted this disturbance regime with traditional agricultural management of the region that promotes homogeneity (traditional treatment). We monitored grassland bird abundance during the breeding seasons of 2001-2003 to determine the influence of altered spatial heterogeneity on the grassland bird community. Focal disturbances of patch burning and grazing that shifted through the landscape over several years resulted in a more heterogeneous pattern of vegetation than uniform application of fire and grazing. Greater spatial heterogeneity in vegetation provided greater variability in the grassland bird community. Some bird species occurred in greatest abundance within focally disturbed patches, while others occurred in relatively undisturbed patches in our patch treatment. Henslow's Sparrow, a declining species, occurred only within the patch treatment. Upland Sandpiper and some other species were more abundant on recently disturbed patches within the same treatment. The patch burn treatment created the entire gradient of vegetation structure required to maintain a suite of grassland bird species that differ in habitat preferences. Our study demonstrated that increasing spatial and temporal heterogeneity of disturbance in grasslands increases variability in vegetation structure that results in greater variability at higher trophic levels. Thus, management that creates a shifting mosaic using spatially and temporally discrete disturbances in grasslands can be a useful tool in conservation. In the case of North American tallgrass prairie, discrete fires that capitalize on preferential grazing behavior of large ungulates promote a shifting mosaic of habitat types that maintain biodiversity and agricultural productivity.

Agriculture↗

Prevalence and significance of heterogeneous testes revealed on sonography: ex vivo sonographic-pathologic correlation.

OBJECTIVE: Heterogeneous or mottled testes in middle-aged or elderly men are often encountered on sonography. To determine the prevalence, cause, and significance of this finding, we examined 50 testes (25 pairs) from autopsy specimens with sonography and gross and microscopic pathology. SUBJECTS AND METHODS: Testicles were obtained at autopsy from a series of 25 male cadavers (age range, 16-80 years; mean, 62 years). Eight subjects had a history of cancer. Ex vivo sonography was performed and two board-certified radiologists graded the testis by consensus as normal, heterogeneous, or "other abnormality" (cyst, dilated rete, echogenic focus, or halo). Microscopic pathology was obtained in all abnormal (sonographic or gross pathologic) testes. The severity of tubular sclerosis (atrophy) was graded on a scale of 0-3+ by a uropathologist. RESULTS; No testicular tumors were detected. Sonography revealed normal testes in 33 specimens, heterogeneous in seven specimens, and other in 10 specimens (one cyst, two dilated rete, three halos, and seven echogenic foci). Histology revealed that all seven cases of mottled or heterogeneous testis corresponded to extensive (grades 2 and 3) regions of tubular sclerosis (atrophy). A new sonographic finding of the "halo" was attributable to a thickened, adherent tunica albuginea. CONCLUSION: The prevalence of heterogeneous testes in this elderly population was 14% and represented seminiferous tubule atrophy and sclerosis. The prevalence of clinically occult testicular cancer or metastases in this autopsy subject group was nil. Older patients with a mottled or heterogeneous testis, normal color Doppler flow, and no palpable abnormality probably do not need sonographic follow-up.

Adolescent↗

Analysis of active renin heterogeneity.

Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices. (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin.

Animals↗

[Flow cytometry analysis of the DNA content of the prostate cancer--study on the tumor heterogeneity in prostate cancer].

PURPOSE: Clinical significance of DNA ploidy pattern and its DNA heterogeneity is examined in prostate cancer. METHODS: Fresh needle biopsy specimens were analyzed with flow cytometry and were compared with histopathological findings in 42 patients. RESULTS: Seven patients had stage B (1 case of B1, 6 cases of B2), 14 had stage C and 21 had stage D disease respectively. Histopathologically, 18 of the cases were well, 12 were moderately and 12 were poorly differentiated adenocarcinoma. Diploid was observed in 20, aneuploid in 22. Though 22 cases showed no DNA heterogeneity, 14 had type A heterogeneity with aneuploid in association with diploid pattern, and 6 cases had type B heterogeneity in which multiple aneuploid patterns with different D.I. values were observed. The heterogeneity was observed in 28% of well, 58% of moderately and 67% of poorly differentiated adenocarcinoma, respectively, and also in 14% of stage B, 50% of stage C and 57% of stage D patients, respectively. CONCLUSION: We conclude that DNA heterogeneity in prostate cancer is more frequently seen in poorer differentiated ones on histologic grade and in more advanced ones on clinical stage.

Adenocarcinoma↗

[The practice of systematic reviews. V. Heterogeneity between studies and subgroup analysis].

Meta-analysis comprises the analysis of the data of similar studies gathered in a systematic review. If the results of the studies differ (strongly), this is called heterogeneity. Possible causes of heterogeneity are: a wrong choice of type of measure of treatment effect, differences of methodological quality between studies, or real differences between studies. Heterogeneity between studies can be assessed by thorough examination of the differences between study characteristics in combination with a visual inspection of the degree of overlap of the confidence intervals of the estimates of effect of the different studies. By applying the random effects model for pooling, (non-systematic) heterogeneity between studies can be addressed. In case of heterogeneity between studies, sources of heterogeneity should be explored by means of subgroup analysis according to strict, present criteria. Subgroup analysis should address subgroups of patients within studies.

Confidence Intervals↗