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Microsatellite analysis of Pinus taeda L. in Zimbabwe.

Deducing the origin of early 20th century introductions of Pinus taeda into Zimbabwe is possible given microsatellite markers and clear population differentiation in ancestral U.S. populations. This study was designed to determine whether P. taeda introductions into Zimbabwe came from one U.S. region or whether the present-day population is an admixture of introductions from east and west of the Mississippi River Valley. Principal components analysis, Cavalli-Sforza and Edwards' chord distances and presence of diagnostic alleles each indicate that the Zimbabwe population is an admixture. There were five novel alleles in the Zimbabwe population not represented in the indigenous U.S. populations, possibly because of de novo mutation, introgression with other introduced North American pines or sampling error.

Alleles↗

Ecological determinants and temporal stability of the within-river population structure in Atlantic salmon (Salmo salar L.).

A gene diversity analysis was performed using microsatellite loci in order to (i) describe the extent and pattern of population structure in Atlantic salmon (Salmo salar L.) within a river system; (ii) establish the importance of quantifying the signal:noise ratio in accurately estimating population structure; and (iii) assess the potential usefulness of two evolutionary models in explaining within-river population structure from the ecological and habitat characteristics of Atlantic salmon. We found weak, yet highly significant microscale spatial patterning after accounting for variance among temporal replicates within sites. Lower genetic distances were observed among temporal samples at four sampling sites whereas no evidence for temporal stability was observed at the other three locations. The component of genetic variance attributable to either temporal instability and/or random sampling errors was almost three times more important than the pure spatial component. This indicates that not considering signal:noise ratio may lead to an important overestimation of genetic substructuring in situations of weak genetic differentiation. This study also illustrates the usefulness of the member-vagrant hypothesis to generate a priori predictions regarding the number of subpopulations that should compose a species, given its life-history characteristics and habitat structure. On the other hand, a metapopulation model appears better suited to explain the extent of genetic divergence among subpopulations, as well as its temporal persistence, given the reality of habitat patchiness and environment instability. We thus conclude that the combined use of both models may offer a promising avenue for studies aiming to understand the dynamics of genetic structure of species found in unstable environments.

Animals↗

The leatherback turtle, Dermochelys coriacea, exhibits both polyandry and polygyny.

The leatherback turtle (Dermochelys coriacea) is an endangered species, and world-wide populations are declining. To understand better the mating structure of this pelagic and fragile species, we investigated paternity in nearly 1000 hatchlings from Playa Grande in Parque Marino Nacional Las Baulas, Costa Rica. We collected DNA samples from 36 adult female leatherbacks and assessed allele frequency distributions for three microsatellite loci. For 20 of these 36 females, we examined DNA from hatchlings representing multiple clutches, and in some cases assessed up to four successive clutches from the same female. We inferred paternal alleles by comparing maternal and hatchling genotypes. We could not reject the null hypothesis of single paternity in 12 of 20 families (31 of 50 clutches), but we did reject the null hypothesis in two families (eight of 50 clutches). In the remaining six families, the null hypothesis could not be accepted or rejected with certainty because the number of hatchlings exhibiting extra nonmaternal alleles was small, and could thus be a result of mutation or sample error. Successive clutches laid by the same female had the same paternal allelic contribution, indicating sperm storage or possibly monogamy. None of 20 females shared the same three-locus genotype whereas there were two instances of shared genotypes among 17 inferred paternal three-locus genotypes. We conclude that both polyandry and polygyny are part of the mating structure of this leatherback sea turtle population.

Animals↗

AFLP utility for population assignment studies: analytical investigation and empirical comparison with microsatellites.

Individual-based population assignment tests have thus far mainly relied on the use of microsatellite loci. However, the logistic difficulty of screening large numbers of loci required to reach sufficient statistical power hampers the usefulness of microsatellites in situations of weak population structuring. Amplified fragment length polymorphisms (AFLP) represents an alternative for overcoming this logistical issue as the technique allows the user to characterize a much larger number of loci with a comparable analytical effort. In this study, an assignment test based on maximum likelihood for dominant markers was used to investigate the potential usefulness of AFLP for population assignment. We also compared assignment success achieved with AFLP with that obtained using microsatellites in a case study of low population differentiation involving whitefish (Coregonus clupeaformis) sympatric ecotypes. The analytical investigation showed that the minimum number of AFLP loci required to reach an assignment success of 95% stood within values that are easily achievable in many situations. This also showed how assignment success varied according to the number of AFLP loci used, their absolute frequency and their frequency differential and sampling errors, as well as the number of putative source populations. The case study showed that given a comparable analytical effort in the laboratory, AFLP were much more efficient than the microsatellite loci in discriminating the source of an individual among putative populations. AFLP resulted in higher assignment success at all levels of stringency and the log-likelihood differences between populations obtained with AFLP for each individual were much larger than those obtained with microsatellites. These results indicate that research involving individual-based population assignment methods should benefit importantly from the use of AFLP markers, especially in systems characterized by weak population structuring.

Data Interpretation, Statistical↗

Population genetic analysis of white shrimp, Litopenaeus setiferus, using microsatellite genetic markers.

The white shrimp (Litopenaeus setiferus) is a commercially and recreationally valuable species, yet little is known of its population structure or genetic diversity. White shrimp are distributed along the Atlantic coast of the United States and from the west coast of Florida to the Bay of Campeche, Mexico. In this study, shrimp were collected from North Carolina, South Carolina (four separate collections were taken from 1995 to 1999), Georgia, the Atlantic and Gulf coasts of Florida, Louisiana, Texas and Mexico. DNA was isolated from these individuals, and genetic variation was assessed at six microsatellite loci. These loci were, for the most part, highly polymorphic with an average expected heterozygosity of 0.68. Deviations from Hardy-Weinberg proportions were observed over all samples, but experimental results suggested the presence of null alleles, which confounded a biological interpretation of this result. Pairwise tests of the similarity of allele frequency distributions and distance measure analyses showed broad-scale genetic homogeneity superimposed over occasional indications of random geographical and temporal differentiation. FST and RST estimates over all loci and samples were 0.002 or less and indicated little population structure. Weak but significant genetic differentiation was evident only between pooled western Atlantic and pooled Gulf of Mexico samples. Within the Gulf of Mexico or within the western Atlantic, the large-scale genetic homogeneity observed may be a consequence of genetic mixing resulting from pelagic larvae and adult migrations, while the random local genetic differentiation may be a result of genetic sampling or experimental sampling error. The weak differentiation between shrimp from the Gulf of Mexico and the western Atlantic can be explained by a relatively recent separation of these two populations and/or small amounts of ongoing gene flow.

Animals↗

Amplified fragment length polymorphism versus random amplified polymorphic DNA markers: clonal diversity in Saxifraga cernua.

Random amplified polymorphic DNA (RAPD) markers are sensitive to changes in reaction conditions and may express polymorphisms of nongenetic origin. Taxa with variable chromosome numbers are particularly challenging cases, as differences in DNA content may also influence marker reproducibility. We addressed these problems by comparing RAPD and amplified fragment length polymorphism (AFLP) analyses of clonal identity and relationships in a chromosomally variable arctic plant, the polyploid Saxifraga cernua, which has been thought to be monoclonal over large geographical distances. Fifty-seven plants from four Greenland populations were analysed using a conservative scoring approach. In total, 26 AFLP and 32 RAPD multilocus phenotypes (putative clones) were identified, of which 21 were identical and each of the remaining five AFLP clones was split into two to three very similar RAPD clones. This minor difference can be explained by sampling error and stochastic variation. The pattern observed in Greenland corroborates our previous results from Svalbard, suggesting that rare sexual events in S. cernua are sufficient to maintain high levels of clonal diversity even at small spatial scales. We conclude that although AFLP analysis is superior in terms of efficiency, RAPDs may still be used as reliable markers in small low-tech laboratories.

Cluster Analysis↗

A topographic study of Helicobacter pylori density, distribution and associated gastritis.

BACKGROUND AND AIMS: The topographic distribution and density of Helicobacter pylori and associated gastritis in the stomach were studied in order to determine which biopsy sites are likely to provide the maximum yield so as to reduce the fallacious results due to sampling error. METHODS: Fifty patients with upper gastrointestinal symptoms were studied. Eleven gastric biopsies from predetermined sites were obtained and subjected to ultra-rapid urease test, imprint cytology and histology. Haematoxylin and eosin stain was used for defining gastritis and other associated histopathological details. Loeffler's methylene blue stain was used to confirm the presence of H. pylori in imprint smears and histological sections. RESULTS: All 50 patients had H. pylori infection and evidence of chronic gastritis at one or more of the 11 biopsy sites. Maximum and minimum percentage positivity were observed at A3 (antral lesser curvature) and B4 (corpus greater curvature), respectively. Various sites in decreasing order of percentage positivity were A3 > A2 > A1 > A4 > B3 > B1 > A5 > B6 > B5 > B2 > B4. Among the biopsies obtained from the corpus, B3 (corpus lesser curvature) was the site with maximum positivity. A3 and B4 had a statistically significant difference in percentage positivity (P < 0.0001) for H. pylori and gastritis. The maximum and minimum density scores of H. pylori and gastritis were found in A3 and the B4, respectively. A3 had a significantly higher (P < 0.0001) mean density score than any other site in the stomach. The difference in the grading of H. pylori between A3 and B3 (sites of maximum positivity in antrum and corpus) was statistically significant (P < 0.0001). A statistically significant (P < 0.001) positive correlation between increasing grades of H. pylori and gastritis was observed at the site of maximum density. Eighty per cent of the patients had antral predominant gastritis and in 82%, H. pylori was predominantly observed in antral biopsies. CONCLUSION: It is concluded that two biopsies taken from A3 are sufficient for confirmation of presence of H. pylori and associated gastritis for initiation of treatment. However, additional biopsies from B3 will help in deciding the topographic pattern of gastritis.

Adult↗

Assessment of DNA content in formalin-fixed, paraffin-embedded tissue of lung cancer by laser scanning cytometer.

A new cytometric device, a laser scanning cytometer was developed to overcome the limitations of flow cytometry (FCM) and image analyses. The purpose of this study was to develop a method that allows laser scanning cytometry (LSC) to be used for measuring the cellular DNA content of paraffin-embedded tissues. Paraffin-embedded lung cancer tissue from 30 patients was analyzed by both FCM (p-FCM) and LSC (p-LSC). In addition, touch preparations from fresh frozen tissues were prepared to provide material for LSC (f-LSC). The limits of agreement for the DNA indices (DI) measured by p-LSC and p-FCM were -0.07 to 0.07, indicating that for a given case, these methods would be expected to differ by no more than 0.07. The limits of agreement for comparisons between the other materials and methods were wider and depended upon the size of the measurements. Agreement between f-LSC and p-FCM was good for small DI values, but poor for large values. Agreement between f-LSC and p-LSC was poor for small and large DI values, but good for moderately sized values. Discordancies in DNA ploidy status between different materials and methods may have been caused by either the heterogeneity within tumors, sampling errors or differences in the interpretation of histograms. This method allows a comparison of the results of DNA analysis with histologic findings from hematoxylineosin-stained sections and the prognosis of the patients.

Aneuploidy↗

Immunohistochemical presentation in non-malignant and malignant Barrett's epithelium.

Barrett's esophagus, which is histologically characterized by metaplastic columnar epithelium, is a common condition observed in approximately 10-20% of patients with gastroesophageal reflux disease. These lesions can typically progress from metaplasia with atypia to low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. It is of great clinical importance to correctly grade these lesions and to identify changes with a high risk of malignant transformation, inasmuch as high-grade dysplasias and early adenocarcinomas in patients with Barrett's esophagus have a high chance for cure. The identification of high-risk lesions in Barrett's esophagus by histologic evaluation has drawbacks, especially regarding sampling errors and frequent intra- and interobserver discrepancies in the histopathologic grading/staging of these lesions. Immunostaining with a variety of antibodies provides a better understanding of the process of malignant transformation and helps to identify early markers of malignant transformation in Barrett's esophagus lesions. In this review, we will summarize the current knowledge about the value of immunostaining in the diagnosis of malignant and non-malignant Barrett's epithelium and its role to better define lesions with high risk for malignancy in this disorder.

Barrett Esophagus↗

New technique to assess the axilla for breast cancer metastases using cell separation technology.

INTRODUCTION: Accurate staging of the axilla for metastatic disease is critical in deciding on the optimal management of patients with breast cancer. Lymph node status is the most powerful prognostic factor. Current standard surgical management of breast cancer involves axillary dissection for staging. Pathological staging by routine histology, however, is known to understage the disease extent because only one or two sections are taken from each node, a sampling of less than 1% of most nodes. Sentinel node biopsy is currently under trial to determine if thorough pathological staging of the most likely involved node is more accurate than standard pathological assessment of all nodes. The present pilot study was undertaken to investigate an alternative method of assessing all axillary nodes for cancer cells. METHODS: After routine material was taken from lymph nodes for standard pathological assessment, discarded parts of nodes were used for the study technique. These node parts were mechanically disaggregated, and the cell suspension centrifuged on a density gradient to separate any tumour cells (into the pellet) from lymphocytes (at the top of the gradient). The pellet was then assessed by haematoxylin and eosin and immunohistochemistry. RESULTS: The results of the present study proved highly significant. The technique detected metastatic cells in three nodes which were negative on routine pathology, in one case changing the status of the patient from node-negative to node-positive. DISCUSSION: It is concluded that the technique examined in the present paper has the potential to reduce sampling error, may offer far more accurate axillary staging than routine histopathology, and should be further evaluated in a controlled trial.

Axilla↗

Fetal gender: antenatal discrepancy between phenotype and genotype.

Sexual discrepancy is reported in both 46,XY females and 46,XX males, and most diagnoses of sex reversal are made in the postpubertal period. We report three cases of sexual discrepancy, which were revealed by karyotyping following genetic amniocentesis, chorionic villus sampling and fetal blood sampling. The etiologies of 46,XX male, 45,X male and 46,XY female subjects are reviewed. When sexual discrepancy between fetal karyotype and ultrasonographic fetal phenotype is encountered, sample error and placental mosaicism should be excluded. A detailed fetal ultrasound examination should be performed to check for syndromic gender discrepancy. When repeat karyotyping is indicated, localization of the Sox related Y chromosome gene should be carried out.

Abnormalities, Multiple↗

The appropriate rate of breast conserving surgery: an evidence-based estimate.

PURPOSE: The objective of the present study was to estimate the proportion of incident cases of breast cancer that should receive breast conserving surgery (BCS), using an evidence-based approach. METHODS: An extensive search of the literature was undertaken to identify eligibility criteria for BCS. The eligibility criteria for BCS were combined with the information about case mix and patient preference to estimate the need for BCS. An epidemiological approach was then used to estimate the incidence of each eligibility criterion for BCS in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of BCS was calculated, and the effect of systematic error using alternative sources of information, was estimated by sensitivity analysis. RESULTS: The analysis showed that 69.6% of breast cancer cases are eligible for BCS, and that 48.0 +/- 6.0% of breast cancer patients are both eligible for BCS and prefer it to mastectomy. Based on sensitivity analysis, the plausible range of the appropriate rate was 42.1% to 49.43%. The proportion of breast cancer cases in which BCS was appropriate was stage dependent; 63.0 +/- 11.5% in ductal carcinoma in-situ; 57.0 +/- 9.9% in stage I; 52.2 +/- 9.4% in stage II, and 27.2 +/- 5.2% in stage III. CONCLUSIONS: This model suggests that BCS is appropriate in 48% of all breast cancer patients. This information may be useful in auditing surgical practice, and may serve as a basis for planning of ancillary services, including radiotherapy.

Breast Neoplasms↗

Eight false negative sentinel node procedures in breast cancer: what went wrong?

AIMS: The purpose of the study was to evaluate the false negative sentinel node procedures in patients with breast cancer at our institution. METHODS: A total of 606 sentinel node biopsies were performed on 599 clinical N0 breast cancer patients between January 1997 and November 2001. RESULTS: The axillary sentinel node revealed metastasis in 204 (36.1%) of the 565 patients in whom it was identified and was false negative in eight patients. Two false negative results came to light by confirmatory axillary lymph node dissection during the learning phase. Tumour-positive lymph nodes were incidentally found in the axillary tail of the simple mastectomy specimen in two patients. Excision of a firm, non-radioactive, unstained but tumour-positive non-sentinel node occurred in three other patients. One patient developed an axillary recurrence 22 months postoperatively. Presumptive causes were surgical delay, pathological sampling error and tumour blocking. CONCLUSION: Intra-operative palpation of the axilla to identify suspicious lymph nodes is recommended. In a two-day protocol, surgery should be performed first thing in the morning. Seven slices of 50-150-micro m strike an acceptable balance between sensitivity and work load for the pathologist.

Adult↗

Cytopathology of thymic epithelial neoplasms.

A cytologic diagnosis of thymoma is extremely challenging. In part, this is because the tumor is uncommon and aspirates are infrequently encountered, a technically proficient interventional radiologist is needed, epithelial cells may be difficult to recognize in lymphoid rich aspirate smears, and there is inherent sampling error in a tumor that frequently displays heterogeneous histopathology. Critical to the cytologic diagnosis of most WHO Type B thymomas is the recognition of a distinct population of epithelial cells mixed with lymphocytes. This is more easily accomplished using Papanicolaou or H&E stains, and often requires a cytokeratin stain for verification (in the correct clinical-radiologic context) because these cells are cytologically bland and have a varying amount of cohesiveness. WHO Type A thymoma may contain only epithelial cells and thus mimic a spindle cell neoplasm, or mesothelial cell clusters. Limitations of the cytologic method include an unproven ability to definitively separate thymoma into specific WHO subtypes using cytology alone, and to determine capsular invasion. Non-neuroendocrine thymic carcinomas mimic their extra-thymic counterparts in cytologic aspirates, and their malignant nature is usually readily recognizable. Thymic neuroendocrine carcinomas (NEC) are also cytologically identical to their more common pulmonary sites of origin, but identification of moderately-differentiated NEC is generally not possible.

Biopsy, Fine-Needle↗

Nuclear medicine studies of the prostate, testes, and bladder.

During the last decade, there has been a significant advancement in imaging of urologic diseases. Transrectal ultrasound (TRUS), computerized tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) are still experiencing new developments in urology. Despite these many technological advances, the initial diagnostic procedure for a patient with suspected prostate cancer (PC) is multiple site blind prostate biopsies. There is a need for a noninvasive metabolic imaging modality to direct the site of biopsy to decrease the sampling error. MRS seems promising but as it is a costly and more time-consuming test, further studies are needed to evaluate its clinical utility. Currently, PET does not play any role to direct biopsy. Acetate and choline appear to be better tracers than FDG for the detection of a prostate lesion, however, further well-organized studies are needed before any of these agents can be used clinically. Incidental detection of intense focal uptake in the prostate during whole body PET scanning should be evaluated with prostate-specific antigen (PSA) and TRUS-guided biopsy. Although FDG is inferior to other tracers for primary staging, it may be useful in selected patients with suspected high-grade cancer. The role of ProstaScint scan is still controversial for detection of recurrent PC. This study may be helpful for evaluating nodal metastases when PSA is elevated and bone scan is negative. Bone scan remains the study of choice when bone metastases are suspected (PSA>15-20 ng/mL+/-bone pain). Acetate and choline provide better accuracy than FDG in the detection of local soft tissue disease, nodal involvement, and distant metastases. High FDG uptake may be indicative of more aggressive and possibly androgen-independent disease. PET/CT with any of the above PET tracers will most likely be preferred to the PET scan alone due to better localization of a hot lesion in PET/CT. Nuclear medicine studies also have been used to evaluate acute scrotum and testicular neoplasms. Scrotal scintigraphy has lost its popularity to Doppler ultrasound in the evaluation of the acute scrotum. In testicular tumors, FDG-PET appears to be superior to conventional imaging modalities in initial staging, detection of residual/recurrence, and monitoring treatment response. Tumor markers after treatment occasionally are elevated and cannot locate the site of recurrence, FDG-PET can play a very important role in this regard. Nuclear medicine studies also have been used to evaluate diseases of the urinary bladder. Radionuclide cystography is more sensitive and has less than 1/20 the radiation exposure of the conventional contrast enhanced micturating cystourethrogram (MCU). However, the utility of FDG-PET in the evaluation of bladder cancer seems to be limited to the evaluation of distant metastases. 11C-Methionine and choline may be a better option for local and nodal disease due to their negligible excretion in the urine.

Humans↗

Noninvasive monitoring of patients with chronic hepatitis C.

Hepatic fibrosis is the main determinant of clinical outcomes of chronic hepatitis C. Liver histology is frequently considered the gold standard for assessing hepatic fibrosis. However, liver biopsy is associated with sampling error, interobserver variability, and potential complications. Thus, there is a need for simple, inexpensive, and reliable noninvasive means to assess disease severity in patients with chronic hepatitis C. Clinical examination is unreliable in differentiating different stages of compensated liver disease. Among the routine laboratory tests, decreased platelet count, increase in the ratio of aspartate to alanine aminotransferase (AST/ALT), and prolonged prothrombin time are the earliest indicators of cirrhosis and portal hypertension. Individual serum fibrosis markers have limited accuracy in predicting hepatic fibrosis. Indices composed of a panel of markers correlate better with histological fibrosis, but their reliability requires further validation. Currently, noninvasive monitoring of patients with chronic hepatitis C relies on clinical evaluation, routine laboratory tests, and ultrasound and endoscopic surveillance in patients with cirrhosis. Initial evaluation should focus on assessment of activity and stage of liver disease for prognostication and decisions regarding treatment, and to rule out coinfections and other causes of liver disease. Subsequent follow-up should focus on detection of liver disease progression and the need for treatment. The frequency of monitoring and the tests used will depend on the patient's age, stage of liver disease, and comorbid conditions. There is an urgent need to develop and validate noninvasive tests that can accurately reflect the full spectrum of hepatic inflammation and fibrosis in chronic hepatitis C.

Biomarkers↗

Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin.

Liver fibrosis and activity indexes were validated in patients infected by hepatitis C virus (HCV) nontreated and treated by interferon. The aim was to validate their usefulness as surrogate markers of histologic features using the data of a randomized trial of combination peginterferon alfa-2b and ribavirin. Three hundred fifty-two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected. Two hundred eight patients received peginterferon alfa-2b 1.5 mcg per kg and ribavirin and 144 patients interferon alfa-2b 3 MU three times a week and ribavirin for 48 weeks. A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow-up (24 weeks after treatment). The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity. For the diagnosis of bridging fibrosis and/or moderate necroinflammatory activity, the area under the receiver operating characteristics curve of the activity index was 0.76 +/- 0.03 at baseline and 0.82 +/- 0.02 at end of follow-up. A cutoff of activity index at 0.30 (range, 0.00-1.00) had 90% sensitivity and 88% positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity. Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error. In conclusion, these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C, both for the initial evaluation and for follow-up.

Adult↗

Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses.

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes. We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia.

Arteries↗