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On estimating census undercount in small areas.

"Net undercount rates in the U.S. decennial census have been steadily declining over the last several censuses. Differential undercounts among race groups and geographic areas, however, appear to persist. In the following, we examine and compare several methodologies for providing small area estimates of census coverage by constructing artificial populations. Measures of performance are also introduced to assess the various small area estimates. Synthetic estimation in combination with regression modelling provide the best results over the methods considered. Sampling error effects are also simulated. The results form the basis for determining coverage evaluation survey small area estimates of the 1900 decennial census."

Americas↗

Diagnostic value of fine-needle aspiration from parotid gland lesions.

BACKGROUND: Fine-needle aspiration is a widely accepted method in the preoperative evaluation of head and neck tumors. However, its effectiveness in the interpretation of salivary gland disorders is controversial. OBJECTIVES: To evaluate the effectiveness of FNA as a preoperative diagnostic tool of parotid lesions. METHODS: Reports of 52 FNA from various parotid gland lesions were compared with the final pathologic diagnoses. RESULTS: We noted 31 true positive, 5 true negative and 16 false negative results. There were no false positive FNA reports. The calculated sensitivity, specificity and accuracy of FNA diagnosis in this study were 66%, 100%, and 69.2% respectively. CONCLUSIONS: The high rate (30.8%) of false negative FNA results was partly explained by sampling errors, therefore specificity of the procedure could be improved by the precise selection of a representative aspiration site.

Adolescent↗

Accuracy of cytological findings in abnormal cervical smears by cytohistologic comparison.

To investigate the accuracy rates of cytology in abnormal cervical smears and the factors contributing to a discrepant diagnosis between cytology and histology repots of cervical intraepithelial and invasive neoplasm. During the four-year period 1993 to 1996, abnormal cervical smear findings, which were followed by cervical biopsy, were available in 709 patients. The cytology and histology slides were reviewed in each case. The accuracy rates of cytology before and after review were investigated. The accuracy rate of cytology was 48%. Following review it became 56%, mainly due to a reduction in the number of cases in which the smear showed a lesser degree of CIN than did the biopsy. The proportion of cases in which the cytological impression of CIN was more severe than the histology was minimally altered. The results suggest that difficulty in the interpretation of cervical smear as well as sampling errors are responsible for reduced accuracy even in smears which are considered representative of the pathological process.

Adenocarcinoma↗

Peritoneal carcinomatosis: role of (18)F-FDG PET.

UNLABELLED: Peritoneal carcinomatosis can be difficult to diagnose, as CT is insensitive, with peritoneal biopsy and lavage often subject to problems of sampling error. The aim of our study was to evaluate the role of (18)F-FDG PET in detecting peritoneal carcinomatosis in patients with stomach, ovarian, and adrenal cancer and mesothelioma and to compare the results with CT scans in the same patient group. Our secondary aim was to identify characteristic patterns of abdominal (18)F-FDG uptake in biopsy-proven peritoneal disease and to correlate these patterns with available histologic and anatomic findings after surgery and structural imaging. METHODS: The medical records of 88 patients with stomach (n = 48), ovarian (n = 13), and adrenal cancer (n = 6) and mesothelioma (n = 21) were reviewed for the presence of peritoneal tumor on (18)F-FDG PET and CT scans. The results were correlated with either contemporaneous peritoneal biopsy or ascitic aspirate or with radiographic or clinical follow-up if histology was negative or unavailable. Of 24 patients with suspected peritoneal tumor, 17 had biopsy-proven findings of peritoneal disease. RESULTS: Of the 24 patients with suspected peritoneal tumor, (18)F-FDG PET was positive in 14 patients, with 1 of these scans being false-positive, CT was positive in 10 patients, and either PET or CT was positive in 18 patients. This yielded sensitivities of 57% (13/23), 42% (10/23), and 78% (18/23), with uniformly high positive predictive values of 93% (13/14), 100% (10/10), and 95% (18/19), respectively. We identified 2 distinctly abnormal scintigraphic patterns of focal and uniform (18)F-FDG uptake corresponding to nodular and diffuse peritoneal disease on pathologic examination. CONCLUSION: (18)F-FDG PET adds to conventional imaging in the staging of peritoneal carcinomatosis. It is also a useful diagnostic tool when peritoneal biopsy is either unavailable or inappropriate. We have identified 2 distinct scintigraphic patterns that appear to predict the presence of either nodular or diffuse peritoneal pathology.

Adrenal Gland Neoplasms↗

Imaging of soft tissue tumors.

In a patient presenting with a soft tissue tumor, radiographs are needed to visualize or exclude osseous involvement. Ultrasound can be used to visualize the lesion for cytologic biopsy. If cytology does not rule out sarcoma, magnetic resonance imaging is indicated to stage the lesion. As a rule staging studies other than MR imaging are not needed to evaluate the local situation. Usually MR imaging does not assist in suggesting a specific diagnosis. In certain instances, however, morphology or the presence of high signal intensity on T1, or low signal intensity on T2-weighted images increases specificity. Thick needle biopsy or open biopsy should be performed following MR imaging. This reduces sample errors and increases the accuracy of preoperative staging.

Diagnostic Imaging↗

[Surveillance in public health: the methodological problems in identifying risk factors].

Identification of clusters of health events as well as more general problems in public-health surveillance are being increasingly debated. The authors discuss the differences between the systematic (epidemiologic surveillance) and non-systematic (episodic identification of clusters and/or sentinel events) observations. In this regard the role played by statistical methods appears to be specially worthy of consideration, so as to define the capabilities of a given surveillance system in identifying increasing risks. To take into account the relationship between size of the risk to be evidenced and probability (= power) that the implemented test may be significant, specific tables have been developed displaying the relationship between 1st and 2nd type error, sample size and minimum detectable risk, under different exposure levels.

Humans↗

Rapid detection of MYCN gene amplification in neuroblastomas using the polymerase chain reaction.

We have used the polymerase chain reaction (PCR) to detect amplification of the MYCN oncogene in neuroblastoma cell lines and to distinguish primary tumors with a single copy from those with MYCN amplification using DNA extracted from frozen sections. Two primer pairs were used to co-amplify a 428-bp fragment of the MYCN oncogene along with a 268-bp fragment of the beta-globin gene (a single-copy reference standard). After 30 cycles of PCR, the products were resolved by agarose gel electrophoresis. MYCN gene amplification was identified by visual comparison of the relative intensities of MYCN and beta-globin PCR product bands on the ethidium bromide-stained gel. This semiquantitative approach, while inadequate for precise determination of copy number, provided a simple, rapid, nonisotopic method for differentiating tumors with MYCN amplification from those with a single copy. Seventy-four primary tumors were classified as amplified or nonamplified by semiquantitative PCR. Twenty-two of 23 tumors known to carry MYCN gene amplification by Southern analysis were correctly identified by PCR. The single false-negative result was due to a sampling error: DNA was extracted from a block of tissue containing small foci of tumor surrounded by normal tissue. Fifty-one of 51 tumors with a single copy of MYCN were also correctly identified by PCR. We conclude that semiquantitative PCR is a reliable, non-isotopic alternative to Southern blotting for detection of MYCN gene amplification that can be performed rapidly on DNA extracted from frozen sections.

Base Sequence↗

Presurgical EEG investigation in frontal lobe epilepsy.

Poor localization of the interictal epileptic abnormality and the rather unreliable EEG localization of ictal onsets in patients with frontal lobe epilepsy may be due to some of the following factors: (1) high risk of EEG sampling error, (2) early seizure spread within and outside the frontal lobe, (3) widespread distribution of the epileptogenic brain tissue responsible for the patient's habitual seizures, and (4) secondary bilateral synchrony and secondary epileptogenesis. The relevance of these factors in the preoperative investigation of patients with frontal lobe epilepsy was studied in: (a) 34 adult patients (mean age: 25 years) who became and persisted seizure free after restrictive surgical removal of the anterofrontal region, the parasagittal region convexity or the fronto-opercular area; (b) 12 patients in whom the pre-operative EEG investigation with extracranial electrodes failed to localize the site of seizure onset, leading to further investigation with depth electrodes.

Adult↗

Intrinsic radiosensitivity of normal human fibroblasts and lymphocytes after high- and low-dose-rate irradiation.

The existence of heritable radiosensitivity syndromes and clinical observations in radiotherapy patients suggests that human cellular radiosensitivity differs among individuals. We report here an in vitro study of radiosensitivity in 30 fibroblast and 29 lymphocyte cultures obtained from cancer patients and controls. In 25 cases, both fibroblasts and lymphocytes were obtained from the same donors. Fibroblasts were cultured from skin biopsy samples, and peripheral T-cell lymphocytes were cultured from blood. Clonogenic survival assays were performed by using high- and low-dose-rate irradiation; lymphocytes were in G0 phase and fibroblasts in confluent plateau phase. Various end points were calculated and compared (i.e., surviving fraction at 2 Gy, initial slope of the survival curve, and doses resulting in 10 and 1% survival, respectively). Depending on the end point, the coefficient of variation of the survival parameters ranged from 31 to 68% for lymphocytes and 21 to 41% for fibroblasts following high-dose-rate irradiation. Similar ranges were obtained after low-dose-rate irradiation. Variance analysis performed on replicate assays in cultures derived from the same patient showed that variation due to technical or sampling errors was significantly lower than variation between individuals (P = 0.00034 and 0.014 for fibroblasts and lymphocytes, respectively). No correlation was observed between the radiosensitivity of lymphocyte and fibroblast cultures derived from the same donors. We conclude that there is significant variation in normal cell radiosensitivity among individuals. On the other hand, comparisons of lymphocyte and fibroblast radiosensitivities suggest that tissue-specific characteristics, such as differentiation status, may variably modulate radiosensitivity.

Breast Neoplasms↗

Meningiomas: loss of heterozygosity on chromosome 10 and marker-specific correlations with grade, recurrence, and survival.

PURPOSE: In a study of 208 meningiomas, we found a high incidence of loss of heterozygosity (LOH) on chromosome 10 in benign (73.4%), atypical (80.0%), and malignant (86.7%) tumors. A large percentage of the benign and atypical tumors and an increasing percentage of malignant tumors had LOH on multiple loci (43.9%, 45%, and 66.7%, respectively). The high incidence of LOH occurring early in meningioma progression suggests that LOH at individual alleles may serve as a marker of clinically relevant alterations useful for patient diagnosis, the subclassification of tumors, and/or the treatment of patients. EXPERIMENTAL DESIGN: To test this, we examined 208 sporadic and recurrent meningiomas of all grades for correlations between LOH at 11 markers on chromosome 10 and tumor location, histology, and grade and patient race, gender, age, recurrence, and survival. RESULTS: Several significant correlations were found. The data indicate that genetic differences occur not only between tumors of different grade, but also between tumors of the same grade, and therefore may be useful to define genetic subsets with clinical implications. LOH at D10S179 (P = 0.001) or D10S169 (P = 0.004) is most likely present in higher-grade meningiomas and, when present in benign tumors, may signify sampling error or a morphologically benign but biologically aggressive tumor. Furthermore, LOH at D10S209 (P = 0.06) and D10S169 (P = 0.01) may predict shorter survival and/or higher rates of recurrence, respectively, in tumors with benign or malignant histology. CONCLUSIONS: We conclude that these chromosome 10 markers deserve further testing as unfavorable prognostic indicators for meningioma patients.

Adult↗

Early diagnosis of esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma has increased dramatically in developed countries during the past 2 decades, and prognosis remains very poor. Gastroesophageal reflux disease is an important risk factor for this cancer that develops in patients with specialized esophageal metaplasia (Barrett's esophagus). Careful periodic endoscopic examinations, with random biopsy sampling of the entire mucosal surface, are usually recommended for the surveillance of these patients. Several innovative techniques have recently been developed to improve the accuracy of diagnosis of intestinal metaplasia, dysplasia, and early adenocarcinoma in Barrett's esophagus. Some of these techniques (eg, chromoendoscopy, magnifying endoscopy, and light-induced fluorescence endoscopy) are intended to identify suspicious areas of the mucosa not visible during conventional endoscopic examination and to perform targeted biopsies toward these areas to avoid sampling errors. Optical coherence tomography and confocal laser scanning microscopy are other powerful techniques that provide real-time cross-sectional tissue images at a resolution close to that of histology. They allow tissue characterization based solely on optical properties and are likely to replace excisional biopsies. Although promising, none of these techniques is currently recommendable for routine surveillance of patients with Barrett's esophagus. Further evaluation is warranted to define the optimal method and standardize the procedures.

Adenocarcinoma↗

Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine cervical carcinomas.

PURPOSE: Hypoxia is associated with adverse outcome for a number of solid tumors, including cervical carcinomas. Direct pO(2) measurement requires specialized equipment and expertise that is not generally available. Immunohistochemical measurement of intrinsic tissue markers of hypoxia is an alternative approach. Recent studies suggest that carbonic anhydrase IX (CA IX), which is regulated via hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia. EXPERIMENTAL DESIGN: Biopsies were obtained from 110 patients with locally advanced cervical carcinoma treated with radiotherapy or chemoradiotherapy. Tissue sections were labeled using an immunofluorescence technique and CA IX expression in the viable tumor area measured using a semiautomated fluorescence image analysis technique. Results were compared with direct pO(2) values obtained using an Eppendorf probe and to patient outcome. Intratumoral heterogeneity of CA IX expression was examined in a subgroup of patient who underwent multiple biopsies. RESULTS: The median percentage of tumor area staining for CA IX was 3.56 (range, 0.01-58.85). CA IX staining did not correlate with the Eppendorf pO(2) measurements. Whereas the latter values were predictive of patient outcome, the CA IX levels were not. Measurement of CA IX in multiple biopsies indicated that intratumoral heterogeneity accounted for 41% of the total variance in the data set. CONCLUSIONS: In contrast to some recent studies, we did not find significant associations between CA IX expression and tumor pO(2) levels or patient outcome in locally advanced carcinomas of the cervix. Probable explanations relate to the problems of sampling error using single biopsies and the existence of biological factors other than hypoxia that influence CA IX levels.

Adult↗

[Barrett's esophagus: new developments in endoscopic surveillance].

The current surveillance strategies for patients with a Barrett's oesophagus are hampered by the poor endoscopic visibility of early neoplastic lesions, the sampling error of random biopsies, the subjectivity of the histological evaluation, and the low incidence of carcinoma. New endoscopic techniques are available for a more reliable evaluation of a Barrett's oesophagus: high-resolution endoscopy, chromoendoscopy, fluorescence endoscopy and optical coherence tomography. The use of molecular markers will probably lead to a better risk stratification of patients. Detection of aneuploid cell populations and assessment of an increase of the number of cells in the S- and G2-phase are possible with DNA flow cytometry; flow cytometric abnormalities may be a more reliable predictor of carcinoma than histological assessment. A combined approach with the new endoscopic techniques and molecular markers may lead to a more efficient and cost-effective surveillance programme.

Barrett Esophagus↗

How "Caucasoids" got such big crania and why they shrank. From Morton to Rushton.

In the 19th century measurements of cranial capacity by Morton and others supported a "Caucasoid>Mongoloid>Negroid" hierarchy of intelligence. This continued through most of the 20th century but was challenged by a nonhierarchical view originating with Boas. Beginning in the 1980s Rushton correlated cranial and IQ measurements and presented a hierarchy with "Mongoloids" at the top. Each of these periods relates to its social context: the 19th-century hierarchy paralleled the height of European world domination; the nonhierarchy of the 20th century reflected world wars, worldwide depression, and the breakup of empires; the "Mongoloid>Caucasoid>Negroid" hierarchy followed the economic success of several Asian nations. Morton's cranial ranking was the result of his sampling error and his acceptance of the hierarchical thinking of his time. But how is it possible for Rushton to support the M>C>N ordering while using the data of several anthropologists who have rejected racial hierarchies on empirical grounds? The answer to this question involves a critique of Rushton's use of the race concept, his aggregation of diverse populations into three traditional races, his claim to explain differences in "cultural achievements" on the basis of variation in brain size, and a number of other problems. The study concludes by noting that the major consequence of these hierarchies is the apparent justification for the exploitation of those at the bottom.

Anthropology↗

Diagnosis of liver fibrosis.

Hepatic fibrosis and cirrhosis represent the main consequence of chronic liver diseases of different origin. Therefore, the clinical assessment of disease severity is a must in the management of patients with chronic liver damage. Although liver biopsy may be associated with sampling error, interobserver variability and potential complications, it still remains the gold standard for establishing the severity of hepatic necroinflammation and fibrosis. In the last years, several non-invasive tests for the assessment of disease activity and stage have been proposed. However, at present all these tests are not totally accurate and reliable and need further evaluation.

Biopsy↗

[Advantages and limitations of the motor unit number estimation techniques].

It is now 30 years since the first motor unit number estimation (MUNE) technique was introduced by Allan McComas as a way of providing an objective, sensitive and reproducible means of measuring the number of motor axons in living human muscle or muscle group. MUNE techniques have substantially evolved over the past decade and have been applied, with increasing frequency, to the study of age effects on motoneurone population and muscle denervating disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, poliomyelitis and different types of inherited and acquired peripheral neuropathies. In the future, one of the most important topics involving MUNE, will probably be its use in monitoring the progress of ALS patients undergoing experimental drug trials. However, among incremental, multiple point stimulation, spike-triggered averaging, F-wave analysis and statistical methods, there is no consensus about the best MUNE method. There is only a general feeling that some techniques are more valid than others. For this reason, in the present review, brief descriptions of the distinct MUNE methods are presented. In the second part of the paper, advantages and limitations (alternation, sampling errors, temporal registration etc...) of the most commonly employed procedures are considered.

Amyotrophic Lateral Sclerosis↗

[Fine needle cytology of the thyroid gland].

BACKGROUND: Application of fine needle cytology (FNC) is important in the preoperative assessment of thyroid lesions. The method is rapid, minimally invasive and cost effective. The aim of this study was to evaluate the role of fine needle cytology at The Norwegian Radium Hospital in the management of thyroid nodules. MATERIAL AND METHODS: Data on FNC and comparable histology results were retrieved from the pathology database during the 5-year-period 1998 through 2003. 1770 FNC samples and corresponding histology results from 443 lesions were compared. Reviews of cytological slides were done in 39 discrepant cases and quality assessment parameters calculated. RESULTS: High complete sensitivity (77.5%) and specificity (90.1%) were found. The false positive rate was 1.2% and the false negative rate 23.7%. Inadequate FNCs were particularly seen in submitted specimens. A review of the discrepant cases showed that the main cause of false negative samples was sampling error. Micropapillary carcinoma was the predominant tumour type with false negative FNC. Eleven malignancies were diagnosed in repeat FNC specimens. INTERPRETATION: FNC is a highly reliable test to assess whether a thyroid nodule is benign or malignant. Diagnostic pitfalls are mainly due to inability to procure the diagnostic material.

Biopsy, Fine-Needle↗

Differentiation of low-grade oligodendrogliomas from low-grade astrocytomas by using quantitative blood-volume measurements derived from dynamic susceptibility contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Histopathologic evaluation remains the reference standard for diagnosis of glioma and classification of histologic subtypes, but is challenged by subjective criteria, tissue sampling error, and lack of specific tumor markers. Anatomic imaging is essential for surgical planning of gliomas but is limited by its nonspecificity and its inability to depict beyond morphologic aberrations. The purpose of our study was to investigate dynamic susceptibility contrast-enhanced (DSC) MR imaging characteristics of the two most common subtypes of low-grade infiltrating glioma: astrocytoma and oligodendroglioma. We hypothesized that tumor blood-volume measurements, derived from DSC MR imaging, would help differentiate the two on the basis of differences in tumor vascularity. METHODS: We studied 25 consecutive patients with treatment-naive, histopathologically confirmed World Health Organization grade II astrocytoma (n = 11) or oligodendroglioma (n = 14). All patients underwent anatomic and DSC MR imaging immediately before surgical resection. Histologic confirmation was obtained in all patients. Anatomic MR images were analyzed for morphologic features, and DSC MR data were processed to yield quantitative cerebral blood volume (CBV) measurements. RESULTS: The maximum relative CBV (rCBV(max)) in tumor ranged from 0.48 to 1.34 (0.92 +/- 0.27, median +/- SD) in astrocytomas and from 1.29 to 9.24 (3.68 +/- 2.39) in oligodendrogliomas. The difference in median rCBV(max) between the two tumor types was significant (P < .0001). CONCLUSION: The tumor rCBV(max) measurements derived from DSC MR imaging were significantly higher in low-grade oligodendrogliomas than in astrocytomas. Our findings suggest that tumor rCBV(max) derived from DSC MR imaging can be used to distinguish between the two low-grade gliomas.

Adult↗