Comparison between emission and transmission computed tomography of the liver.

Emission computed tomography (emission CT) and conventional planar gamma-camera imaging of the liver were compared in 242 patients with suspected metastatic spread to liver. Concordant data were obtained in 171 patients (71%). Single large lesions, multiple small lesions, and diffuse disease were accurately defined with this new radionuclide tomographic technique. The smallest lesion detected by emission CT was 8 mm. Emission CT, planar gamma-camera imaging, and transmission (x-ray) CT were compared in 107 patients. All three methods gave identical results in 76 patients (71%). Assessed against other criteria, such as histological findings and follow-up data, emission CT yielded the highest range of accuracy (92-96%), while transmission CT and planar gamma-camera imaging had similar but lower accuracies (78-81%). Emission CT had a false-positive rate of 2.8% and a false-negative rate of less than 1%. Thus emission CT is highly sensitive in detecting space-occupying disease in the liver.     

Auscultatory percussion of the head.

Eighty-nine consecutive patients with suspected intracranial masses were examined by auscultatory percussion in a blind study to assess the sensitivity of the procedure. Each patient underwent computed tomography (CT) of the brain as part of his medical care, and the results were compared with those of auscultatory percussion. Fifty-one of the patients had abnormal CT scans, of whom 44 (86%) had abnormal (positive) findings on auscultatory percussion; seven (13%) yielded false-negative results. Each of the patients with subdural haematomas had distinctly positive findings by auscultatory percussion. Of the 38 patients with normal CT scans, 11 had strokes with hemiparesis, and each had positive findings in the contralateral hemisphere by auscultatory percussion. The remaining 27 patients with normal CT scans were healthy; 25 had normal findings on auscultatory percussion, two (7%) gave false-positive results. Twenty subjects were studied with phonoscopy. Auscultatory percussion is easy to perform and is clinically useful.     

Reliability of non-lethal surveillance methods for detecting ranavirus infection

Ranaviruses have been identified as the etiologic agent in many amphibian die-offs across the globe. Polymerase chain reaction (PCR) is commonly used to detect ranavirus infection in amphibian hosts, but the test results may vary between tissue samples obtained by lethal and non-lethal procedures. Testing liver samples for infection is a common lethal sampling technique to estimate ranavirus prevalence because the pathogen often targets this organ and the liver is easy to identify and collect. However, tail clips or swabs may be more practicable for ranavirus surveillance programs compared with collecting and euthanizing animals, especially for uncommon species. Using PCR results from liver samples for comparison, we defined false-positive test results as occurrences when a non-lethal technique indicated positive but the liver sample was negative. Similarly, we defined false-negative test results as occurrences when a non-lethal technique was negative but the liver sample was positive. Using these decision rules, we estimated false-negative and false-positive rates for tail clips and swabs. Our study was conducted in a controlled facility using American bullfrog Lithobates catesbeianus tadpoles; false-positive and false-negative rates were estimated after different periods of time following exposure to ranavirus. False-negative and false-positive rates were 20 and 6%, respectively, for tail samples, and 22 and 12%, respectively, for swabs. False-negative rates were constant over time, but false-positive rates decreased with post-exposure duration. Our results suggest that non-lethal sampling techniques can be useful for ranavirus surveillance, although the prevalence of infection may be underestimated when compared to results obtained with liver samples.     

Comparison of light and transmission electron microscopy for the evaluation of body cavity effusions

Evaluation of 282 body cavity effusions by both light and transmission electron microscopy showed that the two methods compare favorably. The major advantages of electron microscopy are higher rates of unequivocally positive diagnoses, improved diagnosis in borderline or suspicious cases and better discrimination between benign and malignant fluids or decreased numbers of inconclusive results. This was obtained without false-positive results. The major disadvantage of the method is the increased time and preparative procedures needed. As with light microscopy, the false-negative rate was high.     

Where have all the interactions gone? Estimating the coverage of two-hybrid protein interaction maps

Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either a high false-discovery rate (interaction sets have low overlap because each set is contaminated by a large number of stochastic false-positive interactions) or a high false-negative rate (interaction sets have low overlap because each misses many true interactions). We extend capture-recapture theory to provide the first unified model for false-positive and false-negative rates for two-hybrid screens. Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported interactions are likely false positives. Membrane proteins have higher false-discovery rates on average, and signal transduction proteins have lower rates. The overall false-negative rate ranges from 75% for worm to 90% for fly, which arises from a roughly 50% false-negative rate due to statistical undersampling and a 55% to 85% false-negative rate due to proteins that appear to be systematically lost from the assays. Finally, statistical model selection conclusively rejects the Erd?s-Rényi network model in favor of the power law model for yeast and the truncated power law for worm and fly degree distributions. Much as genome sequencing coverage estimates were essential for planning the human genome sequencing project, the coverage estimates developed here will be valuable for guiding future proteomic screens. All software and datasets are available in and , -, and -, and are also available from our Web site, http://www.baderzone.org.     

Error detection for genetic data, using likelihood methods.

As genetic maps become denser, the effect of laboratory typing errors becomes more serious. We review a general method for detecting errors in pedigree genotyping data that is a variant of the likelihood-ratio test statistic. It pinpoints individuals and loci with relatively unlikely genotypes. Power and significance studies using Monte Carlo methods are shown by using simulated data with pedigree structures similar to the CEPH pedigrees and a larger experimental pedigree used in the study of idiopathic dilated cardiomyopathy (DCM). The studies show the index detects errors for small values of theta with high power and an acceptable false positive rate. The method was also used to check for errors in DCM laboratory pedigree data and to estimate the error rate in CEPH-chromosome 6 data. The errors flagged by our method in the DCM pedigree were confirmed by the laboratory. The results are consistent with estimated false-positive and false-negative rates obtained using simulation.     

Alpha-fetoprotein concentrations measured by radioimmunoassay in diagnosing and excluding hepatocellular carcinoma.

Serum alpha-fetoprotein (AFP) concentrations were estimated by sensitive radioimmunoassay in 30 patients with cirrhosis complicated by hepatocellular carcinoma and in 100 patients with cirrhosis in whom malignancy was excluded. Twenty-nine of the 30 patients with hepatocellular carcinoma had concentrations above 10 IU/ml (10.5 ng/ml) (median 3500 IU/ml (3675 ng/ml)), whereas only one of the 100 patients with cirrhosis and no tumour development had a raised concentration. Eleven out of 20 patients in whom hepatocellular carcinoma had developed in an apparently normal liver had raised AFP concentrations. In this group the differential diagnosis is usually secondary carcinoma, and three of 50 such patients had AFP concentrations above 10 IU/ml. Noting raised AFP concentrations is thus of considerable value both in detecting and in excluding hepatocellular carcinoma in cirrhosis, for in this case such concentrations gave only 1% false-positive and 3% false-negative results. They are less useful, however, in distinguishing between primary tumours arising in patients without cirrhosis and secondary hepatic deposits, giving 6% false-positive and 45% false-negative results.     

Evaluation of a Semiautomated System for Direct Fluorescent Antibody Detection of Salmonellae

A semi-automatic system under development by Aerojet Medical and Biological Systems for the direct fluorescent antibody detection of salmonellae was evaluated with various food, feed, and environmental samples. All samples were simultaneously examined by Automated Bioassay System (ABS), manual direct fluorescent antibody procedures and cultural procedures. The ABS gave satisfactory results with the processed samples. It detected all of the culturally positive powdered egg and candy samples with no false negative results and gave only 6.6 and 5.3% false positive rates, respectively. With meatmeal samples the ABS failed to detect one culturally positive specimen that was also positive by manual fluorescent antibody and gave one (1.1%) false-positive result. A high rate of false-negative results was obtained by ABS on unprocessed samples of creek water, poultry, and sausage. Adding another enrichment step to the protocol reduced the false-negative rate considerably but severely increased the false-positive rate. The instruments worked reasonably well, but research is needed to improve enrichment procedures for samples to be processed by the system.     

Screening methods for covert bacteriuria in schoolgirls.

Screening tests for bacteriuria based on two different principles were evaluated in1582 schoolgirls aged 5-11 years, and in 26 girls aged 3-16 years attending hospitalwith symptomatic urinary tract infection. Tests for hypoglucosuria, performed by a semi-automated fluorometric method and with Uriglox strips on early-morning urine samples voided after overnight fasting, gave unacceptably high false-negative rates (16.7% and 20.8% respectively). Oxoid and Uricult dipslides were immersed in fresh midstreamspecimens of urine obtained at school and read overnight incubation at 37 degrees C.Both gave comparable results, with low false-positive rates and no false-negative responses. The higher cost of screening by dipslides was halved by using the "dipstream" technique, which also gave no false-negative results. Its false-positive rate of 13.5% could be reduced to 1.8% by disregarding colony counts of 10-8 non-faecal organisms and over per litre, which appear unimportant in schoolchildren. Bacteriuria was found in 2.3% of the schoolgirls; 39% of them had symptons, compared with 7.2% of the healthy girls, and 25% showed vesicoureteric reflux, which in 17% was associated with renalscarring. Since the natural history of covert bacteriuria and its relationship withreflux and scarring remain undetermined further research is required. The dipstreamtechnique offers a simple, reliable, and comparatively cheap screening method which could also be applied in general practice.     

Algorithm for a DNA-cytophotometric diagnosis and grading of malignancy

An algorithm for processing data on nuclear DNA content obtained cytophotometrically was developed (1) to obtain an objective discrimination between benign and malignant lesions in conventional cytologic smears secondarily stained according to Feulgen and (2) to obtain an objective degree of tumor malignancy on a continuous scale of malignancy grades. Investigations in 258 malignant tumors (95 malignant lymphomas, 52 uterine cervix carcinomas, 28 prostate carcinomas, 18 breast carcinomas, 45 malignant bone tumors and 19 larynx carcinomas) and in 74 benign lesions in these organs yielded a diagnostic accuracy of no false-positive, no false-negative and 21% suspicious diagnoses. The probability that "suspicious" cases were malignant was 81%. The overall diagnostic accuracy for non-negative cases thus amounted to 100%. Results in 95 patients with different malignant lymphomas and in 16 patients with squamous-cell carcinoma of the larynx demonstrated the prognostic validity of the DNA-grading system.     

The false classification of extinction risk in noisy environments

Abundance trends are the basis for many classifications of threat and recovery status, but they can be a challenge to interpret because of observation error, stochastic variation in abundance (process noise) and temporal autocorrelation in that process noise. To measure the frequency of incorrectly detecting a decline (false-positive or false alarm) and failing to detect a true decline (false-negative), we simulated stable and declining abundance time series across several magnitudes of observation error and autocorrelated process noise. We then empirically estimated the magnitude of observation error and autocorrelated process noise across a broad range of taxa and mapped these estimates onto the simulated parameter space. Based on the taxa we examined, at low classification thresholds (30% decline in abundance) and short observation windows (10 years), false alarms would be expected to occur, on average, about 40% of the time assuming density-independent dynamics, whereas false-negatives would be expected to occur about 60% of the time. However, false alarms and failures to detect true declines were reduced at higher classification thresholds (50% or 80% declines), longer observation windows (20, 40, 60 years), and assuming density-dependent dynamics. The lowest false-positive and false-negative rates are likely to occur for large-bodied, long-lived animal species.     

Diagnosis of benign and malignant cervical specimens by multifiberoptic microspectrophometry and by flow cytometry

Two techniques for the automation of mass screening for cervical cancer were studied. Microspectrophotometry was tried first, using a novel multifiberoptic scanning system that measured the nuclear size and DNA content of cells in routine smears restained by the Feulgen technique. Specimen diagnoses were based on the percentages of cell types present, as determined by thresholds set for the two parameters. While this method gave good results in the automated detection of severe dysplasias and carcinomas, with only 3 of 72 cases misdiagnosed as negative (4.2%), it had a 22.9% false-positive rate (misdiagnosing 24 of 105 "benign" cases) and a 30.3% false-negative rate for adenocarcinomas (10 of 33 cases misclassified). The second approach involved flow cytometric measurements of specimens that were double stained for the assessment of both the DNA and RNA content, with the results analyzed by preset windows in a two-dimensional plane. This technique gave a 6.1% false-negative rate in 49 positive specimens and a 32.3% false-positive rate in 102 benign specimens, with an overall correct classification rate of 76.2%, including adenocarcinomas.     

梗阻性黄疸MRCP 的循证和临床研究

目的：通过meta、ROC分析以及按病变部位、性质进行的亚组分析分析对目前诊断梗阻性黄疸的非侵入性影像诊断方法（US,Cr和MRCP）进行对比研究。方法：1、采用medline检索。纳入标准为：（a）US、CT和MRCP诊断梗阻性黄疸性疾病的文献（b）病理检查、术中所见或临床、实验室检查结果作为诊断金标准。（c）能够直接或间接获得每个影像方法的真、假阳性数,真、假阴性数。提取数据、文献质量评估通过kappa分析进行一致性检验。统计分析采用漏斗图、SROC分析方法以及协变量分析。2、疑胆胰系疾患接受MRCP检查患者105例,其中同时做US检查者65例。另有同期Cr资料59例,其中同时做US检查者31例。盲法与金标准对比,计算出各诊断方法的真阳性率和假阳性率,ROC分析其诊断效能。同时按病变部位、性质分别计算MR-CP、US及Cr的敏感度、特异度和似然比等指标进行比较分析。结果：1、漏斗图US相关文献分布形状略不规则,CT、MRCP相关文献分布形状类似漏斗形。SROC曲线图MRCP线最靠近左上角,诊断效能高于US和CT、MRCP的Q^＊值（0．9256）高于US（0.8765）和CT（0.8606）。三者间经检验无显著性差别,MRCP和cT问检验Z=0、33,双侧P〉0、25。协变量分析未见对诊断效能有显著性影响因素。2、ROC分析显示,MRCP的曲线最靠近左上角,US次之,Cr在最下面,三者的曲线下面积（Az）分别为0．985,0．981．0、901,均大于0、9,MRCP与Cr间离均差（Z）为0．75,双侧P〉0、25。MRCP、US和Cr诊断胆胰系恶性占位、结石的敏感度分别为100％、83％、82％;92％、71％、76％。经检验,MRCP与US和CT间有显著性差异,P〈0．05。结论：经meta、ROC分析,认为MRCP在诊断梗阻性黄疸疾病中具有优势,诊断效能高于US和Cr。     

Role of percutaneous pelvic node aspiration cytology in the management of bladder carcinoma

Six of the 23 patients with bladder carcinoma who underwent percutaneous pelvic node aspiration biopsy cytology for staging purposes showed positive findings from nodal chains. Pelvic lymphadenectomy revealed no false-positive or false-negative cytologic results. The fine needle aspiration of opacified pelvic nodes under fluoroscopic control is of great diagnostic value, with a high accuracy in detecting nodal extension of bladder carcinoma and providing a rational basis for proper therapy. Positive aspiration results may be accepted as a basis for therapeutic decisions. Since the metastatic involvement of multiple nodes makes any therapeutic treatment as well as cystectomy completely useless, positive aspirations from more than two nodes may spare patients an unnecessary radical surgery.     

Immunodiagnosis of sexually transmitted disease

Methods for detecting microbial antigens in clinical specimens offer an alternative to culture in the diagnosis of some sexually transmitted diseases. Developers of the immunologic methods are faced with a number of problems in evaluating the new tests. Traditionally, these tests are compared to culture as the "gold standard." Unfortunately, culture for Neisseria gonorrhoeae or Chlamydia trachomatis--the two agents most commonly sought--is considerably less sensitive than 100 percent. Immunologic methods may appear to produce false positives when the paired specimens are actually false-negative cultures. Another source of discordant results is sampling variation. These considerations, however, will not account for all false-positive results. Even the best non-culture methods have a low rate of false-positive results. If a new test has a specificity of 97 percent, it, by definition, yields approximately 3 percent false-positive reactions. In low-prevalence settings this false-positive rate will create problems in interpreting the results. For example, in a population with 3 percent prevalence of infection, a positive result in a 97 percent specificity test could only have a predictive value of 50 percent. Most testing for STD agents is performed in low-prevalence settings. None of the currently available immunodiagnostic procedures has a performance profile that suggests it will be satisfactory for diagnostic use in the low-prevalence setting.     

Computed tomography of abdomen in staging and clinical management of lymphoma.

During July 1976 to Demember 1977, 150 patients with Hodgkin''s disease and 138 with non-Hodgkin''s lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin''s lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin''s disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin''s disease.     

Statistical approach to fine needle aspiration diagnosis of breast masses

A statistical algorithm was used for recursively partitioning a consecutive series of 37 benign and 69 malignant fine needle aspirates to produce a decision tree for diagnosing breast masses. Optimal separation between benign and malignant cytology was accomplished by evaluating clump characteristics when clumps were present and evaluating cell integrity when clumps were absent. The 1.5% false-negative and 9.7% false-positive rates obtained through this scheme are better than those reported for most series.     

Diagnostic role of different immunologic methods for laboratory diagnostics of legionellosis

The aim of the study was a comparative analysis of diagnostic value of different laboratoty methods conducted on the basis of results of examination of patients during Legionnaires' disease outbreak in town Verkhnyaya Pyshma. Retrospective analysis of laboratory data from 74 patients with diagnosis of Legionnaires' disease was performed. Complex of laboratory methods was used (polymerase chain reaction (PCR), enzyme immunoassay (EIA), immunochromatography). In group of patients with Legionnaires' disease, the highest proportion of positive results (73%) was obtained by the EIA determining total specific antibodies in urine. Determination of antigen in urine by immunochromatographic express-test yielded 52% of positive results. PCR testing of blood specimens yielded positive results in 65% of samples but was low specific, due to that in 19% of patients from control group false-positive results were obtained. Testing of 3 autopsy samples showed that all specimens contained DNA of the causative agent. Performed analysis allowed to recommend complex use of immunochromatographic express-test of antigen detection and identification of total specific antibodies by EIA during mass people examination.     

Critical evaluation of the cytodiagnosis of fibrogastroendoscopic samples obtained under direct vision

The reliability and efficiency of the cytodiagnosis of fibrogastroendoscopic biopsy samples obtained under direct vision in 676 cases during a five-year period were reviewed. The critical evaluation showed a cytodiagnostic sensitivity of 93.54%, a specificity of 98.79%, a false-negative rate of 6.46%, a false-positive rate of 1.21%, a predictive value of a positive result of 98.01%, a predictive value of a negative result of 96.00%, a prevalence rate of 38.91%, an overall diagnostic accuracy of 96.75% and a chi-square value of 5.50 (P less than .05). These results were comparable to those obtained by histologic study in the same cases; the combined use of both cytology and histology to analyze the samples obtained gave the best results. These findings reemphasize the important role of fibrogastroendoscopic cytodiagnosis in establishing the existence of gastric cancer and shows that the technique is accurate and efficient. The types of statistics useful for assessing such data are discussed.     

Ultrasound screening for clinically occult abdominal aortic aneurysm.

In a review of the records of 74 patients who had undergone repair of an abdominal aortic aneurysm at a community hospital between 1977 and 1983 we found that the aneurysm had been undiagnosed before rupture in 35%; these patients had an operative death rate of 50%, whereas elective repair carried a death rate of 4%. The characteristic patient was an obese man over the age of 55 years with hypertension, coronary artery disease, cerebrovascular disease or peripheral vascular disease. Ultrasound examination was performed in 45 patients with these characteristics, and six aneurysms were diagnosed. Either surgery or computed tomography confirmed the diagnosis. The rate of false-negative results was estimated by review of the charts of 100 men over the age of 55 years who had undergone abdominal ultrasonography for other indications: no undetected aneurysms were discovered over 3 years of follow-up. Routine screening in this high-risk group would improve the rate of diagnosis of this potentially fatal condition before rupture and offer the patient the lower mortality rate associated with elective surgery.