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Diuretic enhanced duplex Doppler sonography in 33 children presenting with hydronephrosis: a study of test sensitivity, specificity and precision.

PURPOSE: We assessed the value of diuretic enhanced Doppler sonography in the diagnosis of pediatric renal obstruction as well as its reproducibility, sensitivity and specificity. MATERIALS AND METHODS: We studied 33 children (68 kidneys) by standard diagnostic techniques and diuretic Doppler sonography. A total of 20 obstructed kidneys was compared to 48 without obstruction and we performed surgery on 13. An average of 2.3 resistive index measurements were made per test and 436 total resistive index values were assessed by Student's t distribution and chi-square analysis before and after surgical repair. The assessor was blinded to the clinical diagnosis. RESULTS: The obstructed mean resistive index before (0.71) and after (0.74) furosemide administration differed significantly from the nonobstructed mean resistive index (0.65, p < 0.02). Postoperative mean resistive index (0.68) was not affected by the diuretic and did not differ from the mean resistive index of nonobstructed kidneys. Resistive index test sensitivity was 76% and specificity was 88%. The precision for 3 values per test was +/- 0.11. CONCLUSIONS: When at least 3 values are obtained per test, diuretic Doppler sonography predicts the actual resistive index average with 98% confidence limits 90% of the time.

Adolescent↗

The effect of different sensitivity, specificity and cause-specific mortality fractions on the estimation of differences in cause-specific mortality rates in children from studies using verbal autopsies.

BACKGROUND: Verbal autopsies (VA) are increasingly being used in developing countries to determine causes of death, but little attention is generally given to the misclassification effects of the VA. This paper considers the effect of misclassification on the estimation of differences in cause-specific mortality rates between two populations. METHODS: The bias in the percentage difference in cause-specific mortality between two populations has been explored under two different models: i) assuming that mortality from all other causes does not differ between the two populations; ii) allowing for a difference in mortality from all other causes. The bias is described in terms of the sensitivity and specificity of the VA diagnosis and the proportion of mortality due to the cause of interest. Methods for adjustment of sample size and adjusting the estimate of effect are also explored. RESULTS: The results are illustrated for a range of plausible values for these parameters. The bias is more extreme as both sensitivity and specificity fall, and is particularly affected even by a small loss of specificity. The bias also increases as the proportion of all deaths due to the cause of interest decreases, and is affected by the size of the true change in mortality due to the cause of interest relative to the change in mortality from other causes. Calculations from existing data suggest prohibitively large sample sizes may often be required to detect important differences in cause-specific mortality rates in studies using existing VA. CONCLUSIONS: Highly specific VA tools are needed before observed differences in cause-specific mortality can be interpreted. Loss of power due to misclassification may obscure real differences in cause-specific mortality.

Autopsy↗

Objective outcome criteria in trials of anti-parkinsonian therapy in the elderly: sensitivity, specificity and reliability of measures of brady- and hypo-kinesia.

1. We compare the sensitivity and specificity of chosen outcome criteria in a placebo-controlled, randomised cross-over study of the efficacy of maintenance therapy with the levodopa/carbidopa combination (Sinemet Plus) alone. Patients were characterised by having idiopathic Parkinsonism with no overt fluctuations in control in relation to individual doses of medication. 2. The effect of omission of a morning dose of maintenance therapy on simple timed tests of mobility and manual dexterity, and on distance/time parameters of gait was studied in fourteen patients (aged 64 to 88 years). Measurements made 2, 4 and 6 h after morning active and placebo treatments were standardised by taking the pre-treatment measurement on that day as baseline. 3. In a linear model, which allowed for the structure of the study, neither the total time taken by each patient to get up from a chair, walk an individually set distance, turn, return to and sit in the chair, nor the rate of progress at fastening the same set of buttons, was sensitive to the treatment effect. 4. Three of the gait parameters, free walking speed, mean stride length and mean double support time, were sensitive to the treatment effect. Correction for the speed of each walk, caused some reduction in the sensitivity of stride length to treatment effect, but that of double support time remained. Speed, and double support time or stride length, appeared to be complementary in defining the treatment effect. 5. The linear modelling revealed the complexity of the treatment effect. Although active treatment, by comparison with placebo, increased free walking speed (P = 0.019), the more levodopa found in the plasma following treatment, (P = 0.0005) and the greater the increment in the concentration of its peripheral metabolite, 3-O-methyldopa (P = 0.006), the less the beneficial effect. This model may reflect reduced uptake into the brain and/or an adverse effect of parent drug or a metabolite. 6. The specificity of free walking speed for the treatment effect was good, as was that of mean stride length, after it had been corrected for speed of each walk, and of mean double support time, after correction for speed and incorporation of the change in lying blood pressure accompanying treatment into the model. 7. The measurements of gait parameters were ranked according to reliability.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Non-small and small cell lung carcinoma cell lines exhibit cell type-specific sensitivity to edelfosine-induced cell death and different cell line-specific responses to edelfosine treatment.

The unique signal transduction pathways that distinguish non-small cell lung carcinoma (NSCLC) from small cell lung carcinoma (SCLC) are poorly understood. We investigated the ability of edelfosine, an inhibitor of phosphatidylinositol-specific phospholipase C (PLC) to inhibit cell viability among four NSCLC cell lines and four SCLC cell lines. The differential sensitivity of cells to edelfosine's cytostatic and cytotoxic effects has been attributed to edelfosine-induced changes in the activities of many enzymes, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), p38 kinase, and poly(ADP-ribose) polymerase (PARP). To investigate the role of these enzymes in edelfosine-induced cytotoxicity, we correlated edelfosine-induced changes in enzyme activity and cell viability among the different NSCLC and SCLC cell lines. We found that NSCLC cells are much more susceptible to the cytotoxic effects of this drug than are SCLC cells. Three out of the four edelfosine-sensitive NSCLC cell lines (NCI-H157, NCI-H520, NCI-H522) exhibit G2/M arrest, significant apoptosis and some degree of JNK activation in response to drug treatment. In contrast, none of the SCLC cell lines exhibit edelfosine-induced G2/M arrest or significant apoptosis. A comparison of the edelfosine-induced effects among the sensitive and resistant lung cancer lines indicates that there is little correlation between edelfosine-induced cytotoxicity and altered activities of JNK, ERK, p38, or cleavage of PARP. These results demonstrate that edelfosine-induced changes in JNK, ERK, p38, or PARP are not good predictors of cell susceptibility to edelfosine-induced cytotoxicity. Thus, edelfosine-induced inactivation of PLC may disrupt signaling cascades downstream of PLC that are unique to individual cellular environments. These findings also identify edelfosine as one of the few potential chemotherapeutic agents that has a greater cytotoxic effect against NSCLC cells than SCLC cells.

Antineoplastic Agents↗

Comparing Rasch analyses probability estimates to sensitivity, specificity and likelihood ratios when examining the utility of medical diagnostic tests.

INTRODUCTION: Medical diagnostic tests are evaluated based on measures of sensitivity (Sn), specificity (Sp), and likelihood ratios (LR). These procedures are limited in the event of a biased gold standard or missing data. Interpretations of these measures are frequently inappropriate. PURPOSE: The Rasch measurement model (RMM) was examined as a method to provide evidence of diagnostic test utility in order to overcome the limitations of Sn, Sp, and LR. METHODS: Patients suspected of a knee ligament tear (n = 825) were studied, by evaluating four diagnostic tests. The RMM probability estimates for each test were compared to estimates of Sn, Sp, and LR. RESULTS: The RMM provided probability estimates for the diagnosis that were comparable to likelihood ratios. These probability estimates correlated with the estimates of Sn, Sp, and LR. The RMM estimates were not affected by missing data. DISCUSSION: The RMM may provide an alternative means to study the utility of medical diagnostic tests to estimate the probability of disease presence/absence.

Anterior Cruciate Ligament Injuries↗

Evaluation of the sensitivity, specificity, and predictive value of monoclonal antibody 3F6 for the detection of Pneumocystis carinii pneumonia in bronchoalveolar lavage specimens and induced sputum.

The sensitivity and specificity of different staining procedures for the detection of Pneumocystis carinii organisms were compared. Three conventional stains (Papanicolaou, Giemsa and Grocott's) and one immunocytochemical stain using 3F6 antibody were used on smears prepared from the same specimen. Bronchoalveolar lavage (BAL) and induced sputum (IS) specimens were used for this purpose. One hundred and sixty-five episodes from 142 patients were investigated by the four different staining techniques. Cysts of P. carinii were detected in 64 episodes from 63 patients. Immunocytochemical staining with 3F6 was found to be slightly more sensitive at detecting the cysts than Grocott's, Giemsa, or Papanicolaou stain.

AIDS-Related Opportunistic Infections↗

The validation of cervical cytology. Sensitivity, specificity and predictive values.

Statistics and methods for the validation of the results of cytologic screening for cervical cancer and its precursors were examined. Many of the methods commonly used, including the calculation of sensitivity and specificity on raw data, contain flaws that undermine their conclusions. Using a large computerized database of 748,871 cytologic screenings of 277,842 women over a ten-year period, the value of screening was examined. Only subsequent histologic examinations within one year were accepted to validate positive initial cytologic diagnoses; only two subsequent cytologic screenings within the next three years were accepted to validate negative initial cytologic diagnoses that had not been followed by a histologic examination. Cases not meeting these criteria were excluded from the initial analysis. From these data, the predictive value of a negative cytologic examination was determined to be 99.8%; the predictive value of a positive cytologic examination was 73.4% for an initial diagnosis of mild-to-moderate dysplasia, 90.6% for a diagnosis of severe dysplasia/carcinoma in situ, 94.5% for a diagnosis of carcinoma in situ or microinvasive carcinoma and 95.5% for an initial diagnosis of invasive carcinoma. Cases with an initial "questionable" cytologic diagnosis had a positive predictive value of only 64.0%. Extrapolation from the validated cases to the entire screened population showed an overall sensitivity of 80% and a specificity of 99.4% for cytologic screening for cervical cancer. The sensitivity was slightly lower for mild and moderate dysplasia (78.1%) and slightly higher for carcinoma in situ and severe dysplasia (81.4%) and invasive carcinoma (82.3%).

Adult↗

[Chronic pancreatitis: sensitivity, specificity and predictive value of the pancreolauryl test].

Assessment of the clinical value of the pancreolauryl test (PLT) in the literature range from "useless" to a specifity of 95% and a sensitivity of 98%. In this work, our own data are presented in relation to various reference methods. The results are derived from the largest collective investigated to data, comprising 40 controls and 391 patients (108 with chronic pancreatitis and 283 with other gastrointestinal disorders). The specifity of the the PLT varies between 81% and 95% according to the "quality" of the control collective. The PLT is particularly frequently pathological in patients with diseases in the region of the gallbladder/bile duct and the gastrointestinal tract. The sensitivity of the PLT for chronic pancreatitis varies between 68% and 100%, depending on 9 different reference methods employed. Based on the prevalence of chronic pancreatitis with exocrine insufficiency in various patient collectives, the predictive value of the PLT for the presence of this disorder can be calculated using our data.

Cholangiopancreatography, Endoscopic Retrograde↗

Conditioning and place-specific sensitization of increases in activity induced by morphine in the VTA.

The conditionability of increases in locomotor activity induced by morphine administration into the ventral tegmental area was studied in rats. Morphine produced a clear increase in locomotor activity that was reversed by the opiate receptor blocker, naloxone, and blocked by the neuroleptic, pimozide, suggesting the mediation of this effect by the ascending mesolimbic dopamine system. The increase in locomotor activity showed sensitization with repeated morphine administrations and this sensitization was found to be specific to the environment in which morphine was administered. Conditioning tests also revealed that, in the absence of morphine, increased locomotor activity was elicited by the administration environment. Pimozide blocked the development of the conditioned sensitization. These data demonstrate that a learned association developed between this excitatory action of morphine and the administration environment. These results have important implications for the role of conditioning factors in relapse to drug use and may provide an explanation for conditioning data obtained when morphine is administered systemically.

Animals↗

Sensitivity, specificity, and predictive values of the Limulus lysate assay for detection of exclusion of gonococcal cervicitis.

The Limulus amoebocyte lysate (LAL) assay was evaluated for its ability to detect or exclude gonococcal cervicitis in two groups of women. The first (positive) group consisted of 100 untreated women who were referred to the venereal disease clinic with culture-proven gonococcal cervicitis. The second (negative) group consisted of 50 normal volunteers who were evaluated on two separate occasions. In the first group, Gram stains and repeat cervical cultures were 53 and 93% sensitive, respectively. In the second group, Gram stains and cultures were negative. For the LAL assay, ectocervical mucus was removed with a sponge, and a depyrogenated cotton-tipped swab was then used to collect endocervical specimens. The swab was placed in 1 ml of diluent (1:1 dilution), and serial twofold dilutions were made and tested for endotoxin by the LAL assay. Incubation was carried out at 37 degrees C for 30 min; positive or negative results were indicated by gelation or lack of gelation, respectively. At a dilution of 1:256, sensitivity and specificity of the LAL assay were 57 and 99%, respectively. The positive predictive values ranged from 36.5 to 97.4% for theoretical prevalence rates of 1 to 40%. At a dilution of 1:8, the sensitivity and specificity were 100 and 78%, respectively. At this dilution, the negative predictive value was 100% regardless of the prevalence rate. Thus, these preliminary results show that at the higher dilution, the LAL assay was comparable to Gram stain in diagnostic accuracy of gonococcal cervicitis, and if used as a screening test at the lower dilution, a negative LAL assay would exclude women without gonococcal cervicitis.

Animals↗

A specific, sensitive and high-capacity immunoassay for PAF.

A specific radioimmunoassay for platelet-activating factor (PAF) sensitive in the range 10-1000 pg (0.02-2 pmoles) has been developed. Detailed quantitative hapten inhibition studies showed specificity for the acetyl group at C-2 of PAF, a requirement for the ether linkage at C-1 and some tolerance for substituents on the choline nitrogen. No significant cross-reactivity was found with phosphatidylcholine and lysophosphatidylcholine or with lysoPAF.

Animals↗

Highly sensitive, specific detection of O6-methylguanine, O4-methylthymine, and O4-ethylthymine by the combination of high-performance liquid chromatography prefractionation, 32P postlabeling, and immunoprecipitation.

A highly sensitive and specific method for the detection of O6-methylguanine (O6-meG), O4-methylthymine (O4-meT), and O4-ethylthymine (O4-etT) has been established by combining prefractionation by high-performance liquid chromatography (HPLC), 32P postlabeling, and immunoprecipitation by monoclonal antibodies (PREPI method). DNA was enzymatically hydrolyzed to 2'-deoxynucleoside-3'-monophosphates (3'-dNps). Each alkyl 3'dNp was separated by reverse-phase HPLC, radiolabeled at the 5' position with [gamma-32P]ATP and polynucleotide kinase. After removing 3'-phosphate for better recognition by the antibodies, the resulting alkyl nucleotides were further fractionated by HPLC and finally precipitated specifically with respective antibodies. The detection limits were 1 fmol for all the alkyl nucleotides analyzed, so that one adduct in 10(8) of its normal counterpart nucleotide can be determined using approximately 100 micrograms (O4-meT and O4-etT) or approximately 150 micrograms (O6-meG) of DNA, i.e., 3-5 x 10(7) cells corresponding to approximately 10 ml of peripheral blood or a few hundred milligrams of tissue. By the use of the PREPI method, three leukocyte and three liver DNA samples from Japanese living in the Tokyo area were analyzed with respect to O-alkyl adduct content. O6-meG was detected in all three of the leukocyte samples (O6-meG:G molar ratio, 1.1 x, 0.8 x, and 1.6 x 10(-8) as molar ratios to guanine). Neither O4-meT nor O4-etT was detected (detection limit, O4-alkylT:thymine molar ratio less than 0.5 x 10(-8)). Among the liver samples analyzed, two cases showed positive O6-meG values (4.2 x and 1.1 x 10(-7) O6-meG:guanine molar ratios). Contrary to the leukocyte DNA, O4-meT (3.9 x, 4.3 x, and 7.5 x 10(-8) as O4-meT:thymine) and O4-etT (1.9 x, 4.9 x, and 8.7 x 10(-8) as O4-etT:thymine) were detected in all the liver samples. These results indicate the validity of the PREPI method for molecular epidemiological studies on DNA alkylation products.

Chromatography, High Pressure Liquid↗

Specific sensitization to the common housefly (Musca domestica) not related to insect panallergy.

BACKGROUND: Allergy to houseflies is rare. We report a case of respiratory allergy from occupational exposure to houseflies in a farmer. CASE REPORT: A 30 year-old female farmer with a long-standing history of grass pollen allergy observed for 2 years rhino-conjunctivitis and mild asthma when entering livestock stables and barns. Allergy retesting revealed sensitization to various pollens but not to animal danders. Houseflies (Musca domestica) occurring on the farm in great quantity were suspected by the farmer herself as the causative agent. RESULTS: Skin prick testing with housefly was positive in the patient and negative in four controls. Experimental radioallergosorbant test was class 3 positive. Sensitization to house dust mite, storage mites and cockroach was not detectable. Western blots with housefly extracts revealed immunoglobulin E (IgE)-binding to bands of 70, 50, and approximately 16 kDa. Tropomyosin in the housefly extract (35 kDa) was recognized by a tropomyosin reference serum but not by the patient. In enzyme-linked immunosorbent assay (ELISA) inhibition assays using housefly as the solid phase, IgE-binding of the patient was inhibited by 75% by M. domestica and by 44% by the closely related lesser housefly (Fannia canicularis), but not by extracts from blowfly (Lucilia spp.), fruit fly (Drosophila spp.), horsefly (Haematopota pluvialis) and mosquito (Culex pipiens). The IgE-binding of the tropomyosin control serum was inhibited by 60-80% by all species. CONCLUSIONS: In accordance with previous reports, this case demonstrates that respiratory sensitization to insects may be highly specific. According to ELISA inhibition, cross-sensitization in the present case was restricted to species of the family of true flies (Muscidae).

Adult↗

Analysis of human immunodeficiency virus type 1 integration by using a specific, sensitive and quantitative assay based on real-time polymerase chain reaction.

A novel real-time nested-PCR assay was developed to quantify integrated human immunodeficiency virus type-1 (HIV-1) DNA with high specificity and sensitivity. This assay reproducibly allowed the detection of three copies of integrated HIV DNA in a background of 100,000 cell equivalents of human chromosomal DNA. The non-specific amplification of unintegrated HIV-1 DNA was significantly inhibited in this assay and the specificity of this assay was much higher than the previously reported method. This assay showed that kinetics in viral DNA synthesis was cell-type dependent and that the kinetics of HIV-1 DNA integration was very rapid in Jurkat T cell line. This method may provide new insights into the integration processes and be useful in evaluating future integrase inhibitors.

Base Sequence↗

[Sensitivity, specificity, positive and negative predictive value].

What does it mean that a screening test has a sensitivity of 80 % and a specificity of 80 %? What conclusion can be drawn as to the probability of a patient tested positive having the target disorder? Is this probability dependent on the prevalence of the target disorder? These are the questions addressed in the present paper. The classical concepts of sensitivity and specificity are presented as well as the more modern and clinically relevant concepts of the predictive values of a positive and a negative test. The author employs different didactic methods such as 2 x 2 tables, graphical illustrations and natural frequencies for elaborating on these often intermixed concepts in a clear and easily understandable way.

Comorbidity↗

A specific, sensitive radioimmunoassay for platelet-activating factor (PAF).

A specific radioimmunoassay (RIA) has been developed for platelet-activating factor (PAF) and shown to be sensitive over the range 10-1000 pg (0.02-2 pmol). The anti-PAF antibodies showed specificity for the acetyl group at the C2 position of the PAF molecule and exhibited no significant cross-reactivity with lyso-PAF or the naturally occurring lipids including lecithin and lysolecithin. The sensitivity of the RIA was at least as good as the platelet-based assays for PAF but the RIA was simpler to perform, had a higher capacity and did not have the drawback of the inherent variability associated with the bioassays.

Animals↗

The western immunoblot for Lyme disease: determination of sensitivity, specificity, and interpretive criteria with use of commercially available performance panels.

Recent recommendations for the serological diagnosis of Lyme disease include statements on quality assurance and the use of performance panels to assess laboratory competency. We used two performance panels--one from the Centers for Disease Control and Prevention (CDC) and one from Boston Biomedica Inc. (West Bridgewater, MA)-to evaluate the sensitivity and specificity of four western blot kits. We used the same panels to compare the interpretive criteria for western blots as proposed by participants in the Centers for Disease Control and Prevention, Association of State and Territorial Public Health Laboratory Directors Conference and those proposed by BBI Clinical Laboratories (BBICL; New Britain, CT). Our results indicated that the BBICL western blots were more sensitive than those of the CDC, MarDx (Carlsbad, CA), or Cambridge Biotech (Rockville, MD). However, use of the CDC criteria with the BBICL western blots increased specificity to 100% but reduced sensitivity to 74.3%. A sample table is provided as an example of the test results obtained with the BBI performance panel. Obviously, this work should be confirmed by other investigators.

Antibodies, Bacterial↗