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Sensitivity, specificity, and predictive value of anti-candida serum precipitin and agglutinin quantification: comparison of counterimmunoelectrophoresis and latex agglutination.

Many serological techniques have been developed to aid in the discrimination of significant candidiasis from other clinical states. Serum anti-candida precipitin and agglutinin quantification by counterimmunoelectrophoresis and latex agglutination were statistically evaluated as to their respective ability to accomplish this discrimination. Forty-five serum specimens from 16 patients with documented disease and 2 with presumptive disease and 81 specimens from 70 control patients were studied. The control population consisted of patients with candida colonization, transient candidemia, bacteremia, other systemic mycoses, and healthy medical personnel. The two techniques were compared as to sensitivity, specificity, and predictive value of a positive and a negative test. Using a precipitin or agglutinin titer of greater than or equal to 1:8 as the criterion for a positive test, we obtained the following results: counterimmunoelectrophoresis, 78, 97, 88, and 94%, respectively; latex agglutination, 94, 50, 33, and 97%, respectively.

Agglutinins↗

Use of simulation modeling to estimate herd-level sensitivity, specificity, and predictive values of diagnostic tests for detection of tuberculosis in cattle.

OBJECTIVE: To estimate herd-level sensitivity (HSe), specificity (HSp), and predictive values for a positive (HPVP) and negative (HPVN) test result for several testing scenarios for detection of tuberculosis in cattle by use of simulation modeling. SAMPLE POPULATION: Empirical distributions of all herds (15,468) and herds in a 10-county area (1,016) in Michigan. PROCEDURE: 5 test scenarios were simulated: scenario 1, serial interpretation of the caudal fold tuberculin (CFT) test and comparative cervical test (CCT); scenario 2, serial interpretation of the CFT test and CCT, microbial culture for mycobacteria, and polymerase chain reaction assay; scenario 3, same as scenario 2 but specificity was fixed at 1.0; and scenario 4, sensitivity was 0.9 (scenario 4a) or 0.95 (scenario 4b), and specificity was fixed at 1.0. RESULTS: Estimates for HSe were reasonably high, ranging between 0.712 and 0.840. Estimates for HSp were low when specificity was not fixed at 1.0. Estimates of HPVP were low for scenarios 1 and 2 (0.042 and 0.143, respectively) but increased to 1.0 when specificity was fixed at 1.0. The HPVN remained high for all 5 scenarios, ranging between 0.995 and 0.997. As herd size increased, HSe increased and HSp and HPVP decreased. However, fixing specificity at 1.0 had only minor effects on HSp and HPVN, but HSe was low when the herd size was small. CONCLUSIONS AND CLINICAL RELEVANCE: Tests used for detecting cattle herds infected with tuberculosis work well on a herd basis. Herds with < approximately 100 cattle should be tested more frequently or for a longer duration than larger herds to ensure that these small herds are free of tuberculosis.

Animals↗

Distortion product otoacoustic emission test of sensorineural hearing loss: performance regarding sensitivity, specificity and receiver operating characteristics.

The performance of distortion product otoacoustic emissions (DPOEs) as a frequency-specific test of sensorineural hearing loss was evaluated in 142 ears of human adults with normal middle-ear function. The DPOE was measured with the stimulus levels of the two tones equal to 65 dB SPL (re 20 mu Pa) and the ratio between the two frequencies 1.2. In the DPOE test, the cochlear function of an ear at a test frequency was predicted to be normal or abnormal depending upon whether the DPOE level with the geometric mean of the two stimulus frequencies at the test frequency was greater or less than a criterion. The DPOE test outcomes were evaluated against the pure-tone hearing threshold as the standard. We found the sensitivity, specificity and predictive efficiency of the test to be 85-89% at 6000 and 4000 Hz, 82-83% at 2000 Hz and 78-79% at 1000 Hz, respectively. The performance was also evaluated using decision theory in terms of the area under the receiver operating characteristics. The latter was found to range from 0.90 (for 1000 Hz) to 0.94 (for 6000 Hz). These findings support the conclusion that the DPOEs can form a useful frequency-specific objective test of cochlear function.

Acoustic Impedance Tests↗

Hydrolysis of artificial substrates by enterokinase and trypsin and the development of a sensitive specific assay for enterokinase in serum.

The activities of highly purified human enterokinase (enteropeptidase, EC 3.4.21.9) and bovine trypsin were tested against three synthetic substrates alpha-N-Benzoyl-L-arginine ethyl ester HCl, alpha-N-Benzoyl-DL-arginine-p-nitroanilide HCl and alpha-N-Benzoyl-DL-arginine-2-naphthylamide HCl. There was no detectable hydrolysis of these substrates by enterokinase whereas the kinetic parameters obtained for trypsin were in close agreement with those previously described by other workers. The values for Km and kcat were dependent on the Ca2+ concentration. Hydrolysis of glycine-tetra-L-aspartyl-L-lysyl-2-naphthylamide (Gly(Asp)4-Lys-Nap) by these protease was also studied. Enterokinase-catalysed hydrolysis obeyed simple steady-state kinetics and values for Km of 0.525 mM and 0.28 mM and for kcat of 21.5 s-1 and 28.3 s-1 were obtained in 0.1 mM and 10 mM Ca2+, respectively. Trypsin-catalysed hydrolysis was complex and the response to Ca2+ was sigmoidal partly due to the lability of trypsin at low Ca2+ concentrations. A sensitive specific assay for enterokinase was developed and applied to the measurement of the enzyme in serum; interference by nonspecific arylamidases was eliminated by the addition of Zn2+.

Animals↗

Identifying the behavioural phenotype in Fetal Alcohol Spectrum Disorder: sensitivity, specificity and screening potential.

BACKGROUND: In most cases of Fetal Alcohol Spectrum Disorder (FASD), the pathognomonic facial features are absent making diagnosis challenging, if not impossible, particularly when no history of maternal drinking is available. Also because FASD is often comorbid with Attention Deficit Hyperactivity Disorder (ADHD), children with FASD are frequently improperly diagnosed and receive the wrong treatment. Since access to psychological testing is typically limited or non-existent in remote areas, other diagnostic methods are needed to provide necessary interventions. OBJECTIVES: To determine if a characteristic behavioural phenotype distinguishes children with FASD from typically developing children and children with ADHD and use this information to create a screening tool for FASD diagnosis. METHODS: Parents and caregivers completed the Child Behavior Checklist (CBCL), a well-established standardized tool for evaluating children's behavioural problems. Results from 30 children with Fetal Alcohol Syndrome or Alcohol-Related Neurodevelopmental Disability, 30 children with ADHD, and 30 typically developing healthy children matched for age and socioeconomic status with FASD were analyzed. Based on our previous work, 12 CBCL items that significantly differentiated FASD and control groups were selected for further analyses. Stepwise discriminant function analysis identified behavioural characteristics most strongly differentiating groups and Receiver Operating Characteristics (ROC) curve analyses determined sensitivity and specificity of different item combinations. RESULTS: Seven items reflecting hyperactivity, inattention, lying and cheating, lack of guilt, and disobedience significantly differentiated children with FASD from controls. ROC analyses showed scores of 6 or higher on these items differentiated groups with a sensitivity of 86%, specificity of 82%. For FASD and ADHD, two combinations of items significantly differentiated groups with high sensitivity and specificity (i) no guilt, cruelty, and acts young (sensitivity = 70%; specificity = 80% (ii) acts young, cruelty, no guilt, lying or cheating, steals from home, and steals outside (sensitivity = 81%; specificity = 72%). These items were used to construct a potential FASD screening tool. CONCLUSIONS: Our findings identifying the behavioural characteristics differentiating children with FASD from typically developing children or children with ADHD have the potential for development of an empirically derived tool for FASD tool to be used in remote areas where psychological services are not readily available. This technique may speed up diagnosis and intervention for children without ready access to formal assessments.

Attention Deficit Disorder with Hyperactivity↗

Cyfra 21-1 as a biologic marker of non-small cell lung cancer. Evaluation of sensitivity, specificity, and prognostic role.

BACKGROUND: Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. Cyfra 21-1 is a cytokeratin-19 fragment that is soluble in serum and may be a useful circulating tumor marker. STUDY OBJECTIVE: The aims of this study were (1) to confirm sensitivity and specificity of Cyfra 21-1 in detecting non-small cell lung cancer (NSCLC) and especially the squamous cell subtype, (2) to assess the potential relationship between Cyfra 21-1 and disease stage of the disease in NSCLC, and (3) to evaluate prognostic effect of Cyfra 21-1 in NSCLC. METHODS: An immunoradiometric assay of serum Cyfra 21-1 was performed in 161 patients with lung cancers and 71 others with benign lung diseases. The ability of Cyfra 21-1 to detect different histologic subtypes of lung cancer vs benign lung diseases was assessed through receiver operating characteristic (ROC) curves and comparisons with other tumor markers such as carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen. Comparisons of Cyfra 21-1 levels according to histologic subtype and disease stage were done using Kruskal-Wallis test. Independent prognostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox's model). RESULTS: Using a threshold of 3.3 ng/mL for Cyfra 21-1, sensitivity and specificity were, respectively, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the subgroup of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-1 levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations > 32 ng/mL had stage IIIB-IV and only one of 14 patients with stage I-II disease had Cyfra 21-1 level > 18 ng/mL. In the multivariate analysis of survival, Cyfra 21-1 was an independent prognostic factor along with performance status and disease stage in NSCLC. CONCLUSIONS: Cyfra 21-1 is a sensitive and specific tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with performance status and disease stage in NSCLC. IMPLICATIONS: A high level of Cyfra 21-1 in apparently early-stage NSCLC should be an indication for more extensive workup before thoracotomy. The independent prognostic role of Cyfra 21-1 level may be useful in stratifying populations with advanced NSCLC or early-stage resected NSCLC as elevated Cyfra 21-1 levels might identify those patients at high risk for treatment failure.

Adenocarcinoma↗

A sensitive, specific, solid-phase enzymeimmunoassay for plasma progesterone.

A homologous enzymeimmunoassay (EIA) for plasma progesterone, using a horseradish peroxidase conjugate as enzyme label and an antiserum raised against a progesterone-11 kappa-hemisuccinyl/BSA conjugate, is described. The antiserum was covalently linked to microcrystalline cellulose to facilitate separation of bound and free steroid; this solid-phase antiserum was stable for at least nine months when stored at 4 degrees C. the freeze-dried enzyme label is also stable, having retained both enzymic and immunological activity for about four years. The EIA developed was specific and had the sensitivity (4.8 pg/tube) required for determining progesterone concentrations in in plasma samples collected at any time during the menstrual cycle. EIA of plasma samples provided results which were in good agreement with a well validated radioimmunoassay (RIA). The specificity and inter- and intra-assay coefficients of variation in the EIA were strictly comparable with those of the RIA. The method described has been in use for two years and has been assessed in external quality assurance programme established by the World Health organization and the United Kingdom Department of Health and Social Security.

Cross Reactions↗

Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat.

Human epidemiological studies have shown that low birth weight is associated with hypertension in adulthood. Rodent models of intrauterine growth retardation (IUGR) support these findings because offspring from undernourished dams develop hypertension. Angiotensin-converting enzyme 2 (ACE2) is a newly described renin-angiotensin system (RAS) component that competes with ACE for angiotensin peptide hydrolysis and therefore may modulate blood pressure. However, ACE2 potential participation in hypertension programming remains unknown, although RAS alterations were reported in IUGR models. Hence, we first investigated the tissue distribution of ACE2 and ACE in the rat and then whether hypertension programming differentially affects both enzymes. Using multiplex RT-PCR and in situ hybridization, we show that ACE2 mRNA is widely expressed and coregionalized with ACE. Moreover, tissues involved in blood pressure homeostasis (lung, heart, and kidney) express high levels of both enzymes. Enzymatic assays reveal that ACE2 and ACE are coactive in these tissues. Adult (4-month-old) offspring from 70% food-restricted dams throughout gestation (FR30 rats) present mild hypertension, impaired renal morphology, as well as elevated plasma angiotensin II and aldosterone, suggesting alterations of the systemic RAS. In FR30 rats, we show that ACE2 and ACE activities are increased only in the lung, whereas their mRNA expression is not significantly altered, showing that the enzymes display tissue-specific sensitivity to programming. Our results indicate that ACE2 and ACE are coexpressed in numerous rat tissues and that their increased activity in the lung of FR30 rats may participate in hypertension programming.

Aldosterone↗

Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample.

OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-epsilon4 allele. METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis. RESULTS: CSF-tau was increased in probable (690+/-341 pg/mL; p < 0.0001) and possible (661+/-447 pg/mL; p < 0.0001) AD, but not in depression (231+/-110 pg/mL) compared with control subjects (227+/-101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL. CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on repeated sampling. Although high CSF-tau is found in some neurologic conditions (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.

Aged↗

Specific, sensitive and accurate quantification of albumin, retinol binding protein and transferrin in human urine and serum by zone immunoelectrophoresis assay (ZIA).

For zone immunoelectrophoresis assay (ZIA) glass tubes, ID 2 mm and 90 mm high, are filled to 2/3 with buffer containing agarose and antibodies against the protein to be quantified, each sample being pipetted on top of separate agarose gel rods. On electrophoresis at 35-150 V for several hours, the sample proteins enter the gel with resultant immunoprecipitates, visualized by staining. The extension of each immunoprecipitation zone from the upper gel surface (measured with a ruler) is directly proportional to the amount of protein in each sample and can easily be quantitated by comparison with a linear calibration curve. ZIA can be used for quantification of several proteins in blood serum and plasma as well as in urine, as is illustrated for albumin, retinol-binding protein (RBP) and transferrin. The recovery of the pure proteins added to urine is often close to 100%. ZIA has many advantages: (i) simple apparatus and procedure (no gel punching nor cooling), (ii) minimal antiserum consumption (1 mL may allow > 1000 assays), (iii) electrophoresis can be performed within a few hours or overnight, (iv) low coefficient of variation (often < 4%), (v) linear calibration curves, (vi) low detection limit (< 20 ng/mL), (vii) wide concentration ranges, (viii) no kits nor unique antisera preparation are required, and (ix) good agreement with the results from other methods.

Albuminuria↗

Estimation of age-specific sensitivity and sojourn time in breast cancer screening studies.

This study investigates statistical approaches to quantitatively describing the age effect on screening sensitivity and sojourn time distribution in breast cancer screening studies. Such an investigation is directly motivated by the need to understand the inherent relationships between age and these important quantities. We incorporate the age effect through generalized linear models under a progressive disease modelling framework and obtain the corresponding parameter estimators using the maximum likelihood method. Among a set of potential models, we use Akeike's information criterion and likelihood ratio test in model selection and inferences. Extensive simulation studies show that the estimators have reasonable accuracy and the model selection criterion works well. The proposed methods are illustrated using data from two large breast cancer screening trials. The results show that the screening sensitivity increases with age at screening examinations based on these two trials.

Adult↗

Evaluation of six presumptive tests for blood, their specificity, sensitivity, and effect on high molecular-weight DNA.

Luminol, leuchomalachite green, phenolphthalein, Hemastix, Hemident, and Bluestar are all used as presumptive tests for blood. In this study, the tests were subjected to dilute blood (from 1:10,000 to 1:10,000,000), many common household substance, and chemicals. Samples were tested for DNA to determine whether the presumptive tests damaged or destroyed DNA. The DNA loci tested were D2S1338 and D19S433. Leuchomalachite green had a sensitivity of 1:10,000, while the remaining tests were able to detect blood to a dilution of 1:100,000. Substances tested include saliva, semen, potato, tomato, tomato sauce, tomato sauce with meat, red onion, red kidney bean, horseradish, 0.1 M ascorbic acid, 5% bleach, 10% cupric sulfate, 10% ferric sulfate, and 10% nickel chloride. Of all the substances tested, not one of the household items reacted with every test; however, the chemicals did. DNA was recovered and amplified from luminol, phenolphthalein, Hemastix, and Bluestar, but not from leuchomalachite green or Hemident.

Aniline Compounds↗

IgA antiendomysial antibodies on the umbilical cord in diagnosing celiac disease. Sensitivity, specificity, and comparative evaluation with the traditional kit.

BACKGROUND: The possibility of assaying antiendomysial antibodies (EmA) on the human umbilical cord instead of monkey esophagus has recently been suggested. We therefore evaluated in patients with celiac disease (CD) the sensitivity and specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord and monkey esophagus. METHODS: We studied 36 patients with CD and atrophy of the intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free diet for 8-12 months (median age, 3.0 years), 36 controls without gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey esophagus were assayed with commercially available kits; the slides with umbilical cord were prepared in our laboratory. RESULTS: There was a perfect concordance between EmA results evaluated on umbilical cord and those on monkey esophagus; there was a doubtful result in only one case on human umbilical cord, which was positive with low titer on monkey esophagus. EmA specificity was 100%; the specificity of AGA IgG varied between 72% and 94% and of AGA IgA between 90% and 100% depending on whether controls without gastrointestinal disorders or patients with CMPE were considered. EmA sensitivity was 97%, AGA IgG was 89%, and AGA IgA 72% sensitive. The only false negative for EmA was positive for AGA IgG and AGA IgA. CONCLUSIONS: Using human umbilical cord as a substrate for EmA may provide the same sensitivity and specificity as offered by the test using monkey esophagus substrate, thus reducing costs and avoiding the use of endangered species.

Adolescent↗

[A sensitive, specific colorimetric method for determining paracetamol in human plasma (author's transl)].

A sensitive and specific colorimetric assay for paracetamol (acetaminophen) in plasma is described. After a selective column extraction (Extrelut) and hydrolysis, paracetamol is determined by the (modified) Axelrod and Brodie procedure. The whole processing is performed in a centrifuge tube. This method yields a high recovery (90%), saves time and only 1 ml of plasma is needed. Due to low blank values, the limit of detection is as low as 0.2 microgram/ml. At a concentration of 10 and 2 microgram/ml the coefficient of variation is 4% and 10%, respectively. In contrast to the often used extraction method, no emulsions are formed with this column procedure. One person is able to perform 50 analysis per day.

Acetaminophen↗

Carpal tunnel syndrome in 100 patients: sensitivity, specificity of multi-neurophysiological procedures and estimation of axonal loss of motor, sensory and sympathetic median nerve fibers.

This prospective study meets all six criteria recently recommended by a quality assurance committee of the AAEM and defines criteria of abnormality, sensitivity and specificity of 19 sensorimotor and sympathetic parameters in 100 patients who were suspected on clinical grounds of having carpal tunnel syndrome (CTS), and in 70 control subjects. Nine parameters reached a specificity of 97%, permitting the electrodiagnosis of CTS in 87% of the patients studied. The results in this study confirm that median sensory nerve conduction studies are more frequently abnormal than are studies of motor nerve conduction. The so far unknown usefulness of parameters such as median F-wave abnormalities and residual latency, terminal latency index and sensory nerve action potential (SNAP) amplitude was assessed; these parameters were not found sensitive enough, yet high specific (SNAP amplitude) or high sensitive yet low specific (F-wave abnormalities, residual latency and terminal latency index) and are therefore of little value in the early clinical electrodiagnostic evaluation of patients with CTS. Finally, in the patients studied, some degree of axonal loss for motor, sensory and sympathetic median nerve fibers was found in 42% of cases and 6 patients had a double-crush syndrome and 6 others had a concomitant ulnar neuropathy at the elbow.

Action Potentials↗

[Sensitivity, specificity and predictive values of methods of evaluation in psychiatry].

Clinical assessments, psychological examinations, biological parameters and other indices are commonly used in psychiatry to measure disease status. These evaluation tools are not perfect and, in general, they will fail to perfectly discriminate "cases" from normal controls. When a gold standard is available, their performances can be evaluated. If the results of a measurement are tabulated with true disease status in a contingency table, the proportions of cases and normals correctly identified (sensitivity and specificity) are useful coefficients of validity of the instrument studied. It is shown that unbiased estimates of the prevalence rate cannot however be derived directly from the proportion of sample respondents identified by a test. Practical examples with a psychiatric rating scale are provided which illustrate the importance and magnitude of this bias. Formulas are subsequently given which permit the calculation of the "true" prevalence rate from the proportion of screen positives when the sensitivity and the specificity of the test are known. The proportion of true cases among those individuals identified by a test is another important property of psychiatric measures, particularly for screening purposes. It is also called the positive predictive value and, like sensitivity and specificity, predictive values are probabilities for which high values are desirable. However, this critical characteristic of a test depends on the prevalence rate, the sensitivity and the specificity of the test used. Using an example, major changes in the probability of a screen positive individual to be truly diseased are shown to depend upon varying levels of the base rate of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Sensitivity, specificity, and positive predictive value of technetium 99-HMPAO SPECT in discriminating Alzheimer's disease from other dementias.

Investigators have reported high sensitivity and specificity values for single photon emission computerized tomography (SPECT) when distinguishing Alzheimer's disease (AD) patients from normal elderly controls or from selected patient groups. The role of SPECT in identifying AD among unselected patients with memory complaints requires investigation. We examined 139 consecutive patients with 99Tc-HMPAO SPECT. NINCDS-ADRDA diagnoses were determined blind to SPECT results, and scans were read and classified by visual inspection blind to clinical diagnoses. Bilateral temporoparietal hypoperfusion (TP) occurred in 75% of probable, 65% of possible, and 45% of unlikely AD patients, yielding a sensitivity of 75% and a specificity of 52% when comparing probable AD versus unlikely AD groups. A positive predictive value of 78% was obtained based on a 69% prevalence of AD in our total clinic population. Patients with false-positive results included a variety of dementing illnesses; all patients with bilateral hypoperfusion had dementia. A pattern of TP on SPECT scans is seen in most patients with AD, but could be found in other dementias as well and cannot be regarded as specific to AD. Reduced TP perfusion discriminated between demented and nondemented individuals. Further strategies for SPECT interpretation that improve diagnostic specificity should be sought.

Aged↗