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[Comparison of rheumatoid test procedures--value and critical interpretation of sensitivity and specificity and their effect on pre-test and post-test probability].

In this prospective study, sera of 440 patients with rheumatic and degenerative joint diseases were tested for the presence of rheumatoid factor (RF). The Latex agglutination test (LFT), Waaler-Rose hemagglutination, laser nephelometry and IgM-Enzyme immunoassay (IgM-EIA) were used for detecting IgM-rheumatoid factors. In addition, rheumatoid factor of IgA isotype was measured by an IgA-Enzyme immunoassay. Sensitivity, specificity, pre-test- and post-test-probability were evaluated based on the data obtained to compare the test systems used. Under prospective patient selection, none of the test systems used reached a sensitivity of 100% concerning its cut off level. Despite this limitation, latex agglutination and IgM-EIA reached the highest sensitivity. Waaler-Rose test (90,8%) showed the best result for specificity. The IgA-EIA held the third position in sensitivity, specificity and efficiency. By comparing sensitivity with specificity, no test system can be recognized as the absolutely best one, since the receiver operating characteristic curves (ROC) overlapped. Practically rheumatoid factor measurement should initially use a highly sensitive assay, such as LFT and IgM-EIA to screen for RF. In the case of a positive result a more specific assay should be used, for example laser nephelometry, to confirm the result.

Adolescent

[Androgen test: comparison of a low test and a high test in the development of the penis in male pseudohermaphroditism].

BACKGROUND: The androgen sensitivity test used in male pseudohermaphroditism for clinical assessment of the androgen sensitivity and prediction of penile development is an important element in choice of gender. However, there is a wide range of testosterone dosage and no standardized test. METHODS AND PATIENTS: Two doses (2.5 mg and 100 mg) of testosterone heptylate were used in six cases of male pseudohermaphrodism with sexual ambiguity and small penis (ages 6 to 18 months). The clinical results were compared with those of the study of androgen receptors. RESULTS: In two cases, both low-dose and high-dose tests resulted in only minimal changes in the penis. In two cases, the low-dose test gave a good result which was confirmed by the high-dose test; on the other hand, in two cases, the low-dose test was considered to be negative whereas the high-dose test led to the development of a normal-sized penis. In all cases except one, there was good concordance between the results of study of androgen receptors and those of the clinical test. CONCLUSION: The high-dose androgen test is thus useful in both diagnosis and treatment and facilitates the gender assignment.

Antineoplastic Agents, Hormonal

Comparison of acidified glycerol lysis test, Pink test and osmotic fragility test in hereditary spherocytosis: effect of incubation.

In this study we compared the results of the acidified glycerol lysis test, the Pink test and the osmotic fragility test in 38 patients with hereditary spherocytosis and in healthy controls. The sensitivity of the acidified glycerol lysis test was 81.6% when performed within 3 h after blood collection. After incubating for 24 h, the sensitivity increased to 100% whereas the specificity remained maximal. Similar incubation did not improve the diagnostic utility of the Pink test. All patients, but none of the controls, showed a positive osmotic fragility test. It is concluded, because of sensitivity and specificity in this study, that the acidified glycerol lysis test after incubation and the osmotic fragility test are superior to the Pink test in detecting spherocytosis.

Adolescent

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria.

OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

Albuminuria

Comparison of a new type of skin test (Phazet) with existing skin test methods and the radioallergosorbent test (RAST).

A new skin test method (Phazet) for diagnosis of immediate-type allergic disease was tested in 232 patients attending the Guy's Hospital Allergy Clinic, and compared with conventional skin test methods, using Bencard and Pharmalgen allergen solutions, and with serum IgE antibody tests (RAST). Six allergens (cat, dust mite, Cladosporium, grass pollen birch pollen and plantain pollen) were used, as well as histamine and a negative control. Phazet proved easy to use and was popular with inexperienced operators (medical and dental students). For the majority of allergens there was reasonably good agreement with the different tests, but overall Phazet and RAST produced fewer positive results than the other skin tests methods. In particular, the frequency of positive histamine tests was lower with Phazet (82%) than with Bencard or Pharmalgen (99%), but this discrepancy was lower in the second part of the study when the minimum time for the insertion of the needle (1 sec) was more scrupulously observed. Phazet offers a convenient and practical alternative to conventional 'wet' skin test methods.

Allergens

[Comparative study of 2 latex tests (rubalex and rubascan) with an immunoenzyme test (enzygnost-rubella) and a hemagglutination inhibition test for the study of anti-rubella antibodies].

Four different assays for detection of rubella IgG antibodies, two latex agglutination (Rubalex and Rubascan), one hemagglutination inhibition (HAI) and one enzyme-linked immunosorbent assay (ELISA IgG), were used to test 372 human serum samples. All samples were also tested with a rubella ELISA IgM test and all of them were found negative. The results obtained in 358 (96.2%) out of 372 samples tested were identical with all procedures. Inconclusive results were obtained in 14 (3.8%) specimens, in that there were positive and negative results for the different assays. These 14 specimens were sent to the Institute of Virology in Turku (Finland) and tested by using a hemolysis in gel and a non commercially-available ELISA IgG test. Results obtained with the two last tests were considered definitive. The two latex tests were found equal or better than HAI and ELISA IgG for sensitivity and specificity. Furthermore they were also cost effective and more simple to perform.

Antibodies

A new glass microfibre-based histamine analysis for allergy testing in children. Results compared with conventional leukocyte histamine release assay, skin prick test, bronchial provocation test and RAST.

A new microfibre method for allergy testing measuring histamine release from human basophil leukocytes is described. Samples of 50 microliter washed blood are challenged with the suspected allergens. Released histamine is bound to microfibres and measured by a spectrofluorometrical method after removal of interfering substances by washing. The microfibre method (HR-MM) was compared to the conventional histamine release assay using the Ficoll-Hypaque gradient method (HR-FH) in 19 allergic children tested with one of three allergens. In addition, a comparison was made between the microfibre method and in vivo provocation tests, i.e. skin prick test (SPT), bronchial provocation test (BPT) and allergen specific serum IgE (RAST). It was found that the same individuals responded with histamine release to the same allergens in both histamine release assays, and the dose-response curves were almost identical. A positive correlation was found between the in vivo and in vitro tests. Thus it is concluded that the new method can provide reproducible, analytically precise (at the nanogram level) histamine release results in pediatric cases where: a positive SPT does not correlate with case history; BPT may be considered too hazardous or inconvenient; confirmation of negative or inconclusive SPT or RAST is needed. In contrast to other histamine release assays it is a convenient diagnostic tool in children since only small amounts of blood are needed and at least 96 tests can be carried out in 2 1/2 h.

Asthma

Quantitative estimation of diphtheria and tetanus toxoids. 2. Single radial immuno-diffusion tests (Mancini) and rocket immuno-electrophoresis test in comparison with the flocculation test.

The concentration in Lf units, of an unknown diphtheria or tetanus toxoid preparation is estimated in the flocculation test relative to reference preparations of tetanus and diphtheria antitoxins, respectively. By replacing the antitoxin reference preparations with toxoid reference preparations it should be possible to use immunological methods other than the flocculation test for the quantitative estimation of toxoids in Lf units. A number of diphtheria and tetanus toxoids were tested by rocket immuno-electrophoresis and single radial immuno-diffusion (Mancini test). The concentrations of the unknown toxoids were expressed relative to a diphtheria toxoid calibrated in Lf units (DIFT) and a tetanus toxoid calibrated in Lf units (TEFT), respectively. These two toxoid preparations are regarded as candidates for establishment as international standard preparations. The results obtained in the two tests were compared with those obtained in the flocculation test. In most cases the differences between the results did not exceed 10%. It is concluded, therefore, that the rocket electrophoresis or the radial immuno-diffusion tests can be used as alternatives to the flocculation test.

Diphtheria Toxoid

[Comparison of the Lithander (Kolt test) pediatric visual acuity test with the standardized Landolt ring test].

The visual acuity values obtained with the four test figures of Lithander's "Kolt-test" have been compared with Landolt ring acuity under standardized conditions which meet the requirements of DIN 58,220 and ISO/DIS 8596/7. For a given test figure size, the Kolt-test optotypes turned out to be somewhat easier legible than the Landolt ring. On average, visual acuity measured with the Kolt-test exceeded Landolt ring acuity by 0.08 log (angle of resolution) units. Thus, according to DIN and ISO criteria, the legibility of the Kolt-test is not equivalent to the standard Landolt ring. Equal acuity values could be obtained by increasing the observation distance proposed by the manufacturer of the Kolt-test by 19%. The legibility of the four optotypes differs on adult subjects: "circle" is more difficult, "cross" is easier legible than "square" and "triangle". Confusion of Kolt-test figures is basically restricted to two pairs of two optotypes ("cross" - "triangle", "square" - "circle").

Adult

A comparison of the multi-test with the prick test and multi-test 2.

Allergy skin testing of infants and small children continues to be time-consuming and nerve-wracking. We hoped to have found the solution to these problems by using the multi-test (MT). The latter consists of an applicator with 8 heads, each head consisting of nine plastic needles on which the allergen solution rests. Thus eight allergens can be tested simultaneously. During routine control skin testing we compared MT with our usual method, the prick test (PT), amongst twenty patients. Twenty-seven per cent of the skin reactions differed by more than 1+. When we compared PT results with the previous PT, the correlation of 16% was better despite several years interval between tests, different persons carrying out the tests, and hyposensitization of patients. We adapted the MT system and produced a model, multi-test 2 (MT-2), which consists of eight sterile disposable needles on a stainless steel base. When we compared the MT-2 with PT, only 6% differed by more than 1+. Thus the MT-2 proves to be a useful alternative to the PT for those children, in whom the PT is too difficult to carry out.

Adolescent

The reproducibility and comparability of tests of the peripheral chemoreflex: comparing the transient hypoxic ventilatory drive test and the single-breath carbon dioxide response test in healthy subjects.

Both the transient hypoxic ventilatory drive test and the single-breath carbon dioxide (CO2) response test have been used to assess peripheral chemoreflex sensitivity. We tested their comparability in 14 healthy adults (10 men, aged 31-73 years, mean 55.4 years). The within-subject reproducibility of both tests was also assessed (n = 7 for each). The mean transient hypoxic ventilatory response was 0.287 +/- 0.0591 min-1 (%Sao2)-1 (mean +/- SEM, range 0.018- 0.718) and single-breath CO2 response was 0.276 +/- 0.0411 min-1T-1 (range 0.081-0.501). Both tests were reproducible with a mean coefficient of variation of 20.1% and 17.7%, respectively. There was, however, no significant correlation between the results of the transient hypoxic and single-breath CO2 tests when data were compared by linear regression analysis (r = 0.23, P = 0.43), suggesting that separate pathways of the peripheral chemoreflex existed for hypoxia and hypercapnia, respectively, and that these tests were specific for each. The authors conclude that these tests are reproducible but need to be used in combination for an adequate assessment of the peripheral chemoreflex.

Adult

Testing of total hip replacements: endurance tests and stress measurements. Part 1: Endurance tests.

This is a paper in two parts. Part 1 gives details of fatigue tests carried out on Howse II hip prostheses. Three types of tests were carried out in accordance with three different draft test standards. Standard (I) was BSI DD91: 1984 in which the load range is 0.3-4.1 kN and the antero-posterior offset angle is 15 degrees. Standard (II) was BSI DD91: 1986 where the load range is 0.3-2.3 kN and the offset angle is 9 degrees. Standard (III) was ISO/DP 7206/3 in which the load range is 0.3-4.1 kN and the offset angle is 0 degrees. Four specimens were tested according to each standard. It was found that all the specimens tested according to standard (I) failed by fatigue after less than 6 x 10(5) cycles. All the specimens tested according to standards (II) and (III) withstood 5 x 10(6) cycles without failure. It is clear that the offset angle has an important influence on the fatigue life of the prosthesis. It is concluded that tests according to standard (I) are too severe, while tests according to standards (II) and (III) are either adequate or lax. This led to Part 2 of the investigation where the stresses in the prostheses were measured and calculated.

Hip Prosthesis

Pancreolauryl and NBT-PABA tests. Are serum tests more practicable alternatives to urine tests in the diagnosis of exocrine pancreatic insufficiency?

Serum fluorescein and p-aminobenzoic acid were measured during a urine pancreolauryl and an N-benzoyl-l-tyrosyl-p-aminobenzoic acid (NBT-PABA) test in 22 healthy controls, 17 patients with gastrointestinal nonpancreatic diseases (normal secretin-pancreozymin test), and 31 patients with abnormal exocrine pancreatic function due to chronic pancreatitis. The optimal cutoff point for separating normal from abnormal pancreatic function was after 210 min in the pancreolauryl test and after 150 min in the NBT-PABA test. The latter test was slightly less sensitive and specific than the pancreolauryl test. Serum tests seem to offer a practicable alternative to the established indirect pancreatic function tests in urine and may be used in the elderly and severely ill, as well as in outpatients in whom correct collection of the urine may be difficult.

4-Aminobenzoic Acid

Predictive testing for Huntington's disease: risk perception, reasons for testing and psychological profile of test applicants.

In the Center for Human Genetics in Leuven, predictive DNA-testing for Huntington's disease is available as a clinical service since November 1987, initially by DNA-linkage and since mid 1993 by direct mutation analysis. The multidisciplinary approach as well as the detailed test protocol are described. The present paper gives a sociodemographic description of the test applicants, their subjective evaluation of the risk and their motives for requesting the predictive test. Major attention is paid to the personality profile of the applicants who proceeded with testing. Psychometric testing revealed that this group of test applicants did not differ significantly from the general population for most characteristics and even had a number of more positive characteristics e.g. a higher ego-strength. The latter may reflect a self-selection of a more resourceful and emotionally healthier subgroup of at-risk persons. Nevertheless psychological evaluation also has identified a number of applicants with extremely high anxiety levels and other problems, who needed extra pretest and posttest counseling. The relatively high number of withdrawals from the test programme is another indication of the importance of adequate pretest counseling.

Adult

Comparison of the latex agglutination test with the hemagglutination inhibition test, enzyme-linked immunosorbent assay, and neutralization test for detection of antibodies to rubella virus.

The ability of a rapid, latex agglutination test to diagnose rubella infection and to measure immune status was evaluated by comparison with the hemagglutination-inhibition (HAI) test, enzyme-linked immunosorbent assay (ELISA), and the neutralization (NT) test. The latex agglutination test accurately detected serological conversions in 74 pairs of sera representing 21 natural infections and 53 immunizations. The antibody levels of 276 sera from the general population were determined by latex agglutination, HAI, and ELISA. The correlation coefficients between the titers obtained by HAI and latex agglutination and by ELISA and latex agglutination were statistically significant. Results on 12 sera did not agree when measured by the three tests. These sera were included among the 196 specimens tested by NT. The correlation coefficient between NT and latex agglutination titers was statistically significant. There was one serum positive by latex agglutination but negative by NT, and five sera were negative by latex agglutination but had titers of 4 to 8 in the NT. The relative sensitivity of detecting antibody was greater by latex agglutination than by HAI. An additional 49 sera containing residual nonspecific hemagglutinin inhibitors were evaluated by latex agglutination and NT. The untreated sera showed no false positive reactions, and 36 of 39 NT positive sera were positive in the latex agglutination test.

Antibodies, Viral

In vitro tests for teratogens: desirable endpoints, test batteries and current status of the micromass teratogen test.

Information from in vitro tests can be usefully used as a component of the risk/hazard assessment process. In vivo studies will be required to confirm the in vitro data. If the in vitro test system is designed around endpoints that reflect changes following in vivo toxic insult then it may be possible to modify the in vitro system to account for some of the discrepancies observed between in vivo and in vitro outcomes. When the discrepancy can be accounted for by low bioavailability in vivo, pharmacokinetic studies may be required to determine the relevance of the in vitro toxic concentrations. Reproductive hazard, especially teratogenicity, has been the subject of intensive in vitro test development. The observation of teratogenicity may affect the development of new products more significantly than any other type or category of reproductive toxicity. The micromass test, involving culture of differentiating rat embryo limb and midbrain cells exposed to test agents, may be useful as part of a battery of in vitro tests for teratogens. The most recent protocol for the micromass test is described, followed by a summary of validation and mechanistic studies confirming its usefulness. The test is robust in its transfer to new laboratories. Interlaboratory variability is small.

Abnormalities, Drug-Induced

Experimental study for the development of an in vitro test for contact allergens. 2. Comparison of the in vitro sensitization test with the guinea pig maximization test for contact allergens.

We have previously reported an in vitro hapten-specific sensitization method using Pam-212 cells (in vitro sensitization test) to identify the potential effectiveness of contact allergens. In the present study, we conducted comparison studies of 11 allergens and 2 irritants in order to evaluate the method as an alternative predictive test. The guinea pig maximization test (GPMT) was developed based on the test described by Magnusson and Kligman. Our assay was carried out as follows: we treated Pam-212 cells with 13 test chemical solutions, while T cells and macrophages of BALB/c mice were cultured with hapten-conjugated Pam-212 cells for 5 days. After incubation, 10(5) T cells were stimulated with mitomycin-C-treated spleen cells conjugated with chemicals. Three days later, the [3H]methyl thymidine incorporation was counted. The results of the GPMT were in agreement with those reported in previous studies except for benzocaine. In our GPMT experiments, benzocaine was negative, but it had been classified as a moderate sensitizer in previous studies. Our assay detected extreme, strong and moderate sensitizers as previously classified by the GPMT They could be summarized as follows: three of five chemicals classified as moderate sensitizers, and 100% of strong or extreme sensitizers were detected by both the GPMT and the in vitro sensitization test. No irritants showed a positive reaction in our assay. These results support the view that the sensitivity of our in vitro test may be equivalent to that of the GPMT and may be useful as a rapid and objective allergen screening test.

Allergens