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PubMed2002

Predictive testing for autoimmunity.

Many chemicals, in particular drugs, cause systemic allergy or autoimmune-like disorders. Due to complex pathogenesis and strong dependence on genetic make-up, these immunotoxicological effects are usually missed in standard toxicity testing. Besides, animal studies that demonstrate chemically induced systemic allergy or autoimmune-like disorders are scarce. Here, animal models are presented that would fit into a predictive two-tiered strategy, designed to allow screening for immunostimulatory potential in the first tier, and more elaborate testing for allergenic or autoimmunogenic potential of selected chemicals in the second tier. The popliteal lymph node assay (PLNA), with or without reporter antigens, would fit in the first tier, and relevant route of exposure protocols with selected strains of mice or rats may be further developed to compose the second tier. To date, the relevant route of exposure models mentioned here (with 'normal' inbred mice and/or Brown Norway rats) has been tested with only a few chemicals, and the PLNA, although tested with over 100 chemicals, is not validated as yet. Conceivably, a major challenge in immunotoxicology is to incorporate the present knowledge on chemical-induced systemic allergy and autoimmunity in further development and validation of predictive models and strategies.

Animals↗
PubMed1995

[Cutaneous pulpar temperature and cold test. Predictive specificity and sensitivity in pharmaco-clinical studies].

The aim of this study was to measure the cutaneous pulpar temperature of the fingers and assess its evolution after one minute of controlateral hand immersion in a water bath at 4 degrees C and during 10 minutes after cooling. This test was carried out in 347 subjects (120 M, 227 F) divided in 5 groups: 117 healthy volunteers (49 M, 68 F) without any vascular diseases, 46 patients (5 M, 41 F) with acrocyanosis, 87 patients (19 M, 68 F) with Raynaud's phenomenon, 31 patients (24 M, 7 F) with peripheral arterial occlusive disease and 66 patients (23 M, 43 F) with other vascular diseases (high blood pressure and coronary disease). The mean initial temperature (TO) analysis in each group, showed that 2 groups, acrocyanosis and especially Raynaud's group, had a finger temperature significantly lower than the control group (27.4 +/- 4.8 degrees C 25.3 +/- 4.9 degrees C versus 30.5 +/- 4.9, p < 0.02). The cooling test showed 3 different cutaneous temperature reactions: subjects without any modification during and after immersion, subjects with a temperature decreasing after immersion and a normal rewarming after 10 minutes and subjects with a decreasing without any total recovery after 10 minutes. In the subjects with cold hands (initial temperature < 30 degrees C), this cooling test can isolate all patients with a temperature decreasing without any rewarming after 10 minutes with a specificity at 100% (no normal subject with cold hands were abnormal to this test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Preliminary evaluation of flicker sensitivity as a predictive test for exudative age-related maculopathy.

Flicker contrast sensitivity was tested in the "good" eyes of 13 patients with monocular exudative age-related maculopathy (ARM). The stimulus was a foveal, long-wavelength, low spatial frequency 2.8 degrees circle in an equiluminant (photopic) surround. Two of these ARM-risk eyes have since developed exudative ARM. Compared to healthy age-matched eyes, the two eyes that developed exudative ARM had significantly lower sensitivity at 10-40 Hz up to 9 mo before exudative symptoms appeared. The implications of these results regarding the time-course of ARM and the predictive value of foveal contrast sensitivity testing are considered. Based upon data and theoretical considerations, the authors speculate that sensitivity loss between 10 and 40 Hz is a good predictor of which eyes will develop exudative ARM. This proposal will be tested by new data from current as well as new ARM-risk subjects.

Aged↗
PubMed1991

Evaluation of in vitro cytotoxic T lymphocyte assays as a predictive test for the occurrence of graft vs host disease.

The potential value of in vitro cytotoxic T lymphocyte (CTL) assays for predicting the occurrence of graft vs host disease (GVHD) following allogeneic bone marrow transplantation was evaluated in 12 mouse donor-host combinations associated with various degrees of GVHD. These donor-host combinations were selected after evaluation of GVHD triggered by minor histocompatibility antigens (MiHA) in 24 allogeneic strain combinations derived from six strains of H-2b mice. Recipients (n = 475), previously submitted to total body irradiation (9.5 Gy), were transplanted with 10(7) bone marrow cells along with 5 x 10(7) spleen cells. While lethal GVHD was observed in half of the strain combinations, it was possible to select 12 donor-host combinations characterized by severe, mild, or absent GVHD. When levels of anti-host CTL activity were assessed following in vivo priming and in vitro boosting, strong CTL-mediated cytotoxicity was observed in all combinations whether they developed GVHD or not. CTL frequency measured by limiting dilution analysis (LDA) ranged from 1/16880-1/306. The Spearman rank test revealed no positive correlation between GVHD intensity and donor anti-host CTL activity assayed either in bulk culture experiments or in LDA conditions. These results indicate that MiHA capable of triggering potent CTL responses in vitro do not necessarily initiate GVHD, and that in vitro measurement of donor CTL activity against host-type Con A blasts is not a predictive assay for anti-MiHA GVHD. However, the possibility to recruit CTL populations targeting host MiHA expressed specifically on hematopoietic cells suggests a novel therapeutic strategy for the cure of hematopoietic malignancies. Indeed, transplantation of donor hematopoietic stem cells supplemented with T cells aimed at MiHA specifically expressed by host hematopoietic cells, could possibly potentiate the desirable graft vs leukemia effect without increasing the risk of GVHD.

Animals↗
PubMed1997

[Is fetal fibronectin a valid test predictive of premature labor?].

This study sought to determine the value of oncofetal fibronectin as predictor of preterm delivery in patients presenting with preterm labor. Patients admitted for preterm labor with intact membrane between 24 and 34 weeks gestation were included. A dacron swab applied to the external os for 10 seconds. The fetal fibronectin is detected bill a biologic membrane test. 90 patients were included. 25 (28%) had positive fetal fibronectin, and 13 (52%) had preterm delivery (specificity and positive value 81% and 52% respectively). Among 65 (72%) with negative fetal fibronectin, only 12 (18%) had preterm delivery (sensitivity 81% and negative predictive value 81%: p < 0.001). Median interval between sampling and delivery was 5 days in the positive compared to 23 in the false negative group. The presence of fetal fibronectin in the cervico-vaginal mucus strongly suggest an eminent delivery within few days after sampling. The sensitivity of the test is the 62% and still more interesting the negative predictive value is 86% (p < 0.001). The fetal fibronectin is a useful test to help the obstetrician discriminating true from false labor in patients with high risk preterm delivery. A negative test is very reassuring according to its high negative predictive value. Allowing to avoid unuseful tocolyse and long hospital.

Adult↗
PubMed2003

A quick test predicts acute coronary events.

Inflammation of the coronary arterial wall plays a major role in atherosclerosis and ultimately thrombosis by contributing to vascular constriction, spasm, and thrombus formation. Measurement of hs-CRP level is a readily available laboratory blood test that serves as a gauge of coronary plaque inflammation. As a result, hs-CRP has become a very useful biological marker for predicting the risk of acute coronary events and for making decisions regarding treatment. It is important to recognize that lipid-lowering therapy decreases plaque inflammation and slows the progression of calcium buildup in the coronary arteries, which is readily verified by reduction in hs-CRP levels. Endothelial dysfunction is a product of plaque inflammation and as such can predict acute CV events. Endothelial function can be assessed during cardiac catheterization by measuring the vasoactive response to pharmacological or physiological stress. However, the routine use of cardiac catheterization to measure drug-induced coronary vasoactivity can have potential adverse effects in patients with unstable coronary disease. Time and costs can also be additional constraints in the routine use of this procedure. Consequently the simple and readily available hs-CRP test is accurate and preferable.

Coronary Disease↗
PubMed2000

Does the Dundee Step Test predict outcome in treated hypertension? A sub-study protocol for the ASCOT trial. Anglo-Scandinavian Cardiac Outcome Trial.

Treated hypertensive subjects may remain five times more likely to die of cardiac and cerebrovascular diseases than normotensive subjects with equivalent resting blood pressure (BP) levels. Research evidence suggests that exercise BP is a better predictor of end-organ damage and mortality than resting BP, and data from our centre show that a significant proportion of treated hypertensives have uncontrolled BP during a 5-min Dundee Step Test. The prognostic usefulness of exercise BP has yet to be translated into clinical practice because of the lack of a suitable technique. The Dundee Step Test is being evaluated in the ASCOT (Anglo-Scandinavian Cardiac Outcome Trial) study, a 5-year follow-up multicentre, multinational trial comparing the effect of newer (amlodipine and perindopril) and older (bendroflumethiazide and atenolol) antihypertensive agents stratified according to cholesterol levels on cardiac outcome. If the value of the Dundee Step Test is proven, then it may be adopted into routine clinical practice for the assessment of exercise BP. This may result in the improved management of hypertension with a subsequent reduction in morbidity and mortality. The publication of this study protocol is meant to be a statement of on-going research which may stimulate interest among those with an interest in this area of research. Journal of Human Hypertension (2000) 14, 75-78.

Adult↗
PubMed1985

Predictive testing in cancer chemotherapy. II. In vitro.

During the last thirty years several in vitro techniques have been developed to predict sensitivity of individual tumours. When the results of these techniques were correlated with the clinical response in larger groups of patients, the accuracy for predicting resistance was greater than for predicting sensitivity. Amongst the culture techniques the colony-forming assays have received much attention. Research with tumour cell lines and the sound biological basis do support this preference on other techniques. Studies on these assays have come from several independent laboratories, who report comparable results. Improvement of the culture technique and more insight into the in vitro pharmacology is needed, before application on wider scale is justified. Colony-forming culture techniques have not only been propagated for individualized chemotherapy, but also for drug screening. New antitumour agents and analogous can be screened in a short time for their sensitivity in many histologic tumour types.

Animals↗
PubMed1992

Second-generation anti-HCV tests predict infectivity.

Twenty-four blood donors found positive for the first-generation hepatitis C antibody (anti-HCV) test (Ortho EIA-I) and 88 of their recipients over the period from 1972 to 1990 were retrospectively investigated with different first- and second-generation anti-HCV tests. The aim of the study was to identify the infective donors and to evaluate the tests. Seven donors, who probably were infective carriers of HCV, were also second-generation test (EIA-II) positive, compared to only 3 out of 17 noninfective donors. Among the infected recipients, 14 out of 29 (48%) were positive for the second-generation test only. The second-generation test identified the infective donors in our study and was more sensitive than the first-generation test. We therefore recommend that blood donors are screened with EIA-II. Positive test results should be confirmed by the recombinant immunoblot assay (RIBA-II), and persons with positive or not conclusive RIBA-II should not be accepted as blood donors.

Blood↗
PubMed1987

Is the dexamethasone suppression test predictive of response to specific antidepressant treatment in major depression?

The authors attempt to correlate the response to dexamethasone suppression test (DST) with a clinical response to antidepressant drugs in 68 patients with major depression. Antidepressants that influence noradrenergic or serotonergic transmission with relative different potencies were selected and used in standard doses for 6 weeks. The response was evaluated weekly by raters blind to DST results and to antidepressant medications prescribed. The retrospective analysis failed to correlate DST response with outcome of treatment. Therefore the present results suggest that this laboratory test does not help to identify subgroups of depressed patients responding preferentially to various antidepressant drugs.

Adult↗