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PubMed1977

Further studies of biochemical predictive tests in breast cancer.

This report extends our observations on the relationship between the therapy of breast cancer, estrogen binding and tissue enzymes. We have compared the dextran-coated charcoal method and the sucrose gradient analysis in determining estrogen receptors, and find a sub-group of receptor positive tumors--identifiable only by the latter technique--which we suggest may lead to an incorrect prediction of response to hormonal therapy. Data are also presented to suggest that enzyme analyses show promise in predicting responsiveness to present modes of combination chemotherapy of breast cancer.

Breast Neoplasms↗
PubMed2006

The impact of expression profiling on prognostic and predictive testing in breast cancer.

Expression profiling has been extensively applied to the study of breast cancer and undoubtedly is changing the way breast cancer is perceived. Over the past few years, several groups have described prognostic "signatures" (gene lists) that are purported to be more accurate prognostic factors than well established clinical and pathological features. In addition, cDNA and oligonucleotide microarrays have also been used to devise predictive "signatures" in the setting of neoadjuvant chemotherapy setting. However, it seems that the enthusiasm with this new technology has led most of us to turn a blind eye to some serious methodological problems which are evident in landmark papers on breast cancer expression profiling. These issues include small and biased cohorts of patients, inappropriate statistical analysis and lack of thorough validation of the technology. In this review, we critically revisit the most relevant cDNA microarray studies on breast cancer prognosis and prediction published to date. Although the results are promising, further optimisation and standardisation of the technique and properly designed clinical trials are required before microarrays can reliably be used as tools for clinical decision making.

Breast Neoplasms↗
PubMed2005

Testing prediction capabilities of an 131I terrestrial transport model by using measurements collected at the Hanford nuclear facility.

A model describing transport of 131I in the environment was developed by SENES Oak Ridge, Inc., for assessment of radiation doses and excess lifetime risk from 131I atmospheric releases from Oak Ridge Reservation in Oak Ridge, Tennessee, and from Idaho National Engineering and Environmental Laboratory in southeast Idaho. This paper describes the results of an exercise designed to test the reliability of this model and to identify the main sources of uncertainty in doses and risks estimated by this model. The testing of the model was based on materials published by the International Atomic Energy Agency BIOMASS program, specifically environmental data collected after the release into atmosphere of 63 curies of 131I during 2-5 September 1963, after an accident at the Hanford PUREX Chemical Separations Plant, in Hanford, Washington. Measurements of activity in air, vegetation, and milk were collected in nine counties around Hanford during the first couple of months after the accident. The activity of 131I in the thyroid glands of two children was measured 47 d after the accident. The model developed by SENES Oak Ridge, Inc., was used to estimate concentrations of 131I in environmental media, thyroid doses for the general population, and the activity of 131I in thyroid glands of the two children. Predicted concentrations of 131I in pasture grass and milk and thyroid doses were compared with similar estimates produced by other modelers. The SENES model was also used to estimate excess lifetime risk of thyroid cancer due to the September 1963 releases of 131I from Hanford. The SENES model was first calibrated and then applied to all locations of interest around Hanford without fitting the model parameters to a given location. Predictions showed that the SENES model reproduces satisfactorily the time-dependent and the time-integrated measured concentrations in vegetation and milk, and provides reliable estimates of 131I activity in thyroids of children. SENES model generated concentrations of 131I closer to observed concentrations, as compared to the predictions produced with other models. The inter-model comparison showed that variation of thyroid doses among all participating models (SENES model included) was a factor of 3 for the general population, but a factor of 10 for the two studied children. As opposed to other models, SENES model allows a complete analysis of uncertainties in every predicted quantity, including estimated thyroid doses and risk of thyroid cancer. The uncertainties in the risk-per-unit-dose and the dose-per-unit-intake coefficients are major contributors to the uncertainty in the estimated lifetime risk and thyroid dose, respectively. The largest contributors to the uncertainty in the estimated concentration in milk are the feed-to-milk transfer factor (F(m)), the dry deposition velocity (V(d)), and the mass interception factor (r/Y)dry for the elemental form of iodine (I2). Exposure to the 1963 PUREX/Hanford accident produced low doses and risks for people living at the studied locations. The upper 97.5th percentile of the excess lifetime risk of thyroid cancer for the most extreme situations is about 10(-4). Measurements in pasture grass and milk at all locations around Hanford indicate a very low transfer of 131I from pasture to cow's milk (e.g., a feed-to-milk transfer coefficient, F(m), for commercial cows of about 0.0022 d L(-1)). These values are towards the low end of F(m) values measured elsewhere and they are low compared to the F(m) values used in other dose reconstruction studies, including the Hanford Environmental Dose Reconstruction.

Adolescent↗
PubMed1984

Predictive testing with the subrenal capsule assay.

Measurement of drug activity as an oncolytic effect, use of the control only to monitor the quality of tissue implanted, and the rapid clearance of necrotic tissue from the subcapsular site, as significant factors incorporated into the design of the assay, have permitted use of a simple tumor size parameter for evaluating drug activity. The simplicity and economy of such a parameter, the predictability and reproducibility of the 6-day assay observed thus far, and evidence that the assay does measure a biological property of the tumor apart from host response, have warranted the continued use of the 6-day time frame and the normal immunocompetent CDF1 mouse as xenograft host. These studies have demonstrated the feasibility of using human tumor explants obtained from a variety of solid human malignancies in a straightforward, short term, in vivo predictive assay system. Preliminary correlations between in vivo (assay) tumor sensitivity and clinical response have given reasonable concurrence. This crucial point will require further study, with larger numbers of patients, under more rigid conditions. Final validation of this, and other, predictive assays will require a prospective, randomized study in large numbers of patients. Our present prospective study is being continued, therefore, with expansion to a multi-institutional design over a broader geographic area.

Altretamine↗
PubMed1996

Chronic hypertension in pregnancy: color Doppler investigation of uterine arteries as a predictive test for superimposed preeclampsia and adverse perinatal outcome.

To determine if uterine artery Doppler velocimetry is useful in identifying chronic hypertensive pregnancies at risk for superimposed preeclampsia and adverse perinatal outcome. Resistance index (RI) was assessed by color velocimetry at the level of uterine arteries at 23-24 weeks of gestation in 42 women with chronic hypertension. The "lowest", the "highest" and the "average" values were compared to select the most predictive index for superimposed preeclampsia, intrauterine growth retardation (IUGR), birth weight lower than 2500 g and gestational age at delivery less than 36 weeks. Nine patients developed superimposed preeclampsia (21%) and 15 delivered before the 36th week of gestation (36%); 4 babies were IUGR (10%) and in 18 cases birth weights were below 2500 g (43%). Statistical analysis of Doppler findings showed that abnormal values of "lowest RI" were significantly correlated with adverse pregnancy outcome. Color Doppler analysis of uterine arteries is able to select chronic hypertensive pregnant women at risk of superimposed preeclampsia and poor perinatal outcome.

Adult↗
PubMed1992

Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients.

It has been shown recently that cyclosporine is largely metabolized by P450IIIA (CYP3A), an enzyme whose catalytic activity varies significantly among patients. To determine whether heterogeneity in P450IIIA activity contributes to interpatient differences in cyclosporine dosing requirements, the oral pharmacokinetics of the drug were determined in 20 stable kidney transplant recipients. P450IIIA activity was then measured in each patient by use of the erythromycin breath test. In the 16 patients who were at steady state, the logarithm of the apparent oral clearance of cyclosporine correlated significantly with the rate of 14CO2 exhaled in breath after intravenous administration of [14C N-methyl]erythromycin (r = 0.55, p = 0.03). No significant correlations existed between apparent oral clearance and age, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol, or hematocrit in these patients. We conclude that heterogeneity in P450IIIA activity significantly contributes to interpatient differences in dosing requirements of cyclosporine in kidney transplant patients.

Adult↗
PubMed1982

What do placental function tests predict? Observations on placental lactogen levels in growth retardation and fetal distress.

Single blood samples were obtained from an unselected population of 527 women between 36 and 40 wk gestation. Serum placental lactogen levels were lower than normal in patients whose infants were growth retarded or developed fetal distress in labor. These associations were independent; the fetal distress group did not contain an excess of subjects with growth retardation. Thus, the results of a biochemical test reflect dynamic aspects of placental function and not simply the overall growth of fetus and placenta.

Female↗
PubMed1999

Helicobacter pylori infection in elderly people: does quantitative serological testing predict gastroduodenal ulcer disease?

Invasive diagnosis of peptic ulcer disease in the aged often carries an increased risk. Recently a correlation between high IgG serum antibody concentrations against H. pylori and a clinical diagnosis has been reported. In this study, we attempted to establish a relationship between the magnitude of serum IgG antibody to H. pylori and the endoscopic diagnoses in H. pylori-infected elderly patients. All the patients aged 60 or older were entered into the study prospectively. Those patients who had ulcerogenic medications or H. pylori eradication therapy prior to testing, or who were seronegative for H. pylori were excluded. Endoscopic diagnoses included duodenal ulcer, gastric ulcer, presence of both gastric ulcer and duodenal ulcer, gastroduodenal erosions, and nonulcer dyspepsia. H. pylori IgG serology was determined by an enzyme-linked immunosorbent assay with values of greater than 50 units/ml being seropositive. In all, 182 seropositive elderly patients were recruited. The age was 68.8+/-6.7 (mean+/-SD) years (range = 60-94 years). The serum IgG titers ranged from 51 units/ml to 800 units/ml with a peak frequency at 50-99 units/ml (30.8%). The quantitation of H. pylori IgG values and the endoscopic diagnoses failed to demonstrate any relationship of statistical significance. Our results indicate that the magnitude of H. pyloni IgG serology cannot be used to predict the presence or absence of peptic ulcer disease in the elderly.

Age Factors↗
PubMed1997

[Reduced serotonin levels are predisposing to violence. A simple blood test predicts dangerous character].

Deficient serotonergic function in the brain is associated with a risk of impulsive violence. The level of serotonergic function can be assessed indirectly in several ways: 1. determination of CSF (cerebrospinal fluid) content of the serotonin metabolite 5-HIAA (5-hydroxyindoleacetic acid); 2. determination of the plasma level of the amino acid tryptophan, the serotonin precursor (passage of tryptophan into the brain is dependent on the ratio of tryptophan to other competing amino acids); 3. analysis of platelet monoamine oxidase content, a putative correlate of serotonergic capacity in the brain; 4. by determining response to an OGTT (oral glucose tolerance test), another putative correlate of serotonergic function.

Emotions↗
PubMed1978

[Prediction test of nomifensine prescription from symptomatic pre-therapeutic status (author's transl)].

Heighty two outpatients, suffering from reactive or neurotic depression have been treated with a daily 100 mg dose of nomifensine. The symptomatic status before treatment was appreciated by a self-rating scale, the Hopkins Symptoms Check List (HSCL). At the end of the study, the patient again filled out this same rating scale, and also a seven-score amelioration questionnaire. The investigator filled out this same questionnaire and a fourscore global impression scale. We tried to find out if by appreciating initial symptoms with the HSCL, it was possible to predict which patients would be responders to the treatment. The only highly significant result was obtained with a discriminant analysis, which combines 22 items of the pre-therapeutic HSCL and with which it is possible to predict the amelioration measured by the difference between the total pre- and post-therapeutic HSCL notations. The authors point out to the interest of this method in psychopharmacology.

Adjustment Disorders↗
PubMed2001

Results of a baseline urine test predict levels of cocaine use during treatment.

Sixty-one cocaine dependent outpatients submitted a single urine sample at least 1 week prior to entry into a 4-week treatment study. Participants were then expected to provide three urine samples per week during the month of treatment. The 61 patients studied here all completed treatment and provided an average of more than 11 of 12 scheduled urine samples. Participants who submitted a cocaine-positive sample prior to treatment provided more positive urine samples during the 4-week trial, were less likely to be completely abstinent during the month, and took longer to reach an initial abstinence criterion of three consecutive cocaine-free urines. Thus, a single pretreatment urine test represents a powerful predictor of subsequent cocaine use. The results suggest that future randomized trials stratify group assignment based on the results of a baseline urine test.

Adult↗
PubMed1993

A predictive test for space motion sickness.

Eye torsion was examined in 13 astronaut subjects, tested during repeated episodes of 0 G and 1.8 G in parabolic flight aboard NASA's KC-135. Four findings are included. 1) A strong relationship between previous history of SMS and ocular torsional disconjugacy in novel gravitational states. 2) Responses were unchanged in 4 subjects retested a year later. 3) Ocular torsional disconjugacy scores increased as exposure to 0 and 1.8 G increased. This was particularly evident in subjects who had had SMS. 4) Torsional studies during 10 to 20 parabolas are required to accurately predict SMS. The hypothesis of otolith asymmetry, compensated in 1 G but becoming unmasked in novel gravitational states, is proposed to explain the torsional disconjugacy and ensuing SMS.

Eye Diseases↗
PubMed1990

[Evaluation of oral health status of a preschool group with a predictive test based on mutans group and clinical studies].

A children's population, aged from 2 to 5 years, was studied for three years. Bacteriological and clinical criteria were followed, with a determination of the M. st level in non-stimulated saliva in the age-groups of 3, 4 and 5 years. We found, as Alaluusua did, a correlation between the M. st level in saliva and the number of caries. With this study, a large number of caries-free children had a low M. st level. The largest amount of caries appears in children with a high M. st level. The highest caries incidence in this population appears at the 4 year children group. It has to be remembered that this is an age-group with specific characteristics. Caries is a disease depending on many factors and the M. st level would be very significant to an early detection of risks, but should be evaluated considering all the parameters as a whole. Its predictive value is not sufficient by itself but it has an unquestionable value when detecting risk patients of an early age. Therefore, treatment has to be the result of an etiological diagnosis addressed to prevention after an evaluation of all the factors related with the caries disease.

Child, Preschool↗
PubMed1988

The potential use of microcalorimetry in predictive tests of the action of antineoplastic drugs on mammalian cells.

The effect of methotrexate (MTX) on cultured T-lymphoma cells in a growing suspension was measured by microcalorimetry. The effect of the drug could be observed within 2 h after its injection into the calorimetric vessel. A dose-response curve was constructed from the calorimetric results obtained with final concentrations of MTX in the range of 0.02-2.00 microM. In another series of experiments calorimetric values were determined after 8 h of MTX-cell interaction. These data were correlated with values for cell counts during an 18 h period following the removal of the drug. A clear correlation was found between the calorimetric and cytotoxicity data. Calorimetric results obtained within 8 h of MTX-cell interaction appear to be of value in predicting the antineoplastic effect of the drug.

Animals↗
PubMed2000

Osmotic behavior of in vitro produced bovine blastocysts in cryoprotectant solutions as a potential predictive test of survival.

The osmotic behavior of bovine blastocysts produced in vitro was filmed during exposure to and dilution of cryoprotectant solutions used for vitrification. The relationship between the changes in the diameter of embryos and their subsequent survival was assessed. Embryos collected on Day 6 and Day 7 postinsemination were exposed to 10% glycerol (GLY) for 5 min, 10% GLY + 20% ethylene glycol (EG) for 5 min, and 25% Gly + 25% EG for 30 s, before dilution in 0.85 M galactose and finally in embryo transfer freezing medium (ETF). Embryos that had a higher probability of survival behaved as perfect osmometers, shrinking, reexpanding, or swelling according to an identical pattern, whereas embryos that deviated from this standard usually did not survive. The initial embryo diameter, duration of shrinkage and expansion in 10% glycerol, duration of reexpansion in ETF, and final embryo diameter were clearly predictive of the ability to hatch after culture in vitro. On a given day postinsemination, larger blastocysts were more likely than smaller blastocysts to survive and hatch after exposure to cryoprotectants with or without vitrification.

Animals↗
PubMed1996

Search for the most predictive tests of fetal well-being in early labor.

The aim of the study was to evaluate the admission CTG alone and in combination with the following tests: fetal acoustic stimulation test (FAST), maternal perception of sound provoked fetal movement (mpSPFM), amniotic fluid index (AFI), and umbilical artery doppler studies in early labor. 1092 singleton pregnancies in cephalic presentation, and with intact amniotic membranes at 37 weeks gestation or more, were admitted in early labor to the labor ward at the National University Hospital, Singapore. Admission tests were performed, and labor managed according to established labor ward protocol. Of all the tests performed, only the results of the admission CTG and color of the amniotic fluid were known to the obstetrician. If the admission CTG is normal, AFI is > 5 cm and there is an acceleratory responses to FAST the incidence of fetal distress is low. In the presence of a reactive admission CTG and in the absence of thick meconium, fetal heart rate response to FAST and the AFI provided a better selection of the high risk fetus that would require closer monitoring or early delivery. When the admission CTG was suspicious, FAST, AFI, and blood flow velocity waveform studies may allow more confident prediction of the ability of the fetus to withstand the stresses of labor.

Acoustic Stimulation↗
PubMed1976

Tamoxifen as an anti-tumour agent: oestrogen binding as a predictive test for tumour response.

Rats with growing 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary carcinomata were biopsied and oestrogen-binding capacity was measured using a Sephadex LH-20 chromatography method. Tumours were measured with calipers and animals were treated for 3 weeks with tamoxifen (50 mug/day, S.C.). Tumour response was determined by the size (cm2) before and after therapy. An increase in tumour regression (ten tumours) was seen with increasing oestrogen-binding sites determined by Scatchard analysis (P less than 0.01). Thirty tumours were used to determine oestrogen binding with a single dose of [3H]-oestradiol. The percentage tumour regression was linearly correlated with oestrogen-binding capacity (P less than 0.01), although some tumours with high oestrogen-binding capacities only partially regressed in response to tamoxifen therapy. The time of the oestrous cycle when biopsy occurred was not a critical factor in determining oestrogen binding for prediction of response. Oestrogen binding was reduced during tamoxifen therapy.

Animals↗