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Dental Caries↗
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Could sperm aneuploidy rate determination be used as a predictive test before intracytoplasmic sperm injection?
Chromosome abnormalities in embryos are a major cause of implantation and development failures. Some couples with normal karyotypes have repeated implantation failures after intracytoplasmic sperm injection (ICSI). In order to value patients at risk for genetic ICSI failures and the validity of sperm aneuploidy analysis, we have studied cytogenetic abnormalities in sperm from ICSI patients. Twenty-nine patients with normal karyotypes were included. Ten patients had at least 4 ICSI treatments without pregnancy (group A). Nine patients had a pregnancy after 1 to 3 ICSI treatments (group B). Ten fertile men with normal semen parameters were studied as controls (group C). Fluorescent in situ hybridization (FISH) was used for sperm nucleus cytogenetic analysis using chromosomes 8, 9, 13, 18, 21, X, and Y specific probes. Aneuploidy for each chromosome and diploidy rates were significantly higher in group A than in group B and in group B than in group C (P < .05). Considering each patient in groups A and B, aneuploidy rate for each chromosome was too variable to be considered as a significant test. We proposed analysis of the total sperm aneuploidy. Chromosomal sperm nuclei profile could be used as a predictive biological test before ICSI in order to improve genetic counseling for oligoasthenoteratozoospermia patients.
Aneuploidy↗
Histocompatibility testing predicts acute rejection risk in early corticosteroid withdrawal regimens.
UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.
Adrenal Cortex Hormones↗
Predictive testing for Wilson's disease using tightly linked and flanking DNA markers.
We studied DNA polymorphisms for five new chromosome 13 markers in 52 Wilson's disease (WD) families from Europe, North America, and the Middle East. There was significant evidence for linkage between the Wilson's disease locus (WND) and all the marker loci. Multilocus linkage analysis, using a genetic linkage map established from reference pedigrees, suggested that WND is most likely between D13S31 and D13S59, at distances of 0.4 and 1.2 centimorgans, respectively. Our results suggest that the chromosomal location of the Wilson's disease gene is the same in all families from the populations studied. This evidence and the availability of many close, flanking, and polymorphic DNA markers make possible accurate and informative testing of potential carriers and WD homozygotes in families with at least one previously affected child. An advantage of a genetic linkage test over other laboratory methods for prediction of genotype in WD is that a reliable diagnosis can be made at a much earlier stage in life, including prenatally. In addition, DNA testing can be used in place of an invasive liver biopsy procedure to confirm a diagnosis in patients with borderline serum ceruloplasmin levels. Presymptomatic identification will also allow therapeutic intervention to prevent symptoms before irreparable liver or neurologic damage occurs. We describe the implementation of prenatal and preclinical diagnosis for two families with WD.
Chromosome Mapping↗
Fetal fibronectin test predicts delivery before 30 weeks of gestation in high risk women, but increases anxiety.
OBJECTIVE: To assess efficacy of cervico-vaginal fetal fibronectin as a predictor of spontaneous preterm birth in a high risk antenatal population, and to evaluate the psychological impact of fetal fibronectin testing. DESIGN: An observational study. SETTING: The antenatal clinic at a tertiary referral hospital. POPULATION: One hundred and forty-six pregnant women with known risk factors for spontaneous preterm birth. METHODS: Women designated as 'at risk' for preterm delivery by clinical history were screened for fetal fibronectin at 24 and again at 27 weeks of gestation. Anxiety levels were assessed by questionnaire and compared with anxiety levels of 206 low risk women also tested for fetal fibronectin. Fetal fibronectin results were disclosed to the woman and her clinician. MAIN OUTCOME MEASURES: Maternal anxiety and efficacy of the 24-week fetal fibronectin test to predict delivery before 30, 34 and 37 weeks of gestation. RESULTS: Maternal anxiety was higher pretesting in those at high risk compared with low risk women undergoing the test. Among the high risk women, anxiety was raised to clinically significant levels in those receiving a positive fetal fibronectin screening test result. In all women, 5%, 9% and 21% delivered <30, <34 or <37 weeks of gestation, respectively. Nine percent (n= 13) tested positive for fetal fibronectin at 24 weeks. Predictive power for fetal fibronectin (24 weeks) was greatest for delivery <30 weeks of gestation, with a likelihood ratio of 15 for a positive test (6/13 positive women delivered before 30 weeks). CONCLUSIONS: Fetal fibronectin was most efficient as a predictor of preterm spontaneous delivery <30 weeks of gestation, but was associated with high levels of anxiety.
Adult↗
The measurement of food preferences in humans: do taste-and-spit tests predict consumption?
Hedonic ratings of foods, obtained by laboratory taste-and-spit tests, are often used to determine the optimal concentration of sugar in a commercial food. However, the predictive value of these tests on actual consumption has not been demonstrated. Does the optimal sugar concentration in a specific food, as determined by a short exposure taste test, induce maximum intake of that food? In the present experiment, a standard food (yogurt) was presented in five sucrose concentrations (from 2% to 29%) to 18 subjects. The five types of yogurts were first tasted and rated for pleasantness. Secondly, they were presented in ad lib consumption tests. Discrepancies appeared between taste test ratings and ingestive responses, e.g., in subjects who preferred medium to high sucrose concentrations, the optimal concentration (in terms of intake) was lower than the "preferred" one (as determined by taste-and-spit tests). The results of taste-and-spit should be taken cautiously when trying to predict ingestion.
Adult↗
Invited contribution: an objective approach to the development of short-term tests predictive of carcinogenicity.
The Carcinogenicity Prediction and Battery Selection procedure was developed to address two problems: (1) the identification of highly predictive, yet cost-effective, batteries of short-term tests and (2) the objective prediction of the potential carcinogenicity of chemicals based upon the results of short-term tests even when a mixture of positive and negative results is obtained. In the present report the usefulness of the Carcinogenicity Prediction and Battery Selection procedure is demonstrated using benzo[a]pyrene, benzoin and diethylstilbestrol as examples. In addition, its applicability in the analysis of all the possible outcomes of a battery is illustrated together with an analysis of the worth of additional testing.
Animals↗
Does the dexamethasone suppression test predict antidepressant treatment success?
The 1 mg dexamethasone suppression test (DST) was carried out in patients with a major depressive illness in order to establish whether the results of this test, given before antidepressant or ECT treatment, could predict eventual therapeutic outcome. No significant difference could be detected in overall therapeutic improvement between those patients with a normal or abnormal DST response respectively, based on the 50 ng/ml cortisol cut-off point. However, using 100 ng/ml as a cut-off point it was found that patients with an abnormal DST response (i.e. a post-DST plasma cortisol concentration greater than or equal to 100 ng/ml) responded significantly better than those who had a normal DST response. These observations were statistically significant for those patients receiving antidepressants and in the combined treatment groups of those patients receiving either antidepressants or ECT.
Antidepressive Agents↗
Chemosensitivity testing predicts survival in ovarian cancer.
The aim of this study was to assess the use of the MTT assay for chemosensitity testing to identify drug resistance and predict survival in patients with advanced ovarian cancer. Samples of ascitic fluid and/or solid biopsies were taken from 120 patients with FIGO stage III or IV ovarian adenocarcinoma at presentation. Cells were exposed for 48 hours to four concentrations of clinically relevant drugs including platinums, anthracyclines and alkylating agents. Cell survival was measured using the 3-4,5-dimethyl-2, 5-diphenyl tetrazolium bromide (MTT) assay allowing patients to be grouped as "sensitive" or "resistant" in vitro. Clinical data including age, residual disease, histological grade, treatment, response after initial treatment and overall survival were collected. There was a highly significant (p<0.0001) correlation of in vitro sensitivity with in vivo response in the patients who completed their therapy, with an 83% positive predictive accuracy for resistance. This translated in the longer term to an increased survival for the patients found to be sensitive in vitro to their therapy with a 5-year survival rate of 24% compared to 12% for the resistant group (p=0.033). These results suggest that MTT chemonsensitivity testing can predict response in ovarian cancer leading to the prospect of increased survival in this devastating disease by customising therapy to individual patients.
Adenocarcinoma↗
The nonreactive nonstress test: predictive value for neonatal anemia in the isoimmunized pregnancy.
OBJECTIVE: To assess the value of the fetal nonstress test (NST) in predicting neonatal transfusion in pregnancies complicated by red cell isoimmunization. METHODS: We retrospectively reviewed the records of all patients evaluated for isoimmunization in pregnancy for the period January 1992 to December 1994. In addition to prenatal care, serial ultrasonography, and invasive testing when indicated, patients had NSTs two times per week. Nonstress tests were interpreted as either reactive or nonreactive using standard criteria. Results of the last NST before delivery were analyzed. Neonatal outcome data were obtained prospectively and by chart review. RESULTS: Sixty patients with isoimmunization were identified during the study period. Fifty-one patients (85%) had reactive NSTs until delivery, and nine (15%) had nonreactive NSTs that prompted delivery. Twelve of 51 (23.5%) patients with reactive NSTs and seven of nine (77.8%) patients with nonreactive NSTs required neonatal transfusion (P = .003, odds ratio 11.4 [95% confidence interval (CI) 1.7-120.2]). The mean (standard error of the mean; range) hematocrit (%) at birth was 38.9 (3.0; 21.3-52.0) in patients with reactive NSTs and 28.3 (3.8; 14.5-45.0) in those with nonreactive NSTs (P < .05). A nonreactive NST had a 77.8% positive predictive value (95% CI 49.0-100) in identifying the need for neonatal transfusion. CONCLUSION: These findings indicate that a nonreactive NST is predictive of subsequent neonatal transfusion in patients with isoimmunization. The antepartum fetal NST is a useful adjunct in the management of isoimmunized pregnancies.
Adult↗
Can provocative growth hormone testing predict the response to recombinant human growth hormone (rhGH) treatment?
Treatment with rhGH has been proven to be useful in children with chronic renal insufficiency and stunted growth. The aim of this study was to assess the usefulness of endocrinological provocative testing in predicting results to rhGH treatment. Endocrinological investigations performed in 14 children on renal replacement therapy did not correlate with increment of height velocity in the first year of rhGH therapy. It is concluded that no endocrinological testing is useful before starting rhGH treatment; other predictors of the response to rhGH administration are needed.
Adolescent↗
Thymidylate synthase quantitation and in vitro chemosensitivity testing predicts responses and survival of patients with isolated nonresectable liver tumors receiving hepatic arterial infusion chemotherapy.
BACKGROUND: Patients with isolated, nonresectable liver tumors may receive regional hepatic arterial infusion (HAI) chemotherapy with response rates of about 50%. The objective of this study was to investigate the value of thymidylate synthase (TS) determination in combination with in vitro chemosensitivity testing to predict the responses and survival of patients receiving HAI. METHODS: TS mRNA expression was quantitated using a reverse transcription-polymerase chain reaction technique with beta-actin as the internal standard. In vitro chemosensitivity testing was performed with tumor cell suspensions using the human tumor colony-forming assay (HTCA). RESULTS: An analysis of the test combination in 24 consecutive patients revealed that 77% (10 of 13) of the sensitive and 9% (1 of 11) of the resistant patients had complete or partial clinical responses. Sensitive patients were 8.5-fold more likely to respond (P = 0.0036) and displayed with 32 months (range, 5-75 months) a longer median survival than resistant patients with 17 months (range, 3-28 months, P = 0.003). Analysis of the Kaplan-Meier curves revealed that sensitive patients had a higher overall survival probability, as determined by the log rank test (P = 0.044). CONCLUSIONS: These results suggest that the clinical outcomes of patients receiving HAI therapy may be predictable with TS quantitation and HTCA. It is possible, therefore, that this combination may be used in the future to select patients with liver tumors who will benefit from HAI before the start of regional chemotherapy.
Adult↗
Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?
BACKGROUND AND OBJECTIVES: Inherited factor VII (FVII) deficiency is a rare bleeding disorder characterized by a poor relationship between reported FVII clotting activity (FVII:C) and bleeding tendency. Our study was aimed at defining biological parameters that are possibly predictive for bleeding risk in this condition. DESIGN AND METHODS: Forty-two FVII-deficient patients (FVII:C <30%) were classified into two opposite clinical groups defined as severe and non-or-mild bleeders. For each patient, plasma samples were collected and then investigated for FVII:C (using a sensitive method and human recombinant thromboplastin as the reagent), FVII antigen, activated FVII coagulant activity (FVIIa:C) and the free-form of tissue factor pathway inhibitor. RESULTS: None of these tests could be used as highly accurate predictors of bleeding. Nevertheless, both FVII:C and FVIIa:C differed significantly between the two clinical groups. Using ROC-curve analysis, two critical values of 8% and 3mIU/mL for FVII:C and FVIIa:C, respectively, could be proposed to discriminate between severe bleeders and non-or-mild bleeders. INTERPRETATION AND CONCLUSIONS: A highly accurate diagnostic test for predicting bleeding tendency in inherited FVII deficiency still eludes definition, highlighting the fact that factors other than FVII itself interfere with the expression of bleeding phenotypes in this condition. Nevertheless, potential critical values using sensitive FVII:C and FVIIa:C methods may be useful in clinical laboratories for FVII-deficient patients. Those patients with FVII:C levels higher than 8% FVII:C or FVIIa:C higher than 3 mIU/mL, with no other hemostatic defect, seem to have a minimal risk of severe bleeding. Extended clinical studies are needed to support these findings.
Adolescent↗
Can 13C urea breath test predict resistance to therapy in Helicobacter pylori infection?
BACKGROUND/AIMS: Results of 13C urea breath test (UBT), a noninvasive test for detecting active H. pylori infection, have been regarded also numerically for a possible predictive value on bacterial load and entity of mucosal inflammation. In the present study we wished to determine whether there is a particular value of Delta Over Baseline (DOB) result which could predict resistance to anti-H. pylori therapy. METHODOLOGY: 570 subjects from 1376 tested received a standard triple anti-H. pylori regimen. After a minimum of 6 weeks subjects underwent control UBT testing. Correlation of DOB values at diagnostic and control UBT and sensitivity of different DOB levels to predict resistance to therapy were calculated using simple linear correlation and Bayes' theorem, respectively. RESULTS: Modest linear correlation was observed between DOB values (r2=0.28). The value of 13.0 at diagnostic UBT showed a sensitivity of 65.5% to predict and further positivity at control testing. CONCLUSIONS: In our large series, UBT numerical DOB value weakly predicted resistance to first-line anti-H. pylori therapy.
Adult↗
"Indeterminate" microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction.
OBJECTIVES: This study tested the hypothesis that an "indeterminate" microvolt T-wave alternans (MTWA) test, when due to ectopy, unsustained MTWA, or low exercise heart rate (HR), has prognostic significance similar to a positive MTWA test. BACKGROUND: MTWA testing, used to stratify risk of sudden or total mortality in patients with structural heart disease, has been limited by a substantial number of "indeterminate" tests. Indeterminate tests are due to patient factors--excessive ventricular ectopy during exercise, unsustained MTWA, or failure to achieve a HR of 105 beats/min for 1 min--or technical factors such as a noisy recording or an exercise protocol that causes an excessively rapid rise in HR. METHODS: Patients in sinus rhythm with left ventricular ejection fraction < or =0.40 underwent MTWA exercise tests, analyzed with the spectral method and classified by a computerized interpretation algorithm. The primary end point was all-cause mortality or documented non-fatal sustained ventricular arrhythmia (SVA). "Indeterminate" tests were reviewed jointly by 2 readers blinded to subsequent events to determine the primary reason for indeterminacy. RESULTS: Participants (N = 549) were 56 +/- 13 years and 71% male; 49% had ischemic cardiomyopathy. There were 40 deaths and 11 non-fatal SVA. Most (94%) indeterminate results were due to patient factors. The 2-year rate for death or SVA was 17.8% in patients with an "indeterminate" MTWA test compared with 12.3% in those with a positive test. CONCLUSIONS: In patients with left ventricular dysfunction, an "indeterminate" MTWA test due to patient factors predicted death or SVA at least as well as a positive test.
Adult↗
Genetic counseling and predictive testing for colorectal cancer risk.
In contrast to our rapidly increasing knowledge of the genetic basis of colorectal cancer and new molecular technologies, we are only in the early stages of characterizing the impact that this information will have on patients, their families and society. From our research and clinical experience with hereditary colorectal cancer syndromes, we have developed a framework for risk assessment that includes criteria for identifying those at higher genetic risk and guidelines for genetic counseling, predictive genetic testing and follow-up management. More research is needed to optimally translate this framework into wider clinical practice, including characterizing genetic heterogeneity and phenotype correlations, documenting the efficacy of screening and surgical interventions, and maximizing the awareness of health professionals on genetic counseling and the promise and limitations of gene tests.
Colorectal Neoplasms, Hereditary Nonpolyposis↗
Does the Williams Manual Test predict service use among subjects undergoing geriatric assessment?
This study examines the utility of the Williams Manual Test (WMT) in predicting those older patients who will eventually require formal services. One hundred seventeen older subjects underwent comprehensive geriatric assessment that included administration of the WMT and questionnaires assessing current service use. Study participants returned at 6 and 12 months for repeat measurement of study variables. The WMT was found to be a significant predictor of additional service use at 12 months (chi 2 = 6.4, P less than .01). The test had high specificity (83%) but relatively low sensitivity (40%). The lack of sensitivity in this study group was likely due to high levels of stress among caregivers whose relative was otherwise not predicted to need services. When the WMT was repeated after 6 and 12 months, the results were highly reproducible. The WMT appears to be a useful predictor of increasing formal service use. However, in certain study groups, its predictive ability may be affected by high levels of caregiver stress.
Activities of Daily Living↗
The evolution of trade-offs: testing predictions on response to selection and environmental variation.
The concept of phenotypic trade-offs is a central element in evolutionary theory. In general, phenotypic models assume a fixed trade-off function, whereas quantitative genetic theory predicts that the trade-off function will change as a result of selection. For a linear trade-off function selection will readily change the intercept but will have to be relatively stronger to change the slope. We test these predictions by examining the trade-off between fecundity and flight capability, as measured by dorso-longitudinal muscle mass, in four different populations of the sand cricket, Gryllus firmus. Three populations were recently derived from the wild, and the fourth had been in the laboratory for 19 years. We hypothesized that the laboratory population had most likely undergone more and different selection from the three wild populations and therefore should differ from these in respect to both slope and intercept. Because of geographic variation in selection, we predicted a general difference in intercept among the four populations. We further tested the hypothesis that this intercept will be correlated with proportion macropterous and that this relationship will itself vary with environmental conditions experienced during both the nymphal and adult period. Observed variation in the phenotypic trade-off was consistent with the predictions of the quantitative genetic model. These results point to the importance of modeling trade-offs as dynamic rather than static relationships. We discuss how phenotypic models can incorporate such variation. The phenotypic trade-off between fecundity and dorso-longitudinal muscle mass is determined in part by variation in body size, illustrating the necessity of considering trade-offs to be multi factorial rather than simply bivariate relationships.
Animals↗