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[Human germline genetic tests].

A guideline for genetic testing by 10 scientific societies was published recently. This can be summarized as follows. 1) Generalized medical care for genetic medicine is necessary when genetic testing is considered. 2) Analytical validity, clinical validity and clinical usefulness must be proven when genetic testing is applied to clinical medicine. 3) Informed consent must be given by the client before genetic testing is performed. 4) Information on an individual's genetic test must be protected tightly and should not be disclosed to others without permission from the client. 5) Genetic counseling must be performed before genetic testing is performed. 6) The purposes of genetic test performed to prepositus ((i) for definite diagnosis of the patient and (ii) for obtaining information by predictive tests for family members) should be clearly distinguished. 7) Genetic tests for detection of carrier status of specific genetic conditions should be carefully performed, because they do not affect the health condition themselves, but can be a cause of discrimination. 8) Predictive genetic tests must be performed very carefully, especially when no procedures of treatment/prevention are available. 9) In general, genetic testing of children should be considered when such tests provide clinical benefits to the children themselves.

Forecasting↗

Diagnosis of gestational diabetes by capillary blood samples and a portable reflectance meter: derivation of threshold values and prospective validation.

Paired capillary-venous samples were obtained from 255 women undergoing a glucose challenge test and 116 women undergoing an oral glucose tolerance test. The capillary equivalents for the venous threshold values were calculated by regression analysis. The glucose challenge test predictions of either normal or abnormal agreed in 82%. The sensitivity, specificity, and positive and negative predictive values for the capillary oral glucose tolerance test were 89%, 90%, 62%, and 98%, respectively. These capillary equivalents were then applied prospectively to 147 women undergoing a glucose challenge test and 141 women undergoing an oral glucose tolerance test. The concurrence rate of the glucose challenge test in the prospective group was 90%. The sensitivity, specificity, and positive and negative predictive values for the capillary oral glucose tolerance test were 64%, 95%, 75%, and 92%. When the venous threshold recommendations of the American Diabetes Association were used instead of those standard at our institution, these values increased to 75%, 98%, 83%, and 96%, respectively. The recommended capillary values of the American Diabetes Association were 100% sensitive but had a positive predictive value of only 20%. Based on the prospective group, the cost per case of gestational diabetes identified would decline 63% if both a capillary glucose challenge test and an oral glucose tolerance test were used and 25% if the capillary glucose challenge test and venous oral glucose tolerance test were used. Combining the data set for new regression equations, the following venous-capillary threshold sets emerged: glucose challenge test, 140 mg/dl/150 mg/dl; fasting oral glucose tolerance test, 105 mg/dl/114 mg/dl; 1 hour, 190 mg/dl/211 mg/dl; 2 hours, 165 mg/dl/183 mg/dl; 3 hours, 145 mg/dl/157 mg/dl. The sensitivity, specificity, and negative predictive values for the capillary oral glucose tolerance test with these thresholds were 80%, 97%, 80%, and 97%. In conclusion, capillary glucose testing for diabetes during pregnancy is feasible and cost-effective.

Blood Glucose↗

In vitro drug testing in patients with acute leukemia with incubations mimicking in vivo intracellular drug concentrations.

The differential staining cytotoxicity (DiSC) assay was evaluated as a predictive test for response to therapy in patients with acute non-lymphoblastic leukemia. Incubations were designed in such a way that the intracellular concentrations of cytostatic drugs in vitro paralleled those in vivo. Leukemic cells were isolated from 53 patients with acute non-lymphocytic leukemia. 13 of these patients died early due to supportive care failure and were not evaluable for the predictive drug testing. Of the remaining 40 patients, 25 entered a complete remission (CR) and 15 had a resistant disease (RD). According to the patients randomization to therapy the cells were incubated with anthracyclines and Ara-C separately and in combination. After 4 days of culturing in liquid medium the in vitro cytotoxicity was determined by dye exclusion according to Weisenthal. The cytotoxic effect in vitro was significantly higher on cells from patients who achieved a CR compared to patients with RD after incubations with anthracyclines 0.2 mumol/l (p less than or equal to 0.005), Ara-C 0.5 mumol/l (p less than or equal to 0.05) and with the combination of anthracyclines with Ara-C (p less than or equal to 0.0005). The best predictive value was achieved when incubations with 0.2 mumol/l anthracyclines and 0.5 mumol/l Ara-C were analyzed together. With these incubations cells from 20 out of 21 patients who achieved CR showed either less than or equal to 60% surviving cells after the anthracycline incubation or less than or equal to 35% surviving cells after the Ara-C incubation. Cells from 11 out of 13 patients with RD did not fulfill either of these criteria. In vitro drug sensitivity was significantly correlated to a prolonged survival (p less than 0.01). We conclude that, when performed with incubations that mimic in vivo tumor cell exposure to cytostatic drugs, the DiSC assay shows a high correlation to clinical outcome for patients with acute non-lymphocytic leukemia.

Adolescent↗

Validation of the stroke drivers screening assessment for people with traumatic brain injury.

Cognitive impairments resulting from brain injury affect driving performance. The question of fitness to drive often arises during rehabilitation. Healthcare professionals need reliable criteria against which decisions about driving fitness can be made. Nouri et al. developed the Stroke Drivers Screening Assessment (SDSA), which was found predictive of on-road driving performance in stroke patients. The purpose of this study was to determine whether the SDSA, either alone or combined with other tests, predicted fitness to drive in brain injured people. Fifty-two participants were assessed on the SDSA plus additional cognitive tests. Their fitness to drive was examined on the public road. The SDSA predictions based on equations developed for stroke patients were not an accurate predictor of road test performance. Discriminant analysis was used to identify tests predictive of fitness to drive. Results indicated that a combination of the SDSA, the Stroop and the AMIPB Information Processing tasks correctly classified 87% of cases and may be useful predictors of driving fitness following brain injury. However, cross-validation on an independent sample of people with brain injury is required.

Adult↗

Prediction models for eye irritation potential based on endpoints of the HETCAM and neutral red uptake tests.

The aim of this study was to explore the possibility of distinguishing between eye irritants (I; EU risk phrases R36 and R41) and nonirritants (NI), by using in vitro endpoints of the hen's egg test on the chorioallantoic membrane (the HETCAM test) and the neutral red uptake (NRU) test. Prediction models were derived by applying binary logistic regression to the in vitro data for these endpoints, which were taken from the report of a German validation study on the use of the HETCAM and 3T3 NRU tests as alternatives to the Draize eye irritation test. Whereas the validation study led to the conclusion that the combined use of the two tests enables a satisfactory discrimination between severe (R41) and nonsevere (NI, R36) eye irritants, the results of the present study indicate that the two in vitro tests can also be used to discriminate between nonirritants (NI) and irritants (R36 and R41).

3T3 Cells↗

Computer predictions of abnormal test results. Effects on outpatient testing.

We developed statistical equations to predict abnormalities on eight commonly ordered diagnostic tests and we gave the predictions to 112 physicians practicing in an academic internal medicine practice. Half of each physician's patients were randomized to intervention status. All diagnostic tests were ordered by microcomputer, and when a physician ordered one of the eight study tests for an intervention patient, the computer displayed the probability (0% to 100%) that the test would be positive for the main abnormality being tested for. The physician could then cancel the test if desired. During a six-month controlled trial, when there were more than 15,000 scheduled patient visits, patient charges for the eight study tests were 8.8% less for the intervention patients. The largest reductions (greater than 10%) were for serum electrolyte level tests and complete blood cell counts, the two most commonly ordered tests. Physicians ordered fewer low-probability tests for intervention patients than for controls, suggesting that with timely predictive information, physicians can target tests to higher-risk patients.

Clinical Laboratory Techniques↗

Hereditary cancer risk notification and testing: how interested is the general population?

PURPOSE: Great interest in predictive testing for hereditary cancer syndromes has been reported. Prior research has focused on testing for specific hereditary syndromes and/or among individuals at high risk for positive carrier status. Given anticipated expansion of both the range of hereditary syndromes for which testing will be available, as well as the clinical settings in which testing will occur, assessment of interest in hereditary cancer risk testing and notification in the general public is warranted. METHODS: As part of an annual statewide telephone survey, adults' (N = 654) interest in hereditary cancer risk testing and notification was assessed. RESULTS: Interest in both risk testing (82%) and risk notification (87%) was high. Logistic regression analyses indicated that disinterest in risk notification was associated with female sex, performance of fewer health protective behaviors, and better perceptions of personal health. Disinterest in risk testing was associated with these same variables as well as older age, less concern over developing cancer, and a more extensive history of cancer in first degree relatives. CONCLUSION: In the absence of risk-reducing behaviors with demonstrable efficacy, hereditary risk testing programs may have difficulty attracting the interest of those at greatest risk for carrier status. In contrast, many individuals at low risk for positive carrier status might seek testing, perhaps as a means of seeking reassurance regarding their low hereditary risk.

Adult↗

Functional census of mutation sequence spaces: the example of p53 cancer rescue mutants.

Many biomedical problems relate to mutant functional properties across a sequence space of interest, e.g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 mutant rescue. We devised a general methodology for conducting a functional census of a mutation sequence space by choosing informative mutants early. The methodology was tested in a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of three (24 iterations). The first double-blind 15-point moving accuracy was 47 percent and the last was 86 percent; r = 0.01 before an epiphanic 16th iteration and r = 0.92 afterward. Useful mutants were chosen early (overall r = 0.80). Code and data are freely available (http://www.igb.uci.edu/research/research.html, corresponding authors: R.H.L. for computation and R.K.B. for biology).

Artificial Intelligence↗

A review of two alternative ultrasound quality assurance programmes.

OBJECTIVE: This study reviewed the results of B-mode Quality Assurance (QA) performance tests on 17 real-time ultrasound scanners, performed over a period of 3 years, in order to assess their value. Following this review we revised and simplified our testing schedules to include two tests for noise and sensitivity. The value of the new schedules was assessed. METHODS: Initially, testing schedules were similar to those recommended by two professional bodies. Results were reviewed to determine whether the tests predicted or confirmed faults. We then introduced a simplified testing programme using alternative measurements, attempting to demonstrate or predict noise related faults that affect the image, but were not demonstrated by current tests. These new tests have been performed on 24 ultrasound machines for up to 18 months. RESULTS: A review of results has shown that measurements occasionally fall outside tolerance due to chance, and that faults that significantly affect the image, e.g. probe faults and noise, are reported by the users without predictive or concomitant changes in test results using our original schedules. Faults occur that do not immediately affect image quality and are not reported by the users. Inappropriate settings, e.g. monitors, are frequently reset at QA, particularly where there are potentially untrained users. The additional tests showed consistent changes in noise (four) or sensitivity (one) on five machines. CONCLUSION: Our earlier tests were inadequate in demonstrating deterioration in the clinical performance of ultrasound imaging equipment. Introduction of a revised testing schedule has resulted in changes in equipment performance being detected and rectified.

Equipment Failure Analysis↗

Evaluation of ionizing radiation sensitivity markers in a panel of lymphoid cell lines.

PURPOSE: To examine the possible associations between radiation sensitivity to doses 2 Gy, and such features of lymphoid cell responses as apoptosis, expression of apoptosis regulatory proteins (Bcl-2 family) and cell cycle progression in relation to biological dosimetry. MATERIALS AND METHODS: The cell lines examined were: Epstein Barr virus transformed lymphoid ataxia-telangiectasia (AT) cell lines, GM00717C, homozygous, and GM00736A, heterozygous, for ATM; human pro-B lymphoblastic leukaemia, Reh; murine L5178Y lymphoma sublines, LY-R and LY-S. Assays performed following X-irradiation with doses from 0.1 to 2 Gy were: terminal deoxyribonucleotidyl transferase (TdT) assay to measure apoptotic fraction, DNA content analysis by flow cytometry to assess cell cycle distribution, trypan blue exclusion test to determine cell viability, cytochalasin block micronucleus assay to assess cytogenetic damage, and Western blotting to detect proteins from the Bcl-2 family. RESULTS: The cell lines in the study were of different but rather high radiation sensitivity, which was unrelated to their propensity to undergo apoptosis or micronucleus frequency. The expression of apoptotic regulatory proteins from the Bcl-2 family (constitutive and expressed 4 or 24 h after irradiation) was not related to radiation sensitivity. CONCLUSION: None of the simple predictive tests used in the study, alone or evaluated together was suitable for detection of radiation hypersensitivity although cells known to be hypersensitive (LY-S and GM00717C) were included in the analysis.

Animals↗

Evaluating microbial safety of slow partial-cooking processes for bacon: use of a predictive tool based on small-scale isothermal meat inoculation studies.

The objective of this study was to develop a predictive tool for evaluating the safety of slow cooking of pork products and identifying associated critical limits. Small-scale (25 g) ground pork isothermal inoculation studies were done to determine Salmonella serovars, Escherichia coli O157:H7, and Staphylococcus aureus estimated critical times (time until growth reached a predefined increase of concern). Estimated critical time values ranged from 720 min at 21 degrees C (S. aureus) to 120 min at 40.6 degrees C (E. coli O157:H7) and were used to develop a multiple-temperature-interval predictive tool for non-isothermal processes. To test predictions, cured-pumped pork bellies were inoculated with Salmonella serovars, E. coli O157:H7, and S. aureus, subjected to slow partial cooking, and quantitatively analyzed for pathogens. Processes lasted 6 to 18 h, with the product interior temperature within the 21 to 46 degrees C range for 263 to 1080 min (high-humidity processes) and 217 to 921 min (low-humidity processes). Growth of Salmonella serovars (>0.3 log), E. coli O157:H7 (>0.3 log), and S. aureus (>1.3 log) in the pork belly interior was predicted for 10, 14, and 5 of 18 trials, respectively. The tool was fail-safe, because pathogen growth, relative to time zero, did not occur anytime regardless of whether it was predicted. For the pork belly surface, the tool performed similarly. Estimated critical time values obtained by fitting the Baranyi equation to isothermal experiment data were also determined and, if used in the predictive tool, would result in even more conservative predictions. Our study substantiates the safety of the tested bacon slow partial-cooking processes and the potential usefulness of our isothermal-based tool in process safety evaluation.

Animals↗

The uncertainty associated with the predictive value of test results.

The uncertainty associated with predictive value of test results was taken into consideration, as concerns both sampling error (related to the size of the statistical reference samples) and analytical imprecision (unavoidably involved by the measurement itself). A software package, developed for the statistical calculations, was used for the treatment of the results obtained for serum free thyroxin in euthyroid and dysthyroid subjects, assumed as an experimental model. Examples are shown for the obtainable functions predictive value vs. estimate and the related uncertainty regions. These data could help in comparing test results and, in particular, in preparing fully informative laboratory reports. The difficulties involved by an extensive application of the procedure are discussed.

Humans↗

Tests of the dipole model of perceived movement in apertures.

Power and Moulden (1992) have proposed a dipole model to account for the apparent movement of gratings in apertures. This includes movement orthogonal to the orientation of the grating, and the barber pole illusion: the illusion that a grating drifting diagonally across a narrow aperture appears to be moving along it. The essence of the model is that movement is signalled by a large number of dipoles, of many orientations and lengths. These dipoles respond if, and only if, one end is stimulated, and then the other. Three experiments intended to test predictions from the model are reported here. In each case a horizontal grating drifted across an aperture and subjects fixated outside the aperture. In experiment 1 subjects fixated just above or below the aperture, and reported the motion aftereffect (MAE) shown by a set of test spots. As predicted by the model, the spots further from the fixation point showed a strong MAE. Experiment 2 combined both viewing conditions of experiment 1, so that test spots above and below the fixation point were viewed simultaneously. The predictions were confirmed, since test spots further from the fixation point exhibited a stronger MAE than test spots closer to the fixation point. In experiment 3 the fixation point in all conditions was below the aperture, and, as predicted, the MAE of a spot near the bottom of the aperture was diagonally upward, although stimulation was horizontal. Again, as predicted, the MAE of a spot in the middle of the aperture appeared to move horizontally. Finally, it was predicted that a test spot at the top of the aperture would appear to move diagonally downwards, but subjects were unable to report unequivocally the direction of motion, since the MAE was occurring too far from the fovea for clear vision. Overall, then, the predictions from the model were confirmed, although there are associated phenomena the model cannot as yet account for.

Adolescent↗

Submaximal exercise testing: clinical application and interpretation.

Compared with maximal exercise testing, submaximal exercise testing appears to have greater applicability to physical therapists in their role as clinical exercise specialists. This review contrasts maximal and submaximal exercise testing. Two major categories of submaximal tests (ie, predictive and performance tests) and their relative merits are described. Predictive tests are submaximal tests that are used to predict maximal aerobic capacity. Performance tests involve measuring the responses to standardized physical activities that are typically encountered in everyday life. To maximize the validity and reliability of data obtained from submaximal tests, physical therapists are cautioned to apply the tests selectively based on their indications; to adhere to methods, including the requisite number of practice sessions; and to use measurements such as heart rate, blood pressure, exertion, and pain to evaluate test performance and to safely monitor patients.

Adolescent↗

Growth of testes and testicular morphology after eight generations of selection for increased predicted weight of testes at 150 days of age in boars.

Weights of testes and epididymides, body weight, and morphometric measurements of testicular tissue of 75 boars of a line selected for eight generations for predicted weight of testes at 150 d of age and 75 boars of a randomly selected control line were used to evaluate the effects of selection on testicular development at 70, 100, 130, 160, and 450 d of age (n = 15 boars per line per age). Body weights for boars of the select and control line did not differ (P < .05) and the shape of the body growth curve was similar for both lines. Boars of the select line had larger testes than control boars at each age (P < .05), but there was a significant line x age interaction. The percentage increase of the select line mean over the control mean for weight of testes was 37% at 70 d, a maximum of 120% at 100 d, and 25% at 450 d. The percentage of the testes made up of seminiferous tubules differed between lines (P < .01). Lines had similar means of approximately 28% at 70 d and 71% at 450 d, but the mean for the select line was larger between 100 and 160 d of age; the greatest difference was 11.6% (control = 43.7, select = 55.3%) at 100 d. After 70 d of age, select-line boars had a greater percentage of seminiferous tubules with lumens that contained elongated spermatids (P < .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Bizarre behavior during intracarotid sodium amytal testing (Wada test): are they predictable?

The intracarotid sodium amytal test (ISAT or Wada Test) is a commonly performed procedure in the evaluation of patients with clinically refractory epilepsy candidates to epilepsy surgery. Its goal is to promote selective and temporary interruption of hemispheric functioning, seeking to define language lateralization and risk for memory compromise following surgery. Behavioral modification is expected during the procedure. Even though it may last several minutes, in most cases it is subtle and easily manageable. We report a series of patients in whom those reactions were unusually bizarre, including agitation and aggression. Apart of the obvious technical difficulties (patients required physical restraining) those behaviors potentially promote testing delay or abortion and more importantly, inaccurate data. We reviewed those cases, seeking for features that might have predicted their occurrence. Overall, reactions are rare, seen in less than 5% of the ISAT procedures. The barbiturate effect, patients' psychiatric profiles, hemisphere dominance or selectiveness of the injection were not validated as predictors. Thorough explanation, repetition and simulation may be of help in lessening the risk of those reactions.

Adolescent↗

Ethical aspects of genetic testing.

This article explores ethical concerns and emerging dilemmas associated with the proliferation of information resulting from the extraordinary advances in molecular genetics. It provides an overview of the ethical and legal challenges associated with predictive testing for inherited disease currently being addressed in the literature. Finally, it offers a framework of ethical principles that can be used to guide nurses and other practitioners in the appropriate application of research findings to the clinical practice setting. The ethical guidelines of self-determination, benefit-burden ratio, and justice promulgated in The Belmont Report are interpreted in the new context of predictive genetic testing. The author concludes by discussing how to balance the technical imperative to advance genetic knowledge for the sake of human health with the ethical imperative to preserve the fundamental rights and liberties of both individuals and communities who are its recipients.

Ethics, Nursing↗

Do psychological measures predict the ability of lower limb amputees to learn to use a prosthesis?

OBJECTIVE: Can psychological tests predict whether, on admission to a rehabilitation ward post amputation, a lower limb amputee will learn to use a prosthesis during the ensuing inpatient rehabilitation programme? DESIGN: A one-sample design in which psychological variables, and transfemoral/transtibial amputation site were tested as predictors of outcome. SETTING: An inpatient rehabilitation unit in the UK offering prosthetic provision. SUBJECTS: Forty-three consecutive patients with peripheral vascular disease (mean age 66.35 years, standard deviation 14.99) who had received an amputation on average 19 days previously on a surgical ward and were transferred to the unit for rehabilitation including assessment for prosthetic provision. MAIN OUTCOME MEASURE: Whether the patient learnt to use a prosthesis independently during the stay on the rehabilitation unit. RESULTS: During their stay in the rehabilitation unit (mean length of stay = 42 days), 31 patients learnt to use a prosthesis and 12 did not. A forward stepwise logistic regression revealed that the Kendrick Object Learning Test score on admission correctly predicted outcome in 70% of cases. The predictive power rose to 81% correct when the amputation site (transfemoral or transtibial) was included amongst the predictors. Anxiety, depression and recovery locus of control scores were not significant predictors of functional prosthetic use in this study. CONCLUSION: A simple test of learning ability and the amputation site can help to predict the patient's ability to learn to use a prosthesis following amputation and is recommended as part of the assessment process.

Aged↗