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PubMed1998

Tramadol induces antidepressant-type effects in mice.

Tramadol is a clinically-effective, centrally-acting analgesic. This drug is a racemic mixture of two enantiomers, each one displaying different mechanisms: (+)tramadol displays opioid agonist properties and inhibits serotonin reuptake while (-)tramadol inhibit preferentially noradrenaline reuptake. The action of tramadol on the monoaminergic reuptake is similar to that of antidepressant drugs. Therefore, we have examined the effects of (+/-)tramadol, (+)tramadol and (-)tramadol in a test predictive of antidepressant activity, the forced swimming test in mice. Both (+/-)tramadol and its (-) enantiomer displayed a dose-dependent reduction on immobility; while the effect induced by the (+) enantiomer was not significant. Inhibition of noradrenaline synthesis, but not of serotonin synthesis, was capable of blocking the effect of (+/-)tramadol. The alpha-adrenoceptor antagonist phentolamine, as well as the alpha2-adrenergic antagonist yohimbine, and the beta-adrenoceptor blocker propranolol countered the immobility-reducing action of (+/-)tramadol. Moreover, neither the serotoninergic blocker methysergide nor the opioid antagonist naloxone antagonized the effect of (+/-)tramadol. Our results show that (+/-)tramadol and (-)tramadol have antidepressant-like effect in mice, probably mediated by the noradrenergic system rather than the serotoninergic or opioidergic ones.

Animals↗
PubMed1997

Generating programs for predicting the activity of functional sites.

The computer system ACTIVITY is intended for generating programs with which to predict the activity of functional sites by nucleotide sequences. ACTIVITY analyzes a basis set of nucleotide sequences with known activity. The novelty of this approach is that Zadeh's fuzzy logic and decision-making theory have been employed for determining the best "sequence-->activity" regression. The best one thus determined is then transformed into the text of a program with which the activity for any nucleotide sequence is to be predicted. Testing with independent data has proved this prediction reliable. We have compared our approach with the two commonly used on identical data sets to find the ACTIVITY-generated programs quite competitive.

Database Management Systems↗
PubMedDate not supplied

Comparison of single and dual platform methodologies for the estimation of CD34+ hematopoietic progenitor cells: correlation with colony assay.

In this study three assays for the enumeration of CD34+ progenitors were compared: 1) a modified version of the Milan protocol, used in the standard dual-platform format; 2) a dual-platform version of the ISHAGE protocol; 3) the ProCOUNT software version 2.0/ProCOUNT kit. The assays were compared to validate the accuracy of CD34+ cell counts in mobilized peripheral blood (PB), apheresis products (AP), and cord blood (CB). The ProCOUNT protocol uses reference beads for absolute CD34+ cell counting, whereas CD34 counts by other techniques are derived from a separate leukocyte count performed by a hematology analyzer. A good correlation between the ISHAGE and ProCOUNT methods was obtained for estimation of CD34+ counts in PB (n=42 samples analyzed) and AP (n=35)--except for samples having a leukocyte count >25 x 10(9)/L or a CD34 count <0.0025 x 10(9)/L)--while a suboptimal correlation between the methods was observed for CB (n=30). The ProCOUNT system proved to be effective in reducing the variability in CD34+ cell counting and appeared to be useful for intralaboratory methodology standardization. The main disadvantage of the ProCOUNT assay was its inability to calculate CD34 counts in leukopenic samples and in CB samples showing a high erythroblast count. As far as the correlation with hematopoietic colonies is concerned, data collected from apheresis samples showed a good correlation between the three flow cytometry methods and colony-forming unit granulocyte-macrophage (CFU-GM) counts, confirming the value of the flow cytometric test as a real-time, truly predictive test to measure the hematopoietic potential of the graft. In summary, all methods are suitable for enumeration of most PB samples, while the single-platform methodology should be preferred for the analysis of AP and CB. We also found the dual-platform format of the ISHAGE method precise and accurate for the estimation of CD34+ cells from CB samples. Based on these data it can be concluded that the single-platform flow cytometry assay format should be the preferred approach for CD34+ stem cell enumeration in different types of samples.

Adolescent↗
PubMed2003

The general practitioner and the "new genetics".

GPs are involved in long term care of patients and families with complex conditions. They juggle the need for medical expertise, the relationships between family members, the cost of expertise, limitations of access, and the medicolegal environment. With this background, the GP is ideally placed to play an active role in the "new genetics". GP consultations involving the new genetics will include diagnostic testing for patients with clinical problems, preconception and prenatal testing for couples in relation to pregnancy, predictive testing for families with some genetic conditions, and community genetic screening in some circumstances. GPs will need to understand the language of the new genetics, undergo continuing education, and receive ongoing support to enable them to communicate effectively with patients and their families. Different models of care incorporating GPs, specialists and allied health professionals can be developed to provide maximum delivery of relevant genetic data for both genetic and common multifactorial disorders.

Family Practice↗
PubMedDate not supplied

Effects of anxiolytic drugs on some behavioral consequences in olfactory bulbectomized rats.

The present study was designed to evaluate the effects of bulbectomy and acute administration of anxiolytic drugs (diazepam, 10 mg/kg; chlordiazepoxide, 10 mg/kg) on the behavior of both sham-operated and olfactory bulbectomized rats in two tests predictive of anxiolytic activity: plus-maze test and Vogel's conflict test. We investigated also the effect of flumazenil (10 mg/kg), a benzodiazepine receptors antagonist, both on control and drug-treated animals. We also evaluated behavior of animals in conditioned place aversion procedure. Our results show the decreased level of anxiety in bulbectomized animals comparing with sham-operated rats. Anxiolytic drugs further deepen this effect.

Animals↗
PubMedDate not supplied

[The AMES test in environmental and occupational medicine].

The authors review the use of the gene mutation test on Salmonella typhimurium, better known as the Ames test, in environmental and occupational health. This test, which was originally intended as a predictive test of the carcinogenicity of chemical substances, has been widely applied in in vitro screening of complex mixtures of substances present in the environment and in the biological monitoring of high risk populations. Data are reported on the main environmental exposures that were positive with the Ames test and it is stressed how this biological assay has contributed to the identification of new classes of genotoxic compounds (nitropyrenes, mutagen X). The Ames test performed on extracts of human urine was used to study exposure to carcinogenic substances in the working environment. Many occupational exposures can cause an increase in mutagenic activity in the exposed subjects (cytostatic drugs, rubber manufacture, polycyclic aromatic hydrocarbons). It is recommended to restrict the use of the urinary mutagenesis test to group studies and carefully check confounding factors (e.g., smoking and diet).

Carcinogenicity Tests↗
PubMedDate not supplied

Field evaluation of predictions of environmental effects from a multispecies-microcosm toxicity test.

The predictive validity of a multispecies-microcosm toxicity test was evaluated. Predictions of biological response to a complex effluent were made from dose-response curves in laboratory tests and compared to observed effects in the receiving system. No effects on protozoan or macroinvertebrate communities were observed at the field site with effluent concentrations less than the chronic value of 1.7% effluent determined in laboratory tests. In addition, the microcosm test accurately predicted the magnitude of decreases in species richness in protozoan and macroinvetebrate communities in the receiving system at the first downstream site. Predictions of environmental effects for stations farther downstream were generally less accurate and too high, perhaps due to lack of persistence in the toxicity of the effluent. Stimulation of total biomass and algal growth were observed in both laboratory and field tests, but laboratory tests greatly overestimated the magnitude of enrichment responses in the receiving system.

Animals↗
PubMed2001

Agreement between clinical examination and quantitative tests of neurologic function among 384 subjects.

BACKGROUND: Quantitative neurological tests are often cheaper and easier than clinical examinations, and provide continuous data which may discriminate between exposed and nonexposed groups with more sensitivity than dichotomous (normal/abnormal) examination data. METHODS: We compare clinical examinations and analogous quantitative tests for arm tremor, postural sway, and vibrotactile sensitivity (finger and toe), for 384 subjects. RESULTS: The "abnormal" clinical outcomes studied were relatively common (range, 3-36%), and did not result in impairment of daily activity for affected subjects. All the quantitative tests were reasonably good predictors of the corresponding clinical outcome. The most predictive test was for toe vibrotactile sensitivity. The probability of an abnormal clinical result for those in the worst quartile for the toe test was 0.63, compared with 0.36 for all subjects. CONCLUSIONS: Our results suggest that certain quantitative tests might be used in epidemiologic studies instead of a physical examination.

Female↗
PubMed2026

Trade-offs in avian parental care: a review of theory and meta-analysis of brood size manipulations.

The selective forces shaping parental care have been studied for over 50&#x2009;years. While theoretical and experimental work has yielded qualitative progress, the large body of empirical work testing predictions about parental investment based on life-history trade-offs has yet to be synthesized. We first provide an overview of the core life-history theory exploring how selection might shape parental care. We then conduct a systematic review and meta-analysis on studies that experimentally manipulated brood size in birds, a widely used experimental approach to manipulate parental investment. We extracted 313 estimates from 62 studies representing 31 species of birds from 19 different families and tested key predictions on trade-offs in parental care derived from theory. Our analysis provides strong support for some predictions about life-history trade-offs in parental care, but weak or equivocal support for others. Specifically, we found that overall, avian parents respond to brood size manipulations as predicted by life-history theory: they increased care in response to brood enlargement, and decreased care in response to brood reductions. Furthermore, for the same relative manipulation size, responses to brood reductions were greater than responses to brood enlargements. This finding is consistent with predictions derived from life-history theory based on some types of non-linear utility curves. However, many predictions derived from theory are not well supported by our comparative analysis. Species' life-history traits such as clutch size (a measure of current reproduction), adult survival, and broods per year (two measures of future reproduction), explained little, if any, among-species variation in response to brood size manipulations. Several factors may explain this. We highlight that brood size manipulations may affect more than just perception of the value of current reproduction, such as altering parents' perception of predation risk. Importantly, these unintended consequences could lead to asymmetric responses like those we observed. Other common experimental approaches - such as hormone manipulations, altering a partner's effort, and food supplementation - often affect multiple traits or fitness components simultaneously, or may involve cues that poorly match the evolved mechanisms guiding parental behaviour. Our review of both theory and experimental approaches suggests that there are multiple opportunities for more precise experiments. We offer several recommendations for effective designs. One is improved understanding of the biology underlying the functions relating to costs and benefits, with careful consideration of not only how the manipulation will affect only one of those, but also the mechanisms that might alter how parents perceive the manipulation. We also emphasize general principles, such as assessing alternative hypotheses and devising multiple independent tests. Armed with these recommendations, we believe there are new opportunities to increase the strength of inference achieved from studies aimed at understanding the trade-offs affecting the evolution of parental care.

Animals↗
PubMed2004

Evaluation of psychosocial effects of pre-symptomatic testing for breast/ovarian and colon cancer pre-disposing genes: a 12-month follow-up.

A prospective study of psychosocial consequences following predictive testing for inherited mutations in breast/ovarian and colon cancer susceptibility genes BRCA1, BRCA2, MLH1, and MSH2 was performed. Eighty-seven healthy women were tested for known family mutations and self-assessment scales were used to evaluate anxiety, depression and quality of life. Extensive pre- and post-test information was given. Questionnaires were responded before testing and four times after during the following year. A statistically significant decrease in anxiety mean scores over time was observed among the studied participants. The levels of depression in cancer genes carriers decreased over time while, surprisingly the levels in non-carriers increased. Compared to a normative Swedish sample all women tested showed similar levels of anxiety but women tested for breast cancer genes showed statistically lower levels of depression. Vitality dropped initially after disclosure of the testing of colon cancer genes carriers, followed by increasing levels. No change in vitality or in other quality of life parameters was seen in the other groups and the levels were similar to Swedish norm data. Most tested individuals were satisfied with the testing procedure including genetic counselling and testing and all of them but one would redo the testing. Healthy self-referred women going through predictive breast/ovarian or colon cancer gene testing, including extensive pre- and post-test information and support, in general, will not experience adverse psychological consequences.

Adult↗
PubMedDate not supplied

Observation evaluation to assess race and educational bias in state-mandated standard testing of nurse aides in nursing homes.

This article presents an assessment of whether race, education, gender, or other testing bias was present in a state-mandated nurse aide competency test. This assessment was carried out with data from two sources: (a) a statewide standardized test for all nurse aides that was given by a nationally known testing company, (b) an independent observational evaluation with a Behaviorally Anchored Rating Scale (BARS) for nurse aides' performance that was carried out by the investigators. The results show that race and education level were predictors of performance on written and manual portions of the standardized test. Gender, age, and years of experience were also shown to predict test success. Comparing data from the two sources suggests that a possible bias in the standardized nurse aid test. The independent observation of performance on the job with the BARS is shown to be less biased.

Adult↗
PubMed1998

Ethics of predictive DNA-testing for hereditary breast and ovarian cancer.

The recent identification of gene mutations involved in hereditary cancers increasingly allows for predictive DNA-testing. There is an urgent need to analyse the ethical issues involved. This article concentrates on the ethics of predictive testing for mutations in the breast (and ovarian) cancer genes BRCA1 and -2. Using international guidelines for presymptomatic DNA-testing for Huntington disease and the Li-Fraumeni syndrome as a model, a provisional protocol, which entails four parts is presented: (i) inclusion and exclusion criteria; (ii) preparing for the test; (iii) informing about the results of the test; (iv) post-test counselling and evaluation. The importance of an integral education of both doctors and the public is stressed.

Adult↗
PubMed1995

Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations.

Individual aspects of heparin or protamine dosing have been better controlled than previously as useful tests have become available. Although many variables including drug potency, drug source, and individual patient response have been separately identified, there has not been an attempt to integrate them into a single management strategy. This study was undertaken to learn whether more precise control of drug variables and patient response would affect blood loss and transfusion requirements. Adult patients having primary cardiac operations were prospectively randomized into two groups. A control group received heparin and protamine by conventional methods. The test group received heparin and protamine according to in vitro predictive tests integrating drugs, tests, and patient response. Supplemental protamine was given in this group only if heparin was specifically found by testing. Anticoagulation in all patients was maintained at an activated coagulation time greater than 400 seconds, and any other treatment for bleeding was at the discretion of the clinical team caring for the patients. Testing and treatment for both groups followed routine practice after patient arrival in the intensive care unit. Test patients received slightly more heparin and a markedly lower dose of protamine than the control patients. Testing identified patients with decreased heparin sensitivity (preoperative heparin therapy) and correctly predicted the effective heparin dose. Supplemental protamine was given twice as often to control patients and frequently when no heparin was detectable (retrospectively). Test patients exhibited less 24-hour chest tube drainage (671 ml versus 1298 ml) and fewer patients received transfusion (9/22 versus 18/24) with fewer donor exposures (22/22 versus 101/24). The management strategy used for heparin and protamine added accuracy and precision, which was associated with improved hemostasis. Although the observation is valid, the mechanism or mechanisms are not completely clear. Nevertheless, it is reasonable to apply basic pharmacologic principles and establishment of consistent, predictable protocols that are beneficial. It is against this background that the efficacy of additional drugs or equipment should be assessed. It is quite possible that only marginal if any improvement in hemostasis may be found in patients having primary, uncomplicated cardiac operation with the addition of more costly drugs or equipment.

Aged↗
PubMed1984

Spatial perception testing in diagnostic radiology.

A test predictive of ultimate radiologic expertise could be of great value in the selection of individuals entering the field. Some individuals have an aptitude superior to others to perceive three-dimensional spatial relations from two-dimensional data. This may enhance their ability to draw radiologic conclusions from clinical images and may favorably affect their performance as radiologists. To test cognitive perceptual ability, a three-dimensional Visual Form Reconstruction Test (form test) was developed and administered to residents and faculty members. All subjects also completed the Thurstone Surface Development Test, a standardized test of spatial visualization ability. The form test results correlated well with resident performance, as measured by overall faculty ratings (predictive validity). Although form test and Thurstone test performance were highly correlated with each other (concurrent validity), the form test was better correlated with resident performance. Intercorrelations among the three subsections of the form test demonstrated high split-part reliability. Performance on the form test was unaffected by level of training. This suggests that an underlying aptitude was measured. These preliminary results indicate that testing of spatial visualization aptitude is predictive of resident performance in radiology. A test such as this could be useful in selection and self-selection of resident candidates.

Aptitude↗
PubMed1982

Adaptation in the long-wavelength pathways.

We describe and test predictions of a model of long-wavelength test sensitivity upon large, uniform backgrounds. The model explains changes in sensitivity in the red-green detection pathways strictly based upon losses of sensitivity in the receptors. We derive the prediction that field mixture data for field-mixtures of mu1 (fixed) and an addend, mu 2, must follow the same shape on different intensities of the fixed background, mu 1. This prediction is not in good agreement with the measurements.

Adaptation, Ocular↗
PubMed1988

Block of conditioned avoidance responding in the rat by substituted phenylpiperazines.

Ortho-methoxyphenylpiperazine (OMPP) and meta-substituted chlorophenylpiperazine (MCPP) blocked conditioned avoidance responding (CAR) in the rat (ED50 values = 5.6 (4.6, 7.3) and 2.4 (1.9, 2.9) mg/kg i.p. (95% confidence limits), respectively) without markedly altering escape responding. Since this test predicts antipsychotic efficacy, the piperazines were examined in radioligand binding assays and found to have no affinity for dopamine (DA) binding sites, but were active at serotonin binding sites. OMPP displaced ligands for the 5-HT1A binding site with high affinity (Ki = 9.5 (5.4, 17.9) nM) but was inactive at 5-HT2 sites (Ki greater than 1000 nM). MCPP, on the other hand, displaced ligands for 5-HT1, 5-HT1A and 5-HT2 binding sites with similar potencies (Ki values = 25 (3, 67), 23 (14, 40) and 40 (33, 48) nM, respectively). Pretreatment with metergoline (1.0 mg/kg i.p. -30 min) reduced MCPP- but not OMPP-induced block of CAR. OMPP, on the other hand, acted as a DA receptor antagonist in vivo blocking amphetamine-induced stereotyped behavior, whereas MCPP did not. Neither produced catalepsy even given in doses 8-10 times those required to block CAR. Insofar as these compounds lack antidopaminergic activity in vivo, yet are active in a test (CAR) predictive of antipsychotic activity in which DA receptor antagonists are active, they may be novel antipsychotic agents, or, perhaps, false positives in the CAR paradigm.

Amphetamine↗
PubMed1992

Risk assessment in immunotoxicology. I. Sensitivity and predictability of immune tests.

We have previously reported on the design and content of a screening battery involving a "tier" approach for detecting potential immunotoxic compounds in mice (Luster et al., 1988, Fundam. Appl. Toxicol. 10, 2-19). This battery has now been utilized to examine a variety of compounds by the NIEHS Immunotoxicology Laboratory, the National Toxicology Program-sponsored laboratories, and by the Cell Biology Department at the Chemical Industry Institute of Toxicology. The database generated from these studies, which consists of over 50 selected compounds, has been collected and analyzed in an attempt to improve future testing strategies and provide information to aid in quantitative risk assessment for immunotoxicity. Studies presented here have established the ability of each of the tests or test combinations in the screening battery to detect immunotoxic compounds. Efforts are currently underway using this database to determine the relationships between these immune tests and susceptibility to challenge with infectious agents or transplantable tumor cells. The present analyses indicated that the performance of only two or three immune tests are sufficient to predict immunotoxic compounds in rodents (greater than 90% concordance). The tests that showed the highest association with immunotoxicity were the splenic antibody plaque forming cell response (78%) and cell surface marker analysis (83%). The relationship between immunotoxicity and carcinogenicity, as well as genotoxicity, was also determined. These analyses suggested that potential immunotoxic compounds are likely to be rodent carcinogens (p = 0.019) although for compounds that are not immunotoxic the carcinogenic status is unclear. There was no relationship observed between immunotoxicity and mutagenicity as determined using in vitro genotoxicity tests. The significance of these observations is discussed in terms of the relationship between immunotoxicity tests and biological/toxicological processes concerned with human health (e.g., infectious disease).

Animals↗
PubMed2001

Cost of genetic counseling and testing for BRCA1 and BRCA2 breast cancer susceptibility mutations.

Counseling and predictive testing are now available for the recently isolated BRCA1 and BRCA2 breast cancer susceptibility genes. We examined the societal costs of providing this counseling and testing to women at risk of having a breast cancer susceptibility mutation. Genetic counselors in a research program prospectively monitored the time necessary to provide counseling and results disclosure. A time-motion study was used to determine time spent on phone calls, preparation, and documentation for counseling. Study participants were surveyed to determine travel time and need for dependent care during counseling. The test cost was calculated using the charge for full BRCA1/2 gene sequencing (Myriad Genetics, Inc.) multiplied by a Medicare-based cost-to-charge ratio. Counselors spent an average of 4.2 h providing genetic counseling for women at risk of having a susceptibility mutation. Genetic counseling without testing cost on average $213, whereas counseling, testing, and disclosure of results totaled $2057. A brief physician-based counseling instead of genetic counselor-based counseling would produce only small reductions in total costs. Providing counseling and testing to the study population averaged $8034 per mutation found. The cost of testing and counseling exceeded $2000. The counseling portion of the cost comprised only 16% of the total cost, with the remainder representing costs associated with testing; thus, alternatives to full genetic counseling that shorten counseling time are unlikely to have a large impact on the overall cost of counseling and testing. The cost of detecting a mutation within a population of women is highly dependent on the prevalence of the mutation in the population.

Adult↗