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PubMed2000

Sensitizing potential of chlorothalonil in the guinea pig and the mouse.

The fungicide chlorothalonil is used extensively under several tradenames for the protection of various horticultural and fruit crops and bananas against fungal infections. It is also used as fungicide in wood preservation and as a preservative in paints. Clinical experience has shown chlorothalonil to be a contact allergen and several cases of allergic contact dermatitis attributed to chlorothalonil have been described. 2 previous guinea pig maximization test studies have shown the sensitizing potential of chlorothalonil to be high. The sensitizing property of chlorothalonil was studied by us with the predictive test methods the local lymph node assay and the cumulative contact enhancement test. In the local lymph node assay, chlorothalonil induced a dose-dependent increase in proliferation with a maximal stimulation index of 19.2 and 27.2. In the cumulative contact enhancement test, a statistically significant dose-dependent high sensitization rate was seen with a maximal sensitization rate of 100%. In conclusion, it is evident that chlorothalonil is an extremely potent contact allergen, inducing sensitization using only topical exposure on intact skin.

Animals↗
PubMed1989

Metacognitive benefits of taking a test for children and young adolescents.

The main purposes of this study were (a) to isolate monitoring of test performance from other forms of monitoring and (b) to determine the effect of taking a test on expectations about future performance. Children in grades 1-2, 4-5, and 7-8 were administered a vocabulary test. They either predicted their performance on tests like the one that was administered before taking the test, predicted after taking the test, or made postdictions about performance on the present test. There was unambiguous improvement in the accuracy of after-test predictions and postdictions compared to before-test predictions at grades 7-8 only. Although all age groups discriminated hard from easy items as they were doing them, such discrimination increased with age. In general, there were few sex differences, although whenever statistically significant sex differences in confidence were detected, boys tended to be more confident than girls. These results are consistent with claims that developmental changes in self-regulation could be tied to developmental changes in monitoring of performance and making predictions about future performance based on past performance.

Achievement↗
PubMed1990

Detection of bovine leukemia virus antibodies in bulk tank milk using an ELISA test: improvement of the predictive value of results by repeated testing.

In 9457 dairy farms located in an area with low prevalence of bovine leukemia virus (BLV) infection, bulk tank milk was examined to detect for the presence of antibodies using an ELISA test. If the result was positive or doubtful, serum of all animals in the farm was tested and bulk tank milk was tested again five times every 8-12 days. The results were used to establish decision rules in the event of a positive or doubtful result during mass screening.

Animals↗
PubMed2000

[Hereditary carcinoma: pathogenesis and diagnosis].

Effective prevention of cancer in patients with a hereditary disposition to malignant tumours was made possible by intensive prevention programs and molecular diagnosis. Taken hereditary non-polyposis colorectal cancer (HNPCC) as an example this article deals with the pathogenesis and molecular diagnosis in hereditary dispositions to cancer. HNPCC is inherited in an autosomal-dominant fashion and caused by germline mutations in genes responsible for detection an removal of DNA-basepair-mismatches (DNA-mismatch-repair-genes). The error rate in DNA replication is reduced thousandfold by these genes. A defective DNA-mismatch-repair results in tumours if the increased mutation rate causes alterations of tumour-suppressor- or oncogenes. HNPCC patients develop colorectal cancer but also tumours of the renal pelvis, the ureter, the small bowel, the endometrium and less often in other organs. The clinical presentation of these tumours may be characteristic, the clinical diagnosis may be guided by different clinical criteria catalogues. The suspicion is proven by the identification of a germline mutation in DNA-mismatch-repair-genes. This laborious diagnostic procedure is often preceded by prescreening procedures as the detection of microsatellite instability or immunohistochemical tests. Once the germline mutation is identified in a affected family member, the first degree relatives may be tested for this mutation. If they have inherited the mutation, they harbour a extremely high risk for developing cancer and therefore may be included in prevention programs. This so called predictive testing must be preceded by genetic counseling.

Base Pair Mismatch↗
PubMed1995

Physician responsibility in conducting genetic testing.

The rapid growth of DNA-based tests raises complex questions about how to integrate them efficiently into clinical medicine and about the medicolegal consequences of rapidly shifting standards of practice. Standards of practice change in response to many factors; the most important are guidelines promulgated by professional bodies or published comments by opinion leaders, malpractice litigation, and legislation. Recently, human geneticists have successfully shaped the clinical use of tests for Huntington's disease and carrier screening for cystic fibrosis. Clinical geneticists, oncologists, and others should work together now to develop practice standards for the use of new DNA-based predictive tests for breast, colon, and other cancers.

Ethics, Medical↗
PubMed2006

A scoring system to predict chronic oxygen dependency.

INTRODUCTION: Chronic oxygen dependency (COD) is a common adverse outcome of very premature birth. It is, therefore, important to develop an accurate and simple predictive test to facilitate targeting of interventions to prevent COD. Our aim was to determine if a simple score based on respiratory support requirements predicted COD development. METHODS: A retrospective study of 136 infants, median gestation age (GA) 28 weeks (range: 23-33 weeks) and a prospective study of 75 infants, median GA 30 weeks (range: 23-32 weeks), were performed. The score was calculated by multiplying the inspired oxygen concentration by the level of respiratory support (mechanical ventilation: 2.5; continuous positive airway pressure: 1.5; nasal cannula or head box oxygen or air: 1.0). Scores were calculated on data from days 2 and 7, and their predictive ability compared to that of the maximum inspired oxygen concentration at those ages and (retrospective study) the results of lung volume measurement. RESULTS: Infants that were oxygen dependent at 28 days and 36 weeks post-menstrual age (PMA) had higher scores on days 2 (p<0.0001, p<0.0001, respectively) and 7 (p<0.0001, p<0.0001, respectively) than the non-oxygen dependent infants in both the retrospective and prospective cohorts. Construction of receiver operator characteristic curves demonstrated the score performed better than the inspired oxygen level and lung volume measurement results. A score on day 7 >0.323 had 95% specificity and 78% sensitivity in predicting COD at 28 days, and 80% specificity and 73% sensitivity in predicting COD at 36 weeks PMA. CONCLUSION: Chronic oxygen dependency can be predicted using a simple scoring system.

Bronchopulmonary Dysplasia↗
PubMedDate not supplied

A short-term in vitro drug sensitivity assay in pediatric malignancies.

A short-term in vitro chemosensitivity test has been applied to 131 specimens from 109 children with various malignancies. The clinical outcome was correlated with in vitro percentage inhibition (PI) of DNA synthesis by the drug tested. In 62 correlations, PIs of responsive and of resistant patients differed significantly, with a cut-off value of 37%. The test predicted clinical resistance in 53/54 cases, with a specificity of 98%, and clinical response in 8/8 cases, with a sensitivity of 100%. This test can be useful particularly in predicting chemoresistance in relapsing patients, to avoid unnecessary toxicity.

Child↗
PubMed1987

Study of the clomipramine-morphine interaction in the forced swimming test in mice.

Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective of the morphine pretreatment dose, but reduction of morphine activity by CMI was non-significant. Acquired tolerance to morphine occurred, but not to CMI. The mechanisms at work were discussed. CMI and desmethylclomipramine (DCMI) plasma levels remained the same after morphine pretreatment, ruling out a pharmacokinetic mechanism. The interaction implied involvement of opiate systems. CMI might have been acting on two different opiate receptor populations, one sensitive to morphine pretreatment, the other not. The mechanism of this action seems to be different from that of morphine.

Animals↗
PubMed2000

Contingency management for accurate predictions of urinalysis test results and lack of correspondence with self-reported drug use among polydrug abusers.

Contingency management procedures have proven effective in the treatment of drug-dependent patients. These procedures, however, often require frequent urine testing, which is too costly for community treatment programs. To make urine-testing procedures more cost effective, the feasibility of reinforcing accurate predictions of urine drug screen (UDS) results was evaluated. Participants made extremely accurate UDS predictions, particularly when they made drug-positive predictions, regardless of whether predictions were reinforced. However, self-reports of recent drug use had poor correspondence with predictions of UDS results. Results suggested that if programs only tested samples predicted to be drug free, considerable cost savings could be incurred. Further research is needed to determine if validity would be enhanced by using a proportion of costs saved to provide nominal reinforcement when samples were verified to be drug free.

Adult↗
PubMed2002

Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients.

Variegate porphyria (VP) is an inherited metabolic disease resulting from the partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in the heme biosynthetic pathway. We have evaluated the clinical and biochemical outcome of 103 Finnish VP patients diagnosed between 1966 and 2001. Fifty-two per cent of patients had experienced clinical symptoms: 40% had photosensitivity, 27% acute attacks and 14% both manifestations. The proportion of patients with acute attacks has decreased dramatically from 38 to 14% in patients diagnosed before and after 1980, whereas the prevalence of skin symptoms had decreased only subtly from 45 to 34%. We have studied the correlation between PPOX genotype and clinical outcome of 90 patients with the three most common Finnish mutations I12T, R152C and 338G-->C. The patients with the I12T mutation experienced no photosensitivity and acute attacks were rare (8%). Therefore, the occurrence of photosensitivity was lower in the I12T group compared to the R152C group (P=0.001), whereas no significant differences between the R152C and 338G-->C groups could be observed. Biochemical abnormalities were significantly milder suggesting a milder form of the disease in patients with the I12T mutation. In all VP patients, normal excretion of protoporphyrin in faeces in adulthood predicted freedom from both skin symptoms and acute attacks. The most valuable test predicting an increased risk of symptoms was urinary coproporphyrin, but only a substantially increased excretion exceeding 1,000 nmol/day was associated with an increased risk of both skin symptoms and acute attacks. All patients with an excretion of more than 1,000 nmol/day experienced either skin symptoms, acute attacks, or both.

Adolescent↗
PubMed2002

Estimating the sensitivity of a genetic test using gene-carrier probability estimates and its application in genetic counselling.

BACKGROUND: The estimation of the sensitivity of a genetic test is of practical importance. If a 'gold standard' (an exact test) is not available, an estimate of the probability of being a gene carrier may be useful for an individual. This information could be based on individual pedigree and family-history data, and a known genetic model for the disease of interest. METHODS: We develop a maximum-likelihood estimate of the sensitivity of a genetic test that may be applied in a situation without a 'gold standard', in which an estimate of the probability of being a gene carrier for an individual is available. RESULTS: A maximum-likelihood estimate for the sensitivity can be obtained through an iterative algorithm. We demonstrate the method using data from a project on familial breast cancer. We further present disease-risk estimates incorporating results from a genetic test with different values of sensitivity, and compare these with disease-risk estimates that are solely based on family-history data. DISCUSSION: We provide a systematic methodology to obtain an estimate of sensitivity of a genetic test when only gene-carrier probability estimates from a genetic model are available. Given a negative result from a genetic test, predictions for lifetime and age-specific disease-risk, accounting for test sensitivity, can then be provided in genetic counselling.

Algorithms↗
PubMed1988

Immunologically mediated disease of the airways after pulmonary transplantation.

Obliterative bronchiolitis has occurred in eleven of 30 recipients of cardiopulmonary allografts who survived at least 4 months after transplantation, has caused significant morbidity, and has been associated with four of eleven late deaths in this series. Although some improvement, or at least stability, of pulmonary function has followed augmented immune suppression, it appears that once the process is recognized clinically, much of the damage to the airways is irreversible. The histopathology, response to therapy, and, most important, the response of donor specific alloreactivity in the lymphocytes from the lung (bronchoalveolar lavage and peripheral blood) suggest immune- mediated basis for bronchiolitis obliterans. The presence of donor specific alloreactivity detected by primed lymphocyte testing predicted obliterative bronchiolitis in five of six recipients (83% sensitivity, 91% specificity) was absent in ten of eleven recipients who have not as yet developed the process (negative predicted value of 91%). Currently, the presence of a positive primed lymphocyte test in the bronchoalveolar lavage of the cardiopulmonary recipient is an indication for early treatment by augmented immune suppression.

Bronchiolitis Obliterans↗
PubMed2005

Factors related to long-duration pain and sick leave among Swedish staff working in the public health service.

The aim of the present study was to provide information about factors related to long-duration pain (LDP) (>3 months), sick leave (SL) and long sick leave (LSL) (>3 months) among staff in the community health services. The specific research question was: To what extent do data on activity, physical function, pain severity, psychological/cognitive factors, expectations of LDP, expectations to be working within 6 months and work satisfaction predict LDP, SL and LSL respectively? Logistic regression analyses were used to test predicted membership in the groups LDP, SL and LSL. In this context prediction refers to statistical prediction only, due to the cross-sectional design. Staff (n = 914) in the public health services in a medium-sized Swedish city completed a questionnaire during the spring of 2000. The results show that musculoskeletal pain and SL for this occupational group are common. Pain severity, expectations of LDP and fear-avoidance increased the odds of being in the LDP group, while kinesiophobia decreased the odds. Pain severity and kinesiophobia increased the odds of being in the SL group, while expectations to be working in 6 months decreased the odds. Only expectations to be working in 6 months predicted membership in the LSL group, decreasing the odds. Although some caution is warranted concerning the representativity of the sample, the results indicate that expectations about pain duration and ability to work are important psychosocial factors in LDP and LSL.

Adult↗
PubMed1991

Evaluation of three theophylline dosing methods in pediatric patients.

Three methods used for individualizing theophylline dosing were prospectively evaluated in 34 pediatric patients to compare the methods' ability to accurately predict steady-state serum theophylline concentrations (STCs) from non-steady-state data. Methods evaluated included a Bayesian weighted sum of squares regression program, an algebraic method developed by Chiou, and a commonly used population-based pediatric dosing algorithm. An expanded retrospective evaluation was also done to further compare the Bayesian and Chiou methods. Patients (aged 1-11 y) admitted to the hospital for acute bronchospasm refractory to inhaled beta agonists and with physician's orders to receive intravenous aminophylline were eligible for participation. Study patients received a 6-mg/kg loading dose aminophylline, followed by a 0.8-1.0 mg/kg/h constant aminophylline infusion. STCs were obtained 0.5 and 5.5 hours postinfusion. Subjects were randomized to one of three dosing method groups (Bayesian, Chiou, or pediatric algorithm). Doses were calculated using the assigned method to attain a target steady-state STC. Predictions from each dosing method were compared with actual serum concentrations for bias and precision. Additionally, analysis of fit-to-the-line-of-identity for predicted versus observed STCs was evaluated for each method. Precision of methods was also compared with regard to their ability to predict within 20 percent of their observed steady-state STC. Results from the prospective evaluation showed no significant difference between the three methods tested. Predicted STCs fell within 20 percent of their observed steady-state concentrations for 18 percent (2/11) of patients in the algorithm group, and 45 percent (5/11) of patients in the Chiou group and 17 percent (2/12) of the patients in the Bayesian group met this criterion. Retrospective analysis of all 34 patients demonstrated that the Bayesian and Chiou methods had similar bias and precision and no statistical difference was found between them. The results from this evaluation suggest that the pediatric dosing algorithm is equivalent in predictive bias and precision to the Bayesian and Chiou methods as well as in its ability to identify doses that result in steady-state STCs within 20 percent of their target values. Given the relative inaccuracy of these methods, cautious use of these techniques is recommended when evaluating non-steady-state STCs obtained from children during the acute stages of reactive airway disease.

Algorithms↗
PubMed2004

Huntington's disease genetics.

Huntington's disease (HD) is a dominantly transmitted neurodegenerative disorder with wide variation in onset age but with an average age at onset of 40 years. Children of HD gene carriers have a 50% chance of inheriting the disease. The characteristic symptoms of HD are involuntary choreiform movements, cognitive impairment, mood disorders, and behavioral changes which are chronic and progressive over the course of the illness. HD is a "trinucleotide repeat" disorder, which is caused by an increase in the number of CAG repeats in the HD gene. Repeats of 40 or larger are associated with disease expression, whereas repeats of 26 and smaller are normal. Intermediate numbers of repeats, between 27 and 35, are not associated with disease expression but may expand in paternal transmission, resulting in the disease in descendents. Repeats of 36-39 are associated with reduced penetrance whereby some develop HD and others do not. The identification of the genetic defect in HD permits direct genetic testing for the presence of the gene alteration responsible for the disease. Tests may be performed in three circumstances: (1) confirmation of diagnosis, (2) predictive testing of persons at genetic risk for inheriting HD, and (3) prenatal testing. Testing is widely available and much experience has been gained with protocols that assist the individual in making an informed choice about test options, and minimize the occurrence of adverse emotional outcomes.

Humans↗
PubMed1994

Assessment of functional vision performance: a new test for low vision patients.

Measures of functional vision are needed to assess elderly low vision patients, their success in using devices, and their ability to manage outside the treatment setting. A new test devised to measure functional ability through the performance of everyday tasks was administered to 94 patients who had acuities of 20/100 or worse in their better eye. Consisting of three versions and four subtests: spot reading, short-term text reading, identifying paper currency and clock reading, the test used standardized items and was timed. In a multiple regression model predicting test performance higher scores were associated with better near acuity (P = .002), higher education (P = .022) and higher levels of self-reported visual skills (P = .072). These predictors plus distance acuity, age and sex only accounted for 35 percent of the variance in test scores. Repeated administration of the test to a different group of 21 patients showed the test to be reliable (intraclass correlation = .85, P < .01) and to have no practice or version effects or differences between raters. This new test may be useful for natural history studies and clinical trials involving low vision patients but further evaluation of its sensitivity to change over time is required.

Adolescent↗
PubMed2003

The clinical geneticist and the "new genetics".

The "new genetics" will provide new genetic tests that can be used for diagnosis, prognosis, treatment selection, carrier and predictive testing in affected families, and potentially for susceptibility testing for later-onset multifactorial disease and population screening. Doctors will increasingly need to consider the family implications of a genetic diagnosis--to identify family members at risk of the disorder or of having affected children and to consider how these individuals might be advised of their situation. Clinical geneticists can be a valuable resource for doctors who need advice about whether genetic testing is available, which tests to pursue, how to access testing services, and how to interpret and act on test results. Clinical geneticists also provide genetic counselling, a process which gives people understandable information about the genetic disorder in the family, and makes the information useful for decision-making given the person's unique circumstances and beliefs. The Internet will increasingly be a key source of information about genetic disorders for patients, their families and healthcare professionals.

Access to Information↗
PubMed1999

Neuroendocrine responses and psychomotor test results in subjects participating in military pilot selection.

BACKGROUND: Military flying sets high demands on the mental performance and stress tolerance of pilots. Neuroendocrine responses could be a method for evaluating stress tolerance. METHODS: Psychological workload and neuroendocrine responses associated with the psychomotor Wiener's test were studied in 80 male volunteers. These personnel had applied for the basic military flying program of the Finnish Air Force (FAF). After the first blood sample at 0930 h, the subjects were randomly assigned to test (n = 40) and control groups (n = 40). The test group performed the psychomotor test, which lasted 10 min. The second blood sample was collected 1 min after the test. The control group was clinically examined and the blood sample was taken in the same way. RESULTS: A high plasma ACTH level before the psychomotor test predicted (r = 0.36, p = 0.02) a poor overall result in the psychomotor test. After the psychomotor test, plasma adrenocorticotropin (ACTH) and beta-endorphin levels were significantly higher than before the test. They were also higher than in the control group. Plasma cortisol and prolactin levels increased after the psychomotor test, but the increase was not statistically significant. High ACTH, cortisol and prolactin increments were specific to a high amount of delayed (over 2 s) psychomotor responses, as a marker of information overload. CONCLUSIONS: Elevated plasma ACTH, cortisol and prolactin levels, after the psychomotor test, were associated with a high amount of the delayed responses. This indicates that high neuroendocrine responses were connected with problems in stress tolerance during information processing. High neuroendocrine reactions under information load could, therefore, be used for identification of lowered stress tolerance.

Adolescent↗