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PubMed1991

The one-site model of human erythrocyte glucose transport: testing its predictions using network thermodynamic computer simulations.

Network thermodynamic computer simulations were carried out using parameters experimentally derived by Lowe and Walmsley ((1987) Biochim. Biophys. Acta 903, 547-550) for two tests of the one-site model of human erythrocyte glucose transport. In the temperature-jump experiment, the simulations predicted the amplitude and relaxation time of accelerated uptake, but underestimated the net uptake due to an unexpectedly low measured basal rate. In the maltose-acceleration experiment, the dissociation constant of maltose was assessed at 0 degrees C by measuring the inhibitory effects of maltose on both cytochalasin B binding and on 3-O-methylglucose uptake, and using this value (52 mM) to calculate the dissociation constant (2.9 mM). The simulated experiment then did show a transient acceleration in uptake comparable in magnitude to that observed experimentally, except that the relaxation time was more than 10-fold longer in the simulations. Measurements of the temperature dependence of the inhibition of cytochalasin B binding by maltose and 3-O-methylglucose indicated that apparent sugar affinity is sensitive to carrier orientation at low temperatures, whereas at more physiologic temperatures the intrinsic dissociation constant predominated.

3-O-Methylglucose↗
PubMed2004

Ankle stress test for predicting the need for surgical fixation of isolated fibular fractures.

BACKGROUND: The purpose of this study was to confirm the prevalence of medial ankle widening among patients with an isolated fibular fracture and to determine the functional outcome of nonoperative treatment despite a diagnosis of a supination-external rotation stage-IV injury based on stress radiography. METHODS: One hundred and one patients with evidence of an isolated fibular fracture and an intact mortise seen on a standard ankle trauma radiograph series were evaluated with stress radiographs. Clinical signs were recorded at the time of presentation. A positive stress test was defined as > or =4 mm of widening of the medial clear space. Patients with a negative stress test were treated nonoperatively, those with a positive stress test and clinical signs of medial injury were treated surgically, and those with a positive stress test and no signs of medial injury were treated according to the preference of the surgeon and patient. The patients were followed prospectively with radiographs and ankle outcome scores. RESULTS: Sixty-six (65%) of the 101 patients had a positive stress radiograph. Thirty-six of them had signs of medial injury, and thirty had no medial injury. With regard to predicting a positive stress radiograph, medial tenderness had a sensitivity of 56% and a specificity of 80%, swelling had a sensitivity of 55% and a specificity of 71%, and ecchymosis had a sensitivity of 26% and a specificity of 91%. Of the subset of patients without signs of medial injury, twenty were treated nonoperatively (group I) and ten were treated operatively (group II). Two of the twenty patients in group I had evidence of persistent widening of the medial clear space at the time of the latest follow-up (mean, 7.4 months); only one of those patients was symptomatic. The average American Orthopaedic Foot and Ankle Society (AOFAS) score was 94 points in group I and 93 points in group II. CONCLUSIONS: We found a high rate of positive stress radiographs for patients who presented with an isolated fibular fracture and an intact ankle mortise on the initial radiographs. Medial tenderness, swelling, and ecchymosis were not sensitive with regard to predicting widening of the medial clear space on stress radiographs. All of the patients with a positive stress radiograph and no clinical symptoms who were treated without surgery had a good or excellent clinical result.

Adult↗
PubMed1986

Significance of angiotensin sensitivity test for prediction of pregnancy-induced hypertension.

In 48 normotensive women with epidemiologic high-risk factors for pregnancy-induced hypertension, the angiotensin sensitivity test was performed serially between 26 and 32 weeks of gestation. If an effective pressor dose of less than 12 ng/kg per minute was considered to be a positive test result, 20 subjects were positive at 30 weeks of gestation and destined to develop pregnancy-induced hypertension. Of ten subjects with a false-positive test result, seven patients developed proteinuria and/or clinically significant edema without apparent hypertension, and only three subjects remained normal throughout their pregnancy. Twenty-eight subjects with negative test results had uneventful pregnancies. Before 30 weeks' gestation, it was difficult to identify all patients destined for pregnancy-induced hypertension. Although high false-positive test results were detected, these results suggest that an angiotensin sensitivity test at 30 weeks' gestation represents an appropriate means of identifying women who remain normal throughout pregnancy. Careful follow-up should be undertaken in all patients with positive test results.

Adult↗
PubMed2004

Pre-treatment urea breath test results predict the efficacy of Helicobacter pylori eradication therapy in patients with active duodenal ulcers.

AIM: To evaluate the association of pre-treatment (13)C-urea breath test (UBT) results with H pylori density and efficacy of eradication therapy in patients with active duodenal ulcers. METHODS: One hundred and seventeen consecutive outpatients with active duodenal ulcer and H pylori infection were recruited. H pylori density was histologically graded according to the Sydney system. Each patient received lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week. According to pre-treatment UBT values, patients were allocated into low (<16 per thousand), intermediate (16-35 per thousand), and high (>35 per thousand) UBT groups. RESULTS: A significant correlation was found between pre-treatment UBT results and H pylori density (P<0.001). H pylori eradication rates were 94.9%, 94.4% and 81.6% in the low, intermediate and high UBT groups, respectively (per protocol analysis, P=0.11). When patients were assigned into two groups (UBT results < or =35 per thousand and >35 per thousand), the eradication rates were 94.7% and 81.6%, respectively (P=0.04). CONCLUSION: The intragastric bacterial load of H pylori can be evaluated by UBT, and high pre-treatment UBT results can predict an adverse outcome of eradication therapy.

Anti-Bacterial Agents↗
PubMed1996

The emerging role of the physician in genetic counselling and testing for heritable breast, ovarian and colon cancer.

As a genetic testing for susceptibility to breast, ovarian and colon cancer becomes more readily available, physicians are faced with an increasing demand for information about inherited cancer risk. Because advances in treatment have not kept pace with advances in predictive testing, the provision of genetic counselling and testing marks a departure from the traditional role of the physician. A systematic framework is needed within which the physician's emerging role in predictive testing for heritable cancer can be delineated. The development of such a framework will require collaboration among professionals in a range of scientific disciplines, as well as the suspension of traditional assumptions about the physicians role.

Breast Neoplasms↗
PubMed1998

Biomarkers, screening and ethics.

Rapid scientific advances, such as those in biomarker technology, have made a significant impact on the ethics and practice of occupational health. Biomarkers are extensively used in occupational health practice. In the pre-employment stage, preventive or predictive testing can be performed. Preventive testing aims to avert accidents that may occur if a medically unfit worker undertakes a job that he is unable to perform. For safety sensitive jobs, routine testing of a worker's functional capacity in the actual job would suffice in most cases. However, a recently quotes application of a test is the screening for mutations of the cardiac myosin-heavy chain and troponin genes among asymptomatic persons with a family history of sudden death from hypertrophic obstructive cardiomyopathy. Predictive testing hopes to forecast the risk of a worker developing an illness. The aims may vary. One aim may be to exclude a susceptible worker from working in a hazardous environment. Another aim may be to avoid employment of a worker who is likely to develop an illness which could lead to higher employer health care costs. A pertinent question to consider is whether the test undertaken is to benefit the individual or to fulfil some administrative or financial need. Among exposed workers, screening may be conducted for biomarkers of exposure or effect. As the aim is to prevent the onset of clinical illness, the physician must take responsibility for initiating requests for screening. The appropriate response to the effect of technical and societal advances on ethics is the updating of ethical guidelines by the profession. However, in the context of unvalidated biomarkers being used for screening, it may be necessary to require a regulatory body to ensure that the tests are accurate and effective, and that they are not used to discriminate against individuals.

Biomarkers↗
PubMed1987

Failure of short-term in vitro mutagenicity tests to predict the animal carcinogenicity of hair dyes.

A number of hair-dye chemicals that have given positive results in various short-term mutagenicity tests have shown no clear evidence of carcinogenicity in animal bioassays. Commercial HC Blue No. 1 and its analogues HC Red No. 3 and HC Blue No. 2 are all mutagenic in the Ames test but only the HC Blue No. 1 is carcinogenic in animals. A carcinogenicity study in mice was carried out on both a commercial sample of HC Blue No. 1 and a highly purified sample which was negative in a battery of short-term tests for mutagenic activity. Both samples, administered at 0.3% in the diet for up to 24 months, were carcinogenic to mice, inducing hepatocellular carcinomas in greater than or equal to 89% of the mice examined. Therefore the presence of mutagenic impurities is not responsible for the carcinogenicity of commercial HC Blue No. 1. Discrepancies between the results of mutagenicity and carcinogenicity tests on hair dyes and other chemicals are discussed, and the value of short-term mutagenicity tests for assessing chemical safety is questioned.

Animals↗
PubMed2002

Laboratory shake flask batch tests can predict field biodegradation of aniline in the Rhine.

The aim of this study was to compare degradation rates of aniline in laboratory shake flask simulation tests with field rates in the river Rhine. The combined events of a low flow situation in the Rhine and residual aniline concentrations in the effluent from the BASF treatment plant in Ludwigshafen temporarily higher than normal, made it possible to monitor aniline at trace concentrations in the river water downstream the wastewater outlet by means of a sensitive GC headspace analytical method. Aniline was analyzed along a downstream gradient and the dilution along the gradient was calculated from measurements of conductivity, sulfate and a non-readily biodegradable substance, 1,4-dioxane. Compensating dilution, field first-order degradation rate constants downstream the discharge of BASF were estimated at 1.8 day(-1) for two different dates with water temperatures of 21.9 and 14.7 degrees C, respectively. This field rate estimate was compared with results from 38 laboratory shake flask batch tests with Rhine water which averaged 1.5 day(-1) at 15 degrees C and 2.0 day(-1) at 20 degrees C. These results indicate that laboratory shake flask batch tests with low concentrations of test substance can be good predictors of degradation rates in natural water bodies--at least as ascertained here for short duration tests with readily degradable compounds among which aniline is a commonly used reference.

Aniline Compounds↗
PubMed1981

Reliability of the rabbit pyrogen test and of the limulus test in predicting the pyrogenicity of vaccines in man.

Commercial vaccines including bacterial as well as live and inactivated viral vaccines were examined in the rabbit pyrogen test and in the limulus test. The laboratory results were compared with the reactivity in humans. A fairly good correlation was found between the temperature rise in rabbits and the frequency of febrile reaction in the vaccinees. Two rabies vaccines and a tick-borne encephalitis virus vaccine, each pyrogenic both in rabbit and in man. were negative in the limulus test. The pyrogenicity of these vaccines is attributed to the vaccine virus itself.

Bacterial Vaccines↗
PubMed1998

Clinical impact of predictive assays for acute and late radiation morbidity.

BACKGROUND: Clinically reliable predictive assays for normal tissue radiation sensitivity would help to avoid severe radiation induced morbidity and result in individualized dose prescriptions. Profound differences of individual fibroblast and lymphocyte radiation sensitivity in vitro have been documented in patients with certain genetic syndromes but also in patients without known genetic disorders. The following review evaluates whether fibroblast or lymphocyte radiation sensitivity measured in vitro correlates with the degree of acute and late radiation induced morbidity. RESULTS: Acute radiation side effects and lymphocyte sensitivity has been investigated in 2 studies. One of them reported an insecure correlation, the other no correlation at all. Fibroblast radiation sensitivity and the extent of acute radiation induced side effects on skin and mucosal sites has been compared in a total of 5 studies. None of these studies found a consistent significant correlation. Lymphocyte radiation sensitivity and late effects have been studied by 2 institutions. Late radiation induced skin and mucosal changes did not correlate with lymphocyte sensitivity in head and neck cancer patients, whereas in breast cancer patients a weak (R2 = 0.06) correlation between the degree of late skin reactions and lymphocyte sensitivity was observed. Late skin or mucosal radiation reactions and fibroblast sensitivity were examined by 5 research groups. Data analysis revealed significant correlations or at least a trend towards a significant correlation in all studies. The quality of the reported correlations expressed as R2 ranged from 0.13 to 0.60, indicating a low predictive value. CONCLUSIONS: Lymphocyte radiation sensitivity as measured by currently available assays does not or only poorly correlate with acute and late effects of radiation in patients, precluding predictive tests based on lymphocyte sensitivity. Fibroblast radiation sensitivity does not correlate with acute but generally correlates with late radiation morbidity. The quality of the later correlation is insufficient for a reliable predictive test with currently available methods to determine cellular radiation sensitivity.

Breast Neoplasms↗
PubMed1998

Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders: comparing questionnaire results with in-depth interviews. Rotterdam/Leiden Genetics Workgroup.

In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression (Hospital Anxiety and Depression Scale), feelings of hopelessness (Beck Hopelessness Scale), and psychological complaints (Symptom Checklist) were assessed to determine their psychological well-being. The manner of discussing the genetic disorder, the test, and its implications during a semistructured interview (reflecting on one's emotions without getting carried away or dismissing or minimizing the subject) was judged in terms of coherence. Participants at risk for neurodegenerative disorders had higher anxiety and depression scores and more psychological complaints than did those at risk for cancer syndromes. Those reporting high intrusion/high avoidance had higher anxiety and depression scores and more psychological complaints than did those reporting low intrusion/low avoidance. However, the scoring of the interview showed that participants reporting high intrusion/high avoidance were more reflective about their emotions without getting carried away or dismissing the subject (e.g., more coherent) than those reporting low intrusion/low avoidance. This result suggests that participants with higher stress scores may be actively dealing with the emotional implications of the test, whereas those with low stress scores may (as yet) be unable to face these implications. It is important to identify the strategy of coping with threat to provide suitable counseling and necessary guidance. However, long-term follow-up is needed to learn the consequences of a denial coping strategy for those participating in a genetic testing program.

Adenomatous Polyposis Coli↗
PubMed1997

Apolipoprotein E genotyping as a diagnostic adjunct for Alzheimer's disease.

Positive predictive value (PPV) estimates how often a particular test predicts the eventual diagnosis, and it is the basis of any test that attempts to establish a diagnosis. Calculating the PPV depends directly on the entrance criteria for considering the diagnosis and the exit criteria of the generally accepted "gold standard" for establishing the ultimate diagnosis. For a relatively common disease such as AD, the practical usefulness of a diagnostic test also relates to the stage of the disease at which the test can be applied. An accurate and predictive test only has practical value when it can be used early in the course of the disease. Apolipoprotein E (Apo E) is the first genetic locus identified as a susceptibility polymorphism for a common complex disease using positional or candidate cloning strategies. There are three common alleles (epsilon 2 to epsilon 4) and six possible genotypes; about 30% of the population carries an epsilon 4 allele, each additional copy of which is associated with an increased risk of AD and earlier age of onset distribution. In patients with cognitive impairment of the Alzheimer type, who have been diagnosed with possible or probable AD, the presence of an Apo E-epsilon 4 allele is likely in more than 50% of patients for whom the PPV is greater than 97%. Apo E genotyping is the only diagnostic adjunct that has been subjected to rigorous measurements of specificity, sensitivity, PPV, and NPV. In the past, testing of dementia patients was directed at "ruling out" other treatable causes. Results from the initial studies of the PPV of Apo E genotyping for AD showed that the PPV of Apo E genotyping was greater than 97%. The paradigm for AD diagnosis is changing. Apo E genotyping can provide useful diagnostic information and that accuracy will improve as other susceptibility genetic risk factors are identified.

Aged↗
PubMed2005

Attitudes and misconceptions about predictive genetic testing for cancer risk.

OBJECTIVE: To describe awareness, knowledge, and attitudes about genetic testing for cancer risk among the general public. RESULTS: Thirty-eight adults participated in focus groups in West Philadelphia, Pennsylvania. Participants' beliefs about what genetic testing is ranged from 'dianetics' to an accurate description of DNA analysis. Themes included misconceptions about genetic tests, the ability to gain control of one's life through genetic testing, anxiety that might be caused by testing, risk of insurance and employment discrimination, use of genetic information for racial or ethnic discrimination, concerns about medical information confidentiality and lack of informed consent. CONCLUSIONS: Although there was some accurate understanding of what genetic testing is and how the results could be used, there also exist significant misconceptions. In many cases, misconceptions may be barriers to uptake of genetic testing. Dispelling these misconceptions is an important step in the translation of advances in human genomics into improvements in health.

Adult↗