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PubMed1993

Cardiovascular and sweating dysfunction in patients with Holmes-Adie syndrome.

A cross-sectional study is reported in which 53 patients with Holmes-Adie syndrome have been subjected to a battery of tests of autonomic nervous function referable to the cardiovascular system, to two objective tests of sweating function, and to subjective assessment of sweating by application of quinizarin powder followed by body heating. The majority of patients were consecutive referrals; none was selected because of clinical indications of autonomic dysfunction. Eighty three per cent of these patients had at least one, 57% at least two, and 40% at least three objective test abnormalities, as defined by values lying outside 95 percentiles of healthy subjects who were matched for age and subjected to the same tests. In the context of multiple testing, the probability of finding outside values was such that a minimum of 3 was required to define abnormality. On this basis 40% of patients were found to have significant evidence of autonomic dysfunction. The most frequent abnormalities were impaired digital vasoconstriction to cold (23%), a reduced heart rate response to the Valsalva manoeuvre (17%), and excessive variability in sweating between test sites (in one of the tests, 43%) which is consistent with patchy loss. Abnormal quinizarin test appearances were seen in 10 patients and in a further five patients the appearances were thought to be suggestive of abnormality. Though assessment of the results of this test are subjective, the observations are consistent with the findings obtained from the objective tests which were applied. Cardiovascular and sweating abnormality did not concur significantly and only the former was found to increase progressively with known duration of the pupillotonia. It is concluded that Holmes-Adie syndrome is commonly accompanied by progressive mild but widespread autonomic involvement but rarely is this symptomatic. If symptoms suggestive of autonomic neuropathy are found in a patient with tonic pupils, a careful search for some other generalised disorder is recommended.

Adie Syndrome↗

PubMed2005

Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats.

PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for monitoring tumor response in rats after administration of combretastatin A4 phosphate. MATERIALS AND METHODS: Study protocol was approved by local ethical committee for animal care and use. Rhabdomyosarcomas implanted subcutaneously in both flanks of 17 rats were evaluated with 1.5-T MR unit by using four-channel wrist coil. Transverse T2-weighted fast spin-echo sequences, T1-weighted spin-echo sequences before and after gadodiamide administration, and transverse echo-planar diffusion-weighted MR examinations were performed before, 1 and 6 hours, and 2 and 9 days after intraperitoneal injection of vascular targeting agent (combretastatin A4 phosphate, 25 mg/kg). Apparent diffusion coefficient (ADC) was automatically calculated from diffusion-weighted MR imaging findings. These findings were compared with histopathologic results at each time point. For statistical analysis, paired Student t tests with Bonferroni correction for multiple testing were used. RESULTS: T1-weighted images before combretastatin administration showed enhancement of solid tumor tissue but not of central necrosis. At 1 and 6 hours after combretastatin injection, enhancement of solid tissue disappeared almost completely, with exception of small peripheral rim. At 2 and 9 days after combretastatin injection, enhancement progressively reappeared in tumor periphery. ADC, however, showed decrease early after combretastatin injection ([1.26 +/- 0.16]x 10(-3) mm2/sec before, [1.18 +/- 0.17]x 10(-3) mm2/sec 1 hour after [P=.0005] and [1.08 +/- 0.14]x 10(-3) mm(2)/sec 6 hours after [P=.0007] combretastatin A4 phosphate injection), histologically corresponding to vessel congestion and vascular shutdown in periphery but no necrosis. An increase of ADC ([1.79 +/- 0.13]x 10(-3) mm2/sec) (P <.0001) 2 days after combretastatin A4 phosphate injection was paralleled by progressive histologic necrosis. A significant (P <.0001) decrease in ADC 9 days after treatment ([1.41 +/- 0.15]x 10(-3) mm2/sec) corresponded to tumor regrowth. CONCLUSION: In addition to basic relaxation-weighted MR imaging and postgadolinium T1-weighted MR imaging to enable prompt detection of vascular shutdown, diffusion-weighted MR imaging was used to discriminate between nonperfused but viable and necrotic tumor tissues for early monitoring of therapeutic effects of vascular targeting agent.

Animals↗

PubMed2004

Leveraging two-way probe-level block design for identifying differential gene expression with high-density oligonucleotide arrays.

BACKGROUND: To identify differentially expressed genes across experimental conditions in oligonucleotide microarray experiments, existing statistical methods commonly use a summary of probe-level expression data for each probe set and compare replicates of these values across conditions using a form of the t-test or rank sum test. Here we propose the use of a statistical method that takes advantage of the built-in redundancy architecture of high-density oligonucleotide arrays. RESULTS: We employ parametric and nonparametric variants of two-way analysis of variance (ANOVA) on probe-level data to account for probe-level variation, and use the false-discovery rate (FDR) to account for simultaneous testing on thousands of genes (multiple testing problem). Using publicly available data sets, we systematically compared the performance of parametric two-way ANOVA and the nonparametric Mack-Skillings test to the t-test and Wilcoxon rank-sum test for detecting differentially expressed genes at varying levels of fold change, concentration, and sample size. Using receiver operating characteristic (ROC) curve comparisons, we observed that two-way methods with FDR control on sample sizes with 2-3 replicates exhibits the same high sensitivity and specificity as a t-test with FDR control on sample sizes with 6-9 replicates in detecting at least two-fold change. CONCLUSIONS: Our results suggest that the two-way ANOVA methods using probe-level data are substantially more powerful tests for detecting differential gene expression than corresponding methods for probe-set level data.

Analysis of Variance↗

PubMed2006

GAIA: an easy-to-use web-based application for interaction analysis of case-control data.

BACKGROUND: The advent of cheap, large scale genotyping has led to widespread adoption of genetic association mapping as the tool of choice in the search for loci underlying susceptibility to common complex disease. Whilst simple single locus analysis is relatively trivial to conduct, this is not true of more complex analysis such as those involving interactions between loci. The importance of testing for interactions between loci in association analysis has been highlighted in a number of recent high profile publications. RESULTS: Genetic Association Interaction Analysis (GAIA) is a web-based application for testing for statistical interactions between loci. It is based upon the widely used case-control study design for genetic association analysis and is designed so that non-specialists may routinely apply tests for interaction. GAIA allows simple testing of both additive and additive plus dominance interaction models and includes permutation testing to appropriately correct for multiple testing. The application will find use both in candidate gene based studies and in genome-wide association studies. For large scale studies GAIA includes a screening approach which prioritizes loci (based on the significance of main effects at one or both loci) for further interaction analysis. CONCLUSION: GAIA is available at http://www.bbu.cf.ac.uk/html/research/biostats.htm.

Case-Control Studies↗

PubMed2003

Integration of association statistics over genomic regions using Bayesian adaptive regression splines.

In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD) with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS). For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test) and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples.

Algorithms↗

PubMed1997

Regulatory harmonization--a vaccine industry perspective.

With growth and diversification of aquaculture has come the dissemination of diseases and the increased need to use control measures, both preventative and therapeutic. Preventative measures include good husbandry practices, adequate nutrition and the use of vaccines. Vaccines for aquaculture have generally fallen under the regulatory control of national veterinary medicinal or biological agencies and with that a diverse range of regulatory requirements for authorization and use. More so than any other food animal industry, aquaculture is an international industry with individual entities holding multinational ownership. This situation has created unique problems for the manufacturers of biologicals attempting to service the industry. In recent years, a concerted effort has been made to harmonize regulations to facilitate international trade of vaccines as well as vaccinated animal stocks and their processed food products within and among trading partners. Standardization of requirements for manufacture and testing would ensure national and international interests and consumers of pure, safe and effective products. As the path to harmonization has been slow and not without disagreements, the question remains: What will the standardized requirements be? The manufacturing philosophies of process control (Good Manufacturing Practice) and governmental final product testing for batch release can create a duplicity of effort on the part of the manufacturer that equates to higher economic costs and greater time constraints. The current lack of standardized quality control test methods often means conducting multiple tests to provide the same result. Although efforts are being made to recognize these differences, historical regulations today are based on injectable vaccines for warm-blooded animals. Administration of vaccine products to cold-blooded aquatic species by immersion, bath and oral routes, as well as by injection, creates interpretive problems for manufacturers and regulators alike. Industry encourages and awaits regulatory harmonization, standardization or equivalence. It also offers and would appreciate an active role in the final process.

Animals↗

PubMed1997

[An opinion from a user: a nurse's point of view].

The focus of this discussion is twofold; to provide an overview patient management in the nursing unit in relation to the Department of Examinations and to propose some strategies for assuring safe, accurate and effective laboratory tests from a nursing perspective. There are four issues identified as weaknesses in the environment of our collaboration; a lack of consistent support for anxious or frightened patients undergoing laboratory tests due to the low volume of information shared by us; a limited clinical laboratory consultation available to nurses because of unfriendly and unclear access to the Dept. of Examinations; a lack of collaboration and flexibility in responding to individual diversity in health problems; a lack of clinical laboratory coordination in scheduling laboratory tests, especially, for patients with multiple tests per day or per week. Based on those issues, five strategies are proposed. Greater involvement of medical technologists in routine laboratory works in the unit such as drawing blood and collecting specimens as needed. Clinical Laboratory tests except for urgent tests should be scheduled to minimize disturbances of life style for inpatients while waiting for the completion of all tests. An information processing system that helps nurses maintain advanced knowledge and skills is necessary to follow the state of art in the specialized area of clinical laboratory tests. It is definitely recommended that effective consultation be offered by the Dept. of Examinations. It is beneficial to patients for medical technologists to actively participate in the cooperative medicine of our hospital by sharing the patient's information with nurses in the unit. Lastly, it would be welcome to have direct communication with patients on the unit. This would facilitate mutual understanding between technologists and nurses. In conclusion, collaboration between the Department of Examinations and nurses of the unit may maximize patient benefits brought by the valuable information obtained from laboratory work through improved communication and mutual understanding.

Anxiety↗

PubMed2025

Biochemical testing for congenital disorders of glycosylation: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Congenital disorders of glycosylation (CDG) are a large and continually expanding group of disorders that present with a variety of clinical findings and have been linked to over 170 genes. Individually, CDGs are rare; however, the true incidence may be underestimated because of the variability of the clinical findings, and the multiple testing strategies needed to diagnosis them across multiple pathways. Testing for CDGs has evolved over recent years with the availability of high-throughput molecular testing and improved gene discovery techniques. Biochemical testing to detect defects in glycosylated proteins or enzymatic deficiency still plays a critical role in the diagnosis of affected individuals, and both testing modalities are often required to finalize a diagnosis. Emerging therapeutic approaches targeting improvements in glycosylation require reliable and reproducible biochemical testing for therapeutic monitoring, dose adjustment, and avoidance of dose-related side effects. To maintain clinical sensitivity and specificity and to ensure reproducibility across laboratories performing complex biochemical testing, the American College of Medical Genetics and Genomics has developed the following technical standard.

Humans↗

PubMed1995

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection.

BACKGROUND & AIMS: Multiple tests are available for determining Helicobacter pylori infection. Our aim was to compare the sensitivity, specificity, and negative and positive predictive value of the most widely available tests for diagnosis of H. pylori. METHODS: A total of 268 patients (mean age, 53.7 +/- 15.8 years; 142 male and 126 female; 125 white and 143 nonwhite) was tested for H. pylori infection by [13C]urea breath test (UBT), measurement of serum immunoglobulin (Ig) G and IgA antibody levels, and antral biopsy specimens for CLO test, histology, and Warthin-Starry stain. No patient received specific treatment for H. pylori before testing. The infection status for each patient was established by a concordance of test results. RESULTS: Warthin-Starry staining had the best sensitivity and specificity, although CLO test, UBT, and IgG levels were not statistically different in determining the correct diagnosis. The absence of chronic antral inflammation was the best method to exclude infection. Stratification of results by clinical characteristics showed that UBT and chronic inflammation were the best predictors of H. pylori status in patients older than 60 years of age. IgA was a better predictor in white patients. CONCLUSIONS: The noninvasive UBT and IgG serology test are as accurate in predicting H. pylori status in untreated patients as the invasive tests of CLO and Warthin-Starry.

Adult↗

PubMed2000

Antimicrobial susceptibility testing for Helicobacter pylori: sensitivity test results and their clinical relevance.

There are multiple test methodologies to determine the antibiogram of an organism. Standardized susceptibility test methods are based upon rapidly growing, aerobic microorganisms in which overnight incubation results in definitive endpoints. In vitro susceptibility testing for fastidious organisms that require complex media for growth, require incubation in atmospheres other than ambient air, or are slow-growing (anaerobes, mycobacteria, filamentous fungi) are problematic and in general are not standardized. H. pylori falls into this category of troublesome organisms. For the microaerobic organism H. pylori, testing is challenging because the organism grows slowly even under optimal culture conditions. Recently the National Committee for Clinical Laboratory Standards (NCCLS) approved the agar dilution method as the test of choice for testing H. pylori. While not entirely reliable in predicting the outcome of treatment for metronidazole resistant organisms, the resistance determined for clarithromycin by this method generally predicts treatment failure. Quality control breakpoints for H. pylori ATCC 43504 were established and breakpoints for clarithromycin were approved by the NCCLS in 1999. Breakpoints are minimum inhibitory concentrations (MIC) of a drug at which an organism is deemed either susceptible or resistant to the antibiotic using standard dosing regimens containing that drug. Significant progress has been made with respect to development of tests to detect antimicrobial resistance, but there still remains no consensus as to the breakpoints for agents used in the treatment of H. pylori infection other than clarithromycin. This article will address the controversies associated with the reporting of antibiotic resistance data and the interpretation of these data.

Cost-Benefit Analysis↗

PubMed1990

The hydrogen sulphide screening test of water quality: its validity compared to a standard multiple-tube technique test.

A study to determine the validity and predictive value of the hydrogen sulphide screening test for water quality compared to a standard multiple-tube technique test was undertaken. The hydrogen sulphide test was found to be highly sensitive and specific with a high predictive value. It is recommended as a screening test for water quality in developing countries where resources are limited. It will be especially useful in monitoring improvement in rural water supplies.

Evaluation Studies as Topic↗

PubMed1997

Activation of gene expression by herpes simplex virus type 1 ICP0 occurs at the level of mRNA synthesis.

ICP0 is a nuclear phosphoprotein involved in the activation of herpes simplex virus type 1 (HSV-1) gene expression during lytic infection and reactivation from viral latency. Although available evidence suggests that ICP0 acts at the level of transcription, definitive studies specifically addressing this issue have not been reported. In the present study we measured the ability of ICP0 to activate gene expression (i) from promoters representing the major kinetic classes of viral genes in transient expression assays and (ii) from the same promoters during viral infection at multiplicities of infection ranging from 0.1 to 5.0 PFU/cell. The levels of synthesis and steady-state accumulation of mRNA, mRNA stability, and levels of protein synthesis were compared in cells transfected with a reporter plasmid in the presence and absence of ICP0 and in cells infected with wild-type HSV-1 or an ICP0 null mutant, n212. In transient expression assays and during viral infection at all multiplicities tested, the levels of steady-state mRNA and protein were significantly lower in the absence of ICP0, indicating that ICP0 activates gene expression at the level of mRNA accumulation. In transient expression assays and during infection at low multiplicities (< 1 PFU/cell) in the presence or absence of ICP0, marked increases in the levels of viral mRNAs accompanied by proportional increases in the levels of protein synthesis were observed with increasing multiplicity. At a high multiplicity (5 PFU/cell) in the presence or absence of ICP0, mRNA levels did not increase as a function of multiplicity and changes in the levels of protein were no longer related to changes in the levels of mRNA. Collectively, these tests indicate that transcription of viral genes is rate limiting at low multiplicities and that translation is rate limiting at high multiplicities, independent of ICP0. Consistent with the lower levels of mRNA detected in the absence of ICP0, the rates of transcription initiation measured by nuclear run-on assays were uniformly lower in cells infected with the ICP0 null mutant at all multiplicities tested, implying that ICP0 enhances transcription at or before initiation or both. No evidence was found of posttranscriptional effects of ICP0 (i.e., effects on the stability of mRNA, nuclear-cytoplasmic distribution, polyribosomal mRNA distribution, or rates of protein synthesis). Taken together, these results suggest that ICP0 activates gene expression prior to or at the level of initiation of mRNA synthesis in transient expression assays and during viral infection. Based on these findings; we hypothesize that the exaggerated multiplicity-dependent growth phenotype characteristic of ICP0 null mutants reflects the requirement for ICP0 under conditions where the steady-state level of mRNA is rate limiting, such as during low-multiplicity infection and reactivation from latency.

Animals↗

PubMedDate not supplied

Growth pattern of overweight preschool children in the Siouxland WIC program.

Demographic, nutritional, and anthropometric data were collected from 134 preschool children enrolled in the Siouxland Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). All children were diagnosed as overweight between the ages of 8 months and 3 years. Weight and length/height z-scores were calculated for birth measurements and for postnatal measurements up to 3 years. The main hypothesis involved stability of weight and length/height z-scores between successive WIC visits. Average changes in z-scores between measurements were calculated and tested for significance using paired t-tests. Multiple regression analysis was used to test relationships between changes in weight z-scores and demographic/nutritional characteristics. The overweight group had a higher percentage of Hispanic children than the total Siouxland WIC population. Overweight children were also significantly different in terms of birthweight, monthly household income, number in the house, and mother's education level. The children displayed a large average increase in weight z-scores between birth and 8 months (P < 0.001). Weight z-scores also increased significantly between 12 and 30 months. Length z-scores increased significantly between 18 and 30 months but remained lower than weight z-scores. Initial weight, sex of child, breastfeeding, and household size were significantly related to changes in weight z-scores among overweight children. Results of recent studies suggest that rapid weight gain in infancy may increase the risk of overweight during later childhood.

Analysis of Variance↗

PubMed2004

Evidence for linkage between regulatory enzymes in glycolysis and schizophrenia in a multiplex sample.

Observations of impaired glucose regulation in schizophrenia are long-standing, although their pathological and etiological significance is uncertain. One approach to the issue that minimizes environmental variables (e.g., medication and diet) is to determine whether genes related to glucose regulation show genetic linkage to schizophrenia. We examined the potential role of glucose metabolism in schizophrenia through a genome scan of affection status in schizophrenia and an empirical method for deriving P-values. Data were utilized from the NIMH Genetics Initiative for Schizophrenia dataset, which comprises a total sample consisting of 71 pedigrees containing 218 nuclear families and 987 individuals. A genome scan with 459 markers spaced at an average of 10 cM intervals was conducted using the linkage analysis program Genehunter separately for European- and African-American groups. Enzymes that regulate glycolysis were identified and the genes regulating these enzymes were located through the Online Mendelian Inheritance in Man (OMIM) website. The focus in this study was on genes located near previously reported schizophrenia susceptibility regions. The genome-wide significance of these genes to schizophrenia was assessed using permutation testing. When results were adjusted for multiple testing within and across ethnic groups, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2; chromosome 1q32.2) achieved genome-wide significance (P = 0.04). In addition, hexokinase 3 (HK3; chromosome 5q35.3) was also suggestive of linkage (P = 0.09). For the European-American sample, PFKFB2 (1q32.2), hexokinase 3 (HK3; 5q35.3), and pyruvate kinase 3 (PK3; chromosome 15q23) achieved significance at the 0.05 level. None of the genes showed significance in the African-American sample. Our results provide further support for the view that genes that regulate glucose metabolism may also influence susceptibility to schizophrenia. More generally, they support the view that relationships between glucose dysregulation and schizophrenia are inherent to the disorder, and are not merely epiphenomena related to medication or other treatment factors.

Black or African American↗

PubMed2004

Serum cytokine profiles in relapsing polychondritis suggest monocyte/macrophage activation.

OBJECTIVE: There is evidence that autoimmunity plays a significant role in the pathogenesis of relapsing polychondritis (RP). This study was designed to investigate circulating levels of various cytokines in relation to the etiology of this rare disorder, and to compare the pattern of cytokine elevations in RP with that in another autoimmune disease, rheumatoid arthritis (RA). METHODS: Serum from 22 patients with active RP and an equal number of age- and sex-matched healthy controls and RA patients were available for analysis. The following cytokines were measured: interleukin-1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-gamma (IFNgamma), tumor necrosis factor alpha, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1beta (MIP-1beta). Results were analyzed by nonparametric Mann-Whitney test with Holm stepdown adjustment for multiple testing. RESULTS: The levels of 3 of these cytokines showed significant differences between RP patients and controls. Compared with controls, mean serum levels of MCP-1, MIP-1beta, and IL-8 were all much higher in patients with active RP. In contrast, RA patients showed a more general increase in all cytokines measured, with much higher levels of IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IFNgamma, G-CSF, GM-CSF, MCP-1, and MIP-1beta compared with controls. CONCLUSION: Levels of 3 serum cytokines were significantly higher in RP patients than in age- and sex-matched controls. One of these 3 cytokines, IL-8, was not significantly elevated in RA samples. Overall, in RP, a more discrete group of cytokines exhibited significantly increased levels than was found in RA. Each of the 3 cytokines that were elevated in RP is a proinflammatory chemokine, characteristic of activation of the monocyte and macrophage lineage, and in the case of IL-8, also of neutrophils. These data suggest a major role for a cell-mediated immune response in the pathophysiology of RP.

Adult↗

PubMed1994

Limited value of two widely used enzyme immunoassays for detection of Chlamydia trachomatis in women.

Enzyme immunoassays (EIAs) are widely used to diagnose chlamydial infections in patients attending genitourinary medicine clinics. They are relatively easy to perform and are suitable for testing large numbers of samples. The objective of this study was to determine what proportion of women with chlamydial infection, defined as the presence of Chlamydia trachomatis in a cervical smear or deposit and/or in the urinary tract, detected by means of a sensitive direct fluorescent antibody test could also be identified by using two commercially available EIAs to test cervical samples. On hundred fifty-one women attending the genitourinary medicine clinic at St. Mary's Hospital, London, were enrolled. The use of the Chlamydiazyme (Abbott Diagnostics, UK) and MicroTrak (Syva, UK) EIAs resulted in the identification of only 56% and 63%, respectively, of women with chlamydial infection detected by direct fluorescent antibody staining. Thus, the EIAs available for detection of chlamydiae in cervical samples are inadequate for identifying all infected women. Improvement might be achieved by testing multiple samples or by resorting to tests of greater sensitivity.

Chlamydia Infections↗

PubMed2005

Nicotine-induced sensitization in mice: changes in locomotor activity and mesencephalic gene expression.

It is believed that drug-induced behavioral sensitization is an important process in the development of substance dependence. In order to explore mechanisms of sensitization, a mouse model of nicotine-induced locomotor sensitization was established, and effects of the sensitization process on mesencepahlic gene expression were examined. A schedule, which included 3 weeks of intermittent nicotine exposure (0.5 mg/kg, s.c.) and 3 weeks of withdrawal, resulted in locomotor sensitization. Effects of sensitization on mesencephalic expression of approximately 14,000 genes were assessed using oligonucleotide microarrays. Signal intensity differences in samples obtained from repeated nicotine- and saline-exposed animals were analyzed with z-test after False Discovery Rate (FDR) multiple test correction. Genes related to GABA-A receptors and protein phosphatases were among 68 genes showing significantly different expression levels between the saline and the nicotine groups. We hypothesize that some of the gene expression changes in the mesencephalon are involved in pathways leading to nicotine-induced sensitization. Down-regulation of GABA-A receptors induced by repeated nicotine exposure may facilitate dopaminergic neuronal transmission and may contribute to increased locomotor activity.

Animals↗

PubMedDate not supplied

Analyzing multivariate neurobehavioral outcomes in occupational studies: a comparison of approaches.

Neurobehavioral studies often employ test batteries and confront issues of multiple testing and comparability between batteries. We have organized our battery of 12 tests into areas of neurobehavioral function to reduce the number of reported results, provide greater statistical power, and improve interpretability of the results. We explored several different organizational and statistical methods of creating summary scores including a priori groupings based upon clinical experience and factor analysis. We compared the sensitivity of these summary scores to performance changes associated with exposure to styrene in the manufacture of reinforced plastics. Our results demonstrated dramatic increases in power to detect exposure related changes compared to using individual test scores. Furthermore, the various methods provided generally compatible and comparable results. We encourage other neurobehavioral investigators to pursue and refine this approach.

Adolescent↗