Response to paper by SP Smith Olecranon fractures--a reliable technique for accurate positioning of the tension band wire.
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Bone Wires↗
Biomedical subjects
D M Nielsen
Publications and source records attributed to D M Nielsen.
Applying data mining techniques to the mapping of complex disease genes.
The simulated sequence data for the Genetic Analysis Workshop 12 were analyzed using data mining techniques provided by SAS ENTERPRISE MINER Release 4.0 in addition to traditional statistical tests for linkage and association of genetic markers with disease status. We examined two ways of combining these approaches to make use of the covariate data along with the genotypic data. The result of incorporating data mining techniques with more classical methods is an improvement in the analysis, both by correctly classifying the affection status of more individuals and by locating more single nucleotide polymorphisms related to the disease, relative to analyses that use classical methods alone.
Chromosome Mapping↗
Association studies under general disease models.
There is great expectation that the levels of association found between genetic markers and disease status will play a role in the location of disease genes. This expectation follows from regarding association as being proportional to linkage disequilibrium and therefore inversely related to recombination value. For disease genes with more than two alleles, the association measure is instead a weighted average of linkage disequilibria, with the weights depending on allele frequencies and genotype susceptibilities at the disease loci. There is no longer a simple relationship, even in expectation, with recombination. We adopt a general framework to examine association mapping methods which helps to clarify the nature of case-control and transmission/disequilibrium-type tests and reveals the relationship between measures of association and coefficients of linkage disequilibrium. In particular, we can show the consequences of additive and nonadditive effects at the trait locus on the behavior of these tests. These concepts have a natural extension to marker haplotypes. The association of two-locus marker haplotypes with disease phenotype depends on a weighted average of three-locus disequilibria (two markers with each disease locus). It is likely that these two-marker analyses will provide additional information in association mapping studies.
Alleles↗
Association mapping: where we've been, where we're going.
This paper provides a review of recent work in the area of marker-phenotype association studies, specifically as used for localizing--or mapping--genes affecting a trait of interest. We describe the basis of association mapping and discuss a number of the commonly used techniques. We have also included references to various papers that have evaluated the use of these methods.
Analysis of Variance↗
Left and right 6-hydroxydopamine lesions of the medial prefrontal cortex differentially affect voluntary ethanol consumption.
Dopaminergic projections to the medial prefrontal cortex (mPFC) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) to examine how dopamine (DA) asymmetry in the mPFC influences voluntary ethanol consumption. Differences in nucleus accumbens (NAS) DA neurotransmission have been related to individual differences in locomotor activity and in the rewarding efficacy of ethanol. Therefore, differences in locomotor activity were used to further characterize the effects of unilateral mPFC 6-OHDA lesions on ethanol consumption. Male Long Evans rats were assessed for high versus low levels of spontaneous locomotor activity. DA terminals in the left or right mPFC were unilaterally lesioned with 6-OHDA, resulting in an average DA depletion of 54% and 50%, respectively. After a minimum seven-day recovery period, preference for a 10% ethanol solution vs. water was determined in a 24-h 2-bottle home-cage free-choice paradigm. Left mPFC 6-OHDA lesions increased and right lesions decreased ethanol consumption. These differential effects of left and right lesions were primarily attributable to rats exhibiting low locomotor activity prior to surgery. The present data suggest that right greater than left cortical DA asymmetry in combination with low endogenous NAS DA (predicted by low locomotor activity levels) may increase the vulnerability to abuse ethanol.
Alcohol Drinking↗
Rotation, locomotor activity and individual differences in voluntary ethanol consumption.
Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict differences in the voluntary consumption of ethanol in male Long-Evans rats. Animals were assessed for their preferred direction of turning behavior and for high vs. low levels of spontaneous locomotor activity, as determined during nocturnal testing in a rotometer. Subsequently, preference for a 10% ethanol solution vs. water was determined in a 24-h two-bottle home-cage free-choice paradigm. Rats exhibiting a right-turning preference consumed more ethanol than rats showing a left-turning preference. While locomotor activity alone did not predict differences in drinking, turning and locomotor activity together predicted differences in ethanol consumption. Low-activity right-turning rats consumed more ethanol than all the other groups of rats. Previous studies from this laboratory have shown that individual differences in turning behavior are accompanied by different asymmetries in dopamine (DA) function in the medial prefrontal cortex (mPFC). Individual differences in locomotor activity are associated with differences in nucleus accumbens (NAS) DA function. The present data suggest that variations in mPFC DA asymmetry and NAS DA function may underlie differences in the voluntary consumption of ethanol.
Alcohol Drinking↗
Ethanol induced differences in medial prefrontal cortex dopamine asymmetry and in nucleus accumbens dopamine metabolism in left- and right-turning rats.
Ethanol (0.5 g/kg i.p.) 15 min prior to sacrifice increased homovanillic acid (HVA) levels in the left medial prefrontal cortex (mPFC) of left-turning rats and in the right mPFC of right-turning rats. In the nucleus accumbens (NAS), ethanol decreased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels in rats that exhibited low levels of locomotor activity but not in rats that exhibited high levels of locomotor activity. This laboratory has previously shown that rats exhibiting differences in turning and locomotor activity behavior display different preferences for ethanol. The present results suggest that ethanol-induced differences in mPFC and NAS DA activity may be related to individual differences in the susceptibility to abuse ethanol.
3,4-Dihydroxyphenylacetic Acid↗
A classical setting for associations between markers and loci affecting quantitative traits.
We examine the relationships between a genetic marker and a locus affecting a quantitative trait by decomposing the genetic effects of the marker locus into additive and dominance effects under a classical genetic model. We discuss the structure of the associations between the marker and the trait locus, paying attention to non-random union of gametes, multiple alleles at the marker and trait loci, and non-additivity of allelic effects at the trait locus. We consider that this greater-than-usual level of generality leads to additional insights, in a way reminiscent of Cockerham's decomposition of genetic variance into five terms: three terms in addition to the usual additive and dominance terms. Using our framework, we examine several common tests of association between a marker and a trait.
Animals↗
Detecting marker-disease association by testing for Hardy-Weinberg disequilibrium at a marker locus.
We review and extend a recent suggestion that fine-scale localization of a disease-susceptibility locus for a complex disease be done on the basis of deviations from Hardy-Weinberg equilibrium among affected individuals. This deviation is driven by linkage disequilibrium between disease and marker loci in the whole population and requires a heterogeneous genetic basis for the disease. A finding of marker-locus Hardy-Weinberg disequilibrium therefore implies disease heterogeneity and marker-disease linkage disequilibrium. Although a lack of departure of Hardy-Weinberg disequilibrium at marker loci implies that disease susceptibilityweighted linkage disequilibria are zero, given disease heterogeneity, it does not follow that the usual measures of linkage disequilibrium are zero. For disease-susceptibility loci with more than two alleles, therefore, care is needed in the drawing of inferences from marker Hardy-Weinberg disequilibria.
Alleles↗
Paw preference, rotation, and dopamine function in Collins HI and LO mouse strains.
Mice have paw preferences that are consistent upon repeated measurement. The Collins HI and LO strains are two populations of mice that have been selectively bred to differ markedly in the degree of paw preference. They represent a unique genetic model of functional cerebral lateralization. Rotation (or circling) behavior in normal unlesioned animals reflects an endogenous lateralization of the functioning brain dopamine (DA) systems. In the present study, rotational behavior and lateralized brain DA neurochemistry were assessed in the Collins HI and LO strain mice. Confirming Collins findings, HI strain mice exhibited stronger paw preferences than LO strain mice. HI strain mice also showed stronger percent directional preferences during nocturnal tests of spontaneous rotation. Neurochemical differences were also apparent between the strains. DA and its metabolites were measured in the medial prefrontal cortex (PFC), nucleus accumbens (NAS), and striatum. Degrees of rotational and paw preference in HI, but not LO, mice were correlated with PFC asymmetries in DA and the DA metabolite dihydroxyphenyl acetic acid (DOPAC), respectively. Hemisphere, paw preference, turning preference, and strain interacted in a complex way to determine measures of DA utilization in the NAS and striatum. Even though the directions of paw preference and rotation were not correlated, HI and LO mice of differing paw and rotational directional preferences showed differences in DA neurochemistry in the NAS and striatum.
Animals↗
Navigating the maze of breast cancer treatment.
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Breast Neoplasms↗
Polar overdominance at the ovine callipyge locus.
An inheritable muscular hypertrophy was recently described in sheep and shown to be determined by the callipyge gene mapped to ovine chromosome 18. Here, the callipyge phenotype was found to be characterized by a nonmendelian inheritance pattern, referred to as polar overdominance, where only heterozygous individuals having inherited the callipyge mutation from their sire express the phenotype. The possible role of parental imprinting in the determinism of polar overdominance is envisaged.
Animals↗
Chronic antidepressant drug treatment reduces turning behavior and increases dopamine levels in the medial prefrontal cortex.
The effects of chronic administration of the antidepressant drugs desipramine, nortryptiline and paroxetine (PAR) (10 mg/kg/day, 21 days) on changes in turning (circling) behavior and on norepinephrine (NE), dopamine (DA) and serotonin and their metabolites 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex (PFC), nucleus accumbens and striatum were evaluated in rats. All three drugs eliminated turning biases in right turning rats. All drugs increased DA concentrations in the PFC while PAR increased NE in the PFC and reduced 5-HIAA in all three structures. The results are discussed with reference to previous findings involving brain asymmetry in depression.
Animals↗
Parental behavior and adolescent self-esteem in clinical and nonclinical samples.
This study investigated the relationships between multiple dimensions of self-esteem and adolescents' perceptions of parental behaviors using nonclinical (n = 119) and clinical (n = 30) samples of adolescents. The Rosenberg Self-Esteem Scale (RSES), a modified version of Osgood's Semantic Differential (OSD), Schaefer's Children's Report of Parental Behavior Inventory (CRPBI) short form), and a demographic questionnaire were administered to participants. Scores from the self-esteem measures were empirically combined and factor analyzed, yielding four dimensions of self-esteem. Multivariate analysis of variance were used to compare self-esteem dimension scores for males and females within both samples. Correlations and partial correlations were conducted to determine the nature of the relationships between each dimension of self-esteem and perceptions of parental behaviors. Nonclinical adolescents scored higher than did clinical adolescents on all self-esteem dimensions. Males scored higher than females only on the dimension of Self-Esteem Competence. Perceptions of parental behaviors were consistently unrelated to dimensions of self-esteem among adolescents in the clinical sample. Among adolescents in the nonclinical sample, perceptions of parental support and autonomy granting were related to multiple dimensions of self-esteem. Perceptions of parental discipline were inconsistently related to dimensions of nonclinical self-esteem.
Adolescent↗
Toward the development of uniform reporting standards for managed care organizations: the Health Plan Employer Data and Information Set (Version 2.0).
The cornerstone of HEDIS 2.0 is measurement. Only by measuring how a plan performs with respect to defined measures will an employer be able to assess a plan's value and also hold a plan accountable for its performance. Because of time and resource constraints, there are many issues related to the development and use of the performance measures contained within HEDIS 2.0 that have been incompletely addressed or not addressed at all. Following are some of the issues that warrant further consideration. Selection of performance measures. The present set of performance measures represents only a first attempt to define measures that document health plan performance in a number of areas of health care delivery. The resulting measures constitute a core data and information set and should not be considered to be an optimum set. Many other areas and measures of health plan performance were considered, including costs of specific episodes of care, age-specific utilization of defined services, patients receiving appropriate follow-up care for identified preventive health services, stage of cancer at time of diagnosis in relationship to preventive services screening, and functional outcome assessment. These measures were not included in this revision of HEDIS because of difficulties in developing specifications for the measure and/or in obtaining reliable data. It will be important to address these areas in the future. Risk adjustment of performance measures. To minimize the effects of population differences, most of the recommended performance measures assess discrete aspects of the process of care delivery (for example, percentage of pregnant women with first-trimester visit) rather than outcomes. However, interpretation of certain measures (for example, low birthweight, hospital readmission rate) will be affected by the specific member characteristics of the health plan population. Health plans and employers need to be aware of this limitation when interpreting and comparing certain performance measures, and further refinements will be needed in future ierations.(ABSTRACT TRUNCATED AT 400 WORDS)
Consumer Behavior↗
Diagnosis and treatment of granulomatous mastitis.
Granulomatous mastitis is a benign inflammatory breast disease of unknown etiology. Although it is rare, it frequently presents in a manner similar to that of breast carcinoma. Surgical resection of the affected tissue has often been the method of treatment, but many patients have experienced recurrences. Corticosteroids have also been used, but the initiation of this therapy is often limited by concerns related to the presence of an infectious etiology. Presented here are two cases that demonstrate the efficacy of corticosteroids in this condition after appropriate evaluation is performed.
Adult↗
Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study.
STUDY OBJECTIVE: To ascertain the efficacy and toxicity of trimethoprim-sulfamethoxazole or pentamidine when either is given alone during the entire treatment period for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective, randomized, noncrossover comparison of trimethoprim-sulfamethoxazole with pentamidine. Trimethoprim-sulfamethoxazole dosage was adjusted to maintain serum trimethoprim at 5 to 8 micrograms/mL. Pentamidine dosage was reduced by 30% to 50% for an absolute rise in serum creatinine of more than 88 mumol/L (1 mg/dL). SETTING: Tertiary care hospital and AIDS clinic. PATIENTS: Thirty-six patients were treated with trimethoprim-sulfamethoxazole and 34 with pentamidine. Pretreatment clinical features and laboratory test results were similar in the two groups. MEASUREMENTS AND MAIN RESULTS: Thirty-six recipients of trimethoprim-sulfamethoxazole and 33 recipients of pentamidine completed therapy without crossover. Trimethoprim-sulfamethoxazole caused a rash (44%) and anemia (39%) more frequently (P less than or equal to 0.03, whereas pentamidine caused nephrotoxicity (64%), hypotension (27%), or hypoglycemia (21%) more frequently (P less than or equal to 0.01). The (A - a)DO2 improved by greater than 1.3 kPa (10 mmHg) 8 days earlier for trimethoprim-sulfamethoxazole recipients (95% CI for the difference in response, -1 to 17; P = 0.04). Thirty-one (86%) patients treated with trimethoprim-sulfamethoxazole and 20 (61%) with pentamidine survived and were without respiratory support at completion of treatment (95% CI for the difference in response, 5% to 45%; P = 0.03). CONCLUSIONS: For most patients with AIDS and P. carinii pneumonia, successful treatment with a single agent is possible. Toxicity associated with the two standard treatments is rarely life-threatening and may be diminished if the trimethoprim-sulfamethoxazole dosage is modified by pharmacokinetic monitoring and the pentamidine dosage is reduced for nephrotoxicity. Oxygenation improved more quickly and survival was better with trimethoprim-sulfamethoxazole.
Acquired Immunodeficiency Syndrome↗
Imipenem/cilastatin therapy for serious bacterial infections.
Imipenem was administered intravenously with cilastatin to patients with suspected or documented significant infections. The mean peak serum level of imipenem 30 min after infusion of a 500 mg dose was 18.4 micrograms/ml, and the mean trough level (30 min before infusion) was 2.4 micrograms/ml. The organisms isolated before therapy included Enterobacteriaceae, Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and anaerobes. The response rate in 25 assessable patients was 96%, with 40% experiencing a complete cure and 56% improvement. Therapy failed in only one instance because an isolate of P. aeruginosa was mistakenly reported to be susceptible on disk testing. Toxicity in the 33 patients treated was generally minimal and included phlebitis, mild liver function abnormalities, eosinophilia, and thrombocytosis. The emergence of resistant organisms during therapy was very uncommon. Imipenem/cilastatin is a promising agent for the treatment of complicated infections.
Aged↗