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Biomedical subjects

J M Meyer

Publications and source records attributed to J M Meyer.

At least 73 records · Page 4Linked to original sources
PubMed1998

Differential sensitivities to risperidone and olanzapine in a human immunodeficiency virus patient.

BACKGROUND: Neuroleptic sensitivity presents a considerable problem for the treatment of psychosis in the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive patient population. As yet, there are few data on the response of these patients to newer atypical antipsychotic medications. METHODS: We present the detailed medication history of a 33-year-old man with AIDS, who had a prior history of extrapyramidal symptoms (EPS) with both typical antipsychotics and risperidone, and was treated with olanzapine for major depression with psychotic features. RESULTS: The patient developed akathisia in a dose-dependent manner at dosages between 10 and 15 mg daily of olanzapine, but no EPS. Akathisia responded to dose reduction and use of beta-adrenergic blockade. CONCLUSIONS: The AIDS patient may exhibit sensitivity even to newer atypical antipsychotics. The lack of EPS and response to a beta-blocker underscore the different mechanisms causing akathisia and EPS.

Adult↗
PubMed1998

Quorum-sensing and siderophore biosynthesis in Pseudomonas aeruginosa: lasR/lasI mutants exhibit reduced pyoverdine biosynthesis.

Cell density-dependent gene expression in Pseudomonas aeruginosa is controlled, in part, by the quorum-sensing regulator LasR. lasR null mutants exhibited a reproducible 2-fold decrease in production of the catecholate-hydroxamate siderophore pyoverdine during grown under iron-limiting conditions. Similarly, lasI mutants defective in the biosynthesis of the autoinducer PAI-1 also exhibited a 2-fold decrease in pyoverdine production which could be largely restored upon addition of exogenous PAI-1. lasR mutants were not altered with respect to expression of the pvdD gene involved in the synthesis of the peptide portion of pyoverdine, indicating that some other pyoverdine biosynthetic gene(s) were affected by the LasRI status of the cell. This represents the first report of quorum-sensing regulation of siderophore production in bacteria and highlights the fact that cell density, while not an essential signal for pyoverdine expression, does enhance production of this siderophore.

Bacterial Proteins↗
PubMed1998

Multiple threshold model for the onset of Alzheimer's disease in the NAS-NRC twin panel.

The three common alleles at the APOE locus influence the onset and lifetime risk of typical late-onset Alzheimer's disease (AD). Other loci may also alter risk of late-onset AD. One may assess the relative influence of APOE on the genetic contribution to AD by estimating the proportion of AD heritability that is explained by APOE polymorphism. To do this requires an initial estimate of the heritability of AD. Traditional methods are not appropriate for this estimation since they do not consider right-censoring (incomplete expression of the genotype owing to death) nor do they model the relation of onset age and disease liability. Here we present an analytic model that addresses both of these issues. Genetic and environmental influences on AD are examined by assuming that onset of dementia in AD is a late event in an extended degenerative process where earlier onset reflects a more rapid course of neurodegeneration. The model is fitted to the occurrence of AD among 9,786 members of the National Academy of Sciences-National Research Council Registry of aging veteran twins. When both additive genetic and common environmental effects are used in the model, they explain 37% and 35%, respectively, of the variation in AD onset. Given the limited numbers of AD cases now available, models containing only additive genetic or shared environmental effects (explaining 75% and 65% of individual differences in disease onset, respectively) cannot be rejected in favor of a model that retains both influences.

Age of Onset↗
PubMed1998

Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities.

BACKGROUND: Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs. METHODS: We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence. Co-occurrence was quantified using odds ratios and conditional probabilities. Multivariate biometrical modeling analyses were used to assess genetic and environmental influences on co-occurrence. RESULTS: Abusing any category of drug was associated with a marked increase in the probability of abusing every other category of drugs. We found evidence for a shared or common vulnerability factor that underlies the abuse of marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. This shared vulnerability is influenced by genetic, family environmental, and nonfamily environmental factors, but not every drug is influenced to the same extent by the shared vulnerability factor. Marijuana, more than other drugs, was influenced by family environmental factors. Each category of drug, except psychedelics, had genetic influences unique to itself (ie, not shared with other drug categories). Heroin had larger genetic influences unique to itself than did any other drug. CONCLUSION: There are genetically and environmentally determined characteristics that comprise a shared or common vulnerability to abuse a range of illicit drugs.

Adult↗
PubMed1998

A registry-based twin study of depression in men.

BACKGROUND: The only large, registry-based twin study of depression using diagnostic criteria assessed by structured interview included only women. We present results from a comparable study of men. METHODS: Data were collected using a standardized telephone interview of men from the Vietnam Era Twin Registry. Both twins from 3372 pairs participated. Proband-wise concordance rates and biometric modeling were used to analyze the data. RESULTS: The diagnosis of major depression (MD), as defined by DSM-III-R, and the subtype of severe/psychotic MD were significantly affected by genetic (h2=0.36 and 0.39, respectively) and nonshared environmental (e2=0.64 and 0.61, respectively) factors but not by family environmental factors. Dysthymia and mild and moderate MD were affected by family environmental (c2=0.27, 0.08, and 0.14, respectively) and nonshared environmental (e2=0.73, 0.92, and 0.86, respectively) factors but not by genetic factors. Early-onset (before age 30 years) and late-onset (after age 30 years) MD were significantly affected by genetic (h2=0.47 and 0.10, respectively) and nonshared environmental (e2=0.53 and 0.90, respectively) factors. Early-onset MD was significantly more heritable than late-onset MD. CONCLUSIONS: The magnitude of genetic and environmental effects on depression in men is similar to that previously reported in women. Also similar to previous findings, more severe and earlier-onset depression may be more strongly affected by genetic factors, but differences in the reliability of reports of depression associated with severity may inflate estimates of the effect of the unique environment and deflate heritability estimates for less severe depression.

Adult↗
PubMed1998

Univariate genetic analyses of epilepsy and seizures in a population-based twin study: the Virginia Twin Registry.

The purpose of this study was to examine the roles of genetic and environmental factors in the etiology of epilepsy and seizures in twins ascertained from the Virginia Twin Registry. Health history information on twins was collected by questionnaire. Concordance rates were calculated and used to estimate degree of concordance for seizure types in monozygotic (MZ) and dizygotic (DZ) twin pairs. Univariate twin analyses were performed for each epilepsy and seizure type to determine models which best explained observed variation. Health history information concerning epilepsy and febrile seizure occurrences was provided by members of 8,655 twin pairs; 6,684 of these supplied additional information reporting absence, complex partial, tonic-clonic, and unspecified seizures. Models including additive genetic and unique environmental factors best explained febrile seizures, epilepsy, complex partial seizures, and unspecified seizures. For complex partial seizures, however, the contributions of genetic and environmental effects did not vary across gender. These results show that, under univariate analysis methods, genetic factors played an important role in the expression of seizures in epilepsy, febrile seizures, unspecified seizures, and complex partial seizures. Additional support for these findings was provided by the concordance results for all categories except male twins reporting complex partial seizure occurrence. However, environmental influences still remained an important factor in seizure expression in these specific categories.

Adolescent↗
PubMed1998

Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role.

Insulin receptor substrate 2 (IRS-2) is a substrate of the insulin receptor and mediates the action of the insulin. Disruption of the IRS-2 gene in mice results in peripheral insulin resistance and relative insulin deficiency. It is therefore possible that defects in the IRS-2 gene contribute to Type II (non-insulin-dependent) diabetes mellitus. We have examined the gene for evidence of linkage to Type II diabetes in Ashkenazi Jewish families. Radiation hybrid panel mapping was used to refine the map position of the IRS-2 gene and, in the absence of polymorphic markers within the gene, to identify nearby markers. The IRS-2 gene was placed 23cR from the marker D13S1265 on chromosome 13q34. 200 affected sib-pairs were genotyped for three markers across the region. Nonparametric linkage analysis (GENEHUNTER) used with this data found no evidence of excess allele sharing in the IRS-2 gene region. We therefore concluded that variation in the IRS-2 gene is unlikely to contribute to Type II diabetes in this discrete Caucasian population.

Animals↗
PubMed1998

Compomers: between glass-ionomer cements and composites.

The term 'compomer' was crafted by the producers of the first commercial material of this kind: a polyacid-modified composite resin, sold as a filling material for some specific applications. This term should recall the composite resins and glass-ionomer cements, since some features of these two generic materials are found in the compomers. Compomers contain a bifunctional monomer, which should be able to react with the pendant methacrylate groups of other monomers, as well as with the cations liberated by the glass particles. Several products of this kind are now available, and the purpose of this paper is to describe some of their specificities and to compare their influence on the mechanical properties, water uptake and fluoride release.

Biocompatible Materials↗
PubMed1998

Assortative mating for major psychiatric diagnoses in two population-based samples.

BACKGROUND: Previous studies on assortment for psychiatric disorders have reported discrepant findings. We aimed to test whether there is a significant association for psychiatric diagnoses, including alcoholism, generalized anxiety disorder, major depressive disorder, panic disorder and phobias between husbands and wives in two population-based samples. We further evaluated whether marital resemblance occurs primarily within or across psychiatric disorders and if assortment for psychopathology is primary or secondary to assortment for correlated variables. METHODS: A model for mate selection addressed whether the correlation between mates for psychiatric disorders arises from direct assortment (primary homogamy) or through correlation with other variables for which assortment occurs (secondary homogamy) or through cross-variable assortment. The model accounted for within-person co-morbidity as well as across-spouse data. RESULTS: Findings suggested that a moderate degree of assortment exists both within and across psychiatric diagnoses. Only a small amount of the observed marital resemblance for mental illness could be explained by assortment for correlated variables such as age, religious attendance and education. Similar results were obtained for the two samples separately and confirmed in their joint analysis, revealing that the co-morbidity and assortment findings, except for the marital correlation for age, religious attendance and education, replicate across samples. CONCLUSIONS: Significant but moderate primary assortment exists for psychiatric disorders. The bias in twin studies that have ignored the small amount of assortment is negligible.

Adolescent↗
PubMed1998

Genetic effects on ADHD symptomatology in 7- to 13-year-old twins: results from a telephone survey.

The magnitude of genetic and environmental factors and the influence of contrast effects on attention-deficit hyperactivity disorder (ADHD) symptomatology were examined on a sample of 900 twin pairs, aged 7-13, participating in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). In addition, the genetic and environmental correlations between ADHD and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatology were estimated. A series of structural models was applied to maternal ratings from a telephone survey, designed to screen for the three dimensions of ADHD symptomatology (hyperactivity, impulsivity, and inattention) and ODD/CD symptomatology. Model-fitting results suggested that ADHD symptomatology is highly heritable and influenced mostly by additive genetic, specific environmental, and contrast effects. However, this analysis could not exclude with statistical significance additional effects from dominance. The results of the best-fitting bivariate model suggested that the genetic correlation between the two traits is 50% and replicated previous findings of a common genetic factor influencing the comorbidity of ADHD and ODD/CD symptomatologies.

Adolescent↗
PubMed1998

Insertion mutagenesis of the ferric pyoverdine receptor FpvA of Pseudomonas aeruginosa: identification of permissive sites and a region important for ligand binding.

Insertion of an 18-amino-acid-encoding sequence within the fpvA gene identified permissive sites at residues Y350, A402, R451, R521, and R558, consistent with these residues occurring in extramembranous loop regions of the protein. Insertions at R451, R521, and R558 did not adversely affect receptor function, although insertions at Y350 and A402 compromised ferric pyoverdine binding and uptake. The latter region likely contributes to or interacts with the ligand-binding site.

Bacterial Outer Membrane Proteins↗
PubMed1998

Levofloxacin and sparfloxacin: new quinolone antibiotics.

OBJECTIVE: To discuss the pharmacology, pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of levofloxacin and sparfloxacin, two new fluoroquinolone antibiotics. DATA SOURCES: Literature was identified by a MEDLINE search from January 1985 to September 1997. Abstracts and presentations were identified by review of program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy from 1988 to 1996. STUDY SELECTION: Randomized, controlled clinical studies were selected for evaluation; however, uncontrolled studies were included when data were limited for indications approved by the Food and Drug Administration (FDA). In vitro data were selected from comparison trials whenever available. Only in vitro trials that provided data on the minimum inhibitory concentrations required to inhibit 90% of isolates were used. Data from North American studies were selected whenever available. DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions. DATA SYNTHESIS: Levofloxacin and sparfloxacin are active against pathogens frequently involved in community-acquired upper and lower respiratory tract infections, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae. Both compounds have enhanced activity compared with ciprofloxacin against most gram-positive bacteria, including enterococci, streptococci, and staphylococci, and retain good activity against most Enterobacteriaceae and Pseudomonas aeruginosa. Sparfloxacin has greater anaerobic activity than levofloxacin, which is more active than ciprofloxacin or ofloxacin. Although many clinical studies are available only in abstract form, the clinical data demonstrate that these new quinolones are effective for most community-acquired upper and lower respiratory tract infections, urinary tract infections, gonococcal and nongonococcal urethritis, and skin and skin structure infections. FDA-approved indications are limited for both compounds to date. CONCLUSIONS: Levofloxacin and sparfloxacin have improved gram-positive activity compared with that of older fluoroquinolones, and are administered once daily. Sparfloxacin-associated photosensitivity may limit its therapeutic usefulness. Clinical trials confirm that these agents are as effective as traditional therapies for the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis, urinary tract infections, acute gonococcal and nongonococcal urethritis, and skin and skin structure infections.

Absorption↗
PubMed1998

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Basal Ganglia Diseases↗
PubMed1997

Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency.

To evaluate the role of tumor necrosis factor (TNF alpha) in bone loss resulting from estrogen deficiency, the effects of ovariectomy were explored in six-month-old transgenic mice expressing high blood levels of a soluble TNF receptor type I (sTNFR1)-FcIgG3 fusion protein, which neutralizes TNF alpha, and in their nontransgenic littermates used as controls. These transgenic mice were identical to control mice in bone mass (evaluated by bone mineral density and content) and strength. 12 weeks after ovariectomy, the decrease in bone mass and increase in osteocalcin (marker of bone turnover) found in control mice were not observed in transgenic mice, which were not different from sham-operated mice, transgenic or not. This observation suggests a critical role for TNF alpha in the pathogenesis of bone loss induced by estrogen deficiency, a common cause of morbidity in postmenopausal women.

Animals↗
PubMed1997

Identification of a cohort of male and female twins aged 65 years or more in the United States.

In this paper, a method with which to identify a national cohort of elderly twins is proposed. Record linkage algorithms were developed and applied to the > 30 million records contained in the Medicare beneficiary file. The matching algorithm for male/male pairs used race (black or white), last name, date of birth, and state of issuance of the Social Security number. Female/female and male/female pairs were selected with matching on race, date of birth, and the first seven digits of the Social Security number to compensate for the absence of maiden names. A stratified random sample of same-sex and opposite-sex white and black pairs (six groups) were selected and surveyed for determination of the actual prevalence of twins. On the basis of these results, the authors conclude that this method could identify an estimated 18,308 male/male, 7,544 female/female, and 204 male/female pairs of twins aged 65 years or more. This would be the largest sample of older twins ever assembled in the United States and represents a significant new resource for epidemiologic studies of the aging population.

Aged↗
PubMed1997

The Virginia Twin Study of Adolescent Behavioral Development. Influences of age, sex, and impairment on rates of disorder.

BACKGROUND: The Virginia Twin Study of Adolescent Behavioral Development is a cohort-longitudinal epidemiological study that uses the genetic twin design to study the development and maintenance of child psychiatric disorders. We determined the rates of DSM-III-R disorders, disorders with impairment, and age, sex, and comorbidity effects. METHODS: Families of 2762 white twins aged 8 to 16 years participated. Twins and their parents were asked systematically about risk factors and current psychiatric symptoms by means of investigator-based psychiatric interviews and questionnaires. The DSM-III-R diagnoses were made for major depressive disorder, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, oppositional defiant disorder, conduct disorder, and attention deficit hyperactivity disorder. RESULTS: The 3-month point prevalence for any DSM-III-R disorders was 413 per 1000, and that for disorders with associated impairment was 142 per 1000. Emotional disorders with impairment occurred in 89 per 1000, with girls being more commonly affected; behavioral disorders had a prevalence of 71 per 1000, with boys being more frequently affected. The proportion with disorder who also had functional impairment varied across disorders; anxiety and phobic disorders were particularly likely not to be accompanied by impairment. Rates of emotional and behavioral disorders increased over the age range. There was extensive comorbidity among disorders. CONCLUSIONS: The prevalence rates and patterns of findings from this study of twins are consistent with those of other epidemiological studies, supporting previous findings of few differences in rates of psychiatric disorder between twins and singletons. The importance of including measures of functional impairment is evident by its effect on rates of disorder and patterns of comorbidity.

Adolescent↗