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Biomedical subjects

J Norton

Publications and source records attributed to J Norton.

At least 55 records · Page 3Linked to original sources
PubMed1997

E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles.

A single base substitution of a glutamic acid to an alanine codon 280 was found in the presenilin-1 (PS-1) gene on chromosome 14 in affected individuals in each of seven Colombian early-onset Alzheimer's disease (AD) kindreds. The mutation segregated with disease in kindreds tested. In the largest kindred (C2), the maximum two-point lod score between the mutation and AD was Z = 8.14 at theta = 0. The presence of a single mutation and the common geographic origin, with all families from the state of Antioquia, suggest a founder effect in this population. This finding is supported by the observation of a rare haplotype inherited with AD in all kindreds. These kindreds form the largest collection of AD cases with the same PS-1 mutation and the same educational, environmental, and ethnic background in which to study the phenotypic effect of putative risk factors, such as the epsilon4 allele of apolipoprotein E (ApoE) or head trauma. Of the few AD cases having a history of head trauma, the age of onset was not lowered. No effect of ApoE genotype on the age of onset was detected. Previous investigations of the effect of ApoE genotype on the age of onset were confounded by small patient numbers, familial clustering of ApoE genotypes, and combining data from unrelated families with different mutations.

Adult↗
PubMed1997

Promoting HIV prevention: a problem identification approach to interventions in post-HIV test counselling.

HIV antibody testing now occurs in a wide variety of clinical settings. Counselling at the time of HIV testing involves more than obtaining informed consent and there can be an active role for HIV prevention strategies. Whilst research has not clearly identified the effectiveness of either HIV testing or counselling for HIV prevention, HIV testing does allow for focused discussions with individuals about risk behaviour. Therefore all efforts to refine interventions to enhance HIV prevention must be encouraged. Interventions which encourage clients to examine beliefs about behaviours and relationships can bring about an increase in perceived choices, and thereby lead to changes in behaviour. A model is presented for conducting post-HIV test counselling for use by health professionals involved in HIV testing. Examples of questions and question styles are provided to illustrate this framework which addresses prevailing beliefs and encourages contributions from clients.

AIDS Serodiagnosis↗
PubMed1997

Childhood sexual and physical abuse. Incidence in patients with vulvodynia.

OBJECTIVE: To compare the incidence of sexual and/or physical abuse in women with vulvodynia (chronic, burning vulvar pain in the absence of clear medical findings) as compared to women with chronic vulvar symptoms due to specific, objective vulvar disease and with women from a general dermatology practice. STUDY DESIGN: An invitation to participate in this questionnaire study was sent to 300 women over 18 years of age from a vulvo-vaginal clinic and 280 women from a general dermatology practice. These questionnaires asked for basic demographic information as well as information on childhood sexual experiences and physical abuse. RESULTS: Questionnaires from 89 patients with vulvodynia, 65 patients with chronic vulvar symptoms due to specific, objective vulvar disease and 166 patients from a general dermatology practice were examined. There were no differences as to the incidence of childhood sexual or physical abuse between patients with vulvodynia and either those with general dermatology complaints or those with chronic vulvar symptoms due to objective disease. CONCLUSION: There is no evidence from these data that women with vulvodynia experience a higher incidence of sexual or physical abuse during childhood as compared to women in a general dermatology office or women with chronic vulvar symptoms from specific, observable pathology.

Adult↗
PubMed1997

Neuropsychological function in patients with Gerstmann-Sträussler-Scheinker disease from the Indiana kindred (F198S).

Three patients with Gerstmann-Sträussler-Scheinker disease (GSS) caused by a serine-for-phenylalanine substitution at codon 198 of the prion protein gene (PRNP) were compared to 9 age- and education-matched non-mutation-carriers from the same large Indiana kindred (GSS-IK) on a comprehensive neuropsychological test battery. Clinically significant impairments in intelligence, secondary memory, attention and cognitive processing speed, executive ability, and manual motor skills were noted in 2 patients. The wide range and the severity of the cognitive deficits indicated generalized cerebral dysfunction consistent with global dementia. One patient, symptomatic for less than 1 year, had more selective deficits involving memory, motor skills, and verbal fluency, suggesting early subcortical involvement.

Adult↗
PubMed1997

Repeat HIV testers at a London same-day testing clinic.

OBJECTIVE: To compare the characteristics of repeat HIV testers with first-time testers in a National Health Service HIV testing clinic in London. SUBJECTS AND METHODS: A self-administered questionnaire was distributed to clinic attenders between September 1995 and January 1996. The sample was stratified by gender and sexual orientation. Repeat and first-time testers were compared with respect to recent sexual risk behaviour, reasons for taking the HIV test, condom use, knowledge of sex partner's HIV status, and sociodemographic and psychosocial variables. RESULTS: Of 965 clinic attenders surveyed, 404 (41.9%) reported at least one previous HIV test outside the window period and were classified as repeat testers: homosexual men, 62.5% (178 out of 285); heterosexual men, 35.1% (126 out of 359); heterosexual women, 31.2% (100 out of 321). Among homosexual men, repeat testers were more likely to report the following: two or more partners in the previous 6 months for both unprotected anal sex (25.8 versus 9.3%; P < 0.01) and unprotected oral sex (53.9 versus 37.4%; P < 0.01); ever having had a sexually transmitted disease (STD) other than HIV (49.4 versus 29.0%; P < 0.01); taking the present test "as part of a regular health check' (48.9 versus 28.0%; P < 0.01); and knowing others who had tested for or been infected with HIV. Repeat testing heterosexual men were more likely to report the following: two or more partners in the previous 6 months for unprotected vaginal sex (42.9 versus 30.9%; P < 0.05) and unprotected oral sex (41.3 versus 25.3%; P < 0.01); ever having had an STD other than HIV (31.7 versus 20.6%; P < 0.05); taking the present test "as part of a regular health check' (36.5 versus 26.2%; P < 0.05); and knowing others who had tested for or been infected with HIV. For heterosexual women, repeat testers were more likely to report ever having had an STD other than HIV (25.0 versus 14.5%; P < 0.05), and knowing others who had tested for or been infected with HIV. CONCLUSIONS: Repeat testing was associated with high-risk sexual behaviour, a previous STD, knowledge of others who have tested for or been infected with HIV, and seeking the test as part of a regular health check. Factors contributing to repeat testing are multi-faceted and vary between groups of different sexual orientation. Use of the impact of knowledge of others infected by HIV and the experience of contracting an STD other than HIV may guide the development of HIV counselling interventions aimed at reducing sexual risk behaviour.

Adult↗
PubMed1996

A homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions.

The function of the dominant negative Id (inhibitor of differentiation) helix-loop-helix (HLH) proteins is to dimerize with, and prevent the DNA binding of basic HLH (bHLH) transcription factors. A three-dimensional homology model was constructed for the HLH domain of human Id3 based on the X-ray crystal structures of the E47, MyoD, and Max bHLH proteins. The model showed that, in contrast to bHLH proteins, Id proteins appear able to dimerize without DNA stabilization because of better packing of the hydrophobic core, and the absence of destabilizing polar loop residues and of repulsive positive charges in the monomer interface at the base of the four alpha-helix bundle. This prediction was tested by in vitro protein-binding experiments, which showed that Id3 did indeed self-associate. It also showed that the inability of Id proteins to bind DNA arises from the non-basic, poorly defined, random coil structure of the region corresponding to that responsible for bHLH DNA-binding. A model of the Id1 protein was constructed and revealed a potential site of charge-charge repulsion in the hypothetical homodimer interface that may explain its observed inability to form homodimers.

Amino Acid Sequence↗
PubMed1996

Concept formation vs. logistic regression: predicting death in trauma patients.

This study compares two classification models used to predict survival of injured patients entering the emergency department. Concept formation is a machine learning technique that summarizes known examples cases in the form of a tree. After the tree is constructed, it can then be used to predict the classification of new cases. Logistic regression, on the other hand, is a statistical model that allows for a quantitative relationship for a dichotomous event with several independent variables. The outcome (dependent) variable must have only two choices, e.g. does or does not occur, alive or dead, etc. The result of this model is an equation which is then used to predict the probability of class membership of a new case. The two models were evaluated on a trauma registry database composed of information on all trauma patients admitted in 1992 to a Level I trauma center. A total of 2155 records. representing all trauma patients admitted for more than 24 h or who died in the Emergency Department, were grouped into two databases as follows: (1) discharge status of 'died' (containing 151 records), and (2) any discharge status other than 'died' (containing 2004 records). Both databases contained the same variables.

Artificial Intelligence↗
PubMed1996

Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies.

The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other.

Bipolar Disorder↗
PubMed1995

Amelioration of the behavioral phenotype in weaver mutant mice through bilateral intrastriatal grafting of fetal dopamine cells.

Weaver mutant mice lose more than two-thirds of their nigral dopamine neurons. Behaviorally, weaver homozygotes display tremor, gait instability, and toppling over to the sides after a few steps. The recovery of functional responses was determined in a battery of behavioral tests in weaver mutants after bilateral transplantation of mesencephalic cell suspensions (prepared from wild-type mice) to the striatum. Equilibrium was tested by the time mice were able to stay on a suspended balance rod before falling off. Locomotor coordination was measured by the number of times mice toppled over to the sides as they moved about in an open-field matrix. Locomotor activity was quantified by the number of square crossings in an open-field matrix. Grafted weaver mutants performed significantly better than non-grafted mutant mice in all of these three tasks. The findings clearly demonstrate that bilateral transplants of foetal DA cells enhance motor performance in the weaver model of chronic nigrostriatal DA deficiency.

Animals↗
PubMed1995

Efficacy of vitamin B6 and magnesium in the treatment of autism: a methodology review and summary of outcomes.

Pauling's orthomolecular hypothesis appeared in 1968, stating that some forms of mental illness and disease are related to biochemical errors in the body. Vitamin therapy is believed to be a means of compensating for such errors. There have been few empirical studies on vitamin therapy in individuals with autism. This article presents a critical analysis of the 12 published studies located through an extensive computerized search. Studies were systematically evaluated to provide an objective assessment of empirical evidence supporting the efficacy of vitamin treatment. The majority of studies report a favorable response to vitamin treatment. However, interpretation of these positive findings needs to be tempered because of methodological shortcomings inherent in many of the studies. For example, a number of studies employed imprecise outcome measures, were based on small samples and possible repeat use of the same subjects in more than one study, did not adjust for regression effects in measuring improvement, and omitted collecting long-term follow-up data. Recommendations are offered to assist researchers in designing future investigations.

Autistic Disorder↗
PubMed1995

Fosinopril: pharmacokinetics and pharmacodynamics in congestive heart failure.

Fosinoprilat, the active product of fosinopril, is eliminated by a hepatic pathway, in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors. Congestive heart failure (CHF) may elevate drug plasma concentrations caused by a reduction in steady-state volume of distribution (Vss) and/or an impairment of clearance. This study compared the pharmacokinetics and pharmacodynamics of fosinopril (intravenous and oral) in 10 patients with established CHF and 10 age-, sex-, and weight-matched normal control subjects. There were no statistically significant differences between the patients with CHF and the control patients with respect to maximum drug concentration (Cmax) or area under the plasma concentration-time curve from 0 to infinity. Absolute bioavailability was approximately 29%. Vss was similar, and protein binding was 99% in both groups. The oral half-life of fosinoprilat was significantly longer than the intravenous half-life for both the patients with CHF and normal subjects, without statistically significant differences between the study groups. Median time to reach Cmax occurred at 4 hours in each group and corresponded to maximum angiotensin converting enzyme inhibition, which was essentially complete through 12 hours and markedly reduced through 24 hours. Thus these data indicate that patients with CHF can receive fosinopril without undue increases in fosinoprilat concentrations. This probably is due to the dual excretory pathways.

Administration, Oral↗
PubMed1995

The dextromethorphan defense: dextromethorphan and the opioid screen.

OBJECTIVE: To determine whether a single oral dose of dextromethorphan produces a falsely positive qualitative urine opioid screen. METHODS: A prospective, randomized, triple-blind, placebo-controlled, crossover exposure study design was used. Twenty adult volunteers participated. All were without routine medications, not pregnant or lactating, without known sensitivity to dextromethorphan, and negative for urine toxicologic screening immediately prior to testing. These volunteers underwent three separate urine Enzyme-Multiplied Immunoassay Technique (EMIT) opioid screens. Each screen was performed six hours after the subject had ingested a single liquid medication, either dextromethorphan, codeine, or placebo. Each volunteer took all three medications randomly, at least 72 hours apart. Half of the volunteers took the standard adult dose of dextromethorphan (20 mg), while the other half ingested twice this amount (40 mg). The amounts of codeine (30 mg) and sucrose placebo (10 mL) remained constant. RESULTS: For these young adults (mean age +/- SD = 30.7 +/- 2.8 years), all urine EMIT assays six hours after ingestion of dextromethorphan, at both dosage levels, were negative for opioids and all other drugs. All assays after codeine and placebo ingestion were positive and negative for opioids, respectively. CONCLUSION: Although dextromethorphan is structurally similar to opioid drugs, the ingestion of a single normal (or even twice normal) dose of dextromethorphan is not likely to produce a falsely positive six-hour urine opioid EMIT screen.

Adult↗
PubMed1995

Degeneration of Sertoli and spermatogenic cells in homozygous and heterozygous weaver mice.

In the neurological mutant mouse weaver (wv/wv), the majority of males are infertile due to hypospermatogenesis. Heterozygous weaver mice (wv/+) cease mating successfully when males reach an average age of 3.5 months. The contents of epididymal fluid were scored for the number of sperm and sperm motility in wv/wv, wv/+ and controls. Testes were examined in mice of the three genotypes at various ages using light and electron microscopy. In wv/+ males, sperm counts were significantly lower than in controls and were significantly higher than in wv/wv. The seminiferous epithelium in weaver mice appears depleted soon after puberty and a wide range of degenerative changes was identified in both germ cells and Sertoli cells. Analogous cellular aberrations were detected in heterozygous males, but they appeared at an older age and were not as severe as in wv/wv. We hypothesize that in weaver homo- and heterozygosity the damage of Sertoli cells may induce degeneration of germinal cells and particularly affect the most advanced spermatogenic cells.

Animals↗
PubMed1995

Concept formation vs. logistic regression: predicting death in trauma patients.

This paper discusses two classification models, one based on concept formation and the other using standard logistic regression. The models are first explained in some detail and then evaluated on the same population of trauma patients. The goal of both systems is to predict the outcome of those patients. The results are summarized and explained in terms of differing algorithms of the two models.

Artificial Intelligence↗
PubMed1994

Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts.

The dopamine (DA) uptake system was investigated in the mesostriatal system of normal and weaver mutant mice, which lose mesencephalic DA neurons, as well as in weaver mutants with ventral mesencephalic grafts to the striatum. Assays of [3H]DA uptake in striatal synaptosomal fractions in vitro and autoradiography of [3H]mazindol binding in brain sections were carried out in wild-type mice (+/+) and in the two hemispheres of homozygous weaver mutants (wv/wv) that had received unilateral grafts of mesencephalic cell suspensions to the right side. Net [3H]DA uptake, expressed as pmol/mg-protein/2-min, was on the average 50.6 in the striatum of wild-type mice, 7.9 in the non-grafted, and 10.1 in the transplanted striatum of weaver mutants. [3H]DA uptake in wild-type mice differed significantly from both the grafted and non-grafted weaver striata (P < 0.001). Paired comparisons for [3H]DA uptake between right and left sides of recipient weaver mice showed a significant side effect (P < 0.02), the right side being 28-38% higher than the left side [mean of all individual (R-L)/L values]. The results of amphetamine-induced turning behavior tests were compared with the biochemical findings. Mice with grafts to the right side rotated an average of 22 turns to the left and 7 turns to the right during the five one-minute sessions; the mean value L/(L + R) was 64%. A plot of (L-R) rotations against (R-L) [3H]DA uptake gave a correlation coefficient of 0.552 (P < 0.05), indicating that animals with a strong rotational bias to the left tended to have higher [3H]DA on the right. Similarly, the animals that were used for [3H]mazindol binding autoradiographic studies displayed on the average 72% rotations to the left side. In the [3H]mazindol binding data, non-grafted weaver mutants showed the severest depletion relative to wild-type in the dorsomedial and dorsolateral caudate-putamen (86% and 87%, respectively). Mice with unilateral grafts to the right side showed an increase in [3H]mazindol binding signal in the transplanted side of 40-64% (depending on dorsoventral topography) over the contralateral, non-grafted side. These findings attest to the functional effects of the grafts at the anatomical, biochemical, and behavioral levels. The parallel measurements of motor performance and DA uptake in the same animals offers an index of behavioral recovery as a function of transmitter-related activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Alterations in dopamine and serotonin uptake systems in the striatum of the weaver mutant mouse.

In the striatum of the homozygous weaver mutant mouse (wv/wv), dopamine content, uptake and tyrosine hydroxylase activity are decreased compared to wild-type (+/+) mice. In mice heterozygous for the weaver gene (wv/+), these dopaminergic parameters exhibit only minor reductions compared to +/+ mice. The wv/wv striatum has recently been shown to have an increase in serotonin content. In the present study, the serotonin uptake system of the weaver striatum was investigated. Synaptosomal uptake of [3H] serotonin was determined in the dorsal portion of wv/wv and +/+ striatum, and serotonin uptake sites were examined by the binding of [3H] citalopram in the striatum of wv/wv, wv/+ and +/+ mice. The dopamine uptake system was also investigated in all three genotypes via the binding of [3H] mazindol. Synaptosomal uptake of [3H] serotonin was increased by 79% in the dorsal portion of the wv/wv striatum compared to that seen in the +/+ striatum. The binding of [3H] citalopram was increased by 62% in the dorsolateral and by 111% in the dorsomedial portions of the wv/wv striatum compared to +/+. [3H] Citalopram binding in the wv/+ striatum was also higher than +/+, but this increase did not reach statistical significance. Within the wv/wv striatum, [3H] mazindol binding was almost completely absent (88-89% reduction) in the dorsal portion and severely reduced in the other striatal areas. These data support the notion that the dorsal portion of the wv/wv striatum, which has the severest reduction in dopamine uptake, is hyperinnervated by serotonin fibers.

Animals↗