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Biomedical subjects

T Cullen

Publications and source records attributed to T Cullen.

11 recordsLinked to original sources
PubMed2005

Testing models of thalamic dysfunction in schizophrenia using neuroimaging.

Neural models of schizophrenia have implicated the thalamus in deficits of early sensory processing and multimodal integration. We have reviewed the existing neuroimaging literature for evidence in support of models that propose abnormalities of thalamic relay nuclei, the mediodorsal thalamic nucleus, and large-scale cortico-thalamic networks. Thalamic volume reduction was found in some but not all studies. Studies of the early stages of schizophrenia suggest that thalamic volume reduction is present early in the course of the illness. Functional imaging studies have revealed task related abnormalities in several cortical and subcortical areas including the thalamus, suggesting a disruption of distributed thalamocortical networks. Chemical imaging studies have provided evidence for a loss of thalamic neuronal integrity in schizophrenia. There is, at present, inadequate data to support the hypothesis that schizophrenia is associated with abnormalities of sensory relay or association nuclei. There is evidence for a perturbation of cortico-thalamic networks, but further research is needed to elucidate the underlying mechanisms at the cellular and systems levels. The challenges ahead include better delineation of thalamic structure and function in vivo, the combination of genetic and imaging techniques to elucidate the genetic contributions to a thalamic phenotype of schizophrenia, and longitudinal studies of thalamic structure and function.

Animals↗
PubMed1996

Intranigral or intrastriatal injections of GDNF: effects on monoamine levels and behavior in rats.

The present studies were designed to determine whether administration of recombinant human glial cell line-derived neurotrophic factor (rhGDNF) into either the substantia nigra or striatum is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats. Single bolus intracranial injections of rhGDNF at either site increased locomotor activity and decreased food and water consumption and body weight in a dose-dependent manner when compared to vehicle-treated animals. These behavioral responses returned to pre-control levels within 3 weeks post rhGDNF administration. Administration of rhGDNF intranigrally increased dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels of the ipsilateral substantia nigra at 2 and 6 weeks post injection but had no augmenting effects on dopamine or its metabolites in the striatum. Administration of rhGDNF intrastriatally increased DOPAC and HVA levels of the ipsilateral striatum, although striatal dopamine levels were unchanged. Ipsilateral nigral dopamine levels were increased after intrastriatal injection of rhGDNF. The effects of intracranial rhGDNF were not specific to the nigrostriatal dopamine system, since nigrostriatal serotonin, 5-hydroxyindoleacetic acid (5-HIAA), epinephrine and norepinephrine transmitter levels were altered depending on administration route for rhGDNF and dose. Taken together, these data demonstrate long-lasting neurochemical and behavioral changes which suggest that rhGDNF can augment function in adult rat dopamine neurons. Therefore, rhGDNF may have therapeutic potential for Parkinson's disease.

Animals↗
PubMed1996

Glial cell line-derived neurotrophic factor: the lateral cerebral ventricle as a site of administration for stimulation of the substantia nigra dopamine system in rats.

The direct application of recombinant human glial cell line-derived neurotrophic factor (rhGDNF) to the deep structures of the nigrostriatum has been shown previously to augment dopamine function and inhibit loss of substantia nigra neurons in rodent models of Parkinson's disease. The present studies were designed to determine whether administration of rhGDNF into the lateral ventricle, a more clinically accessible intracranial target, is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats. Single bolus intracerebroventricular (i.c.v) injections of rhGDNF increased locomotor activity and decreased food and water consumption and body weight gain in a dose-dependent manner. rhGDNF increased concentrations of dopamine and dopamine metabolites in the substantia nigra, ventral tegmental area and hypothalamus, but had no significant effects in the striatum. rhGDNF had no effect on striatal or substantia nigral serotonin (5-HT) and 5-hydroxyindoleacetic acid levels, but these levels were significantly increased in the ventral tegmental area and hypothalamus respectively. The augmentation of the dopamine and 5-HT systems was detected 2 weeks but not 3 days or 6 weeks after rhGDNF administration. After a repeat injection of i.c.v rhGDNF (6 weeks after the initial injection), substantia nigral dopamine, 5-HIAA and noradrenalin levels were increased. These results indicate that i.c. v administration of rhGDNF has an influence on adult rat dopamine neurons. This route of administration may be useful for stimulating dopamine neurons in Parkinson's disease.

Animals↗
PubMed1996

Frustrating patient visits.

OBJECTIVES: This study, part of a national mail survey of dentist malpractice liability claims, reports the reliability and validity of a new 22-item instrument measuring frustrating patient visits. METHODS: The items were subjected to factor analysis and subscales constructed. Reliability was assessed using Cronbach's alpha. Validity was assessed by comparing subscale scores to self-reports of satisfaction and liability claims. RESULTS: Factor analysis revealed four subscales representing unpleasant feelings, lack of communication, compliance, and practice organization (alpha = 0.60-0.86). Compliance was the most important factor. Subscale scores were related to satisfaction with practice and the proportion of patient visits in the practice that were frustrating to the dentist. Dentists who reported frustrating patient visits as quite typical of their practices were more likely to have had a malpractice liability claim within the last five years. CONCLUSION: This instrument may be of value in detecting patient-dentist communication difficulties that are the precursor to liability claims.

Communication↗
PubMed1995

A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins.

To examine the function of the alpha 6 beta 4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that alpha 6 beta 4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-beta 1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous alpha 6 beta 4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail-less beta 4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less beta 4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head-less mutant beta 4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that alpha 6 beta 4-mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin.

Amino Acid Sequence↗
PubMed1994

Malpractice claims during 1988-1992: a national survey of dentists.

Between 1988 and 1992, almost a quarter of surveyed dentists reported at least one patient complaint to malpractice insurance carriers. The incidence of claims more than doubled in that time and payment size increased nearly five times between 1988 and 1991. These and other trends in professional liability are examined in this national survey of general dentists.

Age Factors↗
PubMed1992

Evaluation of fetal arrhythmias.

Fetal arrhythmias occur in approximately 1 to 3 percent of all pregnancies. Successful management depends on early identification and evaluation. Arrhythmias are classified as irregular, bradycardiac or tachycardiac. With proper monitoring, fetuses with irregular arrhythmias can usually be delivered by family physicians. For fetuses with bradyarrhythmias or tachyarrhythmias, referral to a high-risk specialists for ongoing fetal surveillance and delivery is necessary.

Adult↗
PubMed1981

The faculty and continuing medical education: an attitude study.

Meager or nonexistent faculty reward systems hamper continuing medical education (CME) programs conducted by U.S. medial schools. In light of a growing number of mandatory CME regulations and a consequent increase in physician attendance of CME programs, the need for a competent faculty is apparent. A survey of faculty members designed to ascertain the importance of a faculty reward system was conducted by the University of Washington Division of Continuing Medical Education. Results reveal that faculty members are twice as likely to teach in CME programs outside of the university system as within the system. Survey respondents of nonprofessor rand considered faculty advancement the single greatest source of encouragement to participate in CME programs, yet this participation is seldom considered by the university in evaluations for promotion or tenure. If medical schools are to accept a responsibility for the continuing education of medical professionals, a commitment to provide adequate faculty incentive is imperative.

Attitude↗
PubMed1979

Lack of agreement between subjective ratings of instructors and objective testing of knowledge acquisition in a urological continuing medical education course.

Objective scores from multiple-choice questions before and after a postgraduate course were compared to subjective ratings of the instructors at a 3-day seminar. The objective mean scores after the course were significantly higher than the scores before the course (p less than 0.0001). There was no correlation between test results and subjective ratings of instructors.

Education, Medical, Continuing↗