Convergence in dental education: the DENTED Project.
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Databases as Topic↗
Biomedical subjects
J Scott
Publications and source records attributed to J Scott.
Functional role of ionic regulation of Na+/Ca2+ exchange assessed in transgenic mouse hearts.
Na+/Ca2+ exchange is the primary mechanism mediating Ca2+ efflux from cardiac myocytes during diastole and, thus, can prominently influence contractile force. In addition to transporting Na+ and Ca2+, the exchanger is also regulated by these ions. Although structure-function studies have identified protein regions of the exchanger subserving these regulatory processes, their physiological importance is unknown. In this study, we examined the electrophysiological and mechanical consequences of cardiospecific overexpression of the canine cardiac exchanger NCX1.1 and a deletion mutant of NCX1.1 (Delta680-685), devoid of intracellular Na+ (Na+i)- and Ca2+ (Ca2+i)- dependent regulatory properties, in transgenic mice. Using the giant excised patch-clamp technique, normal ionic regulation was observed in membrane patches from cardiomyocytes isolated from control and transgenic mice overexpressing NCX1.1. In contrast, ionic regulation was nearly abolished in mice overexpressing Delta680-685, indicating that the native regulatory processes could be overwhelmed by expression of the transgene. To address the physiological consequences of ionic regulation of the Na+/Ca2+ exchanger, we examined postrest force development in papillary muscles from NCX1.1 and Delta680-685 transgenic mice. Postrest potentiation was found to be substantially greater in Delta680-685 than in NCX1.1 transgenic mice, supporting the notion that ionic regulation of Na+/Ca2+ exchange plays a significant functional role in cardiac contractile properties.
Animals↗
Co-occurring severe mental illness and substance use disorders: a review of recent research.
OBJECTIVE: Understanding the complex diagnostic and treatment issues posed by the co-occurrence of severe mental illness and substance use disorders has become a necessary exercise in current psychiatric practice. The authors reviewed research studies from the past six years that have contributed to our knowledge about effective assessment, diagnosis, course of illness, and treatment approaches. Research on special populations, including women, persons infected with HIV, and violent patients, is highlighted. METHODS: PsycINFO, Silver Platter, and MEDLINE were used to search for English-language studies published in the United States and other countries. To augment the search, selected bibliographies were reviewed with a focus on clinical standards. Information was sought on epidemiology, screening and assessment strategies, course of illness, models of treatment delivery, and cost of care. RESULTS AND CONCLUSIONS: Although estimates of the prevalence of substance use disorders vary by population, a higher prevalence among persons with severe mental illness has been confirmed. Routine screening for and assessment of substance use disorders among persons with severe mental illness has become the accepted standard of care. The course of severe mental illness is negatively influenced by a substance use disorder, and an integrated approach to the treatment of both disorders is generally accepted to be the most promising treatment strategy. Components of this strategy include harm reduction, treatment in stages, motivational interviewing, cognitive-behavioral interventions, and modified 12-step self-help groups.
Adult↗
Services to families of adults with schizophrenia: from treatment recommendations to dissemination.
OBJECTIVE: Data from the Schizophrenia Patient Outcomes Research Team project were examined to determine the extent to which families of adults with schizophrenia receive services and whether training staff in the provision of family services increases service availability. METHODS: For patients with a diagnosis of schizophrenia, paid claims for family therapy were identified in 1991 in a nationally representative sample of Medicare data and one state's Medicaid data. In a field study in two states, 530 patients were asked about services received by their families. A quasiexperimental dissemination of a family intervention was done at nine agencies; staff at four agencies received a standard didactic presentation, and staff at five received that standard presentation paired with intensive training. RESULTS: In the representative national Medicare sample of 15,425 persons with schizophrenia, .7 percent (N=108) had an outpatient claim for family therapy. This figure was 7.1 percent in the Medicaid sample of 5,393 persons with schizophrenia in one state. Of the 530 patients in the field study who reported having contact with their families, 159 (30 percent) reported that their families had received information, advice, or support about their illness, and 40 (8 percent) responded that their families had attended an educational or support program. At the four agencies where staff received only didactic training, no changes in family services were found after one year. Three of the five agencies where staff participated in intensive training enhanced their family services. CONCLUSIONS: A minority of families of persons with schizophrenia receive information about the illness from providers. Implementation of model family interventions is possible with considerable technical assistance. A gap exists between best practices and standard practices for families of persons with schizophrenia.
Adult↗
Case managers' and clients' perspectives on a representative payee program.
OBJECTIVE: Clients with severe and persistent mental illnesses often require a representative payee to help manage benefit funds. This study compared the perceptions of clients and clinical case managers about the benefits of and problems with the representative payee relationship. METHODS: Fifty-four clients receiving assertive community treatment completed an interview that assessed satisfaction with their experience of having a representative payee and the resulting impact on their substance use, budgeting, and housing. The clients' clinical case managers completed a similar questionnaire. Analyses examined associations between providers' and clients' responses and clients' gender, race, diagnosis, previous experience with a representative payee, and duration of the current representative payeeship. RESULTS: Clients and case managers recognized benefits of the representative payeeship in the areas of housing, substance use, and budgeting. Although little evidence was found that the payeeship pervasively interfered with the therapeutic relationship, 44 percent of case managers reported incidents in which clients verbally abused them over management of their funds. Clients' satisfaction with the representative payeeship was initially low but grew over time. Longer duration of the current payeeship and clients' previous experience with representative payeeship were associated with greater satisfaction and fewer problems. Case managers overestimated clients' initial satisfaction and underestimated their current satisfaction. CONCLUSIONS: Findings suggest that both mental health professionals and clients value the representative payee process as helpful in improving outcomes, although the benefits of the arrangement may be more evident with time and experience.
Case Management↗
Abbott IMx homocysteine assay: significant interference by 3-deazaadenosine.
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Artifacts↗
Morphological and functional characteristics of acinar atrophy and recovery in the duct-ligated parotid gland of the rat.
Although acinar atrophy occurs frequently in salivary diseases, the relationship between structural changes and functional decrements is not well-established, and the potential for recovery of histological and functional integrity has not been wholly quantified. We aimed, therefore, to develop further our understanding of pathological acinar atrophy. Stensen's duct was ligated for periods up to six weeks and, in separate experiments, was de-ligated after two weeks and allowed to recover for up to two weeks. Qualitative and quantitative histological analyses were carried out. Additionally, the ability of enzymatically dispersed cells from ligated and de-ligated glands to respond to neurohormonal stimuli was also measured. The results confirmed that totally obstructed glands undergo a rapid, progressive severe atrophy amounting to absolute losses of over 85% of acinar tissue by two weeks. Acinar shrinkage and cell losses through apoptosis accounted for the glandular atrophy. Remaining intralobular epithelia consisted of extremely atrophic acini and numerous duct-like structures with intermediate forms. Dispersed cells from atrophic glands exhibited agonist-induced release of chloride similar to normal. Together, these structural-functional results confirm the persistent viability of acinar-like cells in the obstructed gland and suggest that the duct-like structures are derived from surviving atrophic acini. De-ligated glands exhibited a near-normal recovery of structure by two weeks. Their enzymatically dispersed cells responded normally to agonist stimulation. The results support the view that pathological atrophy is largely similar to physiological atrophy, providing a mechanism for acinar cell survival under adverse conditions, with the possibility of eventual recovery.
Animals↗
Neuropsychological function in euthymic patients with bipolar disorder.
BACKGROUND: The assumption that patients with bipolar disorder make a full inter-episode recovery has been challenged by limited evidence that suggests that neuropsychological dysfunction in bipolar disorder may persist beyond episodes of illness. AIMS: To test the hypothesis that patients with euthymic bipolar disorder show neuropsychological impairment. METHOD: A battery of neuropsychological tests (assessed attention, working memory, learning and executive function) was administered to three matched groups of subjects: good-outcome patients with bipolar disorder (n = 21); poor-outcome patients with bipolar disorder (n = 20); controls (n = 20). All patients were clinically euthymic, although some had low levels of depressive symptoms. RESULTS: Patients performed worse than controls on a number of neuropsychological tests. When age, premorbid IQ and depressive symptoms were controlled for, the results indicated impairment of executive function. CONCLUSIONS: These findings provide good evidence for the existence of neuropsychological impairment in patients with euthymic bipolar disorder, although the possible effect of medication should not be overlooked. This may be of clinical relevance and raises questions about the course and outcome of the illness.
Adult↗
Activity and kinetics of dissociation and transfer of amphotericin B from a novel delivery form.
Recently it has been demonstrated that moderate heat treatment of Amphotericin B/deoxycholate solutions (HAmB-DOC ) leads to a therapeutically interesting supramolecular rearrangement that can be observed by significant changes in light scattering, CD, and absorbance. In this study, we continue the investigation of the physical properties of this new form by evaluating the activity and kinetics of dissociation and dispersion of HAmB-DOC and AmB-DOC in saline, serum, and in model mammalian or fungal lipid biomimetic membrane vesicles. Stopped-flow spectrophotometry combined with singular value decomposition (SVD) and global analysis were used to resolve the components of this process. The dissociation kinetics for both states are complex, requiring multi-exponential fits, yet in most cases SVD indicates only two significant changing species representing the monomer and the aggregate. The kinetic mechanism could involve dissociation of monomers from coexisting spectroscopically similar but structurally distinct aggregates or sequential rearrangements in supramolecular structure of aggregates. Rate constants and amplitudes of dissociation from aggregates to monomer in buffer, whole serum, 10% cholesterol, and ergosterol membrane vesicles are generally greater for AmB-DOC, demonstrating its greater kinetic instability. In addition, at comparable low concentrations, HAmB-DOC and AmB-DOC are nearly equally active at promoting cation selective permeability in ergosterol-containing membranes; however, HAmB-DOC is much less active against mammalian mimetic cholesterol-containing vesicles, despite a higher level of self-association, supporting previous observations that there exists a specific "toxic aggregate" structure.
Amphotericin B↗
The effect of lithium on calcium-induced changes in adrenocorticotrophin levels.
The calcium receptor (CaR) plays a central role in calcium (Ca) sensing by the parathyroid gland and other organs, including the brain. Chronic lithium (Li) therapy causes a significant alteration in Ca-sensing by the CaR-expressing parathyroid chief cells through an unknown mechanism, shifting the PTH set-point (the level of Ca that half-maximally suppresses PTH secretion) to the right. Ca is known to stimulate ACTH levels in normal subjects, and baseline ACTH levels are increased in patients with bipolar disorder. Because the stimulation of ACTH secretion by Ca likely involves the CaR, the aim of this study was to investigate the effects of Li on Ca-induced changes in ACTH levels, using Ca and citrate infusions in seven Li-treated patients and seven controls. During the Ca infusion, increments in serum-ionized Ca concentration (Ca(i)) were accompanied by increments in ACTH levels that were significantly greater in the Li-treated group, P = 0.014, by ANOVA. Also, cortisol levels increased significantly in the Li-treated, but not the control group, during the Ca infusion, P < 0.0001. There was a statistically significant shift in the midpoint of the Ca(i)/ACTH curve, to the right, in the Li-treated group, compared with the controls (P = 0.042), that was largely caused by an effect of Li on Ca(i). However, for comparable levels of Ca(i), there were no significant differences in the levels of ACTH between the two groups. Therefore, within the physiological range of Ca, there was no effect of Li on Ca(i)-induced change in ACTH levels.
Adrenocorticotropic Hormone↗
Longitudinal changes in bone density in hyperparathyroidism.
Primary hyperparathyroidism (HPTH) is a known risk factor for cortical bone loss. The primary objective of this study was to examine the time course and location of changes in bone mass within the first year after parathyroidectomy (PAX). The secondary goal was to evaluate the efficacy of combined estrogen therapy and parathyroidectomy in postmenopausal women. Thirty-two subjects with primary HPTH participated in a prospective, longitudinal study for at least 1 yr. Twenty-seven subjects underwent PTX, while five received no therapy (control). Among the PTX patients, 21 were postmenopausal women, and 8 of these women also received estrogen. Subjects had serial measurements of parathyroid hormone levels, serum chemistries, and bone density at multiple sites. Among all PTX patients, lumbar spine, hip, and whole body bone mineral content increased significantly (3.8-6%; p < 0.005) at 12 mo, with most of the increments observed by 3 mo. In postmenopausal women, estrogen treatment resulted in higher increments in the femoral neck (8.6 +/- 2% vs 4.9 +/- 1.2%, respectively; p = 0.07) and the whole body (6 +/- 2% vs 2.4 +/- 1.6%, respectively; p = 0.07). In HPTH, early and generalized increments in bone mass follow PTX, and the combination of surgery with estrogen therapy may be superior to surgery without estrogen treatment. A randomized, controlled trial including PTX, estrogen, and a combination of the two is needed to determine the optimal therapy in postmenopausal women.
Bone Density↗
Quality of life and treatment satisfaction after the addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens in treatment-experienced patients with HIV infection.
BACKGROUND: Assessments of health-related quality of life and treatment satisfaction were conducted as part of a randomised, double-blind, placebo-controlled 52-week trial conducted in Canada, Australia, Europe, and South Africa (CAESAR). The Medical Outcomes Study HIV Health Survey (MOS-HIV) was self-administered during 3 scheduled clinic visits (baseline, week 28 and the end-of-treatment/withdrawal visit). A single question was used at the end of treatment to assess patient satisfaction with study medications. METHODS: Patients were randomly allocated to receive placebo, lamivudine (150 mg twice daily) or lamivudine (150 mg twice daily) plus loviride (100 mg 3 times daily) in addition to their current treatment regimen, which could be either zidovudine monotherapy, or zidovudine in combination with didanosine or zalcitabine at standard dosages. RESULTS: Statistically significant differences across treatment groups were demonstrated for the Physical and Mental Health Summary scores, and for 5 of 10 MOS-HIV subscales (physical functioning, vitality, cognitive functioning, general health perceptions, social functioning). These differences favoured the lamivudine and lamivudine plus loviride groups over the placebo group (p < 0.05). No significant difference was found between the 3 treatment groups with regard to the percentages of patients who were satisfied with their study medication. CONCLUSION: The results suggest that, for treatment-experienced patients with HIV infection and CD4+ counts < 250 cells/mm3, the addition of lamivudine or lamivudine plus loviride to antiretroviral regimens containing zidovudine maintained patient-reported mental and physical health.
Acetamides↗
Molecular modelling of the biosynthesis of the RNA-editing enzyme APOBEC-1, responsible for generating the alternative forms of apolipoprotein B.
We discovered in 1987 that the shorter form of apolipoprotein B (B48) synthesized in the intestine is due to the action, previously unrecognized in mammalian cells, of an mRNA-editing process, and more recently we demonstrated that this was due to a specific enzyme (APOBEC-1) with cytidine deaminase activity. We show here, by sequence alignment, molecular modelling and mutagenesis, that APOBEC-1 is a cytidine deaminase, responsible for editing apoB mRNA, and that is related in crystal structure to the cytidine deaminase of Escherichia coli (ECCDA). The two enzymes are both homodimers with composite active sites formed with loops from each monomer. In the sequence of APOBEC-1, three gaps compared with ECCDA match the size and contour of the minimal RNA substrate. We propose a model in which the asymmetric binding of one active site to the substrate cytidine which is positioned by the downstream binding of the product uridine and that this helps to target the other active site for deamination.
APOBEC-1 Deaminase↗
Toxicology and pharmacokinetics of intravesical gemcitabine: a preclinical study in dogs.
More active and well-tolerated agents are needed for the treatment of superficial bladder cancer. This study investigated intravesical gemcitabine to establish the toxicology and pharmacokinetics necessary for clinical trials. Beagle dogs (in groups of 2; n = 6) received 100 mg, 350 mg, or 1 g of drug by intravesical administration on alternate days three times/week for 4 weeks. Animals were observed for clinical signs of toxicity; gemcitabine levels and peripheral blood counts were taken three times weekly. The dogs were euthanized, and a full necropsy was performed at days 1 and 14 after the last dose. Intravesical gemcitabine was given at 100 mg (n = 2), 350 mg (equivalent to the 1000 mg/m2 human dose; n = 3), and 3.5 g (n = 1). i.v. gemcitabine was given at 350 mg (n = 2). Plasma samples drawn at time points up to 8 h were analyzed for systemic absorption and clearance of drug. Doses of 100 and 350 mg were well tolerated with no clinical side effects. Necropsies revealed normal bone marrow cellularity and normal bladder histology. At 1 g, signs of severe clinical toxicity were evident, and after only three doses, necropsies demonstrated severe bone marrow hypoplasia, cystitis, and intestinal necrosis. At all intravesical doses, significant systemic absorption was seen. The T1/2 (+/- SD) for intravesical and i.v. administration of 350 mg was 328 (+/-6.8) min and 99.3 (+/-5.2) min, respectively (P<0.001). Intravesical gemcitabine is well tolerated and has no direct bladder toxicity at doses up to 1000 mg/m2. Higher doses result in gastrointestinal, bladder, and bone marrow toxicity.
Absorption↗
Dinner series to incorporate EPEC Project. Education for Physicians on End-of-Life Care.
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Education, Medical, Continuing↗
The impact of training in problem-based interviewing on the detection and management of psychological problems presenting in primary care.
BACKGROUND: The vast majority of mental health problems present to primary care teams. However, rates of under-diagnosis remain worryingly high. This study explores a GP-centred approach to these issues. AIM: To examine the impact of training in problem-based interviewing (BPI) on the detection and management of psychological problems in primary care. METHOD: The detection and management of psychological problems by 10 general practitioners (GPs) who had received PBI training 12 months earlier was compared with that of 10 control GPs matched for age, sex, clinical experience, and practice setting; and had originally applied for, but had not been able to attend, BPI training. Consecutive attendees at one randomly selected surgery undertaken by each GP were invited to participate in the study. Two hundred and eighty patients living in Newcastle upon Tyne met inclusion criteria and gave informed consent. The presence or absence of psychological problems was assessed using patient self-ratings on the 28-item version of the General Health Questionnaire (GHQ) and blind independent observer ratings of the brief Present State Examination (PSE). Patient satisfaction with interviews was rated using the Medical Interview Satisfaction Scale (MISS). After each consultation, the GPs (blind to subjective and observer ratings) recorded their assessment and management of the patients' problems on a Practice Activity Card (PAC). RESULTS: In comparison with control GPs, index GPs demonstrated significantly greater sensitivity in the detection of psychological problems in the GHQ-PAC ratings. The absolute decrease in misdiagnosis of GHQ cases was 9% and of PSE cases was 15%. Patients meeting GHQ criteria for caseness were more likely to be prescribed psychotropic medication by an index GP than compared with a control GP. Length of interview did not differ between the groups and mean scores on the MISS suggested that patients attending PBI-trained GPs, compared with control GPs, were as satisfied or slightly more satisfied with their consultation. CONCLUSION: In comparison with control GPs, PBI-trained GPs were better at recognizing and managing psychological disorders. The potential benefits of BPI training are discussed in light of other attempts to improve mental health skills in primary care.
Adult↗
Publishing in dental education: a history and systematic analysis.
The aim of this paper is to provide an overview of the development of dental education and its present status as evidenced by published articles in the dental literature. The method used has been a stratified sampling review of 3 journals. The analysis of articles in the British Dental Journal (BDJ) covers 4 periods between 1903 and 1994. A separate study of more recent trends sampled the Journal of Dental Education (J Dent Educ) at 5-year intervals between 1977 and 1997 as well as all the articles published in the European Journal of Dental Education (EJDE) in 1997-98. The long-term survey (BDJ) indicated that the subject of dental education was already being seriously addressed in the early years of this century although articles were few. There was a progressive increase in the number and types of article published over the period of the analysis. Many of the issues addressed in the first half of the century were similar to controversial topics in the present day. In the analysis of recent years (J Dent Educ 1977-1997) the number of articles devoted to strictly educational subjects fell to be replaced by articles only indirectly related to dental education. No consistent pattern was discernible in the type of articles published. There was a paucity of review articles throughout the period. Research articles were proportionally higher in the middle years of the period of the study. Both in the J Dent Educ and the EJDE, the highest proportions of articles were those concerned with curriculum, teaching methods, assessment and quality issues. The paper advocates more evidence-based studies, qualitative research and systematic reviews of the dental educational literature. It concludes that there is a need and an opportunity for expansion of both the quantity and quality of published articles in dental education.
Education, Dental↗
Secondary structure for the apolipoprotein B mRNA editing site. Au-binding proteins interact with a stem loop.
The C to U editing of apolipoprotein B (apoB) mRNA converts a glutamine codon in apoB100 mRNA into a stop translation codon thereby generating apoB48. The catalytic subunit of the editing enzyme, APOBEC-1, is an RNA-binding cytidine deaminase that requires auxiliary factors for the editing of apoB mRNA. Computer modeling and ribonuclease probing of the wild-type and mutant apoB RNA substrates reveal a stem loop at the editing site. This structure incorporates the essential sequence motifs required for editing. The localization of the edited cytidine within the loop suggests how it could be presented to the active site of APOBEC-1 for deamination. We have identified 43/45 kDa proteins from chick enterocytes and show evidence for their involvement in auxiliary editing activity. p43/45 demonstrates preferential binding to AU-rich RNA and to the Caauuug motif that forms the loop and proximal stem of the apoB mRNA.
APOBEC-1 Deaminase↗