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Biomedical subjects

G W Stuart

Publications and source records attributed to G W Stuart.

At least 37 records · Page 2Linked to original sources

"Gene-swap knock-in" cassette in mice to study allelic differences in human genes.

Genetic differences in environmental toxicity and cancer susceptibility among individuals in a human population often reflect polymorphisms in the genes encoding drug-metabolizing enzymes (DMEs), drug transporters, and receptors that control DME levels. This field of study is called "ecogenetics", and a subset of this field--concerning genetic variability in response to drugs--is termed "pharmacogenetics". Although human-mouse differences might be 3- to perhaps 10-fold, human interindividual differences can be as great as 20-fold or more than 40-fold. It would be helpful, therefore, to study toxicokinetics/pharmacokinetics of particular environmental agents and drugs in mice containing these "high-" and "low-extreme" human alleles. We hope to use transgenic "knock-in" technology in order to insert human alleles in place of the orthologous mouse gene. However, the knock-in of each gene has normally been a separate event requiring the following: (a) construction of the targeting vector, (b) transfection into embryonic stem (ES) cells, (c) generation of a targeted mouse having germline transmission of the construct, and (d) backcross breeding of the knock-in mouse (at least 6-8 times) to produce a suitable genetically homogeneous background (i.e., to decrease "experimental noise"). These experiments require 1 1/2 to 2 years to complete, making this very powerful technology inefficient for routine applications. If, on the other hand, the initial knock-in targeting vector might include sequences that would allow the knocked-in gene to be exchanged (quickly and repeatedly) for one new allele after another, then testing distinctly different human polymorphic alleles in transgenic mice could be accomplished in a few months instead of several years. This "gene-swapping" technique will soon be done by zygotic injection of a "human allele cassette" into the sperm or fertilized ovum of the parental knock-in mouse inbred strain or by the cloning of whole mice from cumulus ovaricus cells or tail-snip fibroblasts containing the nucleus wherein each new human allele has already been "swapped." In mouse cells in culture using heterotypic lox sites, we and others have already succeeded in gene swapping, by exchanging one gene, including its regulatory regions, with a second gene (including its regulatory regions). It is anticipated that mouse lines carrying numerous human alleles will become commonplace early in the next millennium.

Alleles↗

A meta-analysis of the effectiveness of mental health case management over 20 years.

OBJECTIVE: Meta-analytical methods were used to investigate the effectiveness of case management and to compare outcomes for assertive community treatment and clinical case management. METHODS: Controlled studies of case management published between 1980 and 1998 were identified from reviews and through database searches. The results were quantitatively combined and compared with results of studies of mental health services without case management. Combined effect sizes and significance levels for 12 outcome domains were calculated. Analysis of homogeneity was used to explore differences between models. RESULTS: Forty-four studies were analyzed; 35 compared assertive community treatment or clinical case management with usual treatment, and nine directly compared assertive community treatment with clinical case management. Both types of case management were more effective than usual treatment in three outcome domains: family burden, family satisfaction with services, and cost of care. The total number of admissions and the proportion of clients hospitalized were reduced in assertive community treatment programs and increased in clinical case management programs. In both programs the number of hospital days used was reduced, but assertive community treatment was significantly more effective. Although clients in clinical case management had more admissions than those in usual treatment, the admissions were shorter, which reduced the total number of hospital days. The two types of case management were equally effective in reducing symptoms, increasing clients' contacts with services, reducing dropout rates, improving social functioning, and increasing clients' satisfaction. CONCLUSIONS: Both types of case management led to small to moderate improvements in the effectiveness of mental health services. Assertive community treatment had some demonstrable advantages over clinical case management in reducing hospitalization.

Case Management↗

POU genes in metazoans: homologs in sea anemones, snails, and earthworms.

Previously undescribed POU genes were detected in several invertebrate phyla using redundant primers in a polymerase chain reaction (PCR) that targeted highly conserved sequences encoding known POU-domains. A class IV gene and a gene tentatively assigned to class VI were identified in sea anemones (Condylactis), two distinct class III genes were identified in snails (Biomphalaria), and a single class IV gene was identified in earthworms (Lumbricus). The identification of POU genes in cnidarians, mollusks, and annelids completes a survey of the major metozoan phyla. As POU genes exist in all of these organisms, they appear to be a fundamental characteristic of the metazoan lineage, and may have played a major role in the diversification of these organisms.

Amino Acid Sequence↗

The three-syndrome model of schizophrenia: meta-analysis of an artefact.

In two recent studies, Smith et al. (Smith, D.A., Mar, C.M., Turoff, B.K., 1998. The structure of schizophrenic symptoms: a meta-analytic confirmatory factor analysis. Schizophr. Res. 31, 57-70) and Grube et al. (Grube, B.S., Bilder, R.M., Goldman, R.S., 1998. Meta-analysis of symptom factors in schizophrenia. Schizophr. Res. 31, 113-120) used meta-analysis to examine the syndromal structure of schizophrenia. A limitation of both these studies is that the nine subscale scores from Andreasen's Scales for Assessment of Positive and Negative symptoms formed the basis of the analyses. These nine ratings, only four of which represent positive symptoms, do not adequately respresent the diversity of positive symptoms. A review of studies that examined the correlation between the individual items of these scales failed to support the classification of symptoms into these nine subgroups. Studies that indicated low numbers of syndromes suffered from one or more of the following limitations: (1) samples that were restricted to chronic schizophrenia, (2) exclusion of many items from analysis, and (3) a poor fit of the symptom model to the data. Studies not limited in these ways indicated the presence of at least 11 major dimensions of schizophrenic symptomatology, not including affective symptoms. It is concluded that the three-syndrome model of schizophrenia is largely an artefact of inadequate measurement at the symptom level.

Artifacts↗

Study of stalkers.

OBJECTIVE: This clinical study ws devised to elucidate the behaviors, motivations, and psychopathology of stalkers. METHOD: It concerned 145 stalkers referred to a forensic psychiatry center for treatment. RESULTS: Most of the stalkers were men (79%, N = 114), and many were unemployed (39%, N = 56); 52% (N = 75) had never had an intimate relationship. Victims included ex-partners (30%, N = 44), professional (23%, N = 34) or work (11%, N = 16) contacts, and strangers (14%, N = 20). Five types of stalkers were recognized: rejected, intimacy seeking, incompetent, resentful, and predatory. Delusional disorders were common (30%, N = 43), particularly among intimacy-seeking stalkers, although those with personality disorders predominated among rejected stalkers. The duration of stalking was from 4 weeks to 20 years (mean = 12 months), longer for rejected and intimacy-seeking stalkers. Sixty-three percent of the stalkers (N = 84) made threats, and 36% (N = 52) were assaultive. Threats and property damage were more frequent with resentful stalkers, but rejected and predatory stalkers committed more assaults. Committing assault was also predicted by previous convictions, substance-related disorders, and previous threats. CONCLUSIONS: Stalkers have a range of motivations, from reasserting power over a partner who rejected them to the quest for a loving relationship. Most stalkers are lonely and socially incompetent, but all have the capacity to frighten and distress their victims. Bringing stalking to an end requires a mixture of appropriate legal sanctions and therapeutic interventions.

Adolescent↗

The gap effect and express saccades in the auditory modality.

Latencies of eye movements to peripheral targets are reduced when there is a short delay (typically 200 ms) between the offset of a central visual fixation point and the target onset. This has been termed the gap effect. In addition, some subjects, usually with practice, exhibit a separate population of very short latency saccades, called express saccades. Both these phenomena have been attributed to disengagement of visual attention when the fixation point is extinguished. A competing theory of the gap effect attributes it to disengagement of oculomotor fixation during the temporal gap. It is known that auditory targets are effective in eliciting saccadic eye movements, and also that covert attention operates in the auditory modality. If the gap effect and express saccades are due to disengagement of spatial attention, both should persist in the auditory modality. However, fixation of gaze is largely under visual control. If the gap effect results from disengagement of fixation, then at least a reduced effect should be seen in the auditory modality. Human subjects performed the gap task and a control task in the dark, using auditory fixation points and saccadic targets, on five successive days. Despite this practice, express saccades were not observed. There was a reliable gap effect, but the reduction in saccadic latency was only 17 ms, compared with 32 ms for the same subjects in the visual modality. This suggests that about half the gap effect is due to disengagement of visual fixation. The remainder was not due to non-specific warning effects and could be attributed to offset of the auditory fixation stimulus.

Acoustic Stimulation↗

The treated prevalence of mental disorder amongst immigrants and the Australian-born: community and primary-care rates.

The objective of the study was to explore the relationship between birthplace and the treated prevalence of mental disorder in Australia. Treated prevalence rates were derived from two surveys. These were the 1989-1990 National Health Survey, carried out by the Australian Bureau of Statistics, and the general practice component of a one-day mental health census carried out in the state of Victoria by the authors in 1993. Differences due to the age and sex composition of birthplace groups were controlled statistically. Treated rates of mental disorder, and the use of psychotropic medication, were consistently high amongst those born in Greece, and low amongst those born in the U.K./Ireland or in South East Asia, compared to the Australian-born. Country of birth has a significant effect on the treated prevalence of mental disorder, as reported by patients or their doctor. Further research is needed to reveal the underlying causes of these differences.

Adolescent↗

Object-based visual attention in luminance increment detection?

A cued reaction time task was used to test the hypothesis that there is an 'object-based' component to shifts of attention mediating the detection of luminance increment targets. The test stimulus consisted of two intersecting triangles forming a 'Star of David'. In two experiments, the cue was a brief brightening of one triangle. The target (a bright green dot) appeared on one of the triangles after a delay of 100, 200 or 500 msec. In one experiment, the target was more likely to appear on the cued triangle. In a second experiment, there was no contingency between cue and target. In both cases, reaction times to targets which appeared outside (but not inside) the cued triangle were more than 10 msec longer than other targets, but only at the shorter cue-target delays. This indicates that the attentional system which regulates luminance increment detection cannot select the cued triangle. It appears that the attentional spotlight can be briefly deformed into a triangular shape, and that it is the rapid, fast-decaying and reflexive exogenous system, rather than the slower acting, persistent and voluntary endogenous system, that mediates this effect. A third experiment using a central, symbolic cue showed no significant cue-validity effects, indicating no contribution from the endogenous system. It is concluded that tasks requiring only stimulus detection cannot unequivocally discriminate between spatial and object-based components of attention.

Adolescent↗

Cultural diversity in Australian medical education.

The present study sought to explore the relevance of cultural dimensions and cultural diversity among overseas and local medical students. The main comparison among the fourth year medical students studied was between Asian origin and Anglophone background students. The measures used included cultural variation, reasons for studying medicine, learning approaches and strategies, patient interaction confidence, and medical practices anxieties. Results indicated cultural differences between the two groups, and relationships between cultural variables and, in particular, reasons for studying medicine, learning approaches and strategies, and patient interaction confidence. Results were interpreted according to Hofstede's (1980, 1986) theory of cultural dimensions as they may apply in the educational setting.

Anxiety↗

Professional associations and managed care. How four provider groups are helping their members.

Managed care is facilitating rapid change in the day-to-day practice of many addiction treatment and mental health professionals. It is only natural, therefore, that the associations representing the various disciplines in behavioral healthcare should seek to present short- and long-term plans, advice, and programs for their members. We have asked leaders from four prominent groups to present what their organizations are doing today to assist professionals in adapting to the new realities of the healthcare system. The comments below are by no means conclusive, and are representative of a few efforts and thoughts. It is our mission at Behavioral Healthcare Tomorrow to provide an independent platform for dialogue in the world of mental health and addiction treatment. It is our hope that the proposals and ideas published here stimulate even more planning amongst providers as managed care assertively enters public sector services.

Ethics, Medical↗

Developmental expression of class III and IV POU domain genes in the zebrafish.

Using redundant primers in a PCR based cloning strategy, POU-domain encoding sequences representing two different class III genes (brain-1.1, brain-1.2) and one class IV gene (brain-3.1) were identified in zebrafish. Using the PCR clones to screen a zebrafish gastrula cDNA library, a third class III POU gene was identified (brain-1.0). RT-PCR assays performed with gene-specific primers indicated that the four POU genes exhibited distinct patterns of expression in developing embryos and adult fish. Like their mammalian homologs, the class III genes were expressed early in development and in the adult brain, while the class IV gene was poorly expressed during early development but highly expressed in the adult eye. Since two of the POU PCR clones were obtained from genomic DNA, the fish genes may also be similar to their mammalian homologs in being largely devoid of introns.

Amino Acid Sequence↗

Prevention of bacterial adherence to implant surfaces with a crosslinked albumin coating in vitro.

Titanium surfaces were coated with bovine serum albumin using carbodiimide, a crosslinking agent. The durability of the coated surfaces and the inhibitory effect of the albumin coating on bacterial adherence were tested in vitro for 20 consecutive days at 37 degrees C in phosphate buffered saline, with intermittent agitation. The results showed that only 10% of the coated bovine serum albumin decayed off the surface during the 20-day incubation period. The inhibition rate of the albumin coating on bacterial adherence remained high (greater than 8.5%) throughout the experiment. The results suggested potential use of this crosslinked albumin coating to reduce bacterial adherence and thus the subsequent possibility of prosthetic or implant infection in vivo.

Bacterial Adhesion↗

English language ability and mental health service utilisation: a census.

OBJECTIVE: To explore the relationship between English language proficiency and mental health service utilisation. METHODS: In September 1993, a sample census was conducted of all mental health services in the State of Victoria, including public and private hospital wards, outpatient consultations provided by psychiatrists and clinical psychologists, and primary mental health care provided by general practitioners. Response rates ranged from 37% for monolingual general practitioners (GPs) to 96% for inpatient units. Particular emphasis was placed on patients' English language proficiency and the role played by bilingual clinicians. RESULTS: Over 80% of inpatients received a diagnosis of either dementia or psychosis. This proportion was even greater in the case of patients with English language difficulties. The latter group of patients underutilised specialist outpatient services, and those using these services were less likely to receive psychotherapy than fluent English speakers. They utilised GPs for mental disorder at at least the same rate as other patients. There was a marked preference for bilingual GPs, with 80% of patients with poor English language skills consulting GPs who spoke their native language. CONCLUSION: There appears to be considerable underutilisation of specialist mental health services by patients who are not fluent in English. The liaison-consultation model of psychiatric care may be an effective way of addressing this problem, given the important role already played by billingual GPs in the psychiatric care of those whose native language is not English.

Adolescent↗

POU-domain sequences from the flatworm Dugesia tigrina.

Redundant primers matching well-conserved sequences within vertebrate and invertebrate POU genes were used in the PRC (polymerase chain reaction) to detect three different POU-domain-containing genes within the genome of the flatworm, Dugesia tigrina. Two of these genes appear to be close homologues of class-III POU genes previously identified in Dugesia japonica, while the third represents a new class-III POU gene. Nucleotide sequences encoding highly related POU domains within the two species of planaria exhibited a surprisingly poor degree of shared identity. Since only class-III POU genes have been observed to date in flatworms, these genes may represent ancestral versions of the multiple classes of POU genes that exist in vertebrates, and may play important roles in the development of metazoan nervous tissue.

Amino Acid Sequence↗

Positive and negative symptoms in neuroleptic-free psychotic inpatients.

Andreasen's scales for the assessment of positive (SAPS) and negative (SANS) symptoms and the Brief Psychiatric Rating Scale (BPRS) were administered to a group of 70 neuroleptic-free psychotic inpatients. Individual ratings from the SAPS and SANS, together with the 18-item BPRS, were examined to identify clusters of symptoms. The findings, consistent with our previous studies using medicated patients, did not support a simple positive-negative dichotomy. Independent syndromes representing negative symptoms and thought disorder were apparent, although within the negative syndrome there were three related sub-syndromes of flat affect, alogia and social dysfunctions. Hallucinations and delusions did not form a homogeneous group of symptoms. Paranoia emerged as a distinct syndrome, and the remaining symptoms could be subdivided into hallucinations, grandiose delusions, and 'loss of boundary' delusions (e.g., thought broadcasting, mind reading). These syndromes, with the exception of loss of boundary delusions, which consisted of SAPS delusions alone, correspond to syndromes of psychosis identified by Lorr and his colleagues thirty years ago. It is concluded that the currently popular 'three syndrome' model does not adequately represent the diversity of psychotic symptoms.

Adult↗

Rumor management in nursing systems: role of the psychiatric CNS.

RUMOR MANAGEMENT AND control is particularly important in nursing systems during times of change. In this article, a brief history of the study of rumor and the rumor process is given and applied to nursing, systems thinking and the CNS, and three types of rumor are described. Examples are given and strategies and approaches for managing rumor are prescribed. The first approach, used when a final decision about a planned change has not been made, helps avoid "trickle down" and builds trust and empowerment by soliciting and using input from those who will be affected by the proposed change. The intent of the second approach, used when a decision has been finalized or an event has occurred and rumor has preceded an official announcement, is to debrief from the occurrence or transform the decision. The last approach is used to interrupt a pattern of misinformation and to clarify or inform. The nurse leader or manager must stay in the communication loop and refrain from blaming a speculated source in order to correct information.

Communication↗

The nucleotide sequence of cowpea mottle virus and its assignment to the genus Carmovirus.

The genome of cowpea mottle virus (CPMoV) is a positive ssRNA of 4029 nucleotides with six major open reading frames (ORFs). A non-coding region of 34 nucleotides precedes the first AUG. ORF1 encodes a 25 kDa polypeptide of unknown function and ORF2 encodes a 56 kDa putative RNA replicase. Like other members of carmoviruses, suppression of the amber termination codon of ORF1 would produce a readthrough polypeptide of 83 kDa. ORF3 and ORF4 encode two small proteins of 7.8 and 9.8 kDa, respectively. ORF5 encodes the 40 kDa capsid protein. ORF6 is located within ORF5 but is in a different frame and has no postulated function. CPMoV RNA is blocked at the 5' end and is not polyadenylated at the 3' end. Comparison of the physicochemical properties, genomic arrangement, and predicted amino acid sequences with those of other viruses justify the assignment of CPMoV to the genus Carmovirus, family Tombusviridae.

Amino Acid Sequence↗

Language, culture and psychiatric services: a survey of Victorian clinical staff.

In planning psychiatric services for non-English speaking immigrant communities it is essential to know what resources are available for the implementation of service plans. A survey of 991 professionals from a variety of disciplines working in Victorian state operated inpatient and community psychiatric services demonstrates that, although there is a substantial number of bilingual clinicians working in the system, there is a poor match between languages spoken by patient groups and clinicians, infrequent contact between bilingual clinicians and patients speaking the same language, and inadequate availability of interpreting services. Clinicians' knowledge of cultural issues relevant to assessment and treatment is inadequate, and there is some enthusiasm among clinical staff for remedying this deficiency. Clinicians express the opinions that services to non-English speaking patients are inferior, and clinical outcome is worse than for the Australian-born. There appears to be general support for changes which would seek to more adequately meet the psychiatric service needs of immigrants.

Adult↗