Biomedical subjects
A Morrison
Publications and source records attributed to A Morrison.
Injecting-related harm and treatment-seeking behaviour among injecting drug users.
AIMS: This study aims to identify the physical harm associated with injecting drug use and examine the treatment-seeking behaviour of injecting drug users (IDUs). Specific attention is given to the factors associated with presentation and non-presentation of injecting-related problems. DESIGN: Participants were interviewed by research staff using a semi-structured questionnaire, then physically examined by a medical team. SETTING: Needles exchanges in Glasgow. PARTICIPANTS: One hundred and twelve injecting drug users. FINDINGS: Respondents' accounts of their current injecting-related problems were found to be consistent with the clinician's findings, suggesting that IDUs are able to self-diagnose injecting-related harm. However, almost three-quarters had not sought help for these problems. Qualitative data suggest the main reasons for non-presentation, or delayed presentation, of injecting-related problems are normalization of injecting-related harm and a reluctance to attend available services. Almost half of those seeking treatment for injecting-related problems did so during an emergency or crisis. CONCLUSIONS: Low threshold services, such as needle exchanges, may have to take a more proactive stance to encourage injectors to present with injecting-related problems. This may help reduce injecting-related harms, especially the resulting medical complications, which would in turn relieve the pressure on other services such as hospital Accident and Emergency Departments.
Cross-regulatory interactions between Hox genes and the control of segmental expression in the vertebrate central nervous system.
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Impact of specialised paediatric retrieval teams. Comparison of teams is difficult.
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Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury.
UVB irradiation has previously been shown to significantly increase phospholipase activity and prostaglandin synthesis. Because UVB irradiation is a potent oxidative stress, the role of active oxygen species in regulating UV-induced cPLA2 synthesis and phosphorylation was examined. In the present study, irradiation produced a 3-fold increase in synthesis within 6 h following irradiation. Phosphorylation of cPLA2 was also increased to a similar extent. UVB-induced synthesis and phosphorylation of cPLA2 could be inhibited by pretreatment with the antioxidants 2,2,5,7,8-pentamethyl-6-hydroxychromane (50 microM) or N-acetylcysteine (10 mM). Treatment of unirradiated cultures with the potent oxidant tert-butyl hydroperoxide (500 microM) also increased cPLA2 synthesis and phosphorylation, suggesting that oxidative injury is an important regulator of cPLA2 synthesis. Increased synthesis of cPLA2 correlated well with increased [3H]arachidonic acid release, PGE2 synthesis and lipid peroxidation in epidermis after oxidant or UVB treatment. The results indicate that UVB-induced upregulation of cPLA2 synthesis is mediated by UVB-induced formation of free radicals.
Patients as teachers: an integrated approach to teaching medical students about the ambulatory care of HIV infected patients.
Our experience with medical students in a large inner city hospital left us concerned that students' fears affect their ability to learn about and care for HIV-positive people. Therefore, we decided to create an environment in which the students could feel safe exploring their own attitudes and feelings about HIV. To accomplish the goal, we developed a curriculum in the ambulatory care of HIV-positive people. We recruited and trained patients from an HIV support group at our hospital to work with students in one-on-one sessions to teach interviewing, physical exam, and patient counseling skills. As part of a 4-week ambulatory clerkship for third year students we developed a minicourse which included four sessions with didactic and experiential components. The first week consisted of an orientation and group discussion in which patients told the students about what its like to live with HIV. During each of the following three sessions, students met with a preceptor to learn about HIV in an ambulatory care setting. The didactic session was followed by one-on-one student/patient encounters in which students practised skills discussed that week and patients gave them feedback. At the close of the day, the entire group reconvened to discuss what had happened. As a result of this integrated approach, students are experiencing the relational aspects of providing medical care, often for the first and only time. In the process they are learning to take good social histories and are learning how patients with HIV relate to and sometimes reorganize their family and social support systems. Students have the opportunity to get to know, in depth, a relatively healthy person who is living with a chronic, stigmatizing illness. Both patients and students are talking to each other on a level of intimacy that is rare in the training environment. Patients express a new appreciation of their own role and power in the relationship and a new insight into the struggles of the provider. Faculty experience a renewed commitment to the importance of creating an environment where the students can discover for themselves the joy of the connection between doctor and patient. Students have an opportunity to relate to patients not as pathology, but as people with lives before and beyond the medical system. This model is practical and may be useful in teaching about other chronic diseases in the ambulatory setting.
Reprogramming Hox expression in the vertebrate hindbrain: influence of paraxial mesoderm and rhombomere transposition.
The developing vertebrate hindbrain consists of segments known as rhombomeres, which express combinations of Hox genes implicated in specifying segmental identity. Using chick-chick and chick-transgenic mouse graftings, we show that anterior to posterior rhombomere transpositions result in a progressive posterior transformation and coordinate induction of new Hox expression. This shows that hindbrain plasticity is evolutionarily conserved and implies rhombomeres may be undergoing continual assessment of their identities. The nature of the changes is dependent on both the anteroposterior position of the graft and its origin. Transposed somites from specific axial levels and developmental stages have a graded ability to induce changes in Hox expression, indicating that paraxial mesoderm is a source of the environmental signal responsible for the plasticity.
A comparison of variable-dose patient-controlled analgesia with fixed-dose patient-controlled analgesia.
We examined the effect on the quality of analgesia and side effects of increasing the patient control component of morphine patient-controlled analgesia (PCA) by offering the patient a choice of bolus dose sizes. Using a three-button hand piece, patients could choose between 0.5-, 1.0-, and 1.5-mg boluses of morphine (variable-dose PCA, VDPCA). Successful demands were delivered by a modified Graseby 3400 Anaesthesia Pump controlled by a Toshiba T1900 computer. This system was compared with conventional fixed-dose PCA (FDPCA) (1.0 mg of morphine) delivered by a Graseby 3300 PCA Pump. Both treatment groups had a 5-min lockout interval. Sixty patients were randomly assigned to receive either VDPCA or FDPCA after major abdominal gynecological surgery or hip or knee arthroplasty. Treatment groups did not differ in their duration of PCA therapy, total morphine consumption, or time spent with mild or severe oxyhemoglobin desaturation. There were no differences in their ease of controlling pain, satisfaction with pain control, experience of pain on movement, quality of sleep, severity of nausea, or incidence of vomiting. Although the more complex VDPCA technique provides adequate postoperative analgesia, it does not offer any advantage over conventional FDPCA.
Developing evaluation and review skills.
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Paralogous Hox genes: function and regulation.
The Hox homeobox gene family plays a pivotal role in regulating patterning and axial morphogenesis in vertebrates. Molecular characterization of the four Hox clusters has shown that they are evolutionarily related with respect to sequence, organization, and expression, suggesting they arose by duplication and divergence. Transgenic analysis has clearly demonstrated the functional roles of individual genes in a broad range of embryonic tissues, and in compound mutants has addressed the issues of cooperativity and redundancy. There is an emerging picture of the cis-regulatory elements underlying Hox expression, and for the 3' members of the clusters there is a considerable degree of conservation between paralogous genes with respect to their functional roles and regulatory control.
In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer.
Expression of vertebrate Hox genes is regulated by retinoids in cell culture and in early embryonic development. We have identified a 185-bp retinoid-responsive transcriptional enhancer 5' of the human HOXD4 gene, which regulates inducibility of the gene in embryonal carcinoma cells through a pattern of DNA-protein interaction on at least two distinct elements. One of these elements contains a direct repeat mediating ligand-dependent interaction with retinoic acid receptors, and is necessary though not sufficient for the enhancer function. The HOXD4 enhancer directs expression of a lacZ reporter gene in the neural tube of transgenic mouse embryos in a time-regulated and regionally restricted fashion, reproducing part of the anterior neuroectodermal expression pattern of the endogenous Hoxd-4 gene. Administration of retinoic acid to developing embryos causes alterations in the spatial restriction of the transgene expression domain, indicating that the HOXD4 enhancer is also a retinoid-responsive element in vivo. The timing of the retinoic acid response differs from that seen with more 3' Hox genes, in that it occurs much later. This shows that the temporal window of competence in the ability to respond to retinoic acid differs between Hox genes and can be linked to specific enhancers. Mutations in the direct repeat or in a second element in the enhancer affect both retinoid response in culture and developmental regulation in embryos, suggesting that co-operative interactions between different factors mediate the enhancer activity. These data provide further support for a role of endogenous retinoids in regulation and spatial restriction of Hox gene expression in the central nervous system.
Retinoids and Hox genes.
The vertebrate embryonic body plan is constructed through the interaction of many developmentally regulated genes that supply cells with the essential positional and functional information they require to migrate to their appropriate destination and generate the proper structures. Some molecular cues involved in patterning the central nervous system, particularly in the hindbrain, are interpreted by the Hox homeobox genes. Retinoids can affect the expression of Hox genes in cells lines and embryonic tissues; the hindbrain and branchial region of the head are particularly sensitive to the teratogenic effects of retinoic acid. The presence of endogenous retinoic acid, together with the distribution of retinoid binding proteins and nuclear receptors in the developing embryo, strongly suggest that retinoic acid is a natural morphogen in vertebrate development. The molecular basis for the interaction between retinoic acid and the Hox genes has been aided in part by approaches using deletion analysis in transgenic mice carrying lacZ reporter constructs. Such studies have identified functional retinoic acid response elements within flanking sequences of some of the most 3' Hox genes, suggesting a direct interaction between the genes and retinoic acid. Furthermore, as demonstrated using transgenic mice carrying Hoxb-1/lacZ constructs, multiple retinoic acid response elements may cooperate with positive and negative regulatory enhancers to specify pattern formation in the vertebrate embryo. These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes.
Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.
Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.
Comparative analysis of chicken Hoxb-4 regulation in transgenic mice.
We cloned the chicken Hoxb-4 gene and performed in situ analysis to investigate conservation in patterns of expression between the chicken and mouse. The anterior boundaries of expression for both genes in segmented tissues, such as the hindbrain and paraxial mesoderm, map to the same rhombomere (r) (r6/r7) and somite (s) (s6/s7) limits, showing a direct correlation between expression of a specific Hox gene and patterning identical axial structures in both species. Given this similarity in expression we have tested the functional activity of cis-regulatory regions from the chicken Hoxb-4 gene in transgenic mice to identify and map components conserved between the species. We identified enhancers which contain conserved blocks of sequence identity and which are necessary to mediate mesodermal and neural restricted patterns of expression. However, only the neural enhancer directs the proper anterior boundary of expression (r6/r7), indicating that only a subset of the underlying molecular components regulating Hoxb-4 expression are functionally conserved between species.
Massive cutaneous large cell T-cell non-Hodgkin's lymphoma of the pinna.
We report a patient with a cutaneous large cell T-cell non-Hodgkin's lymphoma of the pinna, a condition that has not been reported before. Despite the large dimensions of the tumour, the patient's ear was restored by electron therapy.
Injecting drug use and body mass index.
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The drug-of-choice phenomenon psychological differences among drug users who preferred different drugs.
The Eysenck Personality Questionnaire, the Sensation Seeking Scale, and the Brief Symptom Inventory were administered to 125 recovering drug users with three or more months abstinent from drugs. Subjects were divided according to drug preference: opiates, stimulants, marijuana, alcohol, and a polydrug preference. Opiate users were significantly higher in Susceptibility to Boredom. Alcohol misusers compared to a combined stimulant, opiate, and polydrug group were significantly lower in Extroversion and Susceptibility to Boredom. Subjects raised in drug/alcohol-using families scored significantly higher on Neuroticism and on the Positive Symptom Total of the BSI, and had a higher rate of suicidality.