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Biomedical subjects

B Hamilton

Publications and source records attributed to B Hamilton.

At least 19 recordsLinked to original sources

Reflections on the process of change on acute psychiatric wards during the City Nurse Project.

The intention of this paper is to discuss the process of therapeutic change on two acute psychiatric wards during a research project that aimed to reduce conflict and containment. Analysis of fieldwork notes, reflection, team discussion and supervision. The City Nurse Project successfully reduced patient aggression, self-harm and absconding. This paper reports on the reflections made over the course of the year as changes and developments to acute wards took place. Specifically discussed are the beneficial effects of an action research approach, the role of the City Nurse, support for ward managers, education and training, clinical supervision as well as difficulties and barriers to the overall process of change. At an interim stage of the project, the staff have shown a willingness to engage in efforts to change and improve two acute wards. This paper shows the potential to improve acute wards and produce positive outcomes using a working model.

Behavior Control↗

Troubling 'insight': power and possibilities in mental health care.

This paper critiques the conventional concept of 'insight' within the mental status assessment, seeking to unseat its taken-for-granted definition and the status it has acquired in research and practice. Drawing on social theory, consumer perspective and interdisciplinary research, the paper focuses on the impact of 'thin' biomedical understandings of insight, in disqualifying and demoralizing persons subjected to assessment and at the same time creating punitive scrutineers out of well-intentioned practitioners. Nurses and their mental health colleagues are encouraged to reconsider their reliance on the concept of insight. We entertain the alternative idea that insight is a quality of perception that mental health practitioners can cultivate, to more deeply understand their work, culture and the self.

Attitude of Health Personnel↗

Container fumigation as a quarantine treatment for Anoplophora glabripennis (Coleoptera: Cerambycidae) in regulated wood packing material.

Anoplophora glabripennis Motschulsky, an Asian cerambicid beetle, was first found in the United States in 1996 and was likely introduced into the United States through infested wood packing materials and dunnage. Methyl bromide (MeBr) fumigation is an internationally accepted treatment for such wood-boring beetles, but the use of MeBr is scheduled for reduction or elimination as alternatives become available. The use of MeBr can be reduced by more efficient and technically sound fumigation techniques, including good circulation and proper loading. Concentration x time products (CxT) reported for A. glabripennis in solid wood timbers were used to test estimated doses in container fumigations conducted in Tianjin and Shanghai, China, during years 2002-2003. We found that CxT products observed were generally adequate and would support reduced doses of MeBr at temperatures intermediate (10.0 and 15.6 degrees C) to the Animal and Plant Health Inspection Service schedule of 80 g and 48 g/m3 at > or =4.4 and > or = 21.1degrees C, respectively. The use of fans is recommended, and loading of the containers should never reach 100% to allow for better circulation and desorption. Proper use of fans will allow for better aeration and increase safety to inspectors and consignees of containerized fumigated commodities.

Animals↗

Absent semicircular canals in CHARGE syndrome: radiologic spectrum of findings.

BACKGROUND AND PURPOSE: This paper describes the CT findings that characterize the middle and inner ear anomalies in coloboma, heart defects, choanal atresia, mental retardation, genitourinary, and ear anomalies (CHARGE) syndrome. With this information, neuroradiologists will be better prepared to provide clinically relevant information to their referring physicians regarding this rare syndrome. MATERIALS AND METHODS: CT studies from 13 patients were reviewed by 2 neuroradiologists with Certificate of Additional Qualification. Each ear was counted separately for a total of 26 ears. Middle and inner ear anomalies associated with CHARGE syndrome were categorized. Investigational review board approval was obtained. RESULTS: Twenty of 26 (77%) ears demonstrated cochlear aperture atresia. Four of these ears were evaluated with MR imaging and were found to lack a cochlear nerve. Twenty-one of 26 (81%) cochlea had some form of dysplasia. Six of 26 (23%) round windows were aplastic. Three of 26 (12%) round windows were hypoplastic. Twenty-one of 26 (81%) oval windows were atretic or aplastic. Fifteen of 26 (58%) vestibules were hypoplastic or dysplastic. There were 5 of 26 (19%) enlarged vestibular aqueducts. Twelve of 26 (46%) vestibular aqueducts had an anomalous course. All cases demonstrated absent semicircular canals. Twenty-three of 26 (88%) facial nerve canals had an anomalous course. Four of 26 (15%) tympanic segments were prolapsed. Three of 26 (12%) temporal bones had an anomalous emissary vein referred to as a petrosquamosal sinus. Twenty-one of 26 (81%) middle ear cavities were small. Twenty-three of 26 (93%) ossicles were dysplastic with ankylosis. Three of 26 (12%) internal auditory canals were small. CONCLUSION: The CT findings that correlate to the anomalies of CHARGE syndrome affect conductive as well as sensorineural hearing. Stenosis of the aperture for the cochlear nerve aperture on CT is suggestive of hypoplasia or absence of the cochlear nerve, which has been demonstrated in some cases by MR. Absence of the cochlear nerve would be a contraindication to cochlear implantation.

Abnormalities, Multiple↗

Perspectives of a nurse, a social worker and a psychiatrist regarding patient assessment in acute inpatient psychiatry settings: a case study approach.

This case study explores what informs and organizes the assessment of patients, as undertaken by a nurse, a social worker and a psychiatrist in public, metropolitan, acute mental health service settings. The research data are the transcripts of in-depth interviews with three experienced practitioners, one from each of the three disciplines. The analysis draws on Foucauldian concepts: discourse as constructed through practices of discipline and the gaze. We explored examples of taken-for-granted assessment practices and their interplay with discourse. The findings suggest that participating practitioners use language in assessment in ways that support the powerful discourses of the professional disciplines. The competing discourse of management, associated with industry and economics, is evident in hospital admission processes, dictating the times and places of assessment. Professional and management discourses both effectively marginalize the perspective of another player in assessment, the patient.

Attitude of Health Personnel↗

Patellar tendinosis as an adaptive process: a new hypothesis.

BACKGROUND: Patellar tendinosis (PT), or "jumper's knee" is a common condition in athletes participating in jumping sports, and is characterised by proximal patellar tendon pain and focal tenderness to palpation. Hypoechoic lesions observed in the proximal patellar tendon associated with the tendinosis are typically described as being a result of degenerative change or "failed healing". We propose a new model for the development of the hypoechoic lesion observed in PT, in which the aetiology is an adaptive response to differential forces within the tendon. METHODS: We assessed the clinical, histopathological, and biomechanical literature surrounding the patellar tendon and integrated this with research into the response of tendons to differential forces. RESULTS AND CONCLUSIONS: We propose that the hypoechoic lesion commonly described in PT is the result of adaptation or partial adaptation of the proximal patellar tendon to a compressive load. We postulate that the biomechanics of the patellar-patellar tendon interface creates this compressive environment. Secondary failure of the surrounding tensile adapted tendon tissue may result in tissue overload and failure, with resultant stimulation of nociceptors. We believe that this "adaptive model" of patellar tendinosis is consistent with the clinical and histological findings.

Adaptation, Physiological↗

Tolerability and compliance with risedronate in clinical practice.

The purpose of this study was to determine compliance with dosing instructions, and the prevalence of possible adverse events, when risedronate is used in clinical practice. 219 patients were studied. We found that despite counseling one in four patients were non-compliant with dosing instructions. Those patients who did not stay upright after taking risedronate were more likely to have an adverse event and to discontinue the drug. Adverse events were experienced by 38% of patients, the commonest being gastrointestinal. Upper GI adverse events occurred in 21% of patients. A previous history of upper GI symptoms applied to 44% of patients and significantly more of them experienced upper GI adverse events than those with no history of GI problems. Forty two (19%) of patients taking risedronate stopped therapy due to adverse events, but only ten of these patients had contacted the Osteoporosis Unit about these symptoms. Approximately one third of the patients who experienced adverse events in this study had attempted a rechallenge with the drug. This was worthwhile, however, as in almost 50% of these patients their symptoms settled and they continued with therapy. This study has highlighted the importance of following up patients on long-term osteoporosis medication to ensure optimal compliance. The use of specialized osteoporosis nurses in clinics or primary care to follow up patients needs to be addressed.

Adult↗

Degradation of conjugated linoleic acid isomers in the yeast Saccharomyces cerevisiae.

Propagation of Saccharomyces cerevisiae cells in conjugated linoleic acid (CLA) medium resulted in activation of the transcriptional machinery that responds to fatty acids. Cells utilized efficiently trans-10,cis-12 CLA, but not the corresponding cis-9,trans-11 isomer, probably due to the formation of cis-3,trans-5-dienoyl-CoA intermediates that are recalcitrant to beta-oxidation.

Carbon-Carbon Double Bond Isomerases↗

Saccharomyces cerevisiae Adr1p governs fatty acid beta-oxidation and peroxisome proliferation by regulating POX1 and PEX11.

Saccharomyces cerevisiae Adr1p is essential for fatty acid degradation and peroxisome proliferation. Here, the role of Adr1p was examined with respect to the transcriptional regulation of the Pip2p-Oaf1p dependent genes POX1 and PEX11. POX1 encodes the rate-limiting enzyme of peroxisomal beta-oxidation, acyl-CoA oxidase. The POX1 promoter was shown to contain a canonical Adr1p element (UAS1), within which the oleate response element (ORE) was nested. PEX11 codes for a peroxin that is critical for normal peroxisome proliferation, and its promoter was shown similarly to contain a UAS1-like element overlapping the ORE. Northern analysis demonstrated that transcriptional up-regulation of both POX1 and PEX11 was abolished in adr1 Delta mutant cells, and immunoblotting confirmed that the abundance of their gene products was dramatically reduced. Studies of an overlapping ORE/UAS1 arrangement in the CTA1 promoter revealed synergy between these elements. We conclude that overlapping ORE and UAS1 elements in conjunction with their binding factors Pip2p-Oaf1p and Adr1p coordinate the carbon flux through beta-oxidation with peroxisome proliferation.

Acyl-CoA Oxidase↗

Peroxisomal degradation of trans-unsaturated fatty acids in the yeast Saccharomyces cerevisiae.

Degradation of trans-unsaturated fatty acids was studied in the yeast Saccharomyces cerevisiae. Propagation of yeast cells on trans-9 elaidic acid medium resulted in transcriptional up-regulation of the SPS19 gene, whose promoter contains an oleate response element. This up-regulation depended on the Pip2p-Oaf1p transcription factor and was accompanied by induction of import-competent peroxisomes. Utilization of trans fatty acids as a single carbon and energy source was evaluated by monitoring the formation of clear zones around cell growth on turbid media containing fatty acids dispersed with Tween 80. For metabolizing odd-numbered trans double bonds, cells required the beta-oxidation auxiliary enzyme Delta(3)-Delta(2)-enoyl-CoA isomerase Eci1p. Metabolism of the corresponding even-numbered double bonds proceeded in the absence of Sps19p (2,4-dienoyl-CoA reductase) and Dci1p (Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase). trans-2,trans-4-Dienoyl-CoAs could enter beta-oxidation directly via Fox2p (2-enoyl-CoA hydratase 2 and d-specific 3-hydroxyacyl-CoA dehydrogenase) without the involvement of Sps19p, whereas trans-2,cis-4-dienoyl-CoAs could not. This reductase-independent metabolism of trans-2,trans-4-dienoyl-CoAs resembled the situation postulated for mammalian mitochondria in which oleic acid is degraded through a di-isomerase-dependent pathway. In this hypothetical process, trans-2,trans-4-dienoyl-CoA metabolites are generated by Delta(3)-Delta(2)-enoyl-CoA isomerase and Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase and are degraded by 2-enoyl-CoA hydratase 1 in the absence of 2,4-dienoyl-CoA reductase. Growth of a yeast fox2sps19Delta mutant in which Fox2p was exchanged with rat peroxisomal multifunctional enzyme type 1 on trans-9,trans-12 linolelaidic acid medium gave credence to this theory. We propose an amendment to the current scheme of the carbon flux through beta-oxidation taking into account the dispensability of beta-oxidation auxiliary enzymes for metabolizing trans double bonds at even-numbered positions.

Acyl Coenzyme A↗

The tetratricopeptide repeat domains of human, tobacco, and nematode PEX5 proteins are functionally interchangeable with the analogous native domain for peroxisomal import of PTS1-terminated proteins in yeast.

In the yeast Saccharomyces cerevisiae, beta-oxidation of fatty acids is compartmentalised in peroxisomes. Most yeast peroxisomal matrix proteins contain a type 1C-terminal peroxisomal targeting signal (PTS1) consisting of the tripeptide SKL or a conservative variant thereof. PTS1-terminated proteins are imported by Pex5p, which interacts with the targeting signal via a tetratricopeptide repeat (TPR) domain. Yeast cells devoid of Pex5p are unable to import PTS1-containing proteins and cannot degrade fatty acids. Here, the PEX5-TPR domains from human, tobacco, and nematode were inserted into a TPR-less yeast Pex5p construct to generate Pex5p chimaeras. These hybrid proteins were examined for functional complementation of the pex5delta mutant phenotype. Expression of the Pex5p chimaeras in pex5delta mutant cells restored peroxisomal import of PTS1-terminated proteins. Chimaera expression also re-established degradation of oleic acid, allowing growth on this fatty acid as a sole carbon source. We conclude that, in the context of Pex5p chimaeras, the human, tobacco, and nematode Pex5p-TPR domains are functionally interchangeable with the native domain for the peroxisomal import of yeast proteins terminating with canonical PTS1s. Non-conserved yeast PTS1s, such as HRL and HKL, did not interact with the tobacco PEX5-TPR domain in the two-hybrid system. HRL occurs at the C-terminus of the peroxisomal protein Eci1p, which is required for growth on unsaturated fatty acids. Although mutant pex5delta cells expressing a yeast/tobacco Pex5p chimaera failed to import a GFP-Eci1p reporter protein, they were able to grow on oleic acid. We reason that this is due to a cryptic PTS in native Eci1p that can function in a redundant system with the C-terminal HRL.

Animals↗

Cross-regulation of Hox genes in the Drosophila melanogaster embryo.

Cross-regulation of Homeotic Complex (Hox) genes by ectopic Hox proteins during the embryonic development of Drosophila melanogaster was examined using Gal4 directed transcriptional regulation. The expression patterns of the endogenous Hox genes were analyzed to identify cross-regulation while ectopic expression patterns and timing were altered using different Gal4 drivers. We provide evidence for tissue specific interactions between various Hox genes and demonstrate the induction of endodermal labial (lab) by ectopically expressed Ultrabithorax outside the visceral mesoderm (VMS). Similarly, activation and repression of Hox genes in the VMS from outside tissues seems to be mediated by decapentaplegic (dpp) gene activation. Additionally, we find that proboscipedia (pb) is activated in the epidermis by ectopically driven Sex combs reduced (Scr) and Deformed (Dfd); however, mesodermal pb expression is repressed by ectopic Scr in this tissue. Mutant analyses demonstrate that Scr and Dfd regulate pb in their normal domains of expression during embryogenesis. Ectopic Ultrabithorax and Abdominal-A repress only lab and Scr in the central nervous system (CNS) in a timing dependent manner; otherwise, overlapping expression in the CNS in tolerated. A summary of Hox gene cross-regulation by ectopically driven Hox proteins is tabulated for embryogenesis.

Animals↗

Complications of laparoscopic procedures after concentrated training in urological laparoscopy.

PURPOSE: To increase the safety and efficiency of laparoscopic surgery clinical training programs have been developed to increase the skill and efficiency of urological trainees. We evaluated the impact of dedicated laparoscopy training on the rate and type of complications after trainees entered clinical practice. MATERIALS AND METHODS: Data were obtained from 13 centers where laparoscopy was performed by a single surgeon with at least 12 months of training in urological laparoscopy before clinical practice. Data included training experience, laparoscopic procedures performed after commencing clinical practice and associated complications. Procedures were classified as easy, moderate and difficult. RESULTS: During training each surgeon participated in a mean of 71 cases. In clinical practice a total of 738 laparoscopic cases were performed with the group reporting an overall complication rate of 11.9%. The rate was unchanged when the initial 20, 30 and 40 cases per surgeon were compared with all subsequent cases (12%, 11.9% and 12% versus 11.8 to 12%, respectively). The re-intervention rate was 1.1%. The complication rate increased with case difficulty. Overall and early complication rates attributable to laparoscopic technique in the initial 20, 30 and 40 cases were identical. The most common complications were neuropathy in 13 patients, urine leakage/urinoma in 9, transfusion in 7 and ileus in 5. CONCLUSIONS: The complication rate of surgeons who completed at least 12 months of laparoscopy training did not differ according to initial versus subsequent surgical experience. Intensive training seems to decrease the impact of the learning curve for laparoscopy.

Humans↗

Predicting the function and subcellular location of Caenorhabditis elegans proteins similar to Saccharomyces cerevisiae beta-oxidation enzymes.

The role of peroxisomal processes in the maintenance of neurons has not been thoroughly investigated. We propose using Caenorhabditis elegans as a model organism for studying the molecular basis underlying neurodegeneration in certain human peroxisomal disorders, e.g. Zellweger syndrome, since the nematode neural network is well characterized and relatively simple in function. Here we have identified C. elegans PEX-5 (C34C6.6) representing the receptor for peroxisomal targeting signal type 1 (PTS1), defective in patients with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p-SKL, and a screen using PEX-5 identified interaction partners that were predominantly terminated with PTS1 or its variants. A list of C. elegans proteins with similarities to well-characterized yeast beta-oxidation enzymes was compiled by homology probing. The possible subcellular localization of these orthologues was predicted using an algorithm based on trafficking signals. Examining the C termini of selected nematode proteins for PTS1 function substantiated predictions made regarding the proteins' peroxisomal location. It is concluded that the eukaryotic PEX5-dependent route for importing PTS1-containing proteins into peroxisomes is conserved in nematodes. C. elegans might emerge as an attractive model system for studying the importance of peroxisomes and affiliated processes in neurodegeneration, and also for studying a beta-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes.

Acyl-CoA Oxidase↗

Adr1p-dependent regulation of the oleic acid-inducible yeast gene SPS19 encoding the peroxisomal beta-oxidation auxiliary enzyme 2,4-dienoyl-CoA reductase.

The role of Saccharomyces cerevisiae Adr1p was examined with respect to the transcriptional regulation of the SPS19 gene encoding the peroxisomal beta-oxidation auxiliary enzyme 2,4-dienoyl-CoA reductase. The SPS19 promoter contains both an oleate response element that binds the Pip2p-Oaf1p transcription factor as well as a canonical Adr1p-binding element, termed UAS1(SPS19). Northern analysis demonstrated that transcriptional up-regulation of SPS19 was abolished in cells devoid of Adr1p. Expression of an SPS19-lacZ reporter gene was shown to be quiescent in the adr1Delta mutant and abnormally elevated in cells containing multiple ADR1 copies. UAS1(SPS19) was able to compete for formation of a specific complex between recombinant Adr1p-LacZ and UAS1(CTA1) representing the corresponding Adr1p-binding element in the promoter of the catalase A gene, and to interact directly with this fusion protein. We conclude that in the presence of fatty acids in the medium transcription of SPS19 is directly regulated by both Pip2p-Oaf1p and Adr1p.

Binding Sites↗

Polymorphism and divergence in the beta-globin replication origin initiation region.

DNA sequence polymorphism and divergence was examined in the vicinity of the human beta-globin gene cluster origin of replication initiation region (IR), a 1.3-kb genomic region located immediately 5' of the adult-expressed beta-globin gene. DNA sequence variation in the replication origin IR and 5 kb of flanking DNA was surveyed in samples drawn from two populations, one African (from the Gambia, West Africa) and the other European (from Oxford, England). In these samples, levels of nucleotide and length polymorphism in the IR were found to be more than two times as high as adjacent non-IR-associated regions (estimates of per-nucleotide heterozygosity were 0.30% and 0.12%, respectively). Most polymorphic positions identified in the origin IR fall within or just adjacent to a 52-bp alternating purine-pyrimidine ((RY)n) sequence repeat. Within- and between-populations divergence is highest in this portion of the IR, and interspecific divergence in the same region, determined by comparison with an orthologous sequence from the chimpanzee, is also pronounced. Higher levels of diversity in this subregion are not, however, primarily attributable to slippage-mediated repeat unit changes, as nucleotide substitution contributes disproportionately to allelic heterogeneity. An estimate of helical stability in the sequenced region suggests that the hypervariable (RY)n constitutes the major DNA unwinding element (DUE) of the replication origin IR, the location at which the DNA duplex first unwinds and new strand synthesis begins. These findings suggest that the beta-globin IR experiences a higher underlying rate of neutral mutation than do adjacent genomic regions and that enzyme fidelity associated with the initiation of DNA replication at this origin may be compromised. The significance of these findings for our understanding of eukaryotic replication origin biology is discussed.

Animals↗