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Biomedical subjects

J Bowyer

Publications and source records attributed to J Bowyer.

18 recordsLinked to original sources

Characterisation of the guinea pig model of osteoarthritis by in vivo three-dimensional magnetic resonance imaging.

OBJECTIVE: To characterise longitudinal changes in joint integrity and cartilage volume in vivo in the guinea pig spontaneous osteoarthritis (OA) model by magnetic resonance imaging (MRI). METHODS: Guinea pigs knee were imaged in vivo by high-resolution three-dimensional (3D) MRI between the ages of 3 and 12 months. Image analysis was performed to assess qualitative knee joint changes between 3 and 12 months (n=16) and quantitative volumetric changes of the medial tibial cartilage between 9 and 12 months (n=7). After imaging, animals were killed and knees were assessed macroscopically and histologically. RESULTS: From 3 to 6 months qualitative observation by MRI and histopathology indicated localised cartilage swelling on the medial tibial plateau. At 6 months, bone cysts had developed in the epiphysis. At 9 months, we observed by MRI and histopathology, fragmentation of the medial tibial cartilage in areas not protected by the meniscus. Cartilage degeneration had intensified at 12 months with evidence of widespread loss of cartilage throughout the tibial plateau. Segmentation of the MR cartilage images showed a 36% loss of volume between 9 and 12 months. CONCLUSIONS: We have achieved 3D image acquisition and segmentation of knee cartilage in a guinea pig model of chronic OA, which permits measurements previously only possible in man. High resolution and short acquisition time allowed qualitative longitudinal characterisation of the entire knee joint and enabled us to quantify for the first time longitudinal tibial cartilage volume loss associated with disease progression.

Animals↗

Visual complications of proton beam therapy for clival chordoma.

PURPOSE: Combining maximal surgical resection with high-dose proton radiation therapy is reported to be currently the best management of patients with clival chordoma. METHOD: Since 1991, four consecutive patients from our institution with this tumour have been referred for postoperative proton beam radiotherapy. RESULT: We have experienced an unusually high complication rate (50%) of delayed radiation optic neuropathy. This has resulted in profound, bilateral visual loss at 1 and 2 years postproton beam treatment. CONCLUSION: It has served as a reminder that proton beam therapy is not an innocuous treatment option and this devastating complication should be taken into account when discussing the management of clivus chordoma. We postulate whether the optic apparatus is particularly sensitive to proton vs photon damage.

Adult↗

The subjective experience of early postoperative pain following retrobulbar anaesthesia for enucleation and primary orbital implant.

INTRODUCTION: We performed a prospective audit of the level of postoperative pain experienced by patients following enucleation with insertion of a primary orbital implant after preincisional regional retrobulbar anaesthesia using bupivacaine 0.75% with 1:100,000 adrenaline. MATERIALS AND METHODS: An 11-point numerical ranking box scale was used to measure the subjective experience of postoperative pain following enucleation with insertion of a primary orbital implant in 40 patients with uveal melanoma. Surgery was performed under general anaesthesia with a supplementary peroperative retrobulbar injection of bupivacaine 0.75%/adrenaline 1:100,000. Pain scores were measured for the first 8 hours following administration of the block. RESULTS: The sample included 19 female and 21 male patients with a mean age of 66.7 years (31-87). At four hours post block, 80% were still pain free with 17% experiencing only mild to moderate pain (BS-11 = 1-4). Thirty-four (85%), twenty-eight (70%) and twenty-seven (67%) patients remained pain free at 2, 3 and 4 hours, respectively with no additional analgesia. The remainder scored BS-11 of 1-4 in 92% of cases. Twenty percent required supplementary analgesia (paracetemol in 78% cases) by 5 hours and 57% by 8 hours. BS-11 at 8 hours were 0 in 50%, 1-4 in 22% and 5-10 in 10% of patients (17% asleep). No complications using this technique were recorded. DISCUSSION: Using a preincisional retrobulbar injection of bupivacaine with adrenaline, BS-11 pain scores remained low with no or minimal additional analgesia for up to 4 hours post surgery. In combination with oral analgesia, effective pain control was provided in most cases for up to 8 hours post block.

Adult↗

Diverse, yet-to-be-cultured members of the Rubrobacter subdivision of the Actinobacteria are widespread in Australian arid soils.

Phylogenetic analyses of ribosomal RNA gene sequences (rDNAs) retrieved from an Australian desert soil sample (Sturt National Park) revealed the presence of a number of clones which branched deeply from the high GC Gram-positive division line of descent. The most abundant group of these clones were related to Rubrobacter. An oligonucleotide probe was designed to have broad specificity to Rubrobacter and relatives. This probe was used to interrogate eight rDNA libraries representing four distinct land forms within the Australian arid zone. Relative abundance of Rubrobacter-relatives in these samples ranged from 2.6 to 10.2%. Clones from these libraries were selected for sequence analysis on the basis of a heteroduplex mobility assay to maximise the diversity represented in the sample. Phylogenetic analyses of these rDNA clones and Rubrobacter-related clones reported in the literature show strong support for three distinct groups. Database-searching revealed 'Rubrobacteria' were relatively abundant in a number of published soil rDNA libraries but absent from others. A PCR assay for group-1 'Rubrobacteria' was used to test for their presence in 21 environmental samples. Only marine and arid-zone soil samples gave positive PCR results. Taken together these results indicate 'Rubrobacteria' are a widespread group of variable abundance and diversity.

Journal Article↗

Naphthyl ketones: a new class of Janus kinase 3 inhibitors.

Potent inhibition of Janus kinase 3 was found for a series of naphthyl(beta-aminoethyl)ketones (e.g. 7, pIC50 = 7.1+/-0.3). Further studies indicated that these compounds fragment in less than 1 h by retro-Michael reaction in the Jak3 in vitro ELISA assay procedure. The breakdown product of 7, 2-naphthylvinyl ketone (22, pIC50 = 6.8+/-0.3) showed very similar inhibitory activity to 7. Compounds 7 (in neutral buffer) and 22 will be useful pharmacological tools for the investigation of the Janus tyrosine kinase Jak3.

Enzyme Inhibitors↗

Heteroduplex mobility assay as a tool for predicting phylogenetic affiliation of environmental ribosomal RNA clones.

Heteroduplex mobility assay (HMA) of partial 16S rRNA gene fragments was tested as a tool for predicting bacterial phylogenetic relationships. Approximately 400-bp fragments were amplified from a selection of cloned environmental DNAs representing a range of sequence identities and phylogenetic relationships. Heteroduplexes between pairs of sequences were formed by mixing equal amounts of PCR products, denaturing and annealing. Annealed mixes were separated on 8% polyacrylamide gels and silver stained. Heteroduplexes were readily distinguished from reannealed homoduplex and unannealed fragments in all sequences where percentage identity was less than 95%. The heteroduplexes showed retarded electrophoretic migration with respect to homoduplexes. The relative retardation was strongly correlated to the percentage sequence identity between the two strands. The HMA is a useful tool for screening environmental clone libraries to systematically select clones representative of the phylogenetic diversity within the sample, or to selectively retrieve members of a particular phylogenetic group for more detailed study.

Bacteria↗

Lung transplantation and life extension in children with cystic fibrosis.

BACKGROUND: Lung transplantation has been available as therapy for end-stage lung disease since the early 1980s, but survival after transplantation remains poor, with continued controversy as to the survival benefit from the procedure. We examined the effect of lung or heart-lung transplantation on the survival of a cohort of children with cystic fibrosis and severe lung disease. METHODS: Between May, 1988, and May, 1998, 124 children with cystic fibrosis were accepted for lung transplantation. 47 received transplants, 68 died while they awaited organs, and nine remained on the active waiting list. We constructed a proportional-hazards model that used variables of prognostic significance in this population. By including transplant status as a time-dependent covariate, we were able to calculate a hazard ratio for transplantation. Date of entry into the study was the date when children were added to the list for transplantation, and measurements were taken at this time. Children were accepted for transplantation if they had a life expectancy of 2 years or less, a poor quality of life, and no contraindications to transplantation. FINDINGS: After 1 year, 35 (74%) children were still alive; after 5 years 12 (33%) children were alive. The univariate hazard ratio for transplantation was 0.41 (95% CI 0.23-0.74; p=0.003). Transplantation remained significantly associated with survival after correction for differences in age, sex, height-corrected forced expiratory volume in 1 s, minimum oxygen saturation during a 12 min walk, haemoglobin concentration, albumin concentration, and age-corrected resting heart rate (hazard ratio 0.31 [0.13-0.72]; p=0.007). INTERPRETATION: If centres follow our criteria for accepting patients for transplantation, and achieve similar survival after transplantation, they could expect a survival benefit for their patients in line with our results.

Adolescent↗

d-Fenfluramine produces neuronal degeneration in localized regions of the cortex, thalamus, and cerebellum of the rat.

d-Fenfluramine is a potent serotonin (5-HT) reuptake inhibitor/releaser and, until its recent recall, was prescribed as an anoretic agent. This study demonstrates that 10 mg/kg d-fenfluramine i.p., when administered to rats in a warm (27 degrees C) environment, produces neuronal degeneration within select brain regions. Degeneration was detected and localized using a recently developed fluorescent marker of neuronal degeneration, Fluoro-Jade. The most extensive cortical damage was in the anterior cingulate region. In the medial thalamus, degeneration was frequently seen within the intralaminar nuclei, and somewhat less frequently observed within the paraventricular nucleus, the mediodorsal nucleus, and the gelatinosis nucleus. Cerebellar damage occurred primarily in medial Purkinje cells and occasionally in granule cells or basket cells. Degeneration was not observed in either saline-injected control animals or in rats given even higher doses of 25 mg/kg d-fenfluramine but kept in a cooler environment (23 degrees C). The degeneration was clearly most prominent in animals with body temperatures of 41 degrees to 42 degrees C, but this degeneration was not seen in animals given saline that became extremely hyperthermic in a 37 degrees C environment. Behavioral signs such as tremors, myoclonus, rigidity, and splayed legs were seen in all animals with extensive neurodegeneration. The areas damaged by d-fenfluramine, when hyperthermia occurs, could play a role in the expression of the serotonin syndrome. Elevated extracellular 5-HT levels alone are probably not sufficient for neurotoxicity, and additional factors such as hyperthermia, regional specificity of 5-HT receptor subtypes, blood flow, and/or neuronal networks may be involved.

Animals↗

Development of a sedation scoring protocol.

The creation of a research and development post within the Intensive Therapy Unit (ITU) environment at St Helier has provided the opportunity to review all aspects of practice to ensure that the care delivered is evidence-based and not merely rooted in routines and rituals. The first aspect of care to be examined was our sedation practice. It was felt that sedation procedures varied at times and that a research-based protocol was necessary to ensure that patients receive optimal levels of sedation consistently. A 'sedation scoring group' was set up in order to achieve this. Questionnaires were sent to all members of staff and the resulting data used to formulate a sedation scoring system and algorithm as well as a protocol which included information on sedative drugs and the effects of over- and under-sedating patients.

Algorithms↗

The sphenoidal sinus in optic nerve decompression.

Surgical decompression of the orbit may be necessary in dysthyroid patients with compressive optic neuropathy. Two-wall decompression with a trans-antral or a trans-conjunctival approach is commonly used. However, in some patients the initial improvement following this surgical procedure is not maintained. Although this may be due to disease progression, a variant of orbital anatomy can contribute to sub-optimal decompression. We report three cases in which recurrence of compressive optic neuropathy occurred following two-wall decompression. The sphenoidal sinus was placed anteriorly in these patients. Further decompression which included the lateral wall of the sphenoidal sinus resulted in improvement. An endoscopic approach provides superior access and visibility for decompression of the optic nerve into the sphenoidal sinus, and this approach may be the surgical treatment of choice in these cases.

Adult↗

Emergency admission of patients to general surgical beds: attitudes of general practitioners, surgical trainees, and consultants in Liverpool, UK.

OBJECTIVES: To determine (a) whether doctors involved in the process of emergency surgical admission could agree about which patients should be admitted, (b) whether there were consistent differences between doctors in different specialty groups, and (c) whether these opinions were greatly influenced by non-clinical factors. DESIGN: Independent assessment of summarised case histories by three "expert" clinicians (two consultant surgeons and one general practitioner (GP)), by a group of 10 GPs, and by a group of 10 junior and senior surgeons. Experts, but not other observers, scored admissions both independently and as a consensus group. Observers indicated for each patient whether they would admit, would not admit, or were unsure. SETTING: An urban general hospital with teaching status. SUBJECTS: Fifty consecutive patients admitted to the general surgical unit as emergencies during 1995. MAIN OUTCOME MEASURES: Proportion of admissions considered unnecessary or uncertain: agreement between observers on these proportions: effect of social and procedural factors on the admission decision. RESULTS: Between 8 and 34% of admissions were considered unnecessary and 20-38% of unclear necessity. Agreement between the groups of clinicians was not good. GPs and consultant surgeons showed the poorest agreement (kappa = 0.08 to 0.25, 4 comparisons), and the GPs scored a higher percentage of admissions as unnecessary (34 v 8-12%). After discussion, the consensus group achieved good to very good agreement (kappa 0.61-0.84). CONCLUSIONS: Different groups of doctors vary widely in their views about the need for emergency surgical admission. Good agreement can be reached by consensus discussion. GPs are less likely than surgeons to consider emergency surgical admission necessary.

Attitude of Health Personnel↗

Supplementary carrying compared with advice to increase responsive parenting as interventions to prevent persistent infant crying.

OBJECTIVE: To compare two interventions (supplementary carrying, increased parental responsiveness) introduced from birth for their effectiveness in reducing the amounts of crying in general community infants at 2, 6, and 12 weeks age. DESIGN AND PARTICIPANTS: Mothers and infants in newborn wards of maternity hospitals were assigned to carrying intervention, responsiveness intervention, or control groups. Follow-up measures were used to confirm that the interventions were implemented and to determine their effects on infant crying. SETTING AND MEASUREMENTS: Diary measurements completed in the home were employed to measure the aspects of parental behavior targeted by the interventions. Audio recordings, diaries, and questionnaires assessed the amounts the infants cried and the impact of the crying on their mothers and the health services. Sample sizes at 6 weeks of age were 59 (carrying intervention), 57 (responsiveness intervention), and 94 infants (control group). RESULTS: The carrying intervention successfully increased the amounts the infants were carried, particularly while settled, to the target levels. The responsiveness intervention led to more limited increases in carrying and to a modest increase in feeding frequency, but did not affect measures of parental interactiveness and play. No differences in amounts of crying and fussing were found between the three groups of infants on any of the measures. Subsidiary analyses confirmed that the dependent variable (infant fuss/crying) and main independent variable (carrying while settled) were not significantly correlated. CONCLUSION: It is not, at present, possible to recommend either supplementary carrying or increased parental responsiveness as primary, preventative interventions to reduce infant crying.

Crying↗

Objective confirmation of crying durations in infants referred for excessive crying.

Parents commonly seek clinicians' help for infant crying that they judge to be excessive. To date there is no independent evidence whether such babies actually cry more than average. To assess this, maternal diary and 24 hour audiotape recordings of the crying periods of 16 infants referred for excessive crying were compared with equivalent measures of a normative sample. The overall amounts of crying measured by the two methods were similar. The referred infants cried substantially more over 24 hours and in the afternoon and evening. The difference approached significance in the morning but was insignificant at night time. Some qualifications to the findings are indicated.

Crying↗

Molecular modelling studies on the binding of phenylurea inhibitors to the D 1 protein of photosystem II.

A hypothetical molecular model of part of the D 1 protein of photosystem II, based on the analogous portion of the L subunit of the Rhodopseudomonas viridis reaction centre, has been used to study the binding of an extended hydrophobic phenylurea inhibitor (N,N-dimethyl-carbamoyl)4-amino-4'-chloro-trans-stilbene) (I) to the QB site. The inhibitor was fitted by eye into a cleft in the site, and a limited part of the inhibitor/D 1 complex was energy minimized. The gross orientation of the inhibitor placed the dimethylurea moiety towards the predicted binding domain of the plastoquinone head group, and the stilbene moiety directed along the quinone isoprenoid side chain binding domain, suggesting a similar pathway of approach of the two molecules from the membrane into the binding site. Binding interactions of the inhibitor included hydrogen bonds to the side chain hydroxyl of ser 264 and the peptide carbonyl group of ala 251, with the side chain hydroxyl of ser 268 as an alternative ligand. Numerous hydrophobic contacts were also possible. Although phenylureas do not bind to reaction centres of Rp. viridis, many of the binding interactions to D 1 could also be detected in Rp. viridis. However, the beta-CH2, and delta-CO2- groups of glu 212 in Rp. viridis are located in the corresponding region of D 1 occupied by the dimethylurea moiety of the inhibitor in our model of its binding to D 1. This may explain why diuron (DCMU) does not bind to Rp. viridis reaction centres.

Amino Acid Sequence↗

Infant crying patterns in Manali and London.

This study sought to assess the generalizability of the crying 'peak' previously found in Western infants at around 6 weeks of age. To this end, maternal reports and audiorecordings were used to compare the crying patterns of 2, 6 and 12-week-old infants in two cultures expected to differ in their approaches to babycare. As anticipated, Manali mothers were less inclined to leave their babies to cry, took them into their own beds more often, were more likely to be breastfeeding and breastfed their babies to an older age. In spite of these differences, both Manali and London mothers reported their babies to have an evening crying peak, most pronounced at 6 weeks, during this age-range; indicating that this is a general feature of infant development rather than a reflection of Western methods of babycare. Although the maternal reports suggested lower incidences of crying in the Manali infants, the study failed to produce convergent, tape-recorded evidence that this was the case. The definitional and methodological implications of the findings are discussed.

Cross-Cultural Comparison↗