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Biomedical subjects

J K Moore

Publications and source records attributed to J K Moore.

At least 19 recordsLinked to original sources
PubMed2003

Anaesthesia for day case surgery: a survey of paediatric clinical practice in the UK.

BACKGROUND AND OBJECTIVE: In October 2000, we conducted a national postal survey of day case consultant anaesthetists in the UK to explore the range and variation in practice of anaesthetizing a patient for day case surgery (paediatrics, urology and orthopaedics). This paper reports the findings of this national survey of paediatric day case anaesthetic practice carried out as part of a major two-centre randomized controlled trial designed to investigate the costs and outcome of several anaesthetic techniques during day care surgery in paediatric and adult patients (cost-effectiveness study of anaesthesia in day case surgery). METHODS: The survey used a structured postal questionnaire and collected data on the duration of surgical procedure; the use of premedication; the anaesthetic agents used for induction and maintenance; the fresh gas flow rates used for general anaesthesia; the use of antiemetics; and the administration of local anaesthesia and analgesia. RESULTS: The overall response rate for the survey was 74 and 63% for the paediatric section of the survey. Respondents indicated that 19% used premedication, 63% used propofol for induction, 54% used isoflurane for maintenance, 24% used prophylactic antiemetics and 85%, used a laryngeal mask. The findings of this national survey are discussed and compared with published evidence. CONCLUSIONS: This survey identifies the variation in clinical practice in paediatric day surgery anaesthesia in the UK.

Ambulatory Surgical Procedures↗
PubMed2003

Clinical and economic choices in anaesthesia for day surgery: a prospective randomised controlled trial.

We compared the cost-effectiveness of general anaesthetic agents in adult and paediatric day surgery populations. We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups. Total costs were calculated from individual patient resource use to 7 days post discharge. Incremental cost-effectiveness ratios were expressed as cost per episode of postoperative nausea and vomiting (PONV) avoided. In adults, variable secondary care costs were higher for propofol induction and propofol maintenance (propofol/propofol; p < 0.01) than other groups and lower in propofol induction and isoflurane maintenance (propofol/isoflurane; p < 0.01). In both studies, predischarge PONV was higher if sevoflurane/sevoflurane (p < 0.01) was used compared with use of propofol for induction. In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).

Adolescent↗
PubMed2003

Propofol and halothane versus sevoflurane in paediatric day-case surgery: induction and recovery characteristics.

BACKGROUND: The aim of this study was to compare the induction and recovery characteristics associated with propofol induction and halothane maintenance with sevoflurane anaesthesia in paediatric day surgery. METHODS: In total, 322 children were assigned randomly to i.v. propofol induction and halothane/nitrous oxide maintenance or sevoflurane/nitrous oxide alone. The patients' age, sex, and type of surgery were recorded, as were the times required for anaesthetic induction, maintenance, recovery and time to discharge home. Postoperative nausea and vomiting, and the incidence of adverse events during induction and recovery were also noted. RESULTS: No significant differences were detected in age, sex, type of surgery performed or intraoperative opioid administration. Excitatory movement was more common during induction with sevoflurane. The mean time required for induction with propofol was 3.1 min compared with 5 min in the sevoflurane group (P<0.001). The recovery time was shorter in the sevoflurane group compared with propofol/halothane (23.2 vs 26.4 min, P<0.002). The incidence of delirium in recovery was greater in the sevoflurane group (P<0.001). There was no difference between groups in the time spent on the postoperative ward before discharge home. On the postoperative ward the incidence of both nausea and vomiting was significantly higher in the sevoflurane group (P=0.034). Five children were admitted to hospital overnight, none for anaesthetic reasons. CONCLUSIONS: The increased incidence of adverse events during induction, postoperative nausea and vomiting and postoperative delirium in the sevoflurane group suggests that sevoflurane is not ideal as a sole agent for paediatric day case anaesthesia.

Adolescent↗
PubMed2003

An initiative to reform senior house officer training in histopathology.

Senior house officer schools in histopathology have been established in Leeds, Leicester and Southampton, each training six new recruits each year. Nine hours of protected teaching time is provided each week giving a ratio of apprenticeship learning to formal teaching of 3:1. Evaluations have been very positive. Much of this success is attributed to careful planning and adequate funding. This may be a useful model for other specialties to follow.

Attitude of Health Personnel↗
PubMed2001

The identification of a novel T cell activation state controlled by a diabetogenic gene.

The cyclin-dependent kinase inhibitor p27(kip) regulates the cell cycle at the G(1)-S phase restriction point. S phase entry and cell cycle commitment in peripheral T cells requires p27(kip) degradation, normally initiated by the receipt of costimulatory signals such as those provided by B7.1 or IL-2. We have previously reported that T cells from BioBreeding (BB)-diabetes-prone (DP) rats exhibit decreased costimulatory requirements for activation and cell cycle entry. In the present study, we find that peripheral T cell subsets from BB-DP rats demonstrate activation-like characteristics, including significantly reduced levels of p27(kip) as well as increased levels of proliferating cell nuclear Ag (PCNA). Since our previous studies have established that expression of extracellular activation markers are relatively low in unmanipulated peripheral BB-DP T cells; this p27(low) PCNA(high) phenotype represents a novel activation state. Analyses of T cell subsets from congenic rats demonstrate that this phenotype segregates with the lyp diabetogenic locus and that the p27(low) PCNA(high) phenotype is T cell specific. This p27(low) PCNA(high) phenotype is not seen in medullary thymocytes, but appears abruptly in the recent thymic emigrant population, suggesting that the lyp locus does not act directly on cell cycle regulators but rather alters the interaction between T cells and the peripheral environment. These results provide a biochemical basis for costimulation-independent activation and suggest a mechanism whereby a diabetes susceptibility gene contributes to disease development.

Animals↗
PubMed2001

Cytoarchitectural and axonal maturation in human auditory cortex.

This study followed the maturation of human auditory cortex from the beginning of the second trimester of gestation to young adulthood. Histological and immunohistochemical techniques were used to trace the development of a laminar cytoarchitecture and an adult pattern of axonal neurofilament expression. From the 16th fetal week to the 4th postnatal month, the cortex progresses from a marginal layer and an undifferentiated cortical plate to incipient lamination. Between the 22nd fetal week and the 4th postnatal month, a two-tiered band of neurofilament-immunoreactive axons develops in layer I, but subsequent to the 4th month, the number of immunopositive axons in this layer is greatly reduced. Between the middle of the first year of life and age 3 years, the laminar pattern of cytoarchitecture becomes fully mature and a network of immunostained axons develops in layers VI, V, IV, and IlIc. This axonal plexus in the deep cortical layers continues to increase in density until age 5. Beginning at 5 years of age, a network of neurofilament-positive axons develops in the superficial layers IIIb, IIIa, and II, and by 11-12 years of age, overall axonal density is equivalent to that seen in young adulthood. This extended time span of axonal maturation has implications for the emergence of auditory cortical function.

Adolescent↗
PubMed2001

State programs for medical diagnosis of child abuse and neglect: case studies of five established or fledgling programs.

OBJECTIVE: To describe the programs for medical diagnosis of child abuse and neglect in three states and efforts to establish state-wide programs in two states. To describe common themes and issues that emerged related to the establishment and maintenance of these programs. METHODS: Five states were selected as case studies to represent a range of experience and type of function embodied in programs that address medical diagnosis of child abuse and neglect. Individuals knowledgeable about the programs or efforts to establish state-wide programs in their home states described these in detail. Inductive analysis was used to identify themes and issues that emerged across the states studied. FINDINGS: Themes emerged in three general areas: funding, services, and training. Findings related to funding were: 1) State funding was vital for initiation of statewide programs; 2) Alliances with other groups with parallel interests were successfully used to garner support for child abuse programs; 3) Services needed to be adequately reimbursed to be sustained; 4) Political climate often affected funding. With regard to services we found: 1) There was no optimal way to organize services, but rather many ways that worked well; 2) It was critical to address local service needs; 3) Provision of standardized quality services was essential. With regard to training: 1) Professional training was an integral part of all statewide programs; 2) New technologies, including televideo, have been explored and implemented to assist in training in statewide programs. CONCLUSIONS: Each state has taken a unique approach to programs for the medical diagnosis of child abuse and neglect. However, there are commonalities, particularly among the states that have been successful in establishing and maintaining comprehensive services and/or training.

Child↗
PubMed2001

Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b.

OBJECTIVE: To evaluate the role of topical interferon alfa-2b (IFNalpha2b) in the treatment of conjunctival and corneal intraepithelial neoplasia (CIN). DESIGN: Noncomparative case series. PARTICIPANTS: Five patients with histologically proven CIN or recurrences of proven CIN were studied prospectively. INTERVENTION: After histologic confirmation, patients were given topical recombinant IFNalpha2b (INTRON A, Schering Plough, Kenilworth, NJ) 1 million IU/ml four times a day. Patients were continued on interferon until complete resolution of the tumor had occurred. MAIN OUTCOME MEASURES: Patients were followed clinically and photographically for evidence of tumor resolution. RESULTS: All patients had complete resolution of the CIN lesion on IFNalpha2b. The mean time to clinical resolution was 11.6 weeks (range, 4-22 weeks). The mean follow-up was 17.6 months (range, 7-28 months). One patient had a clinical recurrence of his corneal CIN 1 year after tumor resolution. This patient was retreated, resulting in clinical resolution within 6 weeks, and has been tumor free for 8 months of follow-up.

Administration, Topical↗
PubMed2001

Phenotypic and functional analysis of T-cell recovery after anti-CD3 immunotoxin treatment for tolerance induction in rhesus macaques.

T-cell reduction utilizing specific antibody has been widely used in human transplantation, and is a cornerstone of several tolerance induction strategies in nonhuman primates. We have established a population of long-term tolerant rhesus macaques induced with an anti-CD3epsilon immunotoxin (IT). This treatment effects transient, specific and profound ablation of T cells in blood and lymphoid tissues. In most instances the IT was used in combination with the NF-kappaB inhibitor, 15-Deoxyspergualin. This 2-week long protocol produces a "window of opportunity" for tolerization in which the animal exhibits an enduring quiescent state of unresponsiveness to the allograft, all accomplished without maintenance immunosuppressive drugs. During this induction period, the treated immune system bears some resemblance to that of the neonate, in that T cell numbers are abnormally low and antigen presentation by dendritic cells is precluded by an arrest in their NF-kappaB dependant maturation. In addition, IL-4 production is prominent during and after the tolerance induction interval. For this study we focused on measuring the monkey's ability to repopulate T cells with particular emphasis on the memory T-cell phenotype. Three "memory" phenotypes were utilized; CD3(+)CD45RO(+), CD3(+)CRTH2(+), and CD3(+)CD4(+)CD8(+). All three phenotypes exhibited different patterns of recovery, all of which included transient bursts in their numbers during repopulation. We also estimated thymic activity after T-cell ablation with the use of a newly-described RTE or recent thymic émigré phenotype (a naïve CD8(+)CD103(+) T cell). This marker revealed production of RTE cells including supranormal levels at approximately 6 months post-transplant, implicating thymic function in the repopulation of T-cells. Finally, we measured antibody responses to a panel of antigens (vaccines, environmental antigen, and foreign proteins) that indicated there was no apparent loss of immunologic function during or after the tolerance induction period. Results of studies of T-cell receptor repertoire expression suggest preservation of the pretreatment repertoire, which is consistent with rapid recovery of immune competence to the test antigens. Taken together, these results suggest that while aggressive, this tolerance induction protocol does not appear to incur a prolonged immunologically-compromised state, if at all.

Animals↗
PubMed2001

Myelination of the human auditory nerve: different time courses for Schwann cell and glial myelin.

The goal of this study was to trace the development of myelin in the human auditory nerve. To do this, we used the Woelcke iron-hematoxylin technique to stain myelin sheaths in sections from fetal temporal bones and brain stems. In the cochlea, aggregations of Schwann cells are seen in the modiolus and along the spiral lamina by the 15th fetal week. By the 22nd fetal week, dense arrays of stained Schwann cells are present on auditory nerve axons within the temporal bone. By the 24th fetal week, light myelin sheaths extend up to, but not beyond, the glial junction. Myelin sheaths are not present in the auditory nerve central to the glial junction until the 26th fetal week or later. These results demonstrate a gap of several weeks between the onset of Schwann cell myelination distally and glial myelination proximally. The period between these two events may represent the time of final maturation of the organ of Corti.

Brain Stem↗
PubMed2000

Organization of the human superior olivary complex.

The distinctive morphology of the human superior olivary complex reflects its primate origins, but functional evidence suggests that it plays a role in auditory spatial mapping which is similar to olivary function in other mammalian species. It seems likely that the well-developed human medial olivary nucleus is the basis for extraction of interaural time and phase differences. The much smaller human lateral olivary nucleus probably functions in analysis of interaural differences in frequency and intensity, but the absence of a human nucleus of the trapezoid body implies some difference in the mechanisms of this function. A window on human olivary function is provided by the evoked auditory brainstem response (ABR), including its binaural interaction component (BIC). Anatomical, electrophysiological, and histopathological studies suggest that ABR waves IV and V are generated by axonal pathways at the level of the superior olivary complex. Periolivary cell groups are prominent in the human olivary complex. The cell groups located medial, lateral, and dorsal are similar to periolivary nuclei of other mammals, but the periolivary nucleus at the rostral pole of the human olivary complex is very large by mammalian standards. Within the periolivary system, immunostaining for neurotransmitter-related substances allows us to identify populations of medial and lateral olivocochlear neurons. The human olivocochlear system is unique among mammals in the relatively small size of its lateral efferent component. Some consideration is given to the idea that the integration provided by periolivary cell groups, particularly modulation of the periphery by the olivocochlear system, is an extension of the spatial mapping function of the main olivary nuclei.

Animals↗
PubMed2000

Durable donor-specific T and B cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic allograft nephropathy.

Tolerance induction can prevent acute kidney allograft rejection without chronic immunosuppression. It is uncertain whether specific tolerance can prevent chronic allograft nephropathy (CAN), which involves both nonimmune and immune injury. This report provides evidence that immunologically tolerant macaques, induced with immunotoxin and deoxyspergualin, developed neither acute rejection nor CAN. Long survivors, bearing MHC-mismatched grafts without chronic immunosuppression for 0.8 to 3.4 years, exhibited general immune competence with donor-specific T and B cell tolerance and no functional or histological evidence of CAN. Stringent criteria for tolerance were satisfied by specific prolongation of donor skin grafts with rapid rejection of third-party skin, followed by indefinite acceptance of a second donor kidney graft and establishment of microchimerism. Primate tolerance with documented absence of CAN may give impetus to the clinical application of tolerance.

Animals↗
PubMed1999

A diabetogenic gene prevents T cells from receiving costimulatory signals.

T cell fate following antigen encounter is determined by several intracellular signals generated by the interaction of the T cell with an antigen-presenting cell. In the periphery activation requires T cell receptor signaling (signal one) in combination with costimulatory signals (signal two), usually provided through the cognate interaction of CD28 and B7 molecules. Provision of signal one alone to purified murine peripheral T cells in vitro induces apoptosis or anergy rather than promoting activation. These T cells can be rescued from apoptosis if they are provided with costimulation supplied, for example, by engaging the CD28 co-receptor with an anti-CD28 monoclonal antibody or by adding an exogenous source of interleukin-2. However, a majority of peripheral T cells from autoimmune, diabetes-prone Biobreeding (BB) rats exhibited different responses to these stimuli. T cells from these rats could not be rescued from apoptosis by costimulation. This was not due to the inability of BB-DP T cells to upregulate CD28 and the IL-2 receptor in response to TCR crosslinking. The failure of these costimulatory interactions to rescue BB-DP T cells segregated with the diabetes-susceptibility gene iddm1. Iddm1 in the rat causes peripheral T cell lymphopenia, which is associated with a dramatically shortened peripheral T cell life span. Our results indicate that a diabetogenic gene may contribute to autoimmunity by negating costimulatory signals important for the survival of long-lived peripheral T cells.

Animals↗
PubMed1999

Expression, purification, crystallization and preliminary X-ray diffraction analysis of uracil phosphoribosyltransferase of Toxoplasma gondii.

Recombinant uracil phosphoribosyltransferase (UPRT) enzyme of Toxoplasma gondii was expressed in Escherichia coli and purified from the cell-free extract by a combination of chromatographic steps. The recombinant protein was enzymatically active when tested in an in vitro UPRT assay. The purified protein was crystallized using the hanging-drop vapor-diffusion technique with ammonium phosphate as precipitant. The crystallized protein also exhibited UPRT activity. Crystals diffract to 2.4 A resolution and belong to space group P3121 or P3221 with unit-cell dimensions a = b = 119.9, c = 70.8 A and two molecules per asymmetric unit.

Animals↗
PubMed1999

The case for early identification of hearing loss in children. Auditory system development, experimental auditory deprivation, and development of speech perception and hearing.

Human infants spend the first year of life learning about their environment through experience. Although it is not visible to observers, infants with hearing are learning to process speech and understand language and are quite linguistically sophisticated by 1 year of age. At this same time, the neurons in the auditory brain stem are maturing, and billions of major neural connections are being formed. During this time, the auditory brain stem and thalamus are just beginning to connect to the auditory cortex. When sensory input to the auditory nervous system is interrupted, especially during early development, the morphology and functional properties of neurons in the central auditory system can break down. In some instances, these deleterious effects of lack of sound input can be ameliorated by reintroduction of stimulation, but critical periods may exist for intervention. Hearing loss in newborn infants can go undetected until as late as 2 years of age without specialized testing. When hearing loss is detected in the newborn period, infants can benefit from amplification (hearing aids) and intervention to facilitate speech and language development. All evidence regarding neural development supports such early intervention for maximum development of communication ability and hearing in infants.

Acoustic Stimulation↗
PubMed1999

RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase.

Telomere length is maintained by the de novo addition of telomere repeats by telomerase, yet recombination can elongate telomeres in the absence of telomerase. When the yeast telomerase RNA component, TLC1, is deleted, telomeres shorten and most cells die. However, gene conversion mediated by the RAD52 pathway allows telomere lengthening in rare survivor cells. To further investigate the role of recombination in telomere maintenance, we assayed telomere length and the ability to generate survivors in several isogenic DNA recombination mutants, including rad50, rad51, rad52, rad54, rad57, xrs2, and mre11. The rad51, rad52, rad54, and rad57 mutations increased the rate of cell death in the absence of TLC1. In contrast, although the rad50, xrs2, and mre11 strains initially had short telomeres, double mutants with tlc1 did not affect the rate of cell death, and survivors were generated at later times than tlc1 alone. While none of the double mutants of recombination genes and tlc1 (except rad52 tlc1) blocked the ability to generate survivors, a rad50 rad51 tlc1 triple mutant did not allow the generation of survivors. Thus RAD50 and RAD51 define two separate pathways that collaborate to allow cells to survive in the absence of telomerase.

Adenosine Triphosphatases↗