Search PubMed⌕ Search

Biomedical subjects

J Kirby

Publications and source records attributed to J Kirby.

At least 37 records · Page 2Linked to original sources

Early results of a non-heartbeating donor (NHBD) programme with machine perfusion.

Freeman Hospital, Newcastle upon Tyne restarted their non-heartbeating donor (NHBD) programme in September 1998 using machine perfusion, due to early poor results with conventional cold storage (45% graft survival, phase II). Since then, 15 NHBD kidneys have been transplanted. The retrieval protocol consisted of in situ perfusion with a double balloon triple lumen cannula in Maastricht category II male donors age range 13-59 years. Mean primary warm ischaemic time was 24.8 min (range 10-44). All kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of total GST (maximum acceptable limit of 200 units/l) and intrarenal vascular resistance (IRVR) was recorded. Fifteen of the 22 kidneys (68.62%) were transplanted. Delayed graft function (DGF) was seen in ten recipients (66.6%), two kidneys had immediate function (IF), one organ was exported, two recipients died of unrelated causes and a further seven kidneys were discarded (two had high tGST, two were infected and three had poor flow characteristics). In phase III, a success rate of 91.7% was thus achieved, which was better than the phase II period (P = 0.027, Fisher 2-tail test). Machine perfusion has been successfully introduced in phase III to the Newcastle NHBD programme and facilitates viability assessment of NHBD kidneys.

Adolescent↗

The impact of cytomegalovirus serology for 7-year graft survival in cadaveric kidney transplantation--the Newcastle experience.

To analyse the contribution of cytomegalovirus (CMV) serology to long-term graft survival in cadaveric kidney transplantation, 404 transplants from a single centre were divided into four subgroups with respect to the combination of donor and recipient CMV antibody status. Graft survival was estimated according to Kaplan-Meier for 1, 3, 5 and 7 years post-transplantation. The single-centre results confirm a negative impact of CMV-positive donor organs for initial graft survival in CMV-negative recipients within the first 3 years after transplantation. However, when 5- and 7-year long-term graft survival was studied, Donor +/Recipient - pairs showed a favourable long-term result, whilst D +/R - pairs had surprisingly a poorer outcome. Therefore, the concept of avoiding transplantation in the D +/R + CMV serology group should be ignored whereas attempts could be made to improve the poor long-term outcome of D +/R + pairs or to reduce its size by organ allocation.

Adolescent↗

Comparison of proteolytic enzymes and glutathione S-transferase levels in non-heart-beating donors' (NHBD) kidney perfusates.

UNLABELLED: In order to identify biochemical markers of kidney damage prior to transplantation, we determined the levels of activity of a range of proteolytic enzymes in kidney perfusate samples from non-heart-beating donor (NHBD) cases. Urinary protease activities have been described as indices of kidney damage in renal disease; their potential as markers of tissue damage in kidneys before transplantation has not been assessed. In an attempt to identify additional/improved biochemical markers, the present study compared the levels of total glutathione S-transferase (GST) with corresponding levels of several proteolytic enzymes in perfusate fluid from machine perfused NHBD kidneys. Proteases were selected to represent factors that may influence enzyme efflux, such as intracellular localization or molecular size. METHODS: Perfusate samples were obtained over an 8-hour period from machine-preserved NHBD kidneys. Protease activities in these samples were determined by fluorometric assays and comparison made with total GST activity. Individual proteases were analysed in the transplanted and non-transplanted kidney groups (discarded on the basis of other viability parameters). RESULTS: A correlation between protease activity and total GST was obtained for only leucyl- and pyroglutamyl aminopeptidase. Furthermore, in the transplanted group, it was possible to set nominal upper limits of activity for alanyl-arginyl- and dipeptidyl IV-aminopeptidase (AP). In the non-transplanted kidney group protease levels were increased above "normal" upper limits for the same enzyme types. By the use of alanyl AP it was possible to discriminate 75% of unsuitable kidneys discarded by the use of other criteria. CONCLUSION: The lack of correlation between total GST and protease activity for most of the enzymes investigated and alanyl AP levels in perfusate samples could be related to differences in cellular localisation, suggesting that assays of alanyl AP may give complimentary biochemical information relating to kidney tissue damage. Quantification of alanyl AP in machine perfusate samples may be a valuable additional independent biomarker of tissue damage.

Endopeptidases↗

Assessment of non-heart-beating donor (NHBD) kidneys for viability on machine perfusion.

UNLABELLED: The shortage of organs has resulted in renewed interest in organs from non-heart-beating donors (NHBD). Viability assessment of such organs may reduce the incidence of delayed graft function and primary non-function. In Phase III of the NHBD programme, introduction of machine perfusion enabled the assessment of these marginal donors. Since then the graft survival has been 88.4% compared with the previous phase where machine perfusion or viability assessment was not done (45.5%). The parameters used were total glutathione S-transferase (GST) in the perfusate, the intrarenal vascular resistance (IRVR) and flow characteristics over time. METHODS: All NHBD kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of the above-mentioned parameters. RESULTS: Forty-two local NHBD kidneys were retrieved and one kidney was imported, of which 19 donors (i.e. 38 kidneys) were of the uncontrolled (category II) donors. After viability assessment on machine perfusion; two kidneys were discarded due to positive tests for syphilis, four kidneys had high total GST levels, five kidneys due to high IRVR and poor flow characteristics and one did not flush on retrieval. Three kidneys were exported after viability tests. In 28 NHBD kidney recipients, immediate graft function was seen in two kidneys, 22 (84.6%) developed delayed graft function. One kidney had primary non-function, and two recipients lost their grafts, due to chronic rejection and renal vein thrombosis. There were two deaths, unrelated to transplantation. Graft survival was achieved in 88.4% (23/26 graft survival in phase III) of cases. CONCLUSION: Machine perfusion and assessment of NHBD kidneys has been successfully introduced to the Newcastle NHBD programme. This approach, using renal transplants from largely category II donors produced a success rate of 88.4% which was significantly better than the phase II period (45.5%) of the program (p=0.023, Fisher 2 tail test).

Humans↗

Prognostic factors for relapse and pelvic lymph node metastases in early stage I adenocarcinoma of the cervix.

OBJECTIVES: The aim of this study was to assess the prognostic significance of local tumor factors in predicting lymph node metastases and/or recurrence in early adenocarcinoma of the cervix. METHODS: Patients were selected from the prospective computerized cervical cancer database of the division of gynecologic oncology. All patients had radical surgery and pelvic lymph node dissection. The study population consisted of all patients with stage I adenocarcinoma having tumor thickness <10 mm. Pathology was re-reviewed to assess histological subtype, depth, volume, grade, and presence of capillary lymphatic space involvement. RESULTS: The study group consisted of 68 patients, with a mean age of 40 years. The median follow-up was 40 months (range 8-102 months). The median tumor depth and volume were 2.8 mm (range 0.3-8.0 mm) and 237 mm(3) (range 0.1-7996 mm(3)), respectively. Twenty-two patients had tumor volumes greater than 600 mm(3), and of these, 5 (23%) patients either had positive pelvic lymph nodes (2) or developed recurrent disease (3) (none node positive) at a median time of 49 months. In comparison, 46 patients (68%) had tumor volumes of less than 600 mm(3), none of whom had positive pelvic lymph nodes or developed recurrence (P<0.005). Only 1 of 20 patients with a depth of invasion <2 mm had a tumor volume >600 mm(3) in comparison to 21 of 48 patients with deeper invasion (P<0.002). CONCLUSION: The incidence of positive pelvic lymph nodes and/or recurrence in this patient population is very low. As all patients with metastatic disease or recurrence had tumor volumes >600 mm(3), volume of disease rather than depth of invasion may be the single most important prognostic factor for the above events. However, many more patients will have to be studied to confirm this.

Adenocarcinoma↗

A comparison of open access endoscopy and hospital-referred endoscopy in a district general hospital.

Open access endoscopy (OAE) is widely used in many hospitals. The aim of this study was to compare the upper gastrointestinal endoscopies referred to as "OGDs" performed under the OAE service and those referred from hospital outpatient clinics (HR) during the initial year in which an OAE service was provided in a district general hospital. A retrospective review of medical records from all patients undergoing OGD during the first year of OAE to identify the waiting time for OGD, the extent of pre-treatment at the time of OGD, the endoscopic findings and the number of endoscopies in which oesophageal or gastric neoplasia was detected. Follow-up endoscopies (n = 41) were excluded. Of 739 OGDs included, 384 (177 male; mean age 48.0 yrs.) were performed under the OAE service, 346 (149 male; mean age 50.7 yrs.) were referred from outpatient clinics and 9 could not be accurately classified. The waiting time was significantly lower in the OAE group compared to the HR group (24.5 v. 29.8 days, p<0.001). Pre-treatment at the time of OGD was significantly more frequent in the OAE group compared to the HR group (295 v. 186, p<0.001). Frequencies of the main endoscopic diagnoses did not differ significantly between the two groups. The OAE service provided faster access to OGD than the HR group and the endoscopic findings were similar in the two groups.

Endoscopy, Digestive System↗

A cysteine desulphurase gene from the cellulolytic rumen anaerobe Ruminococcus flavefaciens.

A gene whose predicted product shows 40-50% sequence identity with the products of nifS genes from nitrogen-fixing bacteria was found downstream from a cellulase gene in a DNA fragment from the cellulolytic rumen anaerobe, Ruminococcus flavefaciens 17. The R. flavefaciens gene product released sulphur from l-cysteine when expressed in Escherichia coli, indicating that the R. flavefaciens NifS enzyme may play a role in sulphuration, perhaps, as in nitrogen-fixing bacteria, supplying sulphur to FeS proteins. Sequences hybridising with the R. flavefaciens 17 nifS-like gene were also detected in R. flavefaciens 007 and in R. albus SY3.

Amino Acid Sequence↗

Reconciling users' needs and formal requirements: issues in developing a reusable ontology for medicine.

A common language, or terminology, for representing what clinicians have said and done is an important requirement for individual clinical systems, and it is a pre-requisite for integrating disparate applications in a distributed telematic healthcare environment. Formal representations based on description logics or closely related formalisms are increasingly used for representing medical terminologies. GALEN's experience in using one such formalism raises two major issues, as follows: how to make ontologies based on description logics easy to use and understand for both clinicians and applications developers; what features are required of the ontology and description logic if they are to achieve their aims. Based on our experience we put forward four contentions: two relating to each of these two issues, as follows: that natural language generation is essential to make a description logic based ontology accessible to users; that the description logic based ontology should be treated as an "assembly language" and accessed via "intermediate representations" oriented to users and "perspectives" adapting it to specific applications; that independence and reuse are best supported by partitioning the subsumption hierarchy of elementary concepts into orthogonal taxonomies, each of which forms a pure tree in which the branches at each level are disjoint but nonexhaustive subconcepts of the parent concept; that the expressivity of the description logic must include support for transitive relations despite the computational cost, and that this computational cost is acceptable in practice. The authors argue that these features will be necessary, though by no means sufficient, for the development of any large reusable ontology for medicine.

Clinical Medicine↗

A prospective study of the predictive value of polymerase chain reaction assay for cytomegalovirus in asymptomatic kidney transplant recipients.

Cytomegalovirus (CMV) infection carries the potential for high morbidity in transplant recipients. The institution of pre-emptive therapy prior to the onset of clinical disease on the basis of CMV-polymerase chain reaction (PCR) is very attractive. We prospectively studied 52 asymptomatic kidney transplant recipients to test the hypothesis that serial CMV-PCR assays during the first 3 months post-transplant would identify patients at risk for CMV disease. Twenty-three patients (44.2%) had positive CMV-PCR tests at least once; 2 (8.6%) developed CMV. None of the 29 patients continuously negative for CMV-PCR developed CMV disease. CMV-PCR status did not influence patient and graft survival or the incidence of acute rejection. We conclude that while a substantial number of kidney transplant recipients become positive for CMV-PCR in the early post-transplant period, only a minority will develop CMV disease. Negative CMV-PCR assay is an accurate negative predictor for CMV disease but the value of CMV-PCR as a guide for pre-emptive anti-CMV therapy in kidney transplant recipients appears limited.

Adult↗

Dockerin-like sequences in cellulases and xylanases from the rumen cellulolytic bacterium Ruminococcus flavefaciens.

Recent analysis of the endA cellulase gene from Ruminococcus flavefaciens 17 has revealed that it encodes a product of 759 amino acids that provides the first example of a multidomain cellulase from a Ruminococcus sp. Following the family 5 catalytic domain in the predicted EndA enzyme is a 282 amino acid domain of unknown function for which no close relationship was found to other protein sequences. However, the C-terminal sequences of EndA contain a 34 amino acid threonine-rich linker connected to an 81 amino acid region, both of which show strong similarities to sequences present in two xylanases from R. flavefaciens 17. A distant relationship is evident between regions of the 80 amino acid sequences of EndA, XynD and XynB and the duplicated 23 amino acid dockerin sequences found in cellulolytic Clostridium sp., suggesting that as in Clostridium sp. these sequences could mediate the binding of enzymatic polypeptides to another component in the cell surface enzyme complex of R. flavefaciens.

Animals↗

The effects of patellar taping on stride characteristics and joint motion in subjects with patellofemoral pain.

Although patellar taping has been reported to be effective in reducing pain, the effects of this procedure on functional outcomes, such as ambulation, have not been documented. The purpose of this study was to compare stride characteristics and joint motion in subjects with patellofemoral pain, with and without the application of patellar taping using the McConnell technique. Fifteen female subjects between the ages of 14 and 41 years with diagnosis of patellofemoral pain participated in this study. Stride characteristics (Stride Analyzer) and sagittal plane joint motion (VICON) were recorded simultaneously during taped and untaped trials of free walking, fast walking, and ascending and descending a ramp and stairs. A repeated measures analysis of variance was used to determine differences between taped and untaped trials. Although subjects reported an average pain reduction of 78% using a visual analogue scale, the only significant change in stride characteristics was an increase in stride length during ramp ascent. Patellar taping did, however, result in a small but significant increase in loading response knee flexion across all conditions tested. We believe this finding demonstrates more willingness by the patellofemoral pain subjects to load the knee joint, thus permitting increased shock absorption, increased quadriceps activity, and tolerance of increased patellofemoral joint reaction force.

Adolescent↗

A compositional approach to nursing terminology.

The development of standardised vocabularies within nursing has been an important research activity for a number of years. Current representations generally take the form of taxonomic vocabularies. These are seen as important as they provide a structure for retrieving and analysing data from automated systems. However, there is increasing evidence to show that traditional taxonomic vocabularies are unsuitable for capturing detailed clinical data. This paper describes how GRAIL (GALEN Representation and Integration Language) is being used within the TELENURSE project to develop a representation of nursing terminology which is sufficiently expressive for documenting detailed clinical data while retaining the benefits of traditional taxonomic vocabularies.

Classification↗

Effects of nitrogen oxides on natural killer cells in glass craftsmen and braziers.

OBJECTIVES: To assess the effect of exposure to nitrogen oxides on peripheral blood natural killer cells. METHODS: Groups of glass craftsmen and braziers exposed to nitrogen oxides and non-exposed controls were studied. Air concentrations of nitrogen oxides were measured. Mononuclear cells isolated from peripheral blood samples were assayed for natural killer cell activity with K562 target cells in a 51Cr release assay and the percentage of natural killer cells (CD16) was measured by flow cytometry. RESULTS: Braziers were exposed to 1.2 ppm nitrogen dioxide and 8.6 ppm nitric oxide and glass craftsmen to 2.9 ppm nitrogen dioxide and 26.5 ppm nitric oxide. The natural killer cell activity of exposed workers was significantly lower than in non-exposed controls (P < 0.05 ANOVA Scheffe test). The percentage of natural killer cells in glass craftsmen was significantly greater than in controls (P < 0.05 ANOVA Scheffe test). Regression of natural killer cell activity against age, smoking habit, number of years worked and current exposure to nitrogen dioxide and nitric oxide gases was not significant. The percentage of natural killer cells was not significantly correlated with age, smoking habit, or numbers of years worked, but was significantly related to air concentrations of nitrogen dioxide (P < 0.01) and nitric oxide (P < 0.001). CONCLUSION: Natural killer cell activity and the percentage of natural killer cells in peripheral blood cells were altered in workers exposed to nitrogen oxides.

Adolescent↗

The PEN&PAD data entry system: from prototype to practical system.

This paper describes some of the issues addressed in the transition of the PEN&PAD from prototype clinical workstation to practical data entry system for use by general practitioners in the UK. Background and motivation of the PEN&PAD and GALEN projects are presented before the operation of the PEN&PAD user interface is described. A number of issues which have arisen in the development of the PEN&PAD Data Entry System are discussed.

Humans↗

Computer-based medical clerking.

All admissions to hospital begin with medical clerking. Thus, it is an essential element of any electronic patient record system. This paper describes some initial experiments to develop a computer-based clerking tool with which doctors can record their clinical observations. The clerking tool uses a structured data entry technique which is based upon an underlying semantic network of clinical terminology. This enables data to be captured and stored in a semantically structured manner, facilitating its use in computer-based record systems and also for audit, management, and decision support purposes. The prototype tool is described, and the evaluation and preliminary results obtained are reported. Initial results indicate that structured data entry is feasible for hospital-based clerking.

Admitting Department, Hospital↗