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D Andrews

Publications and source records attributed to D Andrews.

At least 19 recordsLinked to original sources
PubMed2004

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Animals↗
PubMed2003

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗
PubMed2003

Evaluation of VITEK 2 for analysis of Enterobacteriaceae using the Advanced Expert System (AES) versus interpretive susceptibility guidelines used at Dynacare Kasper Medical Laboratories, Edmonton, Alberta.

OBJECTIVE: To evaluate the applicability and adaptability of the bioMérieux VITEK 2 Advanced Expert System (AES) to the customized interpretive susceptibility guidelines used at Dynacare Kasper Medical Laboratories (DKML). METHODS: Three hundred isolates of Enterobacteriaceae (not more than 30% Escherichia coli) were tested on the VITEK 2 system and the API 20E for identification. Susceptibility testing for these isolates was performed on the VITEK 2 system and the Pasco broth microdilution panels. Minimal inhibitory concentrations (MICs) and interpreted results according to the AES and DKML antimicrobial susceptibility guidelines were compared. RESULTS: Of 300 isolates tested for susceptibility, 13 did not give AES interpretations. Of the remaining 287 isolates, interpretations between AES and DKML guidelines were compared for 10 antibiotics. The overall correlation between the AES and DKML interpretations was 96.2%. CONCLUSION: This study demonstrated the benefits and limitations of the bioMérieux AES. Automated knowledge-based systems provide a useful laboratory tool for the interpretation of susceptibility results.

Alberta↗
PubMed2002

Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary. Routine use of antibiotic ointment and wound healing.

A short cut review was carried out to establish whether topical antibiotics improved the outcome of simple wounds. Altogether 71 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Anti-Bacterial Agents↗
PubMed2002

A comparative study of a new wireless continuous cardiorespiratory monitor for the diagnosis and management of patients with congestive heart failure at home.

Congestive heart failure (CHF) is a major and increasing chronic disease in Western society, with a high mortality, morbidity and cost for unplanned hospital admissions. Continuous cardiorespiratory monitoring is required to detect Cheyne-Stokes respiration (CSR). We have tested a new wireless monitoring system and compared it with polysomnography (PSG) and respiratory inductance plethysmography (RIP) in six CHF patients with CSR in a sleep laboratory. The wireless system compared well with RIP for the detection of CSR but less well with PSG, which had unexpected but significant respiratory sensing errors that led to misclassification of the respiratory disorder present. The wireless system could be used to select CHF patients for better-customized treatment at home as part of a specialist-supported community telemedicine programme.

Heart Failure↗
PubMed2001

Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial.

OBJECTIVE: To determine the effect of injections of botulinum toxin on simple motor tics. BACKGROUND: Case series with unblinded assessments have reported improvement in tic frequency and associated urge with botulinum toxin. METHODS: Patients with suitable simple motor tics were randomized to receive botulinum toxin and placebo in a double blind, crossover design. All outcomes compared week 2 to baseline measurements. The primary outcome measure was the number of treated tics per minute on a videotape segment. Secondary outcome measures were number of untreated tics per minute, the Shapiro Tourette Syndrome Severity Scale score, a numerical assessment of the urge to perform the treated tic (0 to 4), the premonitory sensation associated with the treated tic (0 to 4), and the patient's global impression of change. RESULTS: Eighteen patients completed the study. The median relative change in treated tics per minute with botulinum toxin was -0.39 (or a 39% reduction) versus 0.058 (or a 5.8% increase) with placebo (net effect -0.37, p = 0.0007). The average change in urge scores (score range 0 to 4) was -0.46 in the treatment phase and +0.49 in the placebo phase (net effect 0.94, p = 0.02). Other secondary outcome measures were not significantly different between the two groups. CONCLUSION: Botulinum toxin reduced treated tic frequency and the urge associated with the treated tic. Despite these changes, patients did not report an overall benefit from the treatment. Careful consideration of the contribution of the target tic to the patient's disability is needed before making treatment decisions.

Adolescent↗
PubMed2001

Evaluation of microencapsulation of a Bifidobacterium strain with starch as an approach to prolonging viability during storage.

AIMS: To optimize a spray coating process for the production of encapsulated microspheres containing viable Bifidobacterium cells and to determine whether the readily gelatinized modified starch coating used in this study improved bacterial survival in foods or under acid conditions. METHODS AND RESULTS: An air inlet temperature of 100 degrees C was demonstrated to be optimal for the spray drying process, as it afforded good drying, low outlet temperatures (45 degrees C) and resulted in less than 1 log reduction in bifidobacteria numbers during drying. Maximum recovery yields of 30% were obtained after optimizing the air aspiration conditions. The average size of the Bifidobacterium PL1-containing starch microparticles was determined by scanning electron microscopy to be of the order of 5 microm. The starch-coated cells did not display any enhanced viability compared with free PL1 cells when exposed to acid conditions for 6 h or in two dry food preparations over 20 d storage at ambient temperature (19-24 degrees C). Determination of 1491 nucleotides of the 16S rRNA gene from PL1 indicated that it shared 97% homology with a previously sequenced Bifidobacterium ruminantium strain. CONCLUSIONS: Our data demonstrated that, although spray drying is a valuable process for encapsulating bifidobacteria, further work is required to ascertain a more appropriate coating material that will protect this strain against adverse environmental conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of small, uniformly coated microspheres containing viable bifidobacteria using an affordable and industrially convenient process, such as spray drying, has commercial implications for the production of probiotic products. Although popular for use as a coating polymer by the food industry, this study indicated that modified starches might not be suitable for use as an encapsulating material for probiotic strains.

Aerosol Propellants↗
PubMed2001

Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital. METHODS: The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.

Age Factors↗
PubMed2001

Management of grade IV renal injury in children.

PURPOSE: Conservative nonsurgical management of major renal trauma in children is well established. However, when blunt trauma is accompanied by significant urinary extravasation, options are less than clearly defined. Endoscopic techniques, such as stents and percutaneous drainage, have not been widely used because of small caliber. We present our experience with endoscopic management of grade IV renal trauma. MATERIALS AND METHODS: From 1983 to 1996, 15 children satisfied the criteria for grade IV renal trauma. We retrospectively reviewed the charts to assess the mechanism of injury, associated injury, treatment, hospital stay and transfusion requirement. Patients were followed clinically with blood pressure and creatinine monitoring, and by radiograph with computerized tomography. RESULTS: Nine patients with isolated kidney injury were successfully treated with observation, 1 underwent early partial nephrectomy for persistent anemia and hypotension, and 5 had a urinoma, which was successfully treated with percutaneous drainage only in 2. The other 3 patients underwent cystoscopy and ureteral stent placement for high drainage output, leading to the resolution of urine leakage. In 1 patient who underwent percutaneous drainage only renovascular hypertension developed, requiring partial nephrectomy 3 months after the original injury. The remaining 13 patients had complete radiographic resolution of the injury and no evidence of hypertension. CONCLUSIONS: In the pediatric population grade IV blunt renal trauma usually resolves without intervention. When a symptomatic urinoma develops, percutaneous drainage, accompanied at times by ureteral stenting provides the complete resolution of persistent urine leakage.

Adolescent↗
PubMed2000

Candidate Neisseria meningitidis NspA vaccine.

The highly conserved NspA protein has been found in the outer membrane of every Neisseria meningitidis strain tested so far. Two monoclonal antibodies (MAbs) directed against this protein were used to demonstrate that biologically important epitopes of the NspA protein are exposed at the surface of serologically distinct meningococcal strains. Analysis of sera collected from mice that survived a deadly meningococcal challenge following immunization with recombinant NspA protein (rNspA) revealed the presence of cross-reactive antibodies which efficiently attached to and killed the four serogroup B strains tested. These data are additional proof that the NspA protein is exposed at the surface of intact meningococcal cells, which is an important characteristic for a vaccine candidate.

Amino Acid Sequence↗
PubMed2000

High-dose porcine hematopoietic cell transplantation combined with CD40 ligand blockade in baboons prevents an induced anti-pig humoral response.

BACKGROUND: In pig-to-primate organ transplantation, hyperacute rejection can be prevented, but the organ is rejected within days by acute vascular rejection, in which induced high-affinity anti-Gal alpha1-3Gal (alphaGal) IgG and possibly antibodies directed against new porcine (non-alphaGal) antigenic determinants are considered to play a major role. We have explored the role of an anti-CD40L monoclonal antibody in modifying the humoral response to porcine hematopoietic cells in baboons pretreated with a nonmyeloablative regimen. METHODS: Porcine peripheral blood mobilized progenitor cells obtained by leukapheresis from both major histocompatibility complex-inbred miniature swine (n=7) and human decay-accelerating factor pigs (n=3) were transplanted into baboons. Group 1 baboons (n=3) underwent whole body (300 cGy) and thymic (700 cGy) irradiation, T cell depletion with ATG, complement depletion with cobra venom factor, short courses of cyclosporine, mycophenolate mofetil, porcine hematopoietic growth factors, and anti-alphaGal antibody depletion by immunoadsorption before transplantation of high doses (2-4 x 10(10)/cells/kg) of peripheral blood mobilized progenitor cells. In group 2 (n=5), cyclosporine was replaced by eight doses of anti-CD40L monoclonal antibodies over 14 days. The group 3 baboons (n=2) received the group 1 regimen plus 2 doses of anti-CD40L monoclonal antibodies (on days 0 and 2). RESULTS: In group 1, sensitization to alphaGal (with increases in IgM and IgG of 3- to 6-fold and 100-fold, respectively) and the development of antibodies to new non-alphaGal porcine antigens occurred within 20 days. In group 2, no sensitization to alphaGal or non-alphaGal determinants was seen, but alphaGal-reactive antibodies did return to their pre- peripheral blood mobilized progenitor cells transplant levels. In group 3, attenuated sensitization to alphaGal antigens was seen after cessation of cyclosporine and mycophenolate mofetil therapy at 30 days (IgM 4-fold, IgG 8-30-fold), but no antibodies developed against new porcine determinants. In no baboon did anti-CD40L monoclonal antibodies prevent sensitization to its own murine antigens. CONCLUSIONS: We believe these studies are the first to consistently demonstrate prevention of a secondary humoral response after cell or organ transplantation in a pig-to-primate model. The development of sensitization to the murine elements of the anti-CD40L monoclonal antibodies suggests that nonresponsiveness to cell membrane-bound antigen (e.g., alphaGal) is a specific phenomenon and not a general manifestation of immunological unresponsiveness. T cell costimulatory blockade may facilitate induction of mixed hematopoietic chimerism and, consequently, of tolerance to pig organs and tissues.

Animals↗
PubMed2000

Role of megalin (gp330) in transcytosis of thyroglobulin by thyroid cells. A novel function in the control of thyroid hormone release.

When thyroglobulin (Tg) is endocytosed by thyrocytes and transported to lysosomes, thyroid hormones (T4 and T3) are released. However, some internalized Tg is transcytosed intact into the bloodstream, thereby avoiding proteolytic cleavage. Here we show that megalin (gp330), a Tg receptor on thyroid cells, plays a role in Tg transcytosis. Following incubation with exogenous rat Tg at 37 degrees C, Fisher rat thyroid (FRTL-5) cells, a differentiated thyroid cell line, released T3 into the medium. However, when cells were incubated with Tg plus either of two megalin competitors, T3 release was increased, suggesting that Tg internalized by megalin bypassed the lysosomal pathway, possibly with release of undegraded Tg from cells. To assess this possibility, we performed experiments in which FRTL-5 cells were incubated with either unlabeled or (125)I-labeled Tg at 37 degrees C to allow internalization, treated with heparin to remove cell surface-bound Tg, and further incubated at 37 degrees C to allow Tg release. Intact 330-kDa Tg was released into the medium, and the amount released was markedly reduced by megalin competitors. To investigate whether Tg release resulted from transcytosis, we studied FRTL-5 cells cultured as polarized layers with tight junctions on permeable filters in the upper chamber of dual chambered devices. Following the addition of Tg to the upper chamber and incubation at 37 degrees C, intact 330-kDa Tg was found in fluids collected from the lower chamber. The amount recovered was markedly reduced by megalin competitors, indicating that megalin mediates Tg transcytosis. We also studied Tg transcytosis in vivo, using a rat model of goiter induced by aminotriazole, in which increased release of thyrotropin induces massive colloid endocytosis. This was associated with increased megalin expression on thyrocytes and increased serum Tg levels, with reduced serum T3 levels, supporting the conclusion that megalin mediates Tg transcytosis. Tg transcytosis is a novel function of megalin, which usually transports ligands to lysosomes. Megalin-mediated transcytosis may regulate the extent of thyroid hormone release.

Amitrole↗
PubMed2000

Bcl-2 and Bax regulate the channel activity of the mitochondrial adenine nucleotide translocator.

Bcl-2 family protein including anti-apoptotic (Bcl-2) or pro-apoptotic (Bax) members can form ion channels when incorporated into synthetic lipid bilayers. This contrasts with the observation that Bcl-2 stabilizes the mitochondrial membrane barrier function and inhibits the permeability transition pore complex (PTPC). Here we provide experimental data which may explain this apparent paradox. Bax and adenine nucleotide translocator (ANT), the most abundant inner mitochondrial membrane protein, can interact in artificial lipid bilayers to yield an efficient composite channel whose electrophysiological properties differ quantitatively and qualitatively from the channels formed by Bax or ANT alone. The formation of this composite channel can be observed in conditions in which Bax protein alone has no detectable channel activity. Cooperative channel formation by Bax and ANT is stimulated by the ANT ligand atractyloside (Atr) but inhibited by ATP, indicating that it depends on the conformation of ANT. In contrast to the combination of Bax and ANT, ANT does not form active channels when incorporated into membranes with Bcl-2. Rather, ANT and Bcl-2 exhibit mutual inhibition of channel formation. Bcl-2 prevents channel formation by Atr-treated ANT and neutralizes the cooperation between Bax and ANT. Our data are compatible with a ménage à trois model of mitochondrial apoptosis regulation in which ANT, the likely pore forming protein within the PTPC, interacts with Bax or Bcl-2 which influence its pore forming potential in opposing manners.

Animals↗
PubMed2000

Endoscopic repair of cerebrospinal fluid rhinorrhea.

Endoscopic repair of cerebrospinal fluid rhinorrhea is a promising alternative to traditional repair techniques. This article reports our experience with 21 cases (10 spontaneous, 8 iatrogenic, and 3 traumatic). Various diagnostic radiographic modalities were used, including computer-aided techniques. Most repairs were accomplished with a free fascial graft positioned in the epidural space. Postoperative lumbar drainage was used in 15 cases. Initial repair was successful in 18 cases (85.7%). In all 3 failures, the surgeon had difficulty with proper graft placement. Additionally, 2 of these cases were confounded by early inadvertent removal of the lumbar drain. All patients in whom the procedure failed underwent a second successful endoscopic repair. There were no major complications. In our experience endoscopic repair of cerebrospinal fluid rhinorrhea is a safe and effective approach that can be improved with computer-aided localization devices. Proper graft placement is critical, and lumbar drainage is an important adjunct in selected cases.

Adult↗
PubMed2000

Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies.

Mixed lymphohematopoietic chimerism can be induced in mice with bone marrow transplantation (BMT) after a nonmyeloablative preparative regimen that includes cyclophosphamide, anti-T-cell antibody therapy, and thymic irradiation. These mixed chimeras are resistant to the induction of graft-versus-host disease (GVHD) after delayed donor leukocyte infusions (DLIs), despite a potent lymphohematopoietic graft-versus-host reaction that converts the mixed chimeric state to a full donor one. Based on this animal model, we initiated a trial of nonmyeloablative therapy with HLA-matched or -mismatched donor BMT and DLI for refractory hematologic malignancies. Twenty-one of 36 patients enrolled in this trial received a genotypically (n = 20) or phenotypically (n = 1) HLA-matched donor transplant; results reported here are for those patients only. Preparative therapy consisted of cyclophosphamide in doses of 150 to 200 mg/kg; peritransplant antithymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal radiation therapy); and cyclosporine. Eighteen of 20 evaluable patients developed persistent mixed lymphohematopoietic chimerism as defined by >1% donor peripheral white blood cells until at least day 35 posttransplantation. Ten patients received prophylactic DLI beginning 5 to 6 weeks after BMT for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-leukemia effect. Fourteen of 20 evaluable patients (70%) achieved an antitumor response; 8 of these responses were complete, and 6 were partial. Of the 8 evaluable patients who received prophylactic DLI, 6 showed conversion to full donor chimerism. Five of the 9 evaluable patients (56%) who received prophylactic DLI achieved a complete response, compared with 3 of 11 patients (27%) who did not receive prophylactic DLI. Currently 11 patients are alive, and 7 of these are free of disease progression at a median follow-up time of 445 days (range, 105-548 days) posttransplantation. Transplantation-related complications included cyclophosphamide-induced cardiac toxicity in 3 of 21 patients (14%) and grade II or greater GVHD in 6 patients (29%). One patient (5%) died from a complication of BMT, and 1 patient (5%) died from GVHD after 2 prophylactic DLIs were given for conversion of chimerism. In summary, mixed lymphohematopoietic chimerism was reproducibly induced after a novel nonmyeloablative preparative regimen incorporating chemotherapy, peritransplant antithymocyte globulin, and thymic irradiation, allowing for early administration of DLI in 10 of 21 patients. After treatment, striking antitumor responses were observed in the majority of patients with chemotherapy-refractory hematologic malignancies.

Adult↗