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Biomedical subjects

P Gordon

Publications and source records attributed to P Gordon.

At least 19 recordsLinked to original sources
PubMed2006

Pathogenic Lrrk2 substitutions and Amyotrophic lateral sclerosis.

Pathogenic Lrrk2 Y1699C substitution observed in a large German-Canadian kindred presents a neurodegenerative disorder that is reminiscent of amyotrophic lateral sclerosis and Parkinsonism-Dementia Complex. We screened 54 patients with ALS for seven known Lrrk2 pathogenic substitutions in the Roc, COR and kinase domains. No mutations were observed suggesting that this locus does not have a major influence on the ALS phenotype. However we can not rule out other genetic variation at the LRRK2 locus may play a role in parkinsonian disorders with amyotrophic lateral sclerosis and may be considered candidates for genetic screening.

Adolescent↗
PubMed2004

A one-step large-scale method for T- and B-cell depletion of mobilized PBSC for allogeneic transplantation.

BACKGROUND: The presence of T and B cells in allogeneic grafts contributes to GvHD and to EBV-associated lymphoproliferative disease (LPD). Depletion of T and B cells from the graft decreases the risk of these complications. METHODS: T and B cells were depleted from mobilized peripheral stem cells from volunteer donors (n=5) using anti-CD3 and anti-CD19 Abs conjugated to magnetic microbeads, and the CliniMACS device. The function of the stem cells after depletion was evaluated using colony assays and non-obese diabetic (NOD)/SCID repopulating experiments. RESULTS: The mean mononuclear cell (MNC) count prior to T- and B-cell depletion was 2.19x10(10) (range 1.48-3.53). After depletion, the mean percentage of contaminating T cells was 0.02% (range 0.01-0.04%) with a mean log(10) depletion of 3.4 (range 3-3.8). The mean percentage of contaminating B cells was 0.1% (range 0.01-0.4%) with a mean log(10) depletion of 2.2 (range 1.4-3). The mean recovery of CD3- and CD19-negative MNCs after depletion was 70% (range 54-88%) and the mean recovery of CD34(+) stem cells was 69% (range 52-98%). The mean number of natural killer (NK) cells after T- and B-cell depletion was 5.2x10(8) (range 2-10x10(8)). In vitro colony assays and in vivo NOD/SCID repopulation assays showed no negative impact of this method on the function of the hematopoietic stem cells. DISCUSSION: Our results show that the CliniMACS system can be used to efficiently deplete PBSC of T and B cells simultaneously, without adverse effect on the graft.

Animals↗
PubMed2002

Morphoea and Borrelia burgdorferi: results from the Scottish Highlands in the context of the world literature.

AIMS: Previous studies investigating the link between infection with Borrelia burgdorferi and morphoea have produced conflicting results. Often, these studies have been undertaken in patients from different regions or countries, and using methods of varying sensitivity for detecting Borrelia burgdorferi infection. This study aimed to establish whether a relation could be demonstrated in the Highlands of Scotland, an area with endemic Lyme disease, with the use of a sensitive method for detecting the organism. METHODS: The study was performed on biopsies of lesional skin taken from 16 patients from the Highlands of Scotland with typical clinical features of morphoea. After histological confirmation of the diagnosis, a nested polymerase chain reaction (PCR) using primers to a unique conserved region of the Borrelia burgdorferi flagellin gene was performed on DNA extracts from each biopsy. A literature search was also performed for comparable studies. RESULTS: None of the 16 patients had documented clinical evidence of previous infection with B burgdorferi. DNA was successfully extracted from 14 of the 16 cases but all of these were negative using PCR for B burgdorferi specific DNA, despite successful amplification of appropriate positive controls in every test. The results were compared with those of other documented studies. CONCLUSIONS: Examination of the literature suggests that there is a strong geographical relation between B burgdorferi and morphoea. These results, in which no such association was found, indicate that morphoea may not be associated with the subspecies of B burgdorferi found in the Highlands of Scotland.

Adolescent↗
PubMed2001

Presence of prokaryotic and eukaryotic species in all subgroups of the PP(i)-dependent group II phosphofructokinase protein family.

Inorganic pyrophosphate-dependent phosphofructokinase (PP(i)-PFK) of the amitochondriate eukaryote Mastigamoeba balamuthi was sequenced and showed about 60% identity to PP(i)-PFKs from two eubacteria, Propionibacterium freudenreichii and Sinorhizobium meliloti. These gene products represent a newly recognized lineage of PFKs. All four lineages of group II PFKs, as defined by phylogenetic analysis, contained both prokaryotic and eukaryotic species, underlining the complex evolutionary history of this enzyme.

Amoeba↗
PubMed2001

A 10 year prospective followup of patients with rheumatoid arthritis 1986-96.

OBJECTIVE: To determine the 10 year outcome of hospital patients with established rheumatoid arthritis (RA) treated with disease modifying drugs (DMARD). METHODS: All patients with RA of at least a year duration and attending a single clinician were followed prospectively for 10 years. DMARD treatments changed with time but were continued throughout. Measurements of joint tenderness (Ritchie Index), morning stiffness, grip, and disability (Health Assessment Questionnaire, HAQ) and radiographs of hands and feet were documented. A record of joint surgery was maintained. Patients who stopped attending the clinic were traced and an accurate record of deaths was obtained from the National Registry of Deaths. Paired clinical indices were compared where available between 0, 5, and 10 years. RESULTS: At entry there were 289 patients of variable disease duration. Within 10 years, 71 had died (standardized mortality ratio 1.3) and 92 were alive but unavailable. Median joint tenderness, morning stiffness, grip strength, and hemoglobin were not significantly different at 0, 5, and 10 years. Erythrocyte sedimentation rate (ESR) declined but not significantly. By contrast, HAQ scores and radiographs worsened between 0 and 10 years (p = 0.0004, p = 0.0001, respectively). There was a trend toward lower ESR values and less disability and the lower radiographic scores in those with 10-15 years' disease duration in 1996 compared with those of similar duration in 1986. However, worsening of radiographs occurred in patients with short, medium, and long histories of RA. Correlations between disability, radiographic scores, and joint tenderness were apparent at the start and conclusion of the study. At 10 years, 54 (19%) of the original cohort had undergone at least one large joint replacement. Significantly more women required joint replacement surgery (chi-square 5.44, p = 0.02). CONCLUSION: Over a 10 year period patients with RA exhibited an excess of deaths and a deterioration of radiographs and function despite regular DMARD treatment and apparent clinical containment. Worsening of radiographs occurred in both relatively early and late disease. There was a steady requirement for surgical large joint replacement with time. This study suggests that in the long term. the effect of DMARD treatments may be less than the expectations derived from short term studies.

Adult↗
PubMed2000

Improved characterisation of focal liver tumours: dynamic power Doppler imaging using NC100100 echo-enhancer.

OBJECTIVE: To assess the vascularisation of focal hepatic tumours using NC100100, enhanced power Doppler imaging. METHODS: Twenty-two patients with focal liver tumours (12 metastases and ten hemangiomas) were studied. Using standardised settings, power Doppler imaging with ATL HDI3000 was performed before and after intravenous administration of NC100100 contrast agent. The video-recorded examinations were digitised for off-line analysis on a personal computer. Regions of interest were defined over the entire tumour and a neighbouring area of the normal liver parenchyma. The temporal changes of the mean power Doppler signal intensity (PDSI) was quantified to provide contrast agent wash-in (PDSI-time) curves for the initial 40 s. RESULTS: Liver metastases were characterised by a rapid increase in PDSI, while the PDSI-time curves within hemangiomas were flat. The PDSI within the tumour increased significantly in ten subjects with liver metastases and only one subject with hemangioma. An enhanced rim around hemangiomas was seen in four subjects. There was no clear relationship between the contrast agent dose and the peak PDSI within metastases. CONCLUSIONS: Power Doppler imaging with NC100100 contrast agent enhances tumour visualisation and may aid differential diagnosis of focal liver lesions.

Adult↗
PubMed2000

Discharge planning: an exploratory study.

The desire to reduce the length of waiting lists in the modern health service means that strategies for decreasing the length of hospital stay are exercising the minds of service planners. This has led to renewed emphasis on well planned discharge policies and procedures. The aim of this study was to analyse all discharge policies and procedures currently in use in one large integrated NHS trust in Northern Ireland and formulate a Corporate Discharge Policy for general use in NHS trusts. Objectives of the study included examining the current process of discharge, reviewing the interface between ward staff and district nursing services and examining the quality and standard of documentation in use. Findings indicate the need for standardization of the discharge planning process and sufficient notice of discharge, and for clarification and education regarding staff roles, the importance of multidisciplinary working, and the lack of quality communication between acute and community services.

Hospitals, Public↗
PubMed2000

MAGPIE/EGRET annotation of the 2.9-Mb Drosophila melanogaster Adh region.

Our challenge in annotating the 2.91-Mb Adh region of the Drosophila melanogaster genome was to identify genetic and genomic features automatically, completely, and precisely within a 6-week period. To do so, we augmented the MAGPIE microbial genome annotation system to handle eukaryotic genomic sequence data. The new configuration required the integration of eukaryotic gene-finding tools and DNA repeat tools into the automatic data collection module. It also required us to define in MAGPIE new strategies to combine data about eukaryotic exon predictions with functional data to refine the exon predictions. At the heart of the resulting new eukaryotic genome annotation system is a reverse comparison of public protein and complementary DNA sequences against the input genome to identify missing exons and to refine exon boundaries. The software modules that add eukaryotic genome annotation capability to MAGPIE are available as EGRET (Eukaryotic Genome Rapid Evaluation Tool).

Alcohol Dehydrogenase↗
PubMed2000

Gene content and organization of a 281-kbp contig from the genome of the extremely thermophilic archaeon, Sulfolobus solfataricus P2.

The sequence of a 281-kbp contig from the crenarchaeote Sulfolobus solfataricus P2 was determined and analysed. Notable features in this region include 29 ribosomal protein genes, 12 tRNA genes (four of which contain archaeal-type introns), operons encoding enzymes of histidine biosynthesis, pyrimidine biosynthesis, and arginine biosynthesis, an ATPase operon, numerous genes for enzymes of lipopolysaccharide biosynthesis, and six insertion sequences. The content and organization of this contig are compared with sequences from crenarchaeotes, euryarchaeotes, bacteria, and eukaryotes.

Amino Acid Sequence↗
PubMed2000

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.

Adolescent↗
PubMed1999

Laboratory restructuring in metropolitan Edmonton: a model for laboratory reorganization in Canada.

In 1994 the Alberta government acted to reduce to a decade-long deficit in the provincial budget with draconian reductions in the health, education and welfare expenditures. As a result, funding to Alberta clinical laboratories was to be reduced by approximately 40%. In response, the private and public laboratories in metropolitan Edmonton formed a unique alliance to provide laboratory testing in a more coordinated and efficient manner. Of the five metropolitan hospitals, only University of Alberta Hospital preserved its full service laboratory and its specialty reference testing. The other hospital laboratories were converted to rapid response laboratories with a merged private reference laboratory providing routine testing and support to the four hospitals, and far fewer outpatient collection facilities. This paper describes the steps in the laboratory restructuring from inception to execution.

Alberta↗
PubMed1999

Early postnatal dexamethasone increases the risk of focal small bowel perforation in extremely low birth weight infants.

OBJECTIVE: We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants. METHODS: A case-controlled analysis was performed using all infants born weighing < 1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study. RESULTS: Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens. CONCLUSION: These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.

Anti-Inflammatory Agents↗
PubMed1999

Electron-beam therapy for AIDS-related molluscum contagiosum lesions: preliminary experience.

PURPOSE: To determine the effects of electron-beam therapy on cutaneous molluscum contagiosum lesions in patients with acquired immunodeficiency syndrome (AIDS), because current treatment modalities are limited in their effectiveness and by long-term rates of lesion recurrence. MATERIALS AND METHODS: Five patients with AIDS, with 23 molluscum contagiosum lesion sites, received electron-beam radiation treatment of recurrent molluscum contagiosum lesions. RESULTS: All 23 lesions treated resolved completely and have not recurred during up to 24 months of follow-up. Radiation therapy was well tolerated; mild skin erythema was the only reported side effect. CONCLUSION: The use of electron-beam radiation is a promising alternative to current treatment modalities.

AIDS-Related Opportunistic Infections↗