Nomenclature of human platelet antigens.
Explore the source record for details and available documents.
Advisory Committees↗
Biomedical subjects
J Smith
Publications and source records attributed to J Smith.
Arsenic in Australian environment: an overview.
The most common source of elevated As concentrations in the Australian environment are attributable to anthropogenic activities. Mining activities have contributed to the contamination of soil and water primarily in Western Australia and Victoria. However, other anthropogenic activities such as agriculture, forestry and industry have also contaminated soil and water at a localized scale. Currently there are over 1000 As contaminated sites previously used as cattle dips for eradicating cattle ticks. Although As contamination of the environment may be severe enough to limit plant growth there appears to be few other reports identifying the impacts of the contaminants on other organisms, such as fish, mammals and humans. In Australia the impacts of metal/metalloid contamination of the environment are often unnoticed or ignored. However, the impacts of elements such as As may pass unnoticed by the public or regulators due to the perception of the minimal impact a contaminant has on the environment. This paper presents an overview of As in the Australian environment including the sources of As contamination, soil, water and plant As content, and the pathways of exposure.
Agriculture↗
Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis.
OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.
Arthritis, Rheumatoid↗
Is nCPAP of value in extreme preterms with no access to neonatal intensive care?
This prospective study was undertaken to investigate the efficacy of nasal continuous positive airway pressure (nCPAP) in a group of extremely small infants denied access to a neonatal intensive care unit (NICU) in South Africa. Consecutive infants weighing less than 1200 g and/or of a gestational age below 28 weeks admitted to the neonatal ward with respiratory distress syndrome (RDS), and who were refused admission to the NICU, received either nCPAP (Infant Flow System E.M.E., UK) of headbox oxygen. Of 22 infants, 11 infants were included in the treatment group (nCPAP) and 10 in the control group. Within the first 24 h, two infants (18 per cent) in the nCPAP group and eight infants (80 per cent) in the control group died (p = 0.007) (survival OR = 18; RR = 4.09). A statistically significant improvement in the arterial-alveolar (a/A) oxygen ratio occurred in the nCPAP group between postnatal day 1 and day 3 of life (0.17 vs. 0.36; p < 0.005). Neonatal complications occurred in six (55 per cent) infants who survived the first 24 h of life. Eighty per cent of the infants with intraventricular haemorrhage (IVH) died, as well as all the infants who were born before arrival at the hospital. At the time of discharge from hospital, 45 per cent (five infants) in the nCPAP group survived vs. 20 per cent (two infants) in the control group. The neurodevelopmental outcome of six of the surviving seven infants were evaluated at 1 year of corrected age. The neurodevelopmental outcome as assessed by the Griffith Score was within normal limits in all infants. One infant has sensorineural deafness and one is deaf and has a possible mild spastic diplegia (both in the treatment group). We conclude that nCPAP significantly improves the short-term survival of very low birth-weight (VLBW) infants with moderate to severe respiratory distress syndrome who could not be admitted to intensive care. nCPAP significantly improves the a/A oxygen ratio between day 1 and day 3 of life.
Administration, Intranasal↗
Effect of temperature on the Brugada ECG.
Explore the source record for details and available documents.
Adult↗
Association of acute parvovirus B19 infection with new onset of acute lymphoblastic and myeloblastic leukaemia.
AIMS: To investigate the association of acute parvovirus B19 infection with new onset of acute lymphoblastic and myeloblastic leukaemia. METHODS: Cerebrospinal fluid (CSF) samples from patients with acute myelogenous leukaemia (AML) at diagnosis (n = 2) and acute lymphoblastic leukaemia (ALL) at diagnosis (n = 14) were analysed for parvovirus B19 DNA by means of nested polymerase chain reaction. In addition, samples from patients with benign intracranial hypertension (BIH) (n = 10) and hydrocephalus (n = 13) were tested as controls. RESULTS: Four leukaemia cases were positive-common ALL (n = 2), null cell ALL (n =1), and M7 AML (n = 1)-whereas all controls were negative (Yates corrected chi(2) value, 3.97; p = 0.046; odds ratio, 16.92; confidence interval, 1.03 to 77.18). All four patients were significantly anaemic, but none was encephalitic or had evidence of central nervous system leukaemia. In three of these patients, serum tumour necrosis alpha, interferon gamma, interleukin 6, granulocyte-macrophage colony stimulating factor (range, 34.93-3800.06 pg/ml), and macrophage chemoattractant protein 1 were detectable. All of these four patients carried at least one of the HLA-DRB1 alleles, which have been associated with symptomatic parvovirus B19 infection. CONCLUSION: Erythroid suppression and immune cell proliferation are both associated with B19 infection and may also be important in the pathogenesis of acute leukaemia.
Acute Disease↗
Inequalities in survival from colorectal cancer: a comparison of the impact of deprivation, treatment, and host factors on observed and cause specific survival.
OBJECTIVE: To investigate whether socioeconomic deprivation is associated with cause specific and all cause survival for colorectal cancer and to what extent this is independent of significant prognostic factors. DESIGN: Prospective cohort. SETTING: The former Wessex Health Region, South West England. PARTICIPANTS: All patients resident in Wessex registered with a diagnosis of colorectal cancer over three years (n=5176). Survival analysis was carried out on those patients with compete data for all factors and a positive survival time (n=4419). OUTCOMES: Death from colorectal cancer and all cause over five year follow up from initial diagnosis. MAIN RESULTS: Deprivation was significantly associated with survival for both outcomes in univariate analysis; the unadjusted hazard ratio for dying from colorectal cancer (most deprived compared with most affluent) was 1.12 (95% CI 1.00 to 1.25) and for all cause was 1.18 (1.07 to 1.30). Significant prognostic factors for both outcomes were age, specialisation of surgeon, Dukes's stage, and emergency compared with elective surgery. Comorbidity and gender were only associated with all cause survival. After adjustment for prognostic factors, the effect of deprivation on both cause specific and all cause mortality was reduced, and it was non-significant for colorectal cancer. However, the most deprived group had consistently worse survival than the most affluent. CONCLUSIONS: Factors associated with survival with colorectal cancer depend on the outcome measure. Socioeconomic deprivation is adversely associated with survival in patients with colorectal cancer. This is strongest for non-colorectal cancer death, partly reflecting higher comorbidity, but it is there for colorectal cancer though not statistically significant. Conclusive evidence of the inequalities by socioeconomic status and underlying reasons needs to come from studies using individual based measures of socioeconomic status and more detail on treatment and host related factors.
Adult↗
Raman spectral mapping in the assessment of axillary lymph nodes in breast cancer.
This paper is the first reported description of Raman Spectroscopy in the assessment of axillary lymph nodes in breast cancer patients. Raman Spectroscopy is an inelastic scattering spectroscopic technique appropriate for the assessment of unprocessed complex biological tissues. Spectra represent biochemical signatures of the tissue under scrutiny. The described method of Raman spectral mapping produces false-color spectral images of lymph node sections. These can be compared with standard histopathology slides and white light images of nodal tissue. This method has the potential to allow the detailed biochemical assessment of heterogeneous lymph node features, and to contribute towards the development of an optical diagnostic tool for use in a clinical setting.
Breast Neoplasms↗
An integrated care pathway for the last two days of life.
Explore the source record for details and available documents.
Critical Pathways↗
Failure of T stage to predict survival in patients with non-small-cell lung cancer treated by radiotherapy with or without concomitant chemotherapy.
PURPOSE: Because T stage does not consistently reflect tumor size in non-small-cell lung cancer (NSCLC), we hypothesized that T stage may be of limited prognostic value in patients with locoregional NSCLC treated by nonsurgical means. METHODS AND MATERIALS: The study population consisted of 243 patients with histologically or cytologically proven NSCLC treated in three consecutive prospective trials between 1989 and 1998. The eligibility criteria for this analysis included planned for and began treatment at 60 Gy; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; weight loss < or = 10%; no prior treatment; and no supraclavicular nodes, pleural effusion, or distant metastases. In the first study, 204 patients were randomized to receive conventional or accelerated radiotherapy (RT) with or without concomitant carboplatin. In the second, 15 patients were treated with concomitant cisplatin, etoposide, and RT in a single-arm study. In the third, 24 patients were treated with concomitant carboplatin, 5-fluorouracil, and RT in a dose-escalation study. RESULTS: A total of 231 patients for whom the T and N stage were known met the eligibility criteria. The patient characteristics were 77% male, 64% squamous histologic features, 33% ECOG status of 0, and 69% no weight loss. The nodal status was 36% N0, 7% N1, 52% N2, and 5% N3. The estimated median survival for all patients was 1.4 years (95% confidence interval 1.2-1.6), with an estimated 10% surviving 5 years (95% confidence interval 7-15). No significant difference was found in survival among the three trials (p = 0.16). The estimated median survival time and 5-year survival rate according to T stage were as follows: T1 (n = 29), 1.6 years and 16%; T2 (n = 88), 1.3 years and 9%; T3 (n = 59), 1.4 years and 9%; and T4 (n = 55), 1.4 years and 9%. No significant trend was found in overall survival according to T stage (p = 0.85, log-rank). To test whether a significant effect of T stage on overall survival existed after adjusting for N stage, trial, ECOG status, and weight loss, a multifactor analysis using Cox proportional hazards regression analysis was carried out. There was still no significant effect of T stage on survival (p = 0.66) when all factors were taken into account. CONCLUSION: Although there is some evidence that T stage is an independent prognostic factor in patients with NSCLC treated surgically, it did not appear to be of value in this series of patients treated with RT with and without concomitant chemotherapy.
Adult↗
Germline mutations in the ribonuclease L gene in families showing linkage with HPC1.
Although prostate cancer is the most common non-cutaneous malignancy diagnosed in men in the United States, little is known about inherited factors that influence its genetic predisposition. Here we report that germline mutations in the gene encoding 2'-5'-oligoadenylate(2-5A)-dependent RNase L (RNASEL) segregate in prostate cancer families that show linkage to the HPC1 (hereditary prostate cancer 1) region at 1q24-25 (ref. 9). We identified RNASEL by a positional cloning/candidate gene method, and show that a nonsense mutation and a mutation in an initiation codon of RNASEL segregate independently in two HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway and has been suggested to be a candidate tumor suppressor gene. We found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozyogous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway might provide opportunities for developing therapies for those with prostate cancer.
Adenine Nucleotides↗
The Ensembl genome database project.
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 the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.
Computational Biology↗
Debridement of diabetic foot ulcers.
BACKGROUND: Foot ulceration is thought to affect 15% of people with diabetes at some time in their lives. OBJECTIVES: The aim of this review is to assess the evidence for the effectiveness of debridement as a treatment for diabetic foot ulcers. SEARCH STRATEGY: Searches of electronic databases, hand searching journals, bibliographies and identification of unpublished work by written communication with recognised experts in the diabetic foot. SELECTION CRITERIA: Randomised controlled trials evaluating a method of debridement in the treatment of diabetic foot ulcers. The outcome had to include either complete healing or rate of healing. There was no restriction on articles/trials based on language or publication status. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of study quality were undertaken by one reviewer and checked by an Editor of the Wounds Group. MAIN RESULTS: 5 RCTs of debridement were identified; 3 RCTs assessed the effectiveness of a hydrogel as a debridement method, 1 RCT evaluated surgical debridement and 1 RCT evaluated larval therapy. Pooling the 3 hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or standard care in healing diabetic foot ulcers (absolute risk difference 0.23; 95% CI: 0.10,0.36). Surgical debridement and larval therapy showed no significant benefit in these small trials. Other debridement methods such as enzyme preparations or polysaccharide beads have not been evaluated in RCTs of people with diabetes. REVIEWER'S CONCLUSIONS: There is evidence to suggest that hydrogel increases the healing rate of diabetic foot ulcers. More research is needed to evaluate the effects of a range of widely used debridement methods and of debridement per se.
Combined Modality Therapy↗
Phylogenetic comparison of the genus Lyssavirus using distal coding sequences of the glycoprotein and nucleoprotein genes.
The phylogenetic relationships between all seven genotypes within the genus Lyssavirus were compared at the nucleotide level utilising two distal regions of the viral genome. The resulting analysis of each region produced similar, although not identical, phylogenetic results, suggesting that the evolutionary pressures on individual proteins within the genome vary. These differences are in part due to the increased variability observed within the glycoprotein sequence over the nucleoprotein sequence. Pair-wise comparison using the glycoprotein partial sequence between different isolates demonstrate that within genotypes, viruses show between 80 and 100% sequence identity, whilst between genotypes, viruses show between 50 and 75% identity. This provides a consistent guide to assigning new viruses to existing genotypes. Alignment of the amino acid sequence for the truncated glycoprotein sequence to the Pasteur Virus vaccine strain show significant residue variation between positions 139 and 170. However, residue variation tends to vary with genotype implying that these changes have not evolved due to immunological pressure from the host but have occurred following the separation of viruses into discrete groups. Comparison of the phylogenetic analysis for this partial region of the glycoprotein suggest that it gives comparable results to studies that have used larger regions of the Lyssavirus genome.
Genome, Viral↗
Biosorption of organochlorine pesticides using fungal biomass.
Cladosporium strain AJR(3)18501 was tested for its ability to sorb the organochlorine pesticide (OCP) p,p'-DDT from aqueous media. When p,p'-DDT was added to distilled water, ethanol or 1-propanol solutions in excess of its solubility, p,p'-DDT was sorbed onto the fungal biomass. Increasing the amount of p,p'-DDT in solution by changing the medium composition increased sorbent uptake: p,p'-DDT uptake by the fungal biomass was 2.5 times greater in 25% 1-propanol (17 mg of p,p'-DDT g(-1) dry weight fungal biomass) than in distilled water. When p,p'-DDT was dissolved in 25% 1-propanol (12 mg x l(-1)), rapid p,p'-DDT sorption occurred during the first 60 min of incubation. p,p'-DDT in solution was reduced to 2.5 mg x l(-1) with the remaining p,p'-DDT recovered from the fungal biomass. A number of environmental parameters were tested to determine their effect on p,p'-DDT biosorption. As arsenic (As) is prevalent at DDT-contaminated cattle dip sites, its effect on p,p'-DDT uptake was determined. The presence of As [As(III) or As(V) up to 50 mg x l(-1)] did not inhibit p,p'-DDT uptake and neither As species could be sorbed by the fungal biomass. Changing the pH of the medium from pH 3 to 10 had a small effect on p,p'-DDT sorption at low pH indicating that an ion exchange process is not the major mechanism for p,p'-DDT sorption. Other mechanisms such as Van der Waals forces, chemical binding, hydrogen bonding or ligand exchange may be involved in p,p'-DDT uptake by Cladosporium strain AJR(3)18501.
1-Propanol↗
Structural and mechanical remodelling of the common bile duct after obstruction.
Biliary obstruction in man, most often caused by cholelithiasis, induces remodelling of the bile ducts. Obstruction-induced structural remodelling of the common bile duct (CBD) has been previously described. The mechanical changes that accompany the structural remodelling, however, have not been studied in detail. The aim of this study is to quantify the structural and mechanical changes in the CBD at different time intervals after acute obstruction. The CBD was ligated in the pig, near the duodenum, and studied after 3 h, 12 h, 2 days, 8 days and 32 days (n=5 in each group). One additional animal in each group was sham-operated. At each scheduled time, the CBD was mechanically tested in vitro with a computer-controlled volume infusion system to study the pressure-volume relationship of the CBD segment. A video camera provided simultaneous measurements of the outer dimensions of the CBD at the various pressures. The diameter and wall thickness of the CBD increased about three-fold in the 32-day group compared to the sham group (P < 0.001). The circumferential stress-strain relationship differed between groups (P < 0.001); it was shifted to the right, indicating softening, in the 3-h, 12-h, and 2-day groups and to the left, indicating stiffening, in the 8-day and 32-day group, compared to the sham group. The longitudinal stress-strain curves were all shifted to the left of the circumferential stress-strain curves (P < 0.05). The collagen area increased during obstruction (P < 0.001) but no correlation between the size of the collagen area and the biomechanical parameters was found. A practical implication of the present study serves as a warning to surgeons. A reduction in the wall stiffness in the first several days of obstruction along with an increased duct diameter and a decreased wall thickness suggest that operative procedures such as suturing, anastomosis and procedures related to ERCP must be performed with special care to avoid damage to the CBD.
Animals↗
Pseudomonas fluorescens pseudobacteraemia: a cautionary lesson.
OBJECTIVES: To describe an outbreak of pseudobacteraemia caused by Pseudomonas fluorescens in a paediatric population. To document and highlight the effect this outbreak had on clinical management and the steps taken to determine the source. METHODS: A clinical and microbiological investigation was carried out into a cluster of 38 pseudobacteraemias caused by Pseudomonas fluorescens in paediatric patients over a 10 month period. RESULTS: The source of the outbreak of pseudobacteraemia was found to be contaminated lithium heparin tubes, which were being filled prior to the filling of the blood culture bottle. Cultures of the same tubes yielded Pseudomonas fluorescens. As a result of the initial positive blood cultures, clinical management was altered in 18 cases. A staff education programme was instituted and eventually resulted in a cessation of the pseudobacteraemia. CONCLUSIONS: Pseudobacteraemias are a major cause of potentially inappropriate therapy in febrile children. Attention to detail in the collection of blood cultures can help reduce this outcome. Staff involved in the collection of blood cultures need to be aware of this potential source of contamination.
Adolescent↗
Use of adult isolation facilities in a UK infectious diseases unit.
Explore the source record for details and available documents.
Adult↗