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D Richardson

Publications and source records attributed to D Richardson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nitrate reduction in the periplasm of gram-negative bacteria.

In contrast to the bacterial assimilatory and membrane-associated, respiratory nitrate reductases that have been studied for many years, it is only recently that periplasmic nitrate reductases have attracted growing interest. Recent research has shown that these soluble proteins are widely distributed, but vary greatly between species. All of those so far studied include four essential components: the periplasmic molybdoprotein, NapA, which is associated with a small, di-haem cytochrome, NapB; a putative quinol oxidase, NapC; and a possible pathway-specific chaperone, NapD. At least five other components have been found in different species. Other variations between species include the location of the nap genes on chromosomal or extrachromosomal DNA, and the environmental factors that regulate their expression. Despite the relatively small number of bacteria so far screened, striking correlations are beginning to emerge between the organization of the nap genes, the physiology of the host, the conditions under which the nap genes are expressed, and even the fate of nitrite, the product of Nap activity. Evidence is emerging that Nap fulfills a novel role in nitrate scavenging by some pathogenic bacteria.

Amino Acid Sequence↗
PubMed2001

Towards a biological staging model for operable non-small cell lung cancer.

Non-small cell lung cancer is the most common cause of cancer-related death in North America and Europe. Despite improvements in the diagnosis and treatment of the disease the prognosis remains poor, the overall 5-year survival being 4-14%. An increased understanding of the molecular biology of the disease may identify novel targets for drug development. We evaluated epidermal growth factor receptor (EGFR), HER-2/neu, matrix metalloproteinase (MMP)-2, MMP-9, p53 and bcl-2 expression and microvessel density (MVD) in patients who underwent surgery with curative intent in our department between 1991 and 1996. Co-expression of EGFR/MMP-9, MVD and bcl-2 were found to be independent prognostic variables, which allowed prediction of patient outcome independent of surgical stage. Other prognostic factors identified in our series were gender, surgical stage, platelet count, extent of necrosis, the hypoxia marker carbonic anhydrase-9 and beta-catenin. In collaboration with groups in Oxford and Greece, we were also able to establish the angiogenic growth factors vascular endothelial growth factor and platelet-derived endothelial growth factor as prognostic variables. The inter-relationships between these factors are currently being examined in an expanded patient series. Through this work we hope to be able to construct an integrated biological prognostic model which can be tested in prospective studies. This work has identified several potential targets for novel therapeutic agents currently in development.

Adult↗
PubMed2001

Training for the role of triage in Australasia.

OBJECTIVE: To characterize the prerequisite experience and training undertaken by nurses for the role of triage in emergency departments in Australasia. METHODS: Postal survey of charge nurses/unit nurse managers of all Australasian emergency departments accredited for specialist emergency physician training by the Australasian College for Emergency Medicine. RESULTS: The response rate was 89%. The most common duration of prerequisite experience was 12-18 months. Most programmes use a combination of educational activities, with self-directed learning packages, lectures and mentored experience being the most common. Three hospitals reported no preparation for triage. CONCLUSION: In Australasia, there is wide variability in required training and experience before triage duties are performed. Strategies to set suggested minimum standards in these areas and to make training activities more accessible are recommended.

Australia↗
PubMed2001

Optimizing erythropoietin therapy in hemodialysis patients.

The European Best Practice Guidelines for the management of anemia in patients with chronic renal failure recommend the percentage of hypochromic red blood cells (%HRCs) as the best measure of iron use by erythropoietic tissues. They suggest that "sufficient iron should be administered to attain: serum ferritin 100 ng/mL, HRCs <10%. In practice, to achieve these minimum criteria will mean aiming for optimal levels of serum ferritin 200-500 ng/mL, HRCs <2.5%." We increased prospectively the delivered dose of iron supplements to a large (n = 228) unselected hemodialysis cohort with a sustained (24-month) hemoglobin (Hb) outcome meeting the UK Renal Association minimum standard of 85%, greater than or equal to 10.0 g/dL. This was managed through a computer-aided decision support system for erythropoietin (EPO) and intravenous iron sucrose therapy. Hb outcome was maintained with medians between 11.3 and 11.8 g/dL. Median red blood cell hypochromia (%HRCs) decreased from 8% (interquartile range [IQR], 3 to 15) to 4% (IQR, 2 to 8; P < 0.001, U-Mann Whitney test). Serum ferritin level increased from a median of 188 (IQR, 115 to 256) to 480 ng/mL (IQR, 397 to 595; P < 0.001, U-Mann Whitney test). Median EPO dose decreased from 136 (IQR, 83 to 216) to 72 IU/kg/wk (IQR, 33 to 134), which strongly correlated with median %HRCs through the range less than 10% (Spearman's correlation, 0.73; P < 0.01). These data suggest that EPO responsiveness continues to improve toward the normal range for %HRCs (<2.5%) and aspiring to values much less than 10% is cost-effective. The ferritin outcome required to achieve these lower values for %HRC outcome is greater than the current recommended range, although in steady state, the mean iron treatment dose is similar to that in previous studies (ie, approximately 60 mg/wk).

Anemia↗
PubMed2001

Optimal frequency of changing intravenous administration sets: is it safe to prolong use beyond 72 hours?

OBJECTIVE: To determine the safety and cost-effectiveness of replacing the intravenous (IV) tubing sets in hospitalized patients at 4- to 7-day intervals instead of every 72 hours. DESIGN: Prospective, randomized study of infusion-related contamination associated with changing IV tubing sets within 3 days versus within 4 to 7 days of placement. SETTING: A tertiary university cancer center. PATIENTS AND METHODS: Cancer patients requiring IV infusion therapy were randomized to have the IV tubing sets replaced within 3 days (280 patients) or within 4 to 7 days of placement (232 patients). Demographic, microbiological, and infusion-related data were collected for all participants. The main outcome measures were infusion- or catheter-related contamination or colonization of IV tubing, determined by quantitative cultures of the infusate, and infusion- or catheter-related bloodstream infection (BSI), determined by quantitative culture of the infusate in association with blood cultures in febrile patients. RESULTS: The two groups were comparable in terms of patient and catheter characteristics and the agents given through the IV tubing. Intent-to-treat analysis demonstrated a higher level of tubing colonization in the 4- to 7-day group versus the 3-day group (median, 145 vs 50 colony-forming units; P=.02). In addition, there were three episodes of possible infusion-related BSIs, all of which occurred in the 4- to 7-day group (P=.09). However, when the 84 patients who received total parenteral nutrition, blood transfusions, or interleukin-2 through the IV tubing were excluded, the two groups had a comparable rate of colonization (0.4% vs 0.5%), with no catheter- or infusion-related BSIs in either group. CONCLUSION: In patients at low risk for infection from infusion- or catheter-related infection who are not receiving total parenteral nutrition, blood transfusions, or interleukin-2, delaying the replacement of IV tubing up to 7 days may be safe, as well as cost-effective

Adolescent↗
PubMed2001

Intravenous iron for CAPD populations: proactive or reactive strategies?

BACKGROUND: The European best practice guideline [Nephrol Dial Transplant 1999; 14 (Suppl 5)] (5A) for the management of anaemia suggests that > 85% of the CAPD population should have a haemoglobin level of > 11.0 g/dl. METHODS: We developed and implemented an outpatient-based protocol for intravenous iron sucrose (IV Fe) and erythropoietin (Epo) in CAPD patients showing iron deficiency despite oral iron therapy. We managed a total of 103 patients over 13 months of study. All CAPD patients were included, regardless of co-morbidity. Treatment developed in two phases: in phase 1 (reactive) (months 1-8), patients with markers of iron deficiency (ferritin < 100 ng/ml or ferritin 100-500 and percentage hypochromic red cells (%HRC) > or =5) were converted from oral iron to IV Fe (300 mg) and reviewed after 4-8 weeks according to haemoglobin (Hb). In phase 2 (proactive) (months 9-13), the criteria for iron therapy were extended: ferritin < 150 ng/ml or ferritin 150-500 and %HRC > or = 2. Patients then received IV Fe (200 mg) and were reviewed after 4 weeks according to Hb. RESULTS: The median haemoglobin increased from 11.0 (Inter quartile range, IQR, 10.1-12.6) g/dl to 11.7 (11.0-12.7) g/dl (P = 0.06). The proportion of patients with absolute iron deficiency (ferritin < 100 ng/ml) decreased from 24 to 2%. The percentage of hypochromic red cells (%HRC) decreased from 4 (2-7) to 1 (1-4) (P < 0.01). CONCLUSIONS: An integrated Epo and IV Fe policy increased the number of patients reaching the European guideline from 50 to 75% with no increase in the population median Epo requirements (42 (IQR, 25-95) IU/kg/week vs 45 (27-101) (P = NS)). This study demonstrates the benefit of early (proactive) intervention in achieving population compliance within current guidelines for renal anaemia.

Anemia, Hypochromic↗
PubMed2001

Renal diagnosis without renal biopsy. Nephritis and sensorineural deafness.

Two examples of hereditary nephropathy within the context of clinical syndromes are described. Emphasis is put on the ability to make a renal diagnosis without renal biopsy and the benefits of screening relatives once a diagnosis is achieved. A variant of Alport's syndrome with associated macrothrombocytic thrombocytopenia, known as Epstein's syndrome, is reported. In addition siblings with Alström's syndrome characterized by pigmentary retinal degeneration (causing blindness in early childhood), progressive sensorineural hearing loss, and progressive renal failure are reported. Both cases had previously presented for non-renal pathology in advance of the onset of symptomatic renal failure and may have benefited from appropriate screening.

Adult↗
PubMed2001

Radiation risk estimates in the beginning of the 21st century.

In the early years of the 21st century, results from a number of epidemiologic studies of populations with specific ionizing radiation exposures will become available. These include populations with accidental exposures in the former Soviet Union and elsewhere and populations with occupational exposures from routine operations of nuclear power plants. The strengths and limitations of these studies are reviewed together with the radiation protection questions they may answer. Many of these studies will provide specific information to complement the atomic-bomb survivor studies, particularly the effects of dose-rate and exposure protraction, modifiers of radiation risks (both environmental and host factors), and different types of radiation. These studies will therefore be important as a test of the adequacy of the current scientific bases for the radiation protection of workers and the general public. An example is thyroid cancer risk in young children following the Chernobyl accident, which has brought attention to a very high sensitivity of very young children that was difficult to assess on the basis of atomic-bomb data alone. Radiation protection will also benefit from formal comparisons and combined analyses of data from populations with different exposure patterns and exposures. Finally, future epidemiological studies will be most valuable if they are well focused, designed specifically to answer outstanding radiation protection questions. An integrated approach based on epidemiology and mechanistic studies, in which epidemiologic studies are designed to test specific mechanistic hypotheses and realistic mechanistic models are used for the analysis of epidemiological data, will probably be the most fruitful for radiation protection.

Accidents, Occupational↗
PubMed2001

Dialysis in non-renal organ (liver) transplantation.

The renal management of acute hepatic failure and liver transplantation requires an understanding of the features of liver failure and the causes of liver graft dysfunction. The management of any underlying pathology in addition to supportive care is fundamental to successful management and a return to independent renal function. These issues are discussed particularly in relationship to a case history involving a patient presenting with acute fulminant liver failure secondary to a paracetamol overdose who was successfully treated by liver transplantation and continuous veno-venous haemodiafiltration. The liver can be successfully transplanted but acute renal failure is a severe complication post-transplantation. Its appearance can be predicted in patients with pre-transplant renal dysfunction, severe graft dysfunction, or both. It may be avoided through careful selection of transplant recipients and correct timing of transplantation. Prevention of renal failure, appropriate patient selection for transplantation and timely procurement of a donor organ are vital for best use of limited donor resources. Treatment success depends on patient and donor selection, skilled surgeons, careful post-operative care, and successful immunosuppression.

Acute Kidney Injury↗
PubMed2000

Effects of diets with different calcium and phosphorus contents on the skeletal development and blood chemistry of growing great danes.

The skeletal development of three groups of great dane dogs, fed a diet composed according to the published nutritional requirements for dogs (controls) or with increased calcium or calcium and phosphorus content, was examined radiographically, histologically and biochemically. The diets were fed from the time the dogs first began eating food in addition to their dam's milk, until they were 17 weeks old. Thereafter, the calcium and phosphorus intakes of the dogs in the high calcium groups were normalised for a further 10 weeks. The dogs fed the high calcium diet without a proportionally high phosphorus intake became hypercalcaemic and hypophosphataemic, and had severe disturbances in skeletal development, growth, and mineralisation which were typical for rickets. After their calcium intake was normalised the lesions of rickets resolved but osteochondrotic lesions became apparent. The dogs fed the high calcium and phosphorus diet became slightly hypophosphataemic, their growth was retarded, and they had disturbances in skeletal development resembling osteochondrosis, which had only partly resolved after 10 weeks on the normal calcium and phosphorus diet.

Animal Feed↗
PubMed2000

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Base Sequence↗
PubMed2000

Assignment of enzyme substrate specificity by principal component analysis of aligned protein sequences: an experimental test using DNA glycosylase homologs.

We have studied the relationship between amino acid sequence and substrate specificity in a DNA glycosylase family by characterizing experimentally the specificity of four new members of the family. We show that principal component analysis (PCA) of the sequence family correctly predicts the substrate specificity of one of the novel homologs even though conventional sequence analysis methods fail to group this homolog with other sequences of the same specificity. PCA also suggested, correctly, that another homolog characterized previously differs in its specificity from those sequences with which it clusters by conventional criteria. These results suggest that principal component analysis of sequence families can be a useful tool in annotating genome sequences when there is ambiguity concerning which subfamily a new homolog belongs to. Published 2000 Wiley-Liss, Inc.

Amino Acid Sequence↗