Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 91 records · Page 5Linked to original sources

PubMed2000

Radiochemistry: inconvenient but indispensable

Radiochemistry has always been and still is a crucial tool in the field of radionuclide determination, both for high and low level works; this holds particularly in the case of alpha and beta emitters. Requests to the analyst are increasingly demanding in terms of performance (detection limit, reliability, accuracy, precision,...), but also of economy (cost, time,...) and of flexibility with respect to sample types. In general, chemical and radiochemical analyses consist of four main steps: sample pre-treatment including pre-concentration, dissolution and/or digestion, separation of analytes from the matrix and from each other, transformation of the separated fraction into a source suited for measurement, determination of the amount or the activity of the analytes. The required combination of sub-procedures is determined by the analytes under investigation, their absolute and relative amounts, the matrix composition and by the performance required. IRMM's Analytical Chemistry Unit started several years ago to develop, adapt and/or validate various radiochemical methods and procedures, and apply these to different measurement tasks. This paper gives an overview on recent and ongoing activities.

Journal Article↗

PubMed2000

Results from the international evaluation exercise for uranium enrichment measurements. European Safeguards Research and Development Association NDA-WG Members

An international evaluation exercise for uranium enrichment measurement was organized by the ESARDA (European Safeguards Research and Development Association) Working Group on Techniques and Standards for Non-Destructive Analysis. The aim of this exercise was to test the different methods and more particularly X- and gamma-ray spectrometry methods used in the determination of uranium enrichment. Sets of samples of different uranium enrichments prepared by IRMM (Institute for Reference Materials and Measurements) and BNFL (British Nuclear Fuels) were measured by 15 participants in the IRMM laboratories. A description of this exercise is given here and the final results with their uncertainties are compared to the reference values obtained from mass spectrometry measurements. The main conclusions from this exercise are proposed; in particular, it appears necessary to improve the nuclear data used in the spectral modeling of the XKalpha region.

Journal Article↗

PubMed2000

Detection of sporadic cases of Norwalk-like virus (NLV) and astrovirus infection in a single Irish hospital from 1996 to 1998.

BACKGROUND: 'Norwalk-like viruses' (NLV) and astroviruses are recognised as the most important etiologic agents of viral gastroenteritis, excluding rotaviruses. However, neither of these two groups of viruses is routinely screened for in Irish hospital laboratories. OBJECTIVE: The objective of this study was to examine faeces collected from patients with non-bacterial, non-rotaviral gastroenteritis and examine if NLVs and astroviruses could be identified as the causative agents of the illness. STUDY DESIGN: Faecal specimens were collected from a single Irish hospital from February 1996 to June 1998. Three hundred and sixty samples were tested for the presence of NLVs using newly designed inosine-containing degenerate primers. Two hundred and three faecal specimens from paediatric patients were screened for the presence of astroviruses. RESULTS: the results of the screening study were that 29 (8%) specimens were found to be positive for NLV by reverse transcription polymerase chain reaction (RT-PCR) and 15 (7%) specimens from paediatric patients were found to be positive for astroviruses. Genotyping of the NLV-positive samples determined that four of the isolates were from genotype I (G1) and 25 were G2. The G2 positive specimens were further subtyped by oligonucleotide probing and the majority (n = 21) were found to be subtype P2-B, with four isolates being typed as P2-A. No P1-B isolates were found. CONCLUSIONS: This is the first report of detection of sporadic cases of NLV and astrovirus in Ireland. The results obtained highlight the need for continued surveillance of these viruses and the development of rapid detection systems for use in clinical laboratories.

Adolescent↗

PubMed2000

Combination of hydrostatic pressure and lacticin 3147 causes increased killing of Staphylococcus and Listeria.

The use of hydrostatic pressure and lacticin 3147 treatments were evaluated in milk and whey with a view to combining both treatments for improving the quality of minimally processed dairy foods. The system was evaluated using two foodborne pathogens: Staphylococcus aureus ATCC6538 and Listeria innocua DPC1770. Trials against Staph. aureus ATCC6538 were performed using concentrated lacticin 3147 prepared from culture supernatant. The results demonstrated a more than additive effect when both treatments were used in combination. For example, the combination of 250 MPa (2.2 log reduction) and lacticin 3147 (1 log reduction) resulted in more than 6 logs of kill. Similar results were obtained when a foodgrade powdered form of lacticin 3147 (developed from a spray dried fermentatation of reconstituted demineralized whey powder) was evaluated for the inactivation of L. innocua DPC1770. Furthermore, it was observed that treatment of lacticin 3147 preparations with pressures greater than 400 MPa yielded an increase in bacteriocin activity (equivalent to a doubling of activity). These results indicate that a combination of high pressure and lacticin 3147 may be suitable for improving the quality of minimally processed foods at lower hydrostatic pressure levels.

Animals↗

PubMed2000

Efficient method for the detection of microbially-produced antibacterial substances from food systems.

A novel method for the isolation of microbially-derived inhibitory substances from food sources was developed. The method involves an enrichment step coupled to a killing assay which is initially carried out in multiwell plates. The technique has advantages in that large numbers of samples can be tested in parallel. The assay can be completed in less than 60 h and is more sensitive than direct plating due to the enrichment step. This novel screening approach was compared with the standard direct plating approach in an effort to identify the antimicrobial potential of a number of Kefir grains. Kefir grains were incubated in 10% reconstituted skim milk for 20 h at 32 degrees C to enable production of any potential biopreservatives. Following overnight incubation, fermentates were aliquoted into multi-well plates and a known number of indicator cells was added to each well. The fermentates were incubated for a further 20 h and counts were carried out to determine whether a reduction in indicator cell numbers had occurred. A reduction in cell-forming units indicated the presence of an inhibitory substance and these inhibitory fermentates were selected for further investigation. Using the protocol outlined, Kefir fermentates capable of inhibiting Listeria innocua DPC1770 and Escherichia coli O157:H45 were identified.

Acids↗

PubMed2000

Continuous production of lacticin 3147 and nisin using cells immobilized in calcium alginate.

Bacteriocinogenic strains, Lactococcus lactis subsp. lactis DPC 3147 and L. lactis DPC 496, producing lacticin 3147 and nisin, respectively, were immobilized in double-layered calcium alginate beads. These beads were inoculated into MRS broth at a ratio of 1:4 and continuously fermented for 180 h. Free cells were used to compare the effect of immobilization on bacteriocin production. After equilibrium was reached, a flow rate of 580 ml h(-1) was used in the immobilized cell (IC), and 240 ml h(-1) in free-cell (FC) bioreactors. Outgrowth from beads was observed after 18 h. Bacteriocin production peaked at 5120 AU ml(-1) in both IC and FC bioreactors. However, FC production declined after 80 h to 160 AU ml(-1) at the end of the fermentation. Results of this study indicate that immobilization offers the possibility of a more stable and long-term means of producing lacticin 3147 in laboratory media than with free cells.

Alginates↗

PubMed2000

The use of listeriolysin to identify in vivo induced genes in the gram-positive intracellular pathogen Listeria monocytogenes.

Listeria monocytogenes is capable of growth within the cytoplasm of infected host cells. Escape from the host cell phagosome is mediated primarily through secretion of listeriolysin, a haemolytic factor which functions to actively lyse the phagosomal membrane. Listeriolysin negative mutants of L. monocytogenes are non-haemolytic on blood agar plates and demonstrate a significant reduction of virulence in the mouse model of infection. We have developed a system for the identification of in vivo induced genes in L. monocytogenes which utilizes the listeriolysin gene, hly, as both a reporter of gene expression and as a means of selection of promoter elements expressed in vivo. The system is analogous to in vivo expression technology (IVET) first reported for Salmonella, however, as listeriolysin functions in the environment of the host phagosome the loci identified in this study are most likely expressed during residence in the phagosome. The system was successfully tested using the promoter of the inducible virulence gene plcA. A bank was created by fusing a promoterless copy of hly to random promoter elements in a listeriolysin negative IVET host. Sequential inoculations of mice with this bank resulted in the isolation of clones with increased survival potential in the mouse model relative to a negative control, but which remained haemolysin negative on blood agar plates. Nine in vivo induced loci were identified including genes encoding a DNA topoisomerase III, a cellobiose transporter and a fumarase. Two isolates represented fusions to proteins of unknown function and three isolates contained no significant homologues in the database. A mutant in the fumarase gene demonstrated reduced virulence for mice and an inability to grow in cultured mouse phagocytes.

Animals↗

PubMed2000

Novel type I restriction specificities through domain shuffling of HsdS subunits in Lactococcus lactis.

This study identifies a natural system in Lactococcus lactis, in which a restriction modification specificity subunit resident on a 6159 bp plasmid (pAH33) alters the specificity of a functional R/M mechanism encoded by a 20.3 kb plasmid, pAH82. The new specificity was identified after phenotypic and molecular analysis of a 26.5 kb co-integrate plasmid (pAH90), which was detected after bacteriophage challenge of the parent strain. Analysis of the regions involved in the co-integration revealed that two novel hybrid hsdS genes had been formed during the co-integration event. The HsdS chimeras had interchanged the C- and N-terminal variable domains of the parent subunits, generating two new restriction specificities. Comparison of the parent hsdS genes with other type I specificity determinants revealed that the region of the hsdS genes responsible for the co-integration event is highly conserved among lactococcal type I hsdS determinants. Thus, as hsdS determinants are widespread in the genus Lactococcus, new restriction specificities may evolve rapidly after homologous recombination between these genes. This study demonstrates that, similar to previous observations in Gram-negative bacteria, a Gram-positive bacterium can acquire novel restriction specificities naturally through domain shuffling of resident HsdS subunits.

Amino Acid Sequence↗

PubMed2000

Outcome data on pediatric dialysis patients from the end-stage renal disease clinical indicators project.

Network 1 (New England) initiated the Clinical Indicator Project to survey dialysis adequacy (Kt/V), nutrition (serum albumin level), and anemia management in patients maintained on chronic dialysis. Because little information is available in children, data were specifically recorded covering these variables in patients (age, 1 to 18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD). During the 18 months of data collection, 29 observations were recorded on 23 HD patients (age, 14.3 +/- 3.6 years), and 43 observations were made on 30 PD patients (age,10.6 +/- 4.7 years). Kt/V correlated inversely with the age of the patient (HD, P < 0.004; PD, P < 0.0007). Although serum albumin level was not associated with dialysis adequacy in HD patients, there was a strong inverse relationship between albumin level and Kt/V in PD patients (P < 0.002). Hematocrit values were not significantly different in the two groups (HD, 31.0% +/- 5.5% versus PD, 32.9% +/- 4.8%) and could not be correlated with weekly erythropoietin dose. Weekly erythropoietin dose was directly related to patient age in both groups (HD, P < 0.05; PD, P < 0.02). The weekly erythropoietin dosage needed to maintain the hematocrit was greater in HD patients (HD, 11,211 +/- 7,484 U versus PD, 3,790 +/- 1,968 U; P < 0.0001). We conclude that (1) smaller children in both groups tend to have a greater Kt/V, (2) Kt/V greater than 2.75 in PD patients may not improve nutrition per se and could result in increased albumin losses, and (3) erythropoietin dosing appears to correlate best with patient size (age) rather than degree of anemia.

Adolescent↗

PubMed2000

Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis Of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE).

Many cutpoints have been proposed to categorize continuous variables in childhood acute lymphoblastic leukaemia (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age), and have been used to define therapeutic subgroups. This variation in the choice of cutpoints leads to a bias called the 'Will Rogers phenomenon'. The aim of this study was to analyse variations in the relative risk of relapse or death as a function of continuous prognostic variables in childhood ALL and to discuss the choice of cutpoints. We studied a population of 1545 children with ALL enrolled in three consecutive protocols named FRALLE 83, FRALLE 87 and FRALLE 89. We estimated the risk of relapse or death associated with different values of each continuous prognostic variable by dividing the sample into quintiles of the distribution of the variables. As regards age, a category of children under 1 year of age was distinguished and the rest of the population was divided into quintiles. The floated variance method was used to calculate the confidence interval of each relative risk, including the reference category. The relation between the quantitative prognostic factors and the risk was monotonic for each variable, except for age. For the white blood cell count (WBC), the relation is log linear. The risk associated with WBC values in the upper quintile was 1.9 times higher than that in the lower quintile. The peripheral blast cell count correlated strongly with WBC (correlation coefficient: 0.99). The risk increased with the haemoglobin level, and the risk in the upper quintile was 1.3 times higher than that in the lower quintile. The risk decreased as the platelet count increased: the risk in the lower quintile was 1.2 times higher than that in the upper quintile. The risk increased gradually with increasing age above one year. The small subgroup of patients (2.5% of the population) under 1 year of age at diagnosis had a risk 2.6 times higher than the reference category of patients between 3 and 4.3 years of age. When the risk associated with a quantitative prognostic factor varies monotonously, the selection of a cutpoint is arbitrary and represents a loss of information. Despite this loss of information, such arbitrary categorization may be necessary to define therapeutic stratification. In that case, consensus cutpoints must be defined if one wants to avoid the Will Rogers phenomenon. The cutpoints proposed by the Rome workshop and the NCI are arbitrary, but may represent an acceptable convention.

Adolescent↗

PubMed2000

Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC).

The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2-3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy.

Adult↗

PubMed2000

Outcome of reduction mammaplasty--a patients' perspective.

There have been several studies analysing the outcome of reduction mammaplasty in the literature. Our study is condition specific, with emphasis placed on the patients' subjective experience of treatment. Following a successful pilot study, data were obtained from 74 patients' charts and an anonymous postal questionnaire over a 1-year period. Sixty-six returned the questionnaire complete (89%). Overall satisfaction with the procedure was high (94%). The outcome of surgery with respect to breast size, shape, nipple position, sensation and scarring is documented. All patients expressed marked improvement regarding neck pain, back pain, submammary rash, breast pain and shoulder grooving. Other parameters including psychological wellbeing, quality of life, time on the waiting list, weight of tissue removed and complication rates are analysed. The findings of this study demonstrate overwhelming physical and psychological benefits from surgery. This supports the suggestion that reduction mammaplasty is not primarily cosmetic, producing significant improvement in symptoms.

Esthetics↗

PubMed2000

The psychopathy checklist--screening version: an examination of criteria and subcriteria in three forensic samples.

The development and refinement of psychopathy represent a critical issue in clinical and forensic practice. During the last decade, important advances in the operationalization of psychopathy were achieved, primarily through the development of the Psychopathy Checklist (PCL) and its subsequent versions (PCL-R and PCL:SV). PCL ratings are based primarily on item descriptions or subcriteria. The current study serves to break new ground as the first systematic investigation of PCL:SV subcriteria by addressing their psychometric properties and exploring their construct and criterion-related validation. Previously unanalyzed data from three samples were integrated: female offenders, male forensic patients, and male adolescent offenders. Results largely support the use of subcriteria as homogeneous components of criteria and provide strong initial evidence of their construct validity. Results are less conclusive regarding criterion-related validity. For female offenders, they suggested the potential value of specific PCL:SV subcriteria for predicting verbal aggression. Confirmatory factor analysis provided encouraging results on the applicability of the standard two-factor model of psychopathy. However, a first-order principal axis factoring suggested further refinements in our understanding of psychopathy.

Adolescent↗

PubMed2000

Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of the raltitrexed plus oxaliplatin combination regimen, to explore its safety and pharmacokinetics, and to assess its antitumor activity in patients with advanced solid tumors. PATIENTS AND METHODS: Forty-eight patients received the combination of raltitrexed plus oxaliplatin. Raltitrexed was administered as a 15-minute infusion followed by oxaliplatin as a 2-hour infusion 1 hour later, repeated every 3 weeks. Seven dose levels were explored, ranging from 2 to 3.75 mg/m(2) and from 85 to 130 mg/m(2) for raltitrexed and oxaliplatin, respectively. The pharmacokinetics of both raltitrexed and oxaliplatin was assessed at the last three dose levels. RESULTS: Forty-six patients were assessable for toxicity. Severe toxicities usually occurred from dose level V (raltitrexed 3 mg/m(2) and oxaliplatin 130 mg/m(2)). This combination was not myelosuppressive, eliciting only sporadic grades 3 and 4 neutropenia and/or thrombocytopenia without complications. There was no alopecia. DLTs were asthenia and nausea/vomiting, despite systematic antiemetic prophylaxis. Dose level VI (raltitrexed 3.5 mg/m(2) and oxaliplatin 130 mg/m(2)) was deemed to be the MTD. Eight confirmed partial responses were observed: six patients with malignant mesothelioma (both pretreated and nonpretreated), one with fluorouracil-refractory pancreatic carcinoma, and one with renal carcinoma. Evaluation of the pharmacokinetics of both drugs did not suggest any drug interaction. CONCLUSION: The combination of raltitrexed and oxaliplatin given as consecutive short infusions every 3 weeks seems to be an acceptable regimen that allows a dose-intensity as high as the sum of the recommended doses of each agent given alone. The dose recommended for further phase II studies is raltitrexed 3 mg/m(2) and oxaliplatin 130 mg/m(2) every 3 weeks. Promising antitumor activity has been observed in patients with malignant mesothelioma.

Adult↗

PubMed2000

The renal expression of transforming growth factor-beta isoforms and their receptors in acute and chronic experimental diabetes in rats.

Transforming growth factors-beta (TGF-beta) are fibrogenic factors that have been strongly implicated in the development of diabetic nephropathy. Our aim was to use two animal models [the streptozotocin (STZ)-induced diabetic rat and the genetically prone biobreeding (BB) rat] to fully characterize the responses of the renal TGF-beta system in both short- and long-term diabetes. In this study changes in the entire renal TGF-beta system, at both protein and messenger RNA (mRNA) levels, have been characterized using the techniques of immunocytochemistry, Western blotting, and ribonuclease protection assay. We also used Western blotting of pro-collagen-I C-peptide to demonstrate that the rate of fibrogenesis was highest over the first 2 weeks of diabetes. TGF-beta1, TGF-beta2, and receptor mRNA and protein were detected in the control nondiabetic kidney. It was found that dramatic and dynamic changes occur in all parts of the renal TGF-beta axis in both models of experimental diabetes, but TGF-beta2 and TGF-betaRII proteins were the predominant responsive element, particularly during the acute phase of disease. For example, during the acute phase of disease (0-30 days), although renal TGF-beta1 mRNA levels were elevated, no increases in the corresponding protein were detected in the kidney. By contrast, in the absence of changes in TGF-beta2 mRNA levels, twice as much TGF-beta2 protein was measured in the kidney by day 30 of STZ-induced diabetes compared with day 0 controls analyzed by Western blotting (P < 0.05), and the protein was localized both to the nuclei and cytoplasm of glomerular cells, analyzed by immunocytochemistry. In addition, three times as much TGF-betaRII protein was found by day 90 of STZ-induced diabetes compared with day 0 controls, making this the most responsive receptor type. These results suggest that the entire TGF-beta axis has a role in the etiology of kidney fibrosis and could be manipulated therapeutically to preserve kidney function.

Albuminuria↗

PubMed2000

Protection against Staphylococcus aureus mastitis in dairy cows using a bismuth-based teat seal containing the bacteriocin, lacticin 3147.

We assessed the effectiveness of a novel dry cow treatment containing lacticin 3147 using deliberate challenge studies in lactating cows. Infection-free quarters of lactating cows were infused with Teat seal (Cross Vetpharm Group, Ltd., Dublin, Ireland) combined with the food-grade bacteriocin, lacticin 3147. Natural infection of the teat was simulated by deliberately introducing Staphylococcus aureus into the teat duct and teat sinus. Relative to control quarters, teat seal plus lacticin 3147 reduced the number of teats shedding viable cells when an inoculum of either approximately 1.7 x 10(3) or approximately 6.8 x 10(3) cfu per teat was used. In addition, the numbers of challenge organisms in those teats from which S. aureus was subsequently recovered were also reduced. However, when the concentration of bacteriocin in the teat seal formulation was reduced by approximately 50%, the number of teats shedding S. aureus cells was not reduced. These data indicate the potential for lacticin 3147 to prevent staphylococcal mastitis infections when a sufficient concentration of the bacteriocin is present. This study also highlights the application of a lactating-cow model to assess the effectiveness of antimicrobial intramammary products on mastitic cell populations.

Animals↗

PubMed2000

An effective lacticin biopreservative in fresh pork sausage.

Lacticin 3147 is a novel heat-stable bacteriocin, produced by Lactococcus lactis DPC 3147, that exhibits a broad-range inhibition spectrum similar to nisin. In this study, the effect of lacticin 3147 and nisin on the shelf life of fresh pork sausage and their ability to control pathogens (Clostridium perfringens DSM 756, Salmonella Kentucky AT1) and nonpathogenic Listeria innocua DPC 1770 was investigated. The following preservative regimens were evaluated, both in broth and sausage systems: (i) 450 ppm of sodium metabisulphite; (ii) 500 IU g(-1) or ml(-1) of nisin, (iii) 2500 arbitary units (AU) g(-1) or ml(-1) of lacticin 3147; (iv) 2% sodium lactate and 500 IU of nisin; (v) 2% sodium citrate and 500 IU g(-1) or ml(-1) of nisin; (vi) 2% sodium lactate and 2500 AU g(-1) or ml(-1) of lacticin 3147, (vii) 2% sodium citrate and 2500 AU g(-1) or ml(-1) of lacticin 3147, (viii) 2% sodium lactate, and (ix) 2% sodium citrate. There was no significant difference in the activity of nisin and lacticin 3147 against any of the target strains used, both bacteriocins performing significantly better than sodium metabisulfite against gram-positive strains in broth systems. Trends indicate that the combination of organic acids with either bacteriocin enhanced its activity against Salmonella Kentucky and L. innocua and was particularly effective in the inhibition of C. perfringens in fresh pork sausage. In addition, lacticin 3147 combined with either sodium citrate or sodium lactate maintained significantly lower (P < 0.05) total aerobic plate counts for the duration of the trials and may function as an alternative to sodium metabisulfite in the preservation of fresh pork sausage.

Animals↗

PubMed2000

[Introduction to regression models].

Regression models are widely used. They are viewed by clinicians as a passport for a publication in major journals. The expressions: multivariate, logistic regression and Cox model are synonymous with complexity and appear both magical and seductive. Altogether, most clinicians do not read the results of regression models with a critical eye. Our aim is to describe the most common regression models in a unifying framework, and to explain how to interpret each model. We hope that investigators will then be able to discuss the models with the statisticians.

Logistic Models↗