Biomedical subjects

J G Davies

Publications and source records attributed to J G Davies.

At least 19 recordsLinked to original sources

PubMed2001

A joint approach to treating dental phobics between community dental services and specialist psychotherapy services--a single case report.

A 41-year-old male patient presented at the local dental hospital requesting treatment under IV sedation, a treatment that he had had for the past 25 years. The patient was referred to the specialist psychotherapy services for cognitive behavioural therapy (CBT), and received a 1 hour course of therapy. He was then introduced to dental services, and at this visit had a check-up, OPG, and treatment planning discussion. At a subsequent visit he had local anaesthetic, three fillings, and a scale and polish. The patient is now able to return to general dental practice, after only a brief therapeutic intervention, and subsequent dental treatment. The present and future cost saving to the NHS is substantial compared with the treatment method initially sought by the patient.

Adult↗

PubMed2000

Physicochemical characteristics of triacyl lipid A partial structure OM-174 in relation to biological activity.

The triacylated lipid A partial structure OM-174 was characterized in detail using a variety of physical and biological techniques. OM-174 aggregates adopt the micellar HI structure. The temperature (Tc) of the gel to liquid-crystalline phase transition of the hydrocarbon chains is 0 degrees C, from which high fluidity of the acyl chains at 37 degrees C can be deduced. The molecular area of a single OM-174 molecule at a surface pressure of 30 mN x m-1 is 0.78 +/- 0.04 nm2. Conformational analyses, using IR spectroscopy, of the behavior of the various functional groups of OM-174 as compared with hexa-acyl lipid A suggest altered hydration of the phosphate charges and unusually strong hydration of the ester groups, which is probably related to the high accessibility of these groups to water in the micellar aggregate structure. OM-174 was shown to intercalate into a phospholipid membrane corresponding to the macrophage membrane within seconds in the presence, and within minutes to hours in the absence, of LPS-binding protein. In the Limulus amebocyte lysate assay, the triacyl lipid A is more than 105-fold less active than hexa-acyl lipid A, but only 10-fold less active in inducing IL-6 in human mononuclear cells, and equally active in inducing NO production in murine macrophages. These findings are used to explain the mechanism of the lipid A-induced cell activation.

Animals↗

PubMed2000

Comparison of doses for bedside examinations of the chest with conventional screen-film and computed radiography: results of a randomized controlled trial.

PURPOSE: To compare the radiation doses received by patients during bedside chest radiography when a computed radiography system was used and when a 400-speed screen-film system was used. MATERIALS AND METHODS: A randomized controlled trial was performed whereby all patients who were admitted to an intensive care unit were randomly assigned at admission to have all radiographic chest images obtained with either computed or conventional screen-film radiography. Doses were measured for 1 year, during which 269 patients underwent imaging. For these patients, surface entry doses were measured by means of individual thermoluminescent dosimeters placed on the skin at the center of the radiation beam. In addition, data were collected relating to the patient and examination characteristics, as well as to repeat examinations. Effective doses were calculated. RESULTS: The patients in the two arms of the study were well matched. The surface entry doses were higher in the computed radiography group (median, 0.21 mGy for computed radiography and 0.16 mGy for conventional radiography), and the effective doses were also higher (median, 0.036 mSv for computed radiography and 0.027 mSv for conventional radiography). Fewer examinations were repeated when computed radiography was used. CONCLUSION: When computed radiography was used, patient doses increased. The speed of this computed radiography system, which uses phosphor plate imaging, equates approximately to a 300-speed screen-film system.

Adolescent↗

PubMed1999

Cure of colon cancer metastasis in rats with the new lipid A OM 174. Apoptosis of tumor cells and immunization of rats.

The antitumoral effect of the new lipid A OM 174 was investigated in a model of colon cancer in rats. Peritoneal carcinomatosis were induced in BDIX rats by intraperitoneal injection of syngeneic PROb cancer cells. The treatment started 2 weeks later, when rats had macroscopic peritoneal nodules. An antitumoral effect was first obtained with OM 174 intraperitoneally injected, then an intravenous treatment was developed. When injected 15 times intravenously, at the dose of 1 mg/kg, 2 days apart, OM 174 induced the complete regression of tumors and hemorrhagic ascitis in 90% of the tumor-bearing rats, whereas all the untreated rats died of their tumors. To our knowledge, this treatment is the most effective ever applied to macroscopic tumors. Furthermore, the treatment induced the immunization of rats since the reinjection of PROb tumor cells in OM 174-cured rats did not cause the formation of new tumors while injection of another syngenic colon tumor cells did. Only in treated rats tumors were infiltrated with lymphocytes, macrophages and fibroblasts. The treatment did not increase necrosis but generated apoptotic areas. OM 174 was not directly toxic for tumor cells, and thus the observed effect involved the host-mediated antitumor reaction. Therefore we hypothesize that OM 174 therapy induces tumor cell apoptosis, stimulates the phagocytosis of apoptotic bodies and then activates immune system by antigen presentation.

Animals↗

PubMed1999

Comparison of film, hard copy computed radiography (CR) and soft copy picture archiving and communication (PACS) systems using a contrast detail test object.

This paper describes two experiments where a widely available test object (FAXIL TO20) was used to compare film, hard copy computed radiography (CR) and soft copy picture archiving and communication systems (PACS) images. Baseline images were produced with a fixed mAs. All images were scored by four experienced medical physicists. Contrast detail curves for the three types of images were almost identical. A second series of images was produced with the mAs varying from 1 mAs to 250 mAs. The contrast detail curves were plotted for each mAs value and the wider exposure latitude of CR compared with film was demonstrated. Use of PACS provided no further increase in exposure latitude. The density of the film images increased with mAs but the density of the CR hard copy images remained constant. It is of concern that the wider latitude of the CR images extends to exposures that are much higher than those used for film with no noticeable change in CR image density but with better images at higher exposures, because the potential exists for patient doses to increase. Hard copy CR images provide information about the exposure index which relates to the input dose to the plate and hence approximately to the dose to the patient. However, since such information is currently not available on default soft copy images, the authors suggest that all manufacturers of PACS should provide an indication of dose as a mandatory default setting.

Evaluation Studies as Topic↗

PubMed1998

Use of in vitro models of haemofiltration and haemodiafiltration to estimate dosage regimens for critically ill patients prescribed cefpirome.

BACKGROUND: The physico-chemical properties of cefpirome (low protein binding, high water solubility and low molecular weight) suggest that it may be lost readily from the extracorporeal circulation of intensive care unit patients during continuous renal replacement therapy. METHOD: In order to make informed dosage recommendations for patients receiving artificial renal support, cefpirome loss from human blood has been quantified using in vitro models of continuous haemofiltration and haemodiafiltration. Cefpirome clearance was measured using three membrane types at varying ultrafiltrate (UFR) and dialysis flow rates (Qd). RESULTS: During haemofiltration cefpirome was found to cross hollow fibre polyamide (PA) and polyacrylonitrile (PAN) membranes with equal efficiency. The mean sieving coefficients (S) of both PA and PAN membranes were consistently high (> 0.7) when two different ultrafiltration rates were used. Changing the ultrafiltration rate or membrane type had no significant effect on the sieving coefficient of cefpirome but did result in an increase in cefpirome filter clearance (Fcl). Using the haemodiafiltration model, cefpirome penetrated PAN membranes (flat plate AN69S) more efficiently than hollow fibre PA membranes (FH66D). In each case, increasing the dialysis flow rate reduced the S-value. However, although increasing Qd was associated with a greater Fcl of cefpirome when PAN membranes were employed, no such relationship was found for the PA hollow fibre membrane. CONCLUSION: The information generated can be used to estimate a dosing regimen for intensive care patients prescribed cefpirome and receiving continuous renal replacement therapy.

Cephalosporins↗

PubMed1996

Quinine clearance in continuous venovenous hemofiltration.

OBJECTIVE: To describe a case involving the removal of quinine by continuous venovenous hemofiltration (CVVH) in a patient with malaria and acute renal failure and to present recommendations on the dosing of quinine in such patients. CASE SUMMARY: A 50-year-old white man developed Plasmodium falciparum malaria following a visit to Nigeria. Although he received intravenous quinine, his condition deteriorated and he required intensive care management, including CVVH for the management of his acute renal failure. Quinine plasma concentrations were measured to determine both total body and extracorporeal clearance of the drug. DISCUSSION: To our knowledge this is the first report quantifying the removal of quinine by CVVH. The drug is not significantly removed by this extracorporeal process. The filter clearance accounted for less than 1.5% of the total body clearance. CONCLUSIONS: Initially the dosage of quinine administered to patients presenting with P. falciparum infection should not be reduced because of renal failure. This is particularly important when cerebral involvement is suspected. Subsequent dosage modification should reflect the severity of the patient's clinical condition and the plasma quinine concentration achieved, and should not be limited by the degree of renal impairment present.

Acute Kidney Injury↗

PubMed1993

A test for the assessment of 'hygienic' hand disinfection using rotavirus.

A standardized test procedure is described in which finger tips are inoculated with bovine rotavirus. The level of virus recovered after disinfection of artificially contaminated hands with various disinfectant detergents, alcoholic solutions and alcoholic formulations was determined. The method was found to be easy to perform and reproducible. The most efficient method for removal of virus from fingertips was found to be treatment with alcoholic solutions or products. Soap and water and disinfectant detergents were found to be a much less effective method of removing virus from contaminated hands.

Alcohols↗

PubMed1993

Preliminary study of test methods to assess the virucidal activity of skin disinfectants using poliovirus and bacteriophages.

Two tests for assessing the virucidal activity of antiseptics are proposed. These involve applying either poliovirus (vaccine strain Sabin 1 an) or Escherichia coli bacteriophage (MS2 or K1-5) to the fingertips. Both test viruses are considered safe although poliovirus may be unacceptably tolerant to antiseptics. The use of bacteriophages as test organisms precludes the need for sophisticated recovery systems and can be undertaken readily by any bacteriology laboratory. The virucidal activity of 70%, 80% and 90% ethanol, 7.5% povidone-iodine, and soap and water was assessed using these tests. Thorough cleansing, followed by disinfection with 90% ethanol, was the most effective treatment. Removal of viruses from the gloved hand was also assessed and this was found to be more easily achieved than cleaning and disinfecting the ungloved hand. Wearing gloves protects the hands from viral contamination but changing them after each patient or contact is expensive.

Administration, Topical↗

PubMed1991

Human interleukin-5 expressed in Escherichia coli: assignment of the disulfide bridges of the purified unglycosylated protein.

Human interleukin-5 is a homodimer; each subunit contains two cysteine residues that form two inter-subunit disulfide bonds. The topology of the disulfides in recombinant human interleukin-5 produced in Escherichia coli was studied by proteolytic digestion and peptide mapping. Disulfide linked peptides containing cysteine 42 linked to cysteine 84 were isolated. This indicated that cysteines 42 and 84 of one subunit were linked in an antiparallel manner to cysteines 84 and 42 of the other subunit.

Amino Acid Sequence↗

PubMed1991

A test procedure for evaluating surgical hand disinfection.

A technique for assessing the immediate and prolonged efficacy of surgical scrubs and alcoholic hand rubs is described. A mean baseline count is obtained from all volunteers and logarithmic reductions in resident skin flora immediately after one or more applications, and after wearing gloves for 3 h, are measured. Loose-fitting surgical gloves are used for sampling resident flora. Preparations were applied using a standard technique for 2 min, apart from one test with 70% isopropanol (IPA) in which the application time was 30 s. Two studies are described, one of which compared four chlorhexidine scrubs, and the second 70% IPA, 7.5% povidone-iodine scrub, 2% triclosan cleanser and unmedicated bar soap. In spite of their constituent similarity, the four chlorhexidine scrubs varied considerably in efficacy and user acceptability. A 2 min application of 70% IPA was the most effective treatment, and gave log10 reductions of 1.65 for immediate and 1.58 for prolonged effect. This was marginally more effective than a 30 s application, but the difference was not significant. 'Hibiscrub' was the most effective aqueous formulation and gave reductions of 1.01 for immediate effect and 1.16 for prolonged effect. The test described could be used by reference centres and manufacturers to assess the efficacy of new and existing surgical hand disinfection formulations.

Adolescent↗

PubMed1990

Hygienic hand disinfection tests in three laboratories.

A comparative study was made in three laboratories of a test for hygienic hand disinfection. Staphylococcus aureus was applied to the fingertips of a total of 74 volunteers (49 female and 25 male) and the effect of washing with three chlorhexidine preparations and one non-medicated soap was assessed after one and five applications. Fingertip inoculation is convenient and is a realistic representation of the in-use situation. Although significant differences were obtained between log10 reductions in test organisms using the same formulation in different centres, and different periods in the same centre, the maximum differences after a single application of a preparation were small, e.g. between centres 0.39 and between periods in the same centre 0.55, and after multiple applications the maximum difference between centres was 0.42 and between periods in the same centre it was 0.51. The differences between preparations were similar in all centres. This test compares well with other similar tests and products can be placed in rank order of effectiveness. It is concluded that this test, if carried out under the controlled conditions described, is sufficiently reproducible between laboratories and repeatable within laboratories to be used as a standard test.

Chlorhexidine↗

PubMed1988

Insulin proteinase liberates from glucagon a fragment known to have enhanced activity against Ca2+ + Mg2+-dependent ATPase.

We find, contrary to previous reports, that substantial cleavage of glucagon by insulin proteinase occurs at only one region, namely the double-basic sequence -Arg17-Arg18-. Cleavage takes place almost exclusively between these two residues, liberating fragments glucagon-(1-17) and glucagon-(18-29). Others have shown that the fragment glucagon-(19-29) is 1000-fold more efficient compared with intact glucagon, at inhibiting the Ca2+-activated and Mg2+-dependent ATPase activity and the Ca2+ pump of liver plasma membranes. We show that this fragment is not liberated in detectable quantities by our insulin proteinase preparation. On the other hand, others have shown that glucagon-(18-29), though less active than glucagon-(19-29), was still 100-fold more active than glucagon itself in the above-mentioned system. Our observations represent the first demonstration of the release by insulin proteinase of a hormone fragment having enhanced activity, although it has yet to be shown that the activity of this fragment is important in vivo. Since the formation of glucagon-(19-29) from glucagon-(18-29) would involve merely removal of Arg18, a second enzyme might exist to provide the more active fragment.

Ca(2+) Mg(2+)-ATPase↗

PubMed1988

The chemical characterization of the radioactive products derived from [[3H]PheB1]insulin in the circulation of the rat.

1. Gel filtration of rat plasma taken 1 h after subcutaneous injection of [[3H]PheB1]insulin gives three peaks of radioactivity. 2. The material in these peaks was characterized by electrophoresis and chromatography. 3. We conclude that [[3H]PheB1]insulin is rapidly degraded to free tritiated phenylalanine. The phenylalanine is subsequently used for synthesis of plasma proteins de novo.

Amino Acid Sequence↗

PubMed1988

Engineered rat insulin I analogue having a B16 Tyr/Asp replacement exhibits unchanged susceptibility to cleavage by insulin proteinase.

An analogue of rat insulin I was produced by oligonucleotide-directed mutagenesis of a cloned rat preproinsulin I cDNA, followed by expression of a resulting mutant gene in Escherichia coli K-12 and proteolytic cleavage of mutant proinsulin isolated from this bacterium. The Tyr-to-Asp replacement at residue B16 in the insulin analogue had been expected to diminish the rate of cleavage of the molecule by the enzyme insulin proteinase, since the bond TyrB16-LeuB17, invariant in all mammalian species, had been proposed by other authors as one of the early, major sites of proteolytic attack. In the event the substitution had no measurable effect on the rate of degradation by insulin proteinase. Thus we find no support in these experiments for the hypothesis that the site in question is of primary importance in the degradation of rat insulin I by the enzyme.

Animals↗

PubMed1988

Identification of radioactive insulin fragments liberated by insulin proteinase during the degradation of semisynthetic [3H]GlyA1]insulin and [3H]PheB1]insulin.

(1) We [Muir, Offord & Davies (1986) Biochem. J. 237, 631-637 and Davies, Muir & Offord (1986) Biochem. J. 240, 609-612] have previously identified a major product in the degradation of insulin by insulin proteinase (the N-terminal fragment produced by cleavage between residues LeuA13 and TyrA14, SerB9 and HisB10) together with evidence for a minor cleavage site between HisB10 and LeuB11 or between LeuB11 and ValB12. (2) We now present evidence for minor sites of cleavage between TyrA14 and GlnA15, GluB13 and AlaB14 as well as HisB10 and LeuB11.

Chromatography, High Pressure Liquid↗

PubMed1988

Identification by fast atom bombardment mass spectrometry of insulin fragments produced by insulin proteinase.

We describe the isolation by reversed-phase h.p.l.c. of a number of products of the degradation of insulin by insulin proteinase and their direct analysis by fast atom bombardment mass spectrometry (f.a.b.-m.s.). Various semisynthetically labelled insulins were used, including [[2H2]GlyA1]insulin and [18O]LysB29]insulin. The results obtained confirm and extend the results obtained by non-mass-spectrometric methods [Davies, Muir, Rose & Offord (1988) Biochem. J. 249, 209-214, and papers cited therein]. Cleavage sites were identified between positions A13-A14, A14-A15, B9-B10, B13-B14, B24-B25 and B25-B26. The advantages and disadvantages of the application of f.a.b.-m.s. to such studies are discussed.

Amino Acid Sequence↗

PubMed1988

Hand disinfection: a comparison of various agents in laboratory and ward studies.

The efficacy of 14 handwashing or disinfectant preparations was compared in laboratory tests on staff volunteers. The test organism, Escherichia coli, was applied to the fingertips and log reductions (LR) were measured following treatment with the test agent and control preparations (70% isopropanol and non-medicated bar soap). Alcoholic preparations, particularly n-propanol and isopropanol were the most effective showing LRs of 3.1-3.8. Chlorhexidine (LR 2.9) and povidone-iodine detergent preparations were significantly more effective than non-medicated soap (LR 2.1), but triclosan products were not. In addition the residual effect of several of these formulations was assessed after 10 applications by comparing the survival of E. coli on the fingertips over a 32-min period. This number of handwashes compares favourably with those recorded during an 8 h nursing shift. Chlorhexidine-detergent consistently showed the best residual activity. Alcoholic formulations showed little or no residual effect. The survival studies show that on the whole gram-positive organisms (Staphylococcus aureus and Candida albicans) survive better on the skin than Gram-negative bacilli (GNB). However, it would seem that GNB which are considered to be residents (Acinetobacter calcoaceticus and Enterobacter spp.) survive much better than many other GNB (Pseudomonas aeruginosa, E. coli and Proteus vulgaris). The Klebsiella species varied in survival times. Random sampling of ward staff hands showed that contamination with S. aureus and GNB was greater in dermatological and general wards than in an isolation unit, where handwashing or disinfection was carried out after every patient contact. No cross-infection occurred in the isolation ward during periods of study in which 70% alcohol, chlorhexidine-detergent and non-medicated soap were used.

Alcohols↗