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Biomedical subjects

P Day

Publications and source records attributed to P Day.

At least 19 recordsLinked to original sources
PubMed2006

A sample distribution programme for erythropoietin.

A survey was sent to laboratories participating in the United Kingdom External Quality Assessment Service (UKNEQAS) Haematinics Scheme about the measurement of serum erythropoietin (EPO). Six laboratories, from a total of 120 that returned the survey, were measuring serum EPO concentrations by commercially available immunoassays on site in the United Kingdom. The workload of the laboratories varied from up to 100 specimens per month to more than 100 specimens analysed per week. All laboratories included control material in the assays and none of the laboratories was participating in an external quality assessment scheme for serum EPO. Four laboratories agreed to take part in the first sample distribution programme, with five and six laboratories participating in distributions 2 and 3 respectively. The results from eight kits were compared from the three distributions over a 2-year period. The serum EPO concentrations for the methods showed some variation across the range of 2.9-200 U/l when the serum EPO concentrations for each method were compared with the whole method mean. The results from this scheme have identified a role for an external quality assessment scheme for serum EPO measurements.

Benchmarking↗
PubMed2004

Open vs. closed lateral internal sphincterotomy for idiopathic fissure-in-ano: a prospective, randomized, controlled trial.

PURPOSE: Internal sphincterotomy remains the "gold standard" for treatment of anal fissure but is associated with a risk of imperfect continence. Recent studies have suggested that surgical technique (open vs. closed) may influence incontinence rates after sphincterotomy. This study was designed to assess the short-term and long-term incidence of incontinence after open and closed internal sphincterotomy. METHODS: Seventy-nine patients were randomly assigned to open or closed internal sphincterotomy, performed in standardized fashion by trainee staff. Standardized questionnaires assessing continence (modified Wexner score) were administered preoperatively and at 1, 6, and 52 weeks. Postoperative stay, pain scores, complications, and fissure healing were prospectively assessed by an independent observer. RESULTS: Three patients were lost to follow-up, leaving 36 closed (16 males; mean age, 45.1 years) and 40 open (21 males; mean age, 47.9 years) internal sphincterotomy patients for assessment. All operations were performed as day case procedures with no readmissions. At six weeks postoperative, 96 percent of fissures had healed. There were no significant differences in pain scores between closed and open internal sphincterotomy at Day 1 or Day 3 postoperative. New incontinence of any grade was seen in 6.8 percent of patients at 52-week follow-up. Three patients (4.1 percent, 1 closed, 2 open) suffered major incontinence at 52 weeks. There were no significant differences in continence at 1, 6, or 52 weeks, although more open patients experienced minor imperfections at 1 week. CONCLUSIONS: Incontinence after internal sphincterotomy is not insignificant. The technique (closed vs. open) does not seem to influence incontinence rates.

Adult↗
PubMed2003

Bulk spontaneous magnetization in the new radical cation salt TM-TTF[Cr(NCS)(4)(isoquinoline)(2)] (TM-TTF = tetramethyltetrathiafulvalene).

A new organic-inorganic hybrid salt [TM-TTF][Cr(NCS)(4)(isoquinoline)(2)] (1) (TM-TTF = Tetramethyltetrathiafulvalene) has been synthesized. Compound 1 crystallizes in the triclinic P space group with a = 8.269(1), b = 10.211(2), and c = 11.176(2) A, alpha = 89.244(9), beta = 88.114(6), and gamma = 74.277(7) degrees, V = 907.6(3) A(3), and Z = 1. The crystal structure was resolved in the temperature range between 223 and 123 K, showing that changes in the crystal structure at low temperature result in stronger interactions between anions and cations. The packing of 1 consists of mixed anion-cation layers in the bc plane containing S.S and pi-pi anion-cation interactions, the layers being connected by very short S.S contacts between anions and cations. Magnetic measurements in a small external field show bulk spontaneous magnetization with a T(c) of 6.6 K consistent with the presence of weakly coupled ferrimagnetic order in compound 1. The EPR measurements also demonstrate the interaction between the d and pi electrons and the presence of an internal magnetic field brought about by the magnetic ordering.

Journal Article↗
PubMed2001

Crystal and magnetic structures of afeIIFeIII(C2O4)3 (A = organic cation): two-dimensional honeycomb ferrimagnets.

Ferrimagnetic tris-oxalato-ferrate(II,III) salts with general formula AFeIIFeIII(C2O4)3 (A = quaternary ammonium, phosphonium) all crystallise in two-dimensional hexagonal honeycomb lattices but while some show conventional Néel type Q magnetisation at low temperature others show negative Néet type N magnetisation below a compensation temperature Tcomp. The compounds having negative magnetisation show a discontinuity in the magnetisation at a temperature between Tcomp and Tc suggesting a magneto-strictive transition. For the type Q compounds, hysteresis and frequency dependent AC susceptibility show that the low temperature magnetic state is glassy, either because of frustration of random anisotropy domains below a blocking temperature, or imbalance in the fractions of FeII and FeIII.

Anisotropy↗
PubMed2001

Crystal chemistry and physical properties of superconducting and semiconducting charge transfer salts of the type (BEDT-TTF)(4)[A(I)M(III)(C2O4)3]*PhCN (A(I) = H30,NH4,K; M(III) = Cr, Fe, Co, Al; BEDT-TTF = bis(ethylenedithio)tetrathiafulvalene.

Synthesis, structure determination by single-crystal X-ray diffraction, and physical properties are reported and compared for superconducting and semiconducting molecular charge-transfer salts with stoichiometry (BEDT-TTF)(4)[A(I)M(III)(C(2)O(4))(3)].PhCN, where A(I) = H(3)O, NH(4), K; M(III) = Cr, Fe, Co, Al; BEDT-TTF = bis(ethylenedithio) tetrathiafulvalene. Attempts to substitute M(III) with Ti, Ru, Rh, or Gd are also described. New compounds with M = Co and Al are prepared and detailed structural comparisons are made across the whole series. Compounds with A = H(3)O(+) and M = Cr, Fe are monoclinic (space group C2/c), at 150, 120 K a = 10.240(1) A, 10.232(12) A; b = 19.965(1) A, 20.04(3) A; c = 34.905(1) A, 34.97(2) A; beta = 93.69(1) degrees, 93.25(11) degrees, respectively, both with Z = 4. These salts are metallic at room temperature, becoming superconducting at 5.5(5) or 8.5(5) K, respectively. A polymorph with A = H(3)O(+) and M = Cr is orthorhombic (Pbcn) with a = 10.371(2) A, b = 19.518(3) A, c = 35.646(3) A, and Z = 4 at 150 K. When A = NH(4)(+), M = Fe, Co, Al, the compounds are also orthorhombic (Pbcn), with a = 10.370(5) A, 10.340(1) A, 10.318(7) A; b = 19.588(12) A, 19.502(1) A, 19.460(4) A; c = 35.790(8) A, 35.768(1) A, 35.808(8) A at 150 K, respectively, with Z = 4. All of the Pbcn phases are semiconducting with activation energies between 0.15 and 0.22 eV. For those compounds which are thought to contain H(3)O(+), Raman spectroscopy or C=C and C-S bond lengths of the BEDT-TTF molecules confirm the presence of H(3)O(+) rather than H(2)O. In the monoclinic compounds the BEDT-TTF molecules adopt a beta' ' packing motif while in the orthorhombic phases (BEDT-TTF)(2) dimers are surrounded by monomers. Raman spectra and bond length analysis for the latter confirm that each molecule of the dimer has a charge of +1 while the remaining donors are neutral. All of the compounds contain approximately hexagonal honeycomb layers of [AM(C(2)O(4))(3)] and PhCN, with the solvent occupying a cavity bounded by [M(C(2)O(4))(3)](3-) and A. In the monoclinic series each layer contains one enantiomeric conformation of the chiral [M(C(2)O(4))(3)](3-) anions with alternate layers having opposite chirality, whereas in the orthorhombic series the enantiomers form chains within each layer. Analysis of the supramolecular organization at the interface between the cation and anion layers shows that this difference is responsible for the two different BEDT-TTF packing motifs, as a consequence of weak H-bonding interactions between the terminal ethylene groups in the donor and the [M(C(2)O(4))(3)](3-) oxygen atoms.

Journal Article↗
PubMed2001

Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance.

AIMS: To determine whether various markers of bone turnover and/or plasma cytokines differ in patients with multiple myeloma (MM) compared with patients with monoclonal gammopathies of undetermined significance (MGUS). METHODS: We studied 22 MM patients and 18 MGUS patients presenting over an 18-month period and compared their data with those from 20 age- and sex-matched patients presenting with primary osteoporosis. According to the Salmon and Durie classification, there were eight patients with stage I, nine with stage II and five with stage III disease. All patients had densitometric evidence of osteoporosis and were classified according to bone marrow evidence of plasma cell dyscrasia. Measured variables included markers of bone formation and bone resorption, and plasma cytokines. RESULTS: Patients with MM and MGUS did not differ with respect to their mean age, male : female sex ratio, height, weight, serum calcium, 25-hydroxyvitamin D and parathyroid hormone concentrations. Patients with MM had significantly lower concentrations of haemoglobin (109 vs 135 g/L) and serum transforming growth factor (TGF)-beta (261 vs 348 pg/mL) than patients with MGUS, and higher concentrations of serum paraproteins (31.1 vs 7.4 g/L), beta2-microglobulin (3.5 vs 2.2 g/L), % plasma cell numbers (35.3 vs 2.1%) and urinary deoxypyridinoline excretion rates (u-DPYD; 7.7 vs 5.9 nmol/mmol creatinine; P < 0.05 for all comparisons). In multivariate analysis, the serum paraprotein (beta coefficient = -0.067; 95% confidence intervals (CI), -0.019 to -0.005; P = 0.0012), u-DPYD excretion rates (beta coefficient = -0.012; 95% CI, -0.113 to -0.02; P= 0.0058) and serum TGF-beta concentrations (beta coefficient = -0.002; 95% CI, -0.0002 to -0.02; P= 0.02) were the most important variables differentiating between MM and MGUS, after excluding lytic bone lesions, % plasma cell numbers and haemoglobin concentrations. CONCLUSIONS: The well-established criteria for diagnosing MM include the presence of lytic bone lesions, plasmacytosis, haemoglobin and paraprotein concentrations. The u-DPYD excretion rate, a sensitive non-invasive marker of bone resorption, may help in differentiating between MM and MGUS, as well as serving as a marker of underlying bone disease activity in these patients.

Aged↗
PubMed2001

Dynamics of Epstein-Barr virus DNA levels in serum during EBV-associated disease.

A real-time polymerase chain reaction assay for quantitation of Epstein-Barr virus (EBV) DNA in serum was developed. This assay detected EBV DNA in 24 (89%) of 27 sera from patients with infectious mononucleosis, but only in 9 (18%) of 51 sera from EBV carriers (P < 0.001) and in none of the sera from 32 EBV-seronegative individuals. EBV DNA levels were higher in sera from infectious mononucleosis (median 8,000, range 1833-150,069 copies/ml) than from carriers (median < 2, range < 2-2980; P < 0.001). In sera of 36 children with infectious mononucleosis followed prospectively, EBV DNA levels correlated inversely with the duration of symptoms. Among 18 children with tumors including Hodgkin's disease (n = 7), non-Hodgkin's lymphoma (n = 6), Burkitt's lymphoma (n = 1), lymphoproliferative disorder (n = 4), and osteosarcoma (n = 1), EBV DNA was detected in serum from those 9 (100%) expressing EBV in the tumor (Hodgkin's disease, 3; non-Hodgkin's lymphoma, 2; lymphoproliferative disorder, 4), the levels peaking at diagnosis and correlating with disease activity. Quantitation of EBV DNA in serum may offer a simple means of monitoring patients at risk of EBV-associated lymphoproliferation.

Bone Neoplasms↗
PubMed2000

Predictors of bone mass in healthy older men in the community.

OBJECTIVES: To determine the predictors of bone mass (in lumbar spine and femoral neck) in healthy older men living in the community. DESIGN: Cross-sectional study. Bone mineral density (BMD) was measured and known predictors of bone mass and bone turnover were assessed. SUBJECTS AND SETTING: 113 independent, healthy men (70 years and over), not taking glucocorticoid therapy and without medical conditions known to affect bone mass and bone turnover, were recruited from recreational and sports clubs in southern Sydney in April/May 1997. MAIN OUTCOME MEASURES: BMD (measured by dual-energy x-ray absorptiometry); known predictors of bone mass (height; weight; body mass index; calcium level; serum 25-hydroxyvitamin D and free testosterone levels); and markers of bone turnover (serum bone Gla protein and procollagen-1 concentrations, and urinary deoxypyridinoline excretion rates). RESULTS: The mean age of the men was 76.6 years (range, 70-92 years). Mean (SE) BMD of the lumbar spine was 1.143 (0.019) g/cm2 and that of the femoral neck was 0.897 (0.013) g/cm2. BMD values indicating osteoporosis were found in the lumbar spine in 13 men (11.5%) and in the femoral neck in 35 men (31%). The best predictor of lumbar spine BMD was weight (R = 0.37; P = 0.001), and weight- and age-predicted femoral-neck BMD (R = 0.49; P < 0.001). The study group was analysed in two groups with BMD higher or lower than median bone mass corrected for age. Men with lower femoral-neck BMD for age had significantly lower weight, lower lean mass and higher bone Gla protein concentrations. In addition, men with lower lumbar spine BMD for age also had significantly lower fat mass. CONCLUSIONS: These data indicate that measures of body composition, such as weight and lean mass, are the main predictors of bone mass in healthy, community-dwelling older men.

Absorptiometry, Photon↗
PubMed1999

Independent sector regulation. Privates on parade.

The government's proposal to set up a new regulatory body for the private and voluntary sectors is regrettable. The major hospital groups in the private sector could undertake some system of clinical governance. Whatever form regulation takes, it must be supported by much better information on the private sector, including consultants' activity rates and rates of re-admission and numbers of transfers to NHS hospitals.

Facility Regulation and Control↗
PubMed1998

Differences in cytotoxicity of native and engineered RIPs can be used to assess their ability to reach the cytoplasm.

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.

Amino Acid Sequence↗
PubMed1998

Hip fracture in elderly men: the importance of subclinical vitamin D deficiency and hypogonadism.

OBJECTIVE: To determine the major risk factors for hip fracture in elderly men. DESIGN: Prospective recruitment, followed by analysis of clinical and biochemical variables. PATIENTS AND SETTING: Men aged 60 years and older who presented to St George Hospital (a 650-bed tertiary-care centre) in 1995, comprising all 41 men with hip fractures, as well as 41 hospital inpatient and 41 outpatient control subjects without hip fractures. MAIN OUTCOME MEASURES: Osteoporotic risk factors (including age, body weight, comorbid illnesses, alcohol intake, cigarettes smoked, and corticosteroid use) and serum concentrations of creatinine, urea, calcium, albumin, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and free testosterone. RESULTS: There were no significant differences between the hip fracture and two control groups on any of the osteoporotic risk factors. Men with hip fracture had significantly lower mean serum 25-hydroxyvitamin D concentration (45.6 nmol/L; 95% confidence interval [CI], 36.9-52.3 nmol/L) than both inpatient (61.1 nmol/L; 95% CI, 50.0-72.2 nmol/L) and outpatient (65.9 nmol/L; 95% CI, 59.0-72.8 nmol/L) controls (P=0.007). Subclinical vitamin D deficiency (defined as <50 nmol/L serum 25-hydroxyvitamin D) was 63% in the fracture group, compared with 25% in the control groups combined (odds ratio, 3.9; 95% CI, 1.74-8.78; P=0.0007). Inpatients with and without hip fractures had significantly lower mean serum albumin, calcium and free testosterone concentrations than outpatients (P< 0.05). In a multiple regression analysis, subclinical vitamin D deficiency was the strongest predictor of hip fracture (beta [regression coefficient], 0.34+/-0.19; P=0.013). CONCLUSIONS: Subclinical vitamin D deficiency in Australian men may contribute significantly to the development of hip fracture through the effects of secondary hyperparathyroidism, resulting in increased bone loss.

Aged↗
PubMed1998

Recognition and interaction of small rings with the ricin A-chain binding site.

Ricin A-chain is an N-glucosidase that attacks ribosomal RNA at a highly conserved adenine residue. Our recent crystallographic studies show that not only adenine and formycin, but also pterin-based rings can bind in the active site of ricin. For a better understanding of the means by which ricin recognizes adenine rings, the geometries and interaction energies were calculated for a number of complexes between ricin and tautomeric modifications of formycin, adenine, pterin, and guanine. These were studied by molecular mechanics, semi-empirical quantum mechanics, and ab initio quantum mechanical methods. The calculations indicate that the formycin ring binds better than adenine and pterin better than formycin, a result that is consistent with the crystallographic data. A tautomer of pterin that is not in the low energy form in either the gas phase or in aqueous solution has the best interaction with the enzyme. The net interaction energy, defined as the interaction energy calculated in vacuo between the receptor and an inhibitor minus the solvation energy of the inhibitor, provides a good prediction of the ability of the inhibitor to bind to the receptor. The results from experimental and molecular modeling work suggest that the ricin binding site is not flexible and may only recognize a limited range of adenine-like rings.

Adenine↗
PubMed1998

Evaluation of a lactate sensor for rapid repeated measurements of blood lactate concentration.

In critically ill patients, serial measurements of blood lactate may indicate adequacy of therapy and predict development of multi-organ failure. We studied the accuracy, precision, and repeatability of the newly developed 800 Series Lactate Sensor (Ciba Corning Diagnostic Corp., Medfield, U.S.A.). Lactate levels determined with the sensor were compared with the standard laboratory method (Abbott TDX) in 75 paired arterial blood samples from 20 patients. Agreement between methods was determined and the mean coefficient of variation calculated for repeated measurements. The bias of the sensor was -0.38 mmol/l (CI -0.23 to -0.53), and the precision +/- 0.67. The coefficient of variation for repeated measurements was 1.95% with the sensor, and 11.5% with the TDX (P = 0.007). The new sensor offers a more reproducible, rapid method of measuring lactate, vital for serial measurements. The relatively wide limits of agreement between the methods reflect the greater variability of the TDX assay.

Biosensing Techniques↗
PubMed1998

Mediators of estradiol-stimulated mitosis in the rat uterine luminal epithelium.

The effects of estradiol treatment, which stimulates cell division in rat uterine epithelial cells, on the in vivo expression of heparin-binding epidermal growth factor (HB-EGF), cyclin D1, and cyclin B1 messenger RNA (mRNA) in these cells have been examined using ribonuclease protection assays. Estradiol gave rise to significant increases in steady state levels of HB-EGF 2 and 24 h after treatment. Cyclin D1 mRNA levels were elevated 8 and 10 h after estradiol administration, corresponding to the G1 phase of the mitotic cycle, and cyclin B1 mRNA was only expressed 16-24 h after estradiol treatment, which corresponds to the G2 and M phases of the rat uterine epithelial cell cycle. Estradiol-stimulated increases in HB-EGF mRNA were not affected by treatment with cycloheximide, but were inhibited by the estrogen antagonist compound, ICI 164,384, demonstrating that the estrogen-stimulated increase in HB-EGF mRNA is a primary, estrogen receptor-mediated response of rat uterine epithelium to estradiol. Progesterone treatment, which blocks epithelial cells in G1 of the cycle, suppressed levels of HB-EGF mRNA below those observed in ovariectomized rats. These results indicate that HB-EGF mediates the regulatory effects of both estradiol and progesterone on rat uterine epithelial cell proliferation through an effect on the production of G1 phase molecules such as cyclin D1.

Animals↗
PubMed1997

Structure-based identification of a ricin inhibitor.

Ricin is a potent cytotoxin which has been used widely in the construction of therapeutic agents such as immunotoxins. Recently it has been used by governments and underground groups as a poison. There is interest in identifying and designing effective inhibitors of the ricin A chain (RTA). In this study computer-assisted searches indicated that pterins might bind in the RTA active site which normally recognizes a specific adenine base on rRNA. Kinetic assays showed that pteroic acid could inhibit RTA activity with an apparent Ki of 0.6 mM. A 2.3 A crystal structure of the complex revealed the mode of binding. The pterin ring displaces Tyr80 and binds in the adenine pocket making specific hydrogen bonds to active site residues. The benzoate moiety of pteroic acid binds on the opposite side of Tyr80 making van der Waals contact with the Tyr ring and forming a hydrogen bond with Asn78. Neopterin, a propane triol derivative of pterin, also binds to RTA as revealed by the X-ray structure of its complex with RTA. Neither pterin-6-carboxylic acid nor folic acid bind to the crystal or act as inhibitors. The models observed suggest alterations to the pterin moiety which may produce more potent and specific RTA inhibitors.

Antidotes↗