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G J Williams

Publications and source records attributed to G J Williams.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of sight-threatening uveitis in Scotland.

AIM: To identify and quantify the prevalence of patients with uveitis receiving systemic immunosuppression in Scotland. METHODS: Anonymised data were prospectively collected on all patients with uveitis requiring systemic immunosuppression. Seven health boards participated over a 4-month period between 1 August 2005 and 30 November 2005. RESULTS: 373 patients were identified, of whom 205 (55%) were female. The mean age was 46.4 (range 7-97 years). Using the data from the seven participating health boards, an estimated Scottish prevalence of 9 per 100 000 was calculated. Prevalence varied between 2 and 59 per 100 000. In National Health Service Grampian, all patients with uveitis, whether sight-threatening or not, are followed up at a specialist clinic. Extrapolating this figure to Scotland gives a prevalence of 25 per 100 000. DISCUSSION: The data from National Health Service Grampian suggest that there is a significant shortfall in the number of patients identified by survey. If the "missing population" exists, then where are they? Some might be receiving appropriate treatment at non-specialist clinics, although simple under-reporting may play a part. Greater concern is for those patients receiving inappropriate treatment for their uveitis, or for those within the community who are either oblivious to or in self denial of their condition.

Adolescent↗
PubMed2006

Long-term antibiotics for preventing recurrent urinary tract infection in children.

BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms include fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment consists of a course of antibiotics. Due to acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. OBJECTIVES: To determine the efficacy and harms of long-term antibiotics to prevent recurrent UTI in children. SEARCH STRATEGY: We searched without language restriction MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, the Cochrane Renal Group's Specialised Register, reference lists of review articles and contacted content experts. Date of most recent search: January 2006 SELECTION CRITERIA: Randomised comparisons of antibiotics with other antibiotics, placebo or no treatment to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. A random-effects model was used to estimate relative risk (RR) and risk difference (RD) for recurrent UTI with 95% confidence intervals (CI). MAIN RESULTS: Eight studies (618 children) were identified, five (406) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied from 10 weeks to 12 months. Compared to placebo/no treatment, antibiotics reduced the risk of repeat positive urine culture (RR 0.44, 95% CI 0.19 to 1.00; RD -30%, 95% CI -56% to -4%) No side effects were reported. One study reported that nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). The other study found cefixime was more effective in preventing recurrent UTI than nitrofurantoin (RR 0.74, 95% CI 0.13 to 4.10; RD -3%, 95% CI -17% to -12%). However, 62% of patients receiving cefixime experienced an adverse reaction during the first six months of treatment (18/29) while only 26% (8/31) of patients receiving nitrofurantoin reported an adverse reaction. AUTHORS' CONCLUSIONS: Large, properly randomised, double blinded studies are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.

Acute Disease↗
PubMed2006

Fresnel coherent diffractive imaging.

We present an x-ray coherent diffractive imaging experiment utilizing a nonplanar incident wave and demonstrate success by reconstructing a nonperiodic gold sample at 24 nm resolution. Favorable effects of the curved beam illumination are identified.

Journal Article↗
PubMed2005

Structure-guided saturation mutagenesis of N-acetylneuraminic acid lyase for the synthesis of sialic acid mimetics.

Analogues of N-acetylneuraminic acid (sialic acid, NANA, Neu5Ac), including 6-dipropylcarboxamides, have been found to be selective and potent inhibitors of influenza sialidases. Sialic acid analogues are, however, difficult to synthesize by traditional chemical methods and the enzyme N-acetylneuraminic acid lyase (NAL) has previously been used for the synthesis of a number of analogues. The activity of this enzyme towards 6-dipropylcarboxamides is, however, low. Here, we used structure-guided saturation mutagenesis to produce variants of NAL with improved activity and specificity towards 6-dipropylcarboxamides. Three residues were targeted for mutagenesis, Asp191, Glu192 and Ser208. Only substitution at position 192 produced significant improvements in activity towards the dipropylamide. One variant, E192N, showed a 49-fold improvement in catalytic efficiency towards the target analogue and a 690-fold shift in specificity from sialic acid towards the analogue. These engineering efforts provide a scaffold for the further tailoring of NAL for the synthesis of sialic acid mimetics.

Amides↗
PubMed2004

Directed evolution of enzymes for biocatalysis and the life sciences.

Engineering the specificity and properties of enzymes and proteins within rapid time frames has become feasible with the advent of directed evolution. In the absence of detailed structural and mechanistic information, new functions can be engineered by introducing and recombining mutations, followed by subsequent testing of each variant for the desired new function. A range of methods are available for mutagenesis, and these can be used to introduce mutations at single sites, targeted regions within a gene or randomly throughout the entire gene. In addition, a number of different methods are available to allow recombination of point mutations or blocks of sequence space with little or no homology. Currently, enzyme engineers are still learning which combinations of selection methods and techniques for mutagenesis and DNA recombination are most efficient. Moreover, deciding where to introduce mutations or where to allow recombination is actively being investigated by combining experimental and computational methods. These techniques are already being successfully used for the creation of novel proteins for biocatalysis and the life sciences.

Catalysis↗
PubMed2004

Effect of field pea replacement level on intake and digestion in beef steers fed by-product-based medium-concentrate diets.

Four ruminally and duodenally cannulated steers (703.4 +/- 41 kg initial BW) were used in a 4 x 4 Latin square to evaluate the effects of field pea inclusion level on intake and site of digestion in beef steers fed medium-concentrate diets. Steers were offered feed ad libitum at 0700 and 1900 daily and were allowed free access to water. Diets consisted of 45% grass hay and 55% by-products based concentrate mixture and were formulated to contain a minimum of 12% CP (DM basis). Treatments consisted of (DM basis) 1) control, no pea; 2) 15% pea; 3) 30% pea; and 4) 45% pea in the total diet, with pea replacing wheat middlings, soybean hulls, and barley malt sprouts in the concentrate mixture. Experimental periods consisted of a 9-d dietary adjustment period followed by a 5-d collection period. Grass hay was incubated in situ, beginning on d 10, for 0, 2, 5, 9, 14, 24, 36, 72, and 98 h; and field pea and soybean hulls for 0, 2, 5, 9, 14, 24, 36, 48, and 72 h. Total DMI (15.0, 13.5, 14.1, 13.5 +/- 0.65 kg/d) and OM intake (13.4, 12.0, 12.6, 12.0 +/- 0.58 kg/d) decreased linearly (P = 0.10) with field pea inclusion. Apparent ruminal (17.5, 12.0, 0.6, 6.5 +/- 4.31%) and true ruminal CP digestibility (53.5, 48.7, 37.8, 46.2 +/- 3.83) decreased linearly (P < 0.10) with increasing field pea. Neutral detergent fiber intake (8.9, 7.9, 7.8, 7.0 +/- 0.3 kg/d) and fecal NDF output (3.1, 2.9, 2.6, 2.3 +/- 0.2 k/d) decreased linearly (P < 0.03) with increasing field pea. No effects were observed for microbial efficiency or total-tract digestibility of OM, CP, NDF, and ADF (P > or = 0.16). In situ DM and NDF disappearance rates of grass hay and soybean hulls decreased linearly (P < 0.05) with increasing field pea. Field pea in situ DM disappearance rate responded quadratically (P < 0.01; 5.9, 8.4, 5.5, and 4.9 +/- 0.52%/h, for 0, 15, 30, and 45% field pea level, respectively). Rate of in situ CP disappearance of grass hay decreased linearly (P < 0.01) with increasing field pea level. Field pea is a suitable ingredient for beef cattle consuming medium-concentrate diets, and the inclusion of up to 45% pea in by-products-based medium-concentrate growing diets decreased DMI, increased dietary UIP, and did not alter OM, NDF, or ADF digestibility.

Animal Feed↗
PubMed2003

Three-dimensional imaging of microstructure in Au nanocrystals.

X-ray diffraction using a coherent beam involves the mutual interference among all the extremities of small crystals. The continuous diffraction pattern so produced can be phased because it can be oversampled. We have thus obtained three-dimensional images of the interiors of Au nanocrystals that show 50 nm wide bands of contrast with [111] orientation that probably arise from internal twinning by dynamic recrystallization during their formation at high temperature.

Journal Article↗
PubMed2001

Reconstruction of the shapes of gold nanocrystals using coherent x-ray diffraction.

Inverse problems arise frequently in physics: The magnitude of the Fourier transform of some function is measurable, but not its phase. The "phase problem" in crystallography arises because the number of discrete measurements (Bragg peak intensities) is only half the number of unknowns (electron density points in space). Sayre first proposed that oversampling of diffraction data should allow a solution, and this has recently been demonstrated. Here we report the successful phasing of an oversampled hard x-ray diffraction pattern measured from a single nanocrystal of gold.

Journal Article↗
PubMed2001

Long-term antibiotics for preventing recurrent urinary tract infection in children.

BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven years, 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms are systemic rather than localised in early childhood and consist of fever, lethargy, anorexia, and vomiting. UTI is caused by E. coli in over 80% of cases and treatment consists of a course of antibiotics. Due to the unpleasant acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. However these medications may cause side effects and promote the development of resistant bacteria. OBJECTIVES: To determine the efficacy and side effects of long-term antibiotics given to prevent recurrent UTI in children. SEARCH STRATEGY: A search of MEDLINE (1966 to Jan 2001), EMBASE (1988 to Jan 2001) and the Cochrane Controlled Trials Register for relevant randomised controlled trials without language restriction; reference lists of review articles; contact with content experts. SELECTION CRITERIA: Randomised comparisons of two or more antibiotics and placebo with one or more antibiotics to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information. For each trial, information was collected on the methods of the trial, participants, interventions and outcomes. A random-effects model was used to estimate a summary relative risk (RR) and a summary risk difference (RD) for recurrent UTI. Heterogeneity tests and subgroup analyses were carried out based on a priori hypothesis of plausible effect modification. MAIN RESULTS: There were three trials (n = 151) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied among the studies (10 weeks to 12 months). The method of allocation concealment in the three trials was inadequate, unclear and adequate. The overall rate of recurrent UTI in the placebo/no treatment group was 63% (48/76). Compared to placebo/no treatment, antibiotics reduced the risk of recurrent UTI (RR 0.36, 95% CI 0.16 to 0.77; RD -46%, 95% CI -59% to -33%). No side effects were described in any of these three trials. There was one double-blinded trial (n = 120) with unclear allocation concealment that compared two different types of antibiotics to prevent recurrent UTI. Nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) than patients receiving trimethoprim (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). REVIEWER'S CONCLUSIONS: Most published studies to date have been poorly designed with biases known to overestimate the true treatment effect. Large, properly randomised, double blinded trials are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.

Anti-Infective Agents, Urinary↗
PubMed2000

Effects of propofol containing EDTA on mineral metabolism in medical ICU patients with pulmonary dysfunction.

OBJECTIVE: To determine whether the addition of disodium edetate (EDTA) to propofol significantly alters mineral metabolism, adverse events, and outcome in critically ill medical patients with acute pulmonary dysfunction. DESIGN: Multicentre, double-randomised, double-blind, comparative trial. SETTING: Medical intensive care units of 5 health centres. PATIENTS: A total of 85 haemodynamically stable men and women aged 18-81 years who had pulmonary dysfunction or adult respiratory distress syndrome as a primary diagnosis or complication and who were expected to require at least 48 hours of sedation and mechanical ventilation. INTERVENTIONS: Patients were randomised to receive propofol with or without EDTA and then to 1 of 2 sedation levels: light (Modified Ramsay Sedation Scale [MRSS] score of 2 to 3) or deep (MRSS score of 4 to 5). Propofol was administered by continuous infusion at an initial rate of 5 microg/kg per min and titrated as needed. MEASUREMENTS AND RESULTS: Approximately 63 % of patients had a high severity of illness as indicated by an Acute Physiology and Chronic Health Evaluation II score > or = 19. As expected, these patients had a higher mortality rate but did not require a higher dose of propofol or propofol with EDTA. Extensive evaluation of cation homeostasis showed that ionised calcium and magnesium concentrations remained remarkably stable during treatment. Total calcium concentration was low as a result of hypoalbuminemia. Parathyroid hormone (PTH) concentration was elevated in both study groups at baseline, on day 4, and at the end of sedation. There were no significant differences in electrolyte levels and no progression to renal dysfunction. There were also no significant differences in haemodynamic or adverse-event profiles. Treatment-related adverse events occurred in 5 patients in each group; 4 of these (in 3 patients receiving propofol and 1 patient receiving propofol with EDTA) were considered serious. Because a large percentage of patients experienced a change in sedation level, no analyses were performed using sedation level. CONCLUSIONS: The addition of EDTA to propofol does not alter calcium and magnesium homeostasis in critically ill patients with acute pulmonary dysfunction. The reason for the elevation in PTH concentrations in such patients is not known.

Adult↗
PubMed2000

Developments in cardiac ultrasound.

This article gives an overview of recent developments in cardiac ultrasound for the general hospital physician. It discusses contrast echocardiography, harmonic imaging, three-dimensional echocardiography, Doppler tissue imaging and perfusion imaging and give an outlook on future perspectives.

Contrast Media↗
PubMed1999

Antibody isotype responses, infection and re-infection for Schistosoma japonicum in a marshland area of China.

Antibody isotype responses to adult worm antigen (AWA) of Schistosoma japonicum and two recombinant proteins (paramyosin (PMY) and a 22 kDa tegumental membrane-associated antigen (TEG)) were analyzed in 137 individuals from an area moderately endemic for schistosomiasis in the Dongting Lake region, Hunan Province, China. The prevalence and geometric mean (GM) intensity of infection before the implementation of curative chemotherapy were 28.5% and 234.4 epg, respectively, but 9 months after treatment the prevalence (6.6%) and intensity (38.3 epg) had decreased. There was no significant difference in either the prevalence or intensity of infection between males and females. Specific IgG (total), IgG4, IgG2, IgA and IgE responses to AWA, PMY and TEG were measured by ELISA. Males produced significantly (P < 0.05) more anti-AWA total IgG, IgE, IgA, IgG4 and IgG2 antibodies, and anti-TEG IgG2 antibody than their female counterparts. The OD450 levels of anti-AWA, PMY and TEG antibody isotypes did not present clear age-dependent trends except for peak levels of anti-AWA IgG4 antibodies evident among subjects 20-29 years of age. The total IgG and IgG4 antibody profiles against AWA correlated well with current S. japonicum infections while anti-AWA IgG2, IgA and IgE antibodies did not show such an association. Anti-AWA-specific IgE antibody levels were positively correlated (r = 0.55) with anti-AWA specific IgG4 antibody levels. In addition, the overall percentage of responders (using a cut-off value obtained from normal controls) to all isotypes to AWA were higher than those observed for both the recombinant antigens. Only 18.2%, 16.8% and 7.3% of the study population were IgE responders to AWA, PMY and TEG. A longer follow-up period is required before we can more fully understand the role of IgE, if any, in protective immunity against schistosomiasis japonica.

Adolescent↗
PubMed1999

Morphology of the elastic pulmonary arteries in pulmonary hypertension: a quantitative study.

Recent studies of intravascular ultrasound of the pulmonary arteries suggest that the technique can detect intimal and medial thickening in patients with pulmonary hypertension, potentially providing a method of assessing severity of pulmonary vascular disease in life. A major drawback of the technique is that only the elastic pulmonary arteries are accessible to current ultrasound catheters. The aim of this study was to determine whether morphological changes in vessels accessible to intravascular imaging reflect severity of pulmonary vascular disease and are of a sufficient degree to be detectable by current ultrasound catheters. Morphometric studies of the elastic pulmonary arteries were performed in specimens of lungs from 24 patients who had died with pulmonary hypertension (aged 3 weeks-9 years) and compared with measurements from infants who had died from sudden infant death syndrome. Morphological changes evident in the elastic pulmonary arteries in pulmonary hypertension included luminal dilation and medial thickening but these changes were too variable to be predictive of the severity of peripheral pulmonary vascular disease. Intimal thickening and atherosclerosis were present only in those with advanced pulmonary hypertensive disease. The changes of medial thickening and luminal dilation, nonetheless, are too variable to be predictive of the severity of peripheral pulmonary vascular disease. Thus, imaging by intravascular ultrasound may help confirm advanced pulmonary vascular disease, but is unlikely to differentiate less severe pulmonary vascular disease when the patient may still potentially be operable.

Child↗
PubMed1998

Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin.

BACKGROUND: The safety and efficacy of idarubicin, etoposide, and carboplatin as remission induction therapy for patients younger than 60 years with untreated acute myeloid leukemia was studied as an alternative to standard regimens based on cytarabine plus anthracycline. METHODS: Eligible patients received idarubicin (36-40 mg/m2), etoposide (500 mg/m2), and carboplatin (1000-1500 mg/m2) over 5 days. Those who achieved complete remission received a single course of cytarabine 1.5 gm/m2 every 12 hours for a total of 12 doses. D-xylose absorption was studied as a marker for cytotoxic therapy-induced gut mucosal damage. Cytogenetic and immunophenotyping studies were performed at the time of diagnosis and examined for prognostic importance. RESULTS: Remission was achieved in 29 (67%) of 43 patients with a single induction course. The median leukemia free and overall survival times were 15.4 months (95% CI 6.5-24.2) and 12.5 months (95% CI 5.9-19.1), respectively. Induction mortality was 14%. Karyotype (normal, simple, or complex vs. very complex) was the strongest predictor of remission (79% vs. 25%, P=0.01), leukemia free survival (odds ratio [OR] 19.3, 95% CI 2.7-138.9), and overall survival (OR 5.4, 95% CI 2.1-13.9). Dose-limiting gut mucosal toxicity was greatest during Weeks 2 and 3. Bloodstream infections occurred in 49% of patients at a median of 12 days. Grade 3-4 diarrhea, nausea, stomatitis, esophagitis/dysphagia, and vomiting developed in 33%, 26%, 23%, 9%, and 2% of cases, respectively, at a median of 17, 16, 11, 15.5, and 21 days, respectively. CONCLUSIONS: This regimen was active in adults younger than 60 years with untreated acute myeloid leukemia and normal, simple, or complex karyotypes. Remission duration was confounded by karyotype. Mucosal toxicity limited the tolerability of this regimen. These adverse effects might be overcome by increasing the intensity of postremission therapy and modifying the dosing schedule.

Acute Disease↗
PubMed1998

Comparative study of the pharmacodynamic and pharmacologic effects of Betaseron and AVONEX.

The aim of this 1 week study was to compare the biologic effects induced by Betaseron and AVONEX using their approved dose, route, and schedule. Sixteen healthy volunteers were randomly assigned to receive either a single i.m. dose of AVONEX (6 million International Units [MIU]) or, every other day s.c. doses of Betaseron (8 MIU). Common side effects associated with interferon-beta (IFN-beta) treatment and biologic response parameters (neopterin, beta2-microglobulin, interleukin-10 [IL-10], and MxA protein levels in blood) were measured. Ibuprofen was administered to all subjects throughout the study. Fever, chills, and myalgia occurred most frequently and with the greatest severity between 6 and 12 h after the first dose of either IFN-beta. Despite the additional dosing of subjects in the Betaseron group, the incidence, duration, and severity of the side effects were not significantly different from those in the AVONEX group. Biologic response parameters reached similar maximum concentrations in both treatment groups. In the Betaseron group, neopterin and beta2-microglobulin levels remained significantly greater than baseline throughout the 7 day study, whereas those in the AVONEX group were elevated only through day 5. Betaseron treatment significantly increased IL-10 levels above baseline, but AVONEX treatment did not. The overall induction of neopterin, beta2-microglobulin, and IL-10 (as measured by area under the concentration-time curve) was significantly greater in the Betaseron group than the AVONEX group (p = 0.031). The results of this study demonstrate that the approved Betaseron dosing regimen, in combination with ibuprofen use, provided a significantly greater and more consistently elevated biologic response compared with that of AVONEX and did so with a side effects profile comparable to that of once a week AVONEX dosing.

Adjuvants, Immunologic↗
PubMed1998

Expression of p53 predicts treatment failure in aggressive non-Hodgkin's lymphomas.

Approximately 50% of patients with aggressive non-Hodgkin's lymphomas (NHL) achieve a complete remission (CR) and cure with combination chemotherapy. The International Index is a useful clinical measure that predicts the patients' tolerance of therapy and likelihood of achieving CR, but it is not a direct measure of chemosensitivity. In this study we have investigated the predictive value of the tumor suppressor gene, p53, as a biological marker for response to treatment in the aggressive NHL. A retrospective study was carried out on 50 patients with aggressive NHL who were treated with CHOP chemotherapy. Treatment outcome was correlated with the expression of p53 in the lymphoma, as measured by routine immunohistochemistry using the monoclonal antibody Do-7. Forty percent of the lymphomas had >5% of the cells staining positively for p53 and this finding correlated significantly with response to treatment. Fifty percent of patients with p53 positive tumors achieved a CR versus 77% of patients with p53 negative tumors. In addition, the relapse rate and time to relapse were significantly different in the two groups. In the p53 positive group, 60% of patients relapsed in a median time of 6 months, whereas 26% of the p53 negative group relapsed with the time to relapse being >22 months. The overall survival of the p53 positive group (17 months) was significantly shorter than that of p53 negative group (>24 months). These results suggest that the immunohistochemical assessment of p53 is a simple and important prognostic measure for patients with aggressive NHL who are treated with CHOP chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗