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Biomedical subjects

R Dixon

Publications and source records attributed to R Dixon.

At least 55 records · Page 3Linked to original sources
PubMed1999

Patient doses from neuroradiological procedures.

Patient doses have been determined for a sample of 20 patients in a hospital department undergoing various interventional neuroradiological procedures. Skin entrance dose, dose-area product and effective dose have been estimated. Effective dose was estimated from published conversion factors. The highest dose on the patients body was recorded as the maximum skin entrance dose. The maximum skin entrance dose varied from 0.2 to 2.3 Gy. The largest maximum skin entrance dose is similar to the threshold for skin injuries (erythema). The effective dose varied from 2 to 34 mSv. The results of this study are compared with the results of other studies on radiation dose to patients from neuroradiological procedures.

Adolescent↗
PubMed1998

Properties of a mutant form of the prokaryotic enhancer binding protein, NTRC, which hydrolyses ATP in the absence of effectors.

The mutation S170A in the proposed nucleotide binding site of the transcriptional activator protein NTRC abolishes its ability to catalyse open promoter complex formation by the sigma(N)-RNA polymerase holoenzyme. NTRC(S170A) has significant ATPase activity, which, in contrast to the wild-type protein, is unaffected by phosphorylation or binding to enhancer sites on DNA. The mutant protein appears to oligomerise normally on DNA in response to phosphorylation but the ATPase activity is apparently not responsive to changes in oligomerisation state. The defect in transcriptional activation is discussed in relation to mutations in other sigma(N)-dependent activators.

Adenosine Triphosphatases↗
PubMed1998

Electron donation to the flavoprotein NifL, a redox-sensing transcriptional regulator.

Transcriptional control of the nitrogen fixation (nif) genes in response to oxygen in Azotobacter vinelandii is mediated by nitrogen fixation regulatory protein L (NifL), a regulatory flavoprotein that modulates the activity of the transcriptional activator nitrogen fixation regulatory protein A (NifA). CD spectra of purified NifL indicate that FAD is bound to NifL in an asymmetric environment and the protein is predominantly alpha-helical. The redox potential of NifL is -226 mV at pH 8 as determined by the enzymic reduction of NifL by xanthine oxidase/xanthine in the presence of appropriate mediators. The reduction of NifL by xanthine oxidase prevented NifL from acting as an inhibitor of NifA. In the absence of electron mediators NifL could also be reduced by Escherichia coli flavohaemoprotein (Hmp) with NADH as reductant. Hmp contains a globin-like domain with haem B as prosthetic group and an FAD-containing oxidoreductase module. The carboxyferrohaem form of Hmp was competent to reduce NifL, suggesting that electron donation to NifL originates from the flavin in Hmp rather than by direct electron transfer from the haem. Spinach ferredoxin:NAD(P) oxidoreductase, which adopts a folding similar to the FAD- and NAD-binding domains of Hmp, also reduced NifL with NADH as reductant. Re-oxidation of NifL occurs rapidly in the presence of air, raising the possibility that NifL might sense intracellular oxygen. We propose a physiological redox cycle in which the oxidation of NifL by oxygen and hence the activation of its inhibitory properties occurs rapidly, in contrast with the switch from the active to the reduced form of NifL, which occurs more slowly.

Azotobacter vinelandii↗
PubMed1998

Effect of hepatic impairment on the pharmacokinetics of zolmitriptan.

Zolmitriptan, an oral 5HT1D agonist for the acute treatment of migraine, is cleared from the systemic circulation mainly by hepatic metabolism. Consequently, changes in hepatic function may result in changes in the pharmacokinetics of zolmitriptan. This open, parallel-group study was conducted to compare the pharmacokinetics and tolerability of a single 10-mg dose of zolmitriptan in healthy subjects and patients with hepatic impairment. A total of 37 participants entered and completed the study, including 10 healthy volunteers, 11 patients with moderate hepatic impairment, 10 patients with severe hepatic impairment without ascites, and 6 patients with severe hepatic impairment with ascites. The metabolism of zolmitriptan was reduced in patients with severe hepatic impairment compared with healthy subjects, resulting in higher peak plasma concentrations (47%), increased exposure (226%), and prolonged half-life (157%). The changes were similar in the presence and absence of ascites. Smaller changes were observed in patients with moderate hepatic impairment. Plasma concentrations of the three major metabolites of zolmitriptan were reduced in the patients with hepatic impairment. Patients with moderate hepatic impairment require no dosage adjustment, but the recommended daily intake of zolmitriptan may need to be reduced in patients with severe hepatic impairment.

Adult↗
PubMed1998

The oxygen-responsive NIFL-NIFA complex: a novel two-component regulatory system controlling nitrogenase synthesis in gamma-proteobacteria.

The high energetic requirements for nitrogen fixation and the extreme oxygen sensitivity of the nitrogenase enzyme impose physiological constraints on diazotrophy that necessitate stringent control of nitrogen fixation (nif) gene expression at the transcriptional level. In the gamma-subdivision of the Proteobacteria, this control is maintained by a regulatory complex comprising an enhancer-binding protein (NIFA), which activates transcription at sigmaN-dependent nif (nitrogen fixation) promoters, and a sensor protein (NIFL), which inhibits NIFA activity in response to fixed nitrogen and external concentrations of molecular oxygen. Inhibition of NIFA activity by NIFL apparently requires stoichiometric amounts of the two proteins, implying direct protein-protein interaction rather than catalytic modulation of NIFA activity. NIFL contains FAD as a prosthetic group and is a novel type of flavoprotein in which the oxidation state of the bound flavin acts as a molecular switch to control transcriptional activation by NIFA. The FAD-binding domain of NIFL contains a motif common to a large family of redox sensory proteins. In addition to its ability to act as a redox sensor, the activity of NIFL is also responsive to adenosine nucleotides, particularly ADP, suggesting that formation of the inhibitory complex might be regulated by the ATP/ ADP ratio. Proposed mechanisms for the inhibition of NIFA activity by NIFL are beginning to emerge.

Amino Acid Sequence↗
PubMed1998

An in-vitro test for assessing the viability of Ascaris suum eggs exposed to various sewage treatment processes.

A simple procedure using Ascaris suum as a model for Ascaris lumbricoides in testing the ability of sludge treatment processes to kill the eggs of parasitic roundworms was developed. Unembryonated and embryonated A. suum eggs were placed in a mesophilic anaerobic sludge digester or a sludge lagoon, or stored at 4 degrees C. Unembryonated eggs were recovered and incubated at 32.5 degree C and 90-95% r.h. for 48 h and viable eggs developed embryos consisting of two or more clearly defined cells. This viability was confirmed by further incubation for 30 days, when motile first-stage larvae were seen. Infectivity was demonstrated by administering larvated eggs to worm-fee pigs and recovering adult worms from the small intestine at necropsy. After 1 week in a mesophilic anaerobic digester, 95% of A. suum eggs produced two-cell larvae into vitro, with 86% progressing to motile larvae. After 5 weeks in the digester 51% progressed to motile larvae. Between 42% and 49% of eggs stored in a sludge lagoon for 29 weeks were viable and able to develop motile larvae. In the case of eggs that were embryonated before treatment, > 98% survived up to 5 weeks in the digester and were able to develop motile larvae. More than 90% of embryonated eggs survived for 29 weeks in the sludge lagoon and were able to develop motile larvae.

Anaerobiosis↗
PubMed1998

The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains.

Azotobacter vinelandii NIFL is a nitrogen fixation-specific regulatory flavoprotein that modulates the activity of the transcriptional activator NIFA in response to oxygen and fixed nitrogen in vivo. NIFL is also responsive to ADP in vitro. Limited proteolysis of NIFL indicates that it comprises a relatively stable N-terminal domain and a C-terminal domain that is protected from trypsin digestion in the presence of adenosine nucleotides. ATP protects the protein from cleavage in the vicinity of potential nucleotide-binding sites in the C-terminus, whereas ADP protects the entire C-terminal domain. NIFL has an apparent Kd of 130 microM for ATP and 16 microM for ADP. The purified N-terminal domain has an identical UV/visible absorption spectrum to the wild-type protein and is reduced by sodium dithionite, demonstrating that it is a flavin-binding domain. The isolated N-terminal domain does not inhibit NIFA activity. A subdomain fragment containing 160 residues of the C-terminal region, including the nucleotide-binding sites, is also not competent to inhibit NIFA. Removal of the first 146 residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in a large family of sensory proteins from eubacteria, archea and eukarya eliminates the redox response. However, this truncated protein remains competent to inhibit NIFA activity in response to ADP in vitro and to the level of fixed nitrogen in vivo. The redox and nitrogen-sensing functions of A. vinelandii NIFL are therefore separable and are discrete functions of the protein.

Adenosine Diphosphate↗
PubMed1998

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers.

Zolmitriptan (Zomig) is a 5HT1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg + diazepam 10 mg, zolmitriptan 5 mg + diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.

Adult↗
PubMed1998

Black Sea TeleDiab: diabetes computer system with communication technology for Black Sea region.

BlackSea TeleDiab (BSTD) is a multidisciplinary research project whose aim is to promote the exchange of healthcare information between clinicians and scientists in countries of the Black Sea area to provide a means by which the care of patients with diabetes may be enhanced. The project is built on an existing organizational framework provided by the WHO Diabcare Quality Network (Q-Net) and the Black Sea Diab Action Project. The aim is to develop a standardized software package (in the national languages of the CCE/NIS Black Sea partners) for the storage and transfer of medical information and healthcare data between participating institutions. It will utilize a standard format for medical records based on the Good European Health Record (GEHR), a project within the Advanced Informatics in Medicine (AIM) program, which aims to develop and propagate a common architecture for computerized health records across Europe that can be used across clinical domains, countries, and computer systems.

Computer Communication Networks↗
PubMed1998

Frequency of cervical intraepithelial neoplasia following large loop excision of the transformation zone.

AIM: To determine the frequency of cervical intraepithelial neoplasia (CIN) following large loop excision of the transformation zone of the cervix (LLETZ) according to grade and completeness of excision of CIN. METHODS: A retrospective study of 669 patients who had LLETZ biopsies showing CIN 1, 2, or 3. The patients were subdivided according to the grade and completeness of excision of CIN. The follow up period was 1.5 to 3.5 years. Risk of persistent/recurrent CIN was assessed by the frequency of histological diagnosis of CIN during the follow up period. RESULTS: Frequency of persistent/recurrent CIN increased with the grade of CIN reported: 6.7% of patients with CIN 1, 13.4% with CIN 2, and 21.7% with CIN 3 developed persistence or recurrence. The frequency of CIN persistence/recurrence was significantly lower where LLETZ showed complete excision of CIN (8.4%) than where it was incomplete (31.3%) (p < 0.0001) or equivocal (27.8%) (p < 0.0001). CONCLUSIONS: Patients with incomplete or equivocal excision of all grades of CIN merit careful, preferably colposcopic, follow up. Patients with completely excised high grade CIN require careful cervical cytologic surveillance.

Adolescent↗
PubMed1998

Maternal anxiety and attitudes to universal neonatal hearing screening.

Neonatal hearing screening of all babies within the maternity unit is now feasible using transient evoked otoacoustic emission (TEOAE) recording. However, in many maternity units in the United Kingdom, the majority of babies are discharged within the first 48 hours. During the first two days of life, there is a higher proportion of babies in whom emissions cannot be recorded. A universal TEOAE hearing screen has been implemented in Whipps Cross Hospital. As 70% of the babies are discharged from the maternity unit before they are 48 hours old, a two stage screen was implemented, with failure at the initial TEOAE test being followed by a retest after 4-6 weeks. The maternal anxiety caused by this model was investigated in 288 mothers enrolled for the initial TEOAE test. Generally, anxiety was low and attitudes towards the screen were positive. Ninety-seven per cent of mothers considered the screen to be worthwhile at the initial test with 15% feeling it had caused some anxiety but less than 1% being very worried. The mothers who had some anxieties were not dissatisfied with the screen, and within this group there was no increase in the proportion of babies who had failed the initial test. At the retest, two of 57 mothers (3.5%) considered they were very worried, but there was no significant deterioration in attitude towards the screen. Spielberger's State-Trait Anxiety Inventory revealed no significant difference in the anxiety state of the retest group when compared with a control group whose babies had not received a neonatal hearing test. The results of the initial test and the retest did not influence the anxiety state of the mothers. Ways of minimizing anxiety caused to a minority of mothers whilst maintaining positive attitudes to the screen are discussed.

Anxiety↗
PubMed1997

Torsional constraints on the formation of open promoter complexes on DNA minicircles carrying sigma 54-dependent promoters.

A topoisomer gel retardation assay has been used to examine the topological requirements for the formation of open promoter complexes on DNA minicircles carrying sigma 54-dependent promoters. In the absence of intercalators, individual topoisomers carrying both the nifL and nifF promoters could be resolved as discrete species by electrophoresis, but exhibited anomalous electrophoretic behavior at relatively high negative superhelical density, indicative of a structural transition. In the presence of phosphorylated activator protein NTRC, ATP, and sigma 54 RNA polymerase holoenzyme, discrete topoisomer shifts were detected associated with the formation of open promoter complexes. At the nifL promoter open complexes could be formed on all negatively supercoiled topoisomers examined as well as on nicked circular DNA, but not on the DeltaLk = 0 topoisomer or positively supercoiled DNA. Minicircles carrying the sigma 54-dependent glnAp2 promoter could not be resolved in the electrophoresis system, but using a combination of potassium permanganate footprinting and topoisomerase I relaxation assays, we found in contrast to the nifL promoter, that open complexes were formed not only on negatively supercoiled topoisomers but also on relaxed minicircles and the Delta Lk = +1 topoisomer. These results indicate there is a thermodynamic barrier to the formation of open complexes on DNA minicircles carrying the nifL promoter which is not evident at glnAp2.

Bacterial Proteins↗
PubMed1997

Fear of cancer recurrence--a literature review and proposed cognitive formulation to explain exacerbation of recurrence fears.

Modern treatments for cancer are resulting in cancer patients living longer with the risk of the disease returning at a later stage. Many patients who experience a recurrence blame themselves (Mahon et al., 1990), while those in remission live with the constant fear that the cancer may return. Although fear of recurrence is recognised in the literature, few researchers have focused on this aspect as a precursor to psychological distress. This paper reviews the literature about fear of recurrence and its measurement. Leventhal's Self Regulation Model of Illness is presented to help understand patients' reactions to cancer and fears for the future. The authors propose a formulation for fear of recurrence and examples of interventions that are indicated.

Adaptation, Psychological↗
PubMed1997

Effects of liver disease on the disposition of the opioid antagonist nalmefene.

OBJECTIVES: The pharmacokinetics of nalmefene and its glucuronide metabolite were investigated in 12 patients with liver disease (four patients with mild, five patients with moderate, and three patients with severe liver disease) and 12 age-, weight-, and gender-matched control subjects. METHODS: Subjects received a single intravenous bolus 2.0 mg dose of nalmefene. Multiple blood and urine samples were collected for 48 hours. Within 1 week of nalmefene administration, antipyrine and galactose clearances were determined as general markers of hepatic metabolism and effective liver plasma flow, respectively. Plasma concentrations of nalmefene were determined by radioimmunoassay. RESULTS: The antipyrine and galactose clearance values were 56% and 33% lower, respectively, in the patients with liver disease compared with the normal healthy control subjects. The systemic clearance of nalmefene was reduced by 32% (0.61 +/- 0.21 versus 0.90 +/- 0.27 L/hr/kg [mean +/- SD]) and the terminal elimination half-life was increased by 31% (10.5 +/- 1.9 versus 8.0 +/- 2.2 hours) in the patients with liver disease. This was primarily the result of a 31% reduction (0.181 +/- 0.067 versus 0.263 +/- 0.072 L/hr/kg) in nalmefene glucuronide formation clearance. There were no significant differences in nalmefene volumes of distribution or protein binding. There was a significant inverse relationship between nalmefene clearance and Pugh score (r = -0.57; p = 0.004), indicating decreasing nalmefene clearance with increasing severity of liver disease. CONCLUSIONS: The clearance of nalmefene was significantly reduced in the presence of liver disease. However, because nalmefene will be primarily used in the acute care setting for reversal of opioid-induced effects, it is not likely that these alterations will necessitate a dosage modification.

Adult↗
PubMed1997

Antigen-specific blastogenesis assays for duck hepatitis B virus using duck peripheral blood and splenic mononuclear cells.

An antigen-specific lymphoblastogenesis assay for duck hepatitis B surface antigen (DHBsAg) and duck hepatitis B core antigen (DHBcAg) was developed using mononuclear cells from the peripheral blood (PBMC) or spleens (SMC) of immune ducks. Optimal culture conditions for the assay were determined by testing a number of variables, including antigen concentration, cell numbers/well, and the day of harvest. The specificity of the assay was assessed. The assay used 10% pooled duck serum supplement, and 8 x 10(5) cells/well for PBMC or 5 x 10(5) cells/well for SMC. The optimum antigen concentration ranged from 0.01 to 0.1 microgram/ml for both DHBsAg and DHBcAg. Maximum antigen-specific blastogenesis occurred between 4 to 7 days after establishment of the culture. The use of PHA (10 micrograms/ml) mitogenesis could predict the optimal cell numbers/well for antigen-specific blastogenesis. The assay demonstrated specific responses by immune ducks compared with those of unexposed ducklings and adult ducks (for DHBsAg P < 0.001; DHBcAg P < 0.05). For immune ducks, PBMC from all 8 ducks responded to DHBsAg, however, cells from only 4 of 7 immune ducks, responded to DHBcAg. Splenic mononuclear cells from all immune ducks responded to either DHBsAg or DHBcAg or both antigens.

Animals↗
PubMed1997

The pharmacokinetics and effects on blood pressure of multiple doses of the novel anti-migraine drug zolmitriptan (311C90) in healthy volunteers.

AIMS: Zolmitriptan (311C90), a novel, selective, centrally and peripherally acting 5-HT1D-receptor agonist is under development as an acute treatment for migraine. The tolerability, pharmacokinetics and effects on blood pressure and heart rate of multiple doses of 5 or 10 mg (5 doses administered over 24 h) were compared, in healthy adult volunteers, with those after placebo and single doses of zolmitriptan. METHODS: Twelve subjects participated in a randomized, balanced, crossover comparison. Plasma and urine concentrations of zolmitriptan and its metabolites, pulse rate and blood pressure were measured at intervals after drug. Ten volunteers completed the study. RESULTS: Zolmitriptan was well tolerated after single and multiple doses throughout the study. There was no evidence of significant changes in the pharmacokinetic parameters of zomitriptan or its metabolites after the last dose compared to the first, except for an expected rise in peak concentrations and a small, apparent increase in the amount of drug excreted in urine and hence in CLR. After the last 10 mg dose, mean dosing interval zolmitriptan AUC was 80.3 ng ml-1 h compared with 86.5 ng ml-1 h after the single 10 mg dose (95% CI for ratio 0.76-1.13). There was no evidence of changes in the pharmacokinetic parameters of zolmitriptan and its metabolites after 10 mg compared with 5 mg, except a small increase in zolmitriptan CLR. There were no statistically significant increases in peak systolic or diastolic blood pressure after the last doses of zolmitriptan compared to placebo or in peak blood pressure after the last dose compared to the first. There were no significant differences between blood pressure immediately before the first and last doses of each multiple dose regimen. Peak erect systolic blood pressure after the last 10 mg dose (137 mmHg) was significantly lower than that after placebo (147 mmHg, 95% CI for difference -18, -2) and that after the last 5 mg dose (148 mmHg, 95% CI -19, -3). CONCLUSIONS: Repeated doses of 5 or 10 mg zolmitriptan are well tolerated despite higher plasma concentrations than expected from single doses.

Administration, Oral↗
PubMed1997

The interaction between propranolol and the novel antimigraine agent zolmitriptan (311C90).

AIMS: Zolmitriptan (Zomig, formerly known as 311C90), a selective 5HT1B/1D agonist is under development as an acute oral treatment for migraine. Despite the use of prophylactic medication, such as propranolol, breakthrough attacks often occur in patients. Consequently we investigated the effects of propranolol on the pharmacokinetics of, and cardiovascular responses to, zolmitriptan. METHODS: A double-blind, randomized, crossover study of the effects of pre-treatment with propranolol 160 mg daily for 7 days or placebo on the pharmacokinetics and effects on blood pressure of a single 10 mg dose of zolmitriptan in 12 healthy volunteers. RESULTS: Propranolol increased mean zolmitriptan Cmax and AUC by 56% and 37% respectively; mean t1/2 was prolonged from 3.1 to 4.0 h. Mean Cmax and AUC of the pharmacologically active N-desmethyl metabolite were reduced by 24% and 11% respectively and the metabolite:parent AUC ratio (AUCm/AUCp) fell from 0.46 to 0.26. Mean Cmax and AUC for the inactive indole acetic acid metabolite were both reduced by 13% and AUCm/AUCp from 1.04 to 0.59. A small pressor effect of short duration was observed following zolmitriptan with mean peak rises of 13 and 11 mmHg in systolic and diastolic pressures respectively; propranolol had no effect on the pressor response. CONCLUSIONS: The results suggest that propranolol inhibits biotransformation of zolmitriptan but with no change in the small pressor response to zolmitriptan. It is therefore unlikely that the pharmacokinetic changes will lead to clinically important changes in pharmacological effects and dosage adjustment of zolmitriptan is not required in patients taking propranolol for migraine prophylaxis.

Adrenergic beta-Antagonists↗