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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 91 records · Page 5Linked to original sources
PubMed1999

Assessing educational effectiveness: the impact of a specialist course on the delivery of care.

An exploratory study was undertaken in South Wales to assess the changes in clinical practice brought about by a specialized pharmacology module designed for Community Mental Health Nurses (CMHNs), in our institution. The respondents were the seven CMHNs who completed the course in 1997 and returned to clinical practice, and seven CMHN comparators, matched on the basis of work experience and location. In order to assess the impact of the module, the practice, attitudes and knowledge of the respondents were investigated before and after the course and 6 months later, using semistructured interviews, nonparticipant observation and questionnaires. The three data sets were analysed using the constant-comparative method, and relevant themes were identified and refined. While we obtained some objective measures of positive educational impact, these should be considered in relation to contextual and confounding variables. Both reported and observed behaviours indicated that the main benefit from the course was increased awareness and monitoring of the side-effects of medication. Respondents had not implemented change uniformly; several factors determined how they modified working practices, including service pressures and the support of colleagues.

Cohort Studies↗
PubMed1999

Novel ribosomal mutations affecting translational accuracy, antibiotic resistance and virulence of Salmonella typhimurium.

Many mutations in rpsL cause resistance to, or dependence on, streptomycin and are restrictive (hyperaccurate) in translation. Dependence on streptomycin and hyperaccuracy can each be reversed phenotypically by mutations in either rpsD or rpsE. Such compensatory mutations have been shown to have a ram phenotype (ribosomal ambiguity), increasing the level of translational errors. We have shown recently that restrictive rpsL alleles are also associated with a loss of virulence in Salmonella typhimurium. To test whether ram mutants could reverse this loss of virulence, we have isolated a set of rpsD alleles in Salmonella typhimurium. We found that the rpsD alleles restore the virulence of strains carrying restrictive rpsL alleles to a level close to that of the wild type. Unexpectedly, three out of seven mutant rpsD alleles tested have phenotypes typical of restrictive alleles of rpsL, being resistant to streptomycin and restrictive (hyperaccurate) in translation. These phenotypes have not been previously associated with the ribosomal protein S4. Furthermore, all seven rpsD alleles (four ram and three restrictive) can phenotypically reverse the hyperaccuracy associated with restrictive alleles of rpsL. This is the first demonstration that such compensations do not require that the compensating rpsD allele has a ribosomal ambiguity (ram) phenotype.

Alleles↗
PubMed1999

Bolus dose remifentanil for control of haemodynamic response to tracheal intubation during rapid sequence induction of anaesthesia.

The effect of three bolus doses of remifentanil on the pressor response to laryngoscopy and tracheal intubation during rapid sequence induction of anaesthesia was assessed in a randomized, double-blind, placebo-controlled study in four groups of 20 patients each. After preoxygenation, anaesthesia was induced with thiopental 5-7 mg kg-1 followed immediately by saline (placebo) or remifentanil 0.5, 1.0 or 1.25 micrograms kg-1 given as a bolus over 30 s. Cricoid pressure was applied just after loss of consciousness. Succinylcholine 1 mg kg-1 was given for neuromuscular block. Laryngoscopy and tracheal intubation were performed 1 min later. Arterial pressure and heart rate were recorded at intervals until 5 min after intubation. Remifentanil 0.5 microgram kg-1 was ineffective in controlling the increase in heart rate and arterial pressure after intubation but the 1.0 and 1.25 micrograms kg-1 doses were effective in controlling the response. The use of the 1.25 micrograms kg-1 dose was however, associated with a decrease in systolic arterial pressure to less than 90 mm Hg in seven of 20 patients.

Adolescent↗
PubMed1999

Low-dose clonidine infusion during labour.

In this study, we have compared two different doses of clonidine (bolus of 25 micrograms and infusion of 19 micrograms h-1; bolus of 50 micrograms and infusion of 37 micrograms h-1, both added to 0.03% bupivacaine) with a control group of 0.03% bupivacaine alone. The study was performed in a randomized, double-blind manner, and a total of 45 patients were studied. Both clonidine regimens resulted in marked local anaesthetic sparing, with no change in the quality of analgesia. There was no difference in the severity of lower limb motor weakness and no difference in maternal sedation, although only a small number of patients were studied. No adverse maternal haemodynamic effects were observed. The newborn infants were not sedated on delivery. The number of fetal cardiotocographic traces judged to be of concern was higher in both clonidine groups. However, this just failed to reach statistical significance (P = 0.055).

Adolescent↗
PubMed1999

Aberrant nodulation response of Vigna umbellata to a Bradyrhizobium japonicum NodZ mutant and nodulation signals.

The (Brady)rhizobium nodulation gene products synthesize lipo-chitin oligosaccharide (LCO) signal molecules that induce nodule primordia on legume roots. In spot inoculation assays with roots of Vigna umbellata, Bradyrhizobium elkanii LCO and chemically synthesized LCO induced aberrant nodule structures, similar to the activity of these LCOs on Glycine soja (soybean). LCOs containing a pentameric chitin backbone and a reducing-end 2-O-methyl fucosyl moiety were active on V. umbellata. In contrast, the synthetic LCO-IV(C16:0), which has previously been shown to be active on G. soja, was inactive on V. umbellata. A B. japonicum NodZ mutant, which produces LCO without 2-O-methyl fucose at the reducing end, was able to induce nodule structures on both plants. Surprisingly, the individual, purified, LCO molecules produced by this mutant were incapable of inducing nodule formation on V. umbellata roots. However, when applied in combination, the LCOs produced by the NodZ mutant acted cooperatively to produce nodulelike structures on V. umbellata roots.

Bacterial Proteins↗
PubMed1999

Prevalence of celiac disease and its endoscopic markers among patients having routine upper gastrointestinal endoscopy.

OBJECTIVE: The aim of this study was to determine the prevalence of duodenal villous atrophy (VA) among patients undergoing routine upper gastrointestinal (GI) endoscopy and the value of endoscopic markers for VA in selecting patients for duodenal biopsy. METHODS: One hundred and fifty adult patients with upper GI symptoms or iron-deficiency anemia had inspection and biopsy of the second part of the duodenum during endoscopy. Endoscopic markers for VA sought were mosaic or nodular mucosa, scalloping of duodenal folds, and reduction in number or absence of duodenal folds. RESULTS: Endoscopic markers were seen in seven patients (5%): scalloped folds with mosaic pattern mucosa (three patients), scalloped folds, reduced in number with mosaic pattern mucosa (three patients), and nodular mucosa with reduction in fold numbers (one patient). All seven patients had partial, subtotal, or total VA. One of 143 patients with no endoscopic abnormality had patchy VA. The prevalence of VA was thus 1:19 (8 of 150). Endoscopic markers had a sensitivity of 87.5% (7 of 8), specificity of 100% (142 of 142), positive predictive value of 100% (7 of 7), and negative predictive value of 99% (142 of 143). Of the eight patients with VA, the indications for endoscopy were upper GI symptoms in seven patients (two with anemia) and anemia without GI symptoms in one. After 6 months of dietary gluten exclusion, improvement by at least one criterion was documented in all eight patients. CONCLUSIONS: Careful inspection of the duodenum during routine upper GI endoscopy allows accurate selection of patients for biopsy but may not detect patchy VA or milder enteropathy. Celiac disease should be considered as a cause of dyspeptic and reflux symptoms, as well as of iron-deficiency anemia.

Adolescent↗
PubMed1999

Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals.

Germ line mutations in the breast cancer susceptibility gene BRCA2 predispose to early-onset breast cancer, but the function of the nuclear protein encoded by the gene is ill defined. Using the yeast two-hybrid system with fragments of human BRCA2, we identified an interaction with the human DSS1 (deleted in split hand/split foot) gene. Yeast and mammalian two-hybrid assays showed that DSS1 can associate with BRCA2 in the region of amino acids 2472 to 2957 in the C terminus of the protein. Using coimmunoprecipitation of epitope-tagged BRCA2 and DSS1 cDNA constructs transiently expressed in COS cells, we were able to demonstrate an association. Furthermore, endogenous BRCA2 could be coimmunoprecipitated with endogenous DSS1 in MCF7 cells, demonstrating an in vivo association. Apparent orthologues of the mammalian DSS1 gene were identified in the genome of the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Yeast strains in which these DSS1-like genes were deleted showed a temperature-sensitive growth phenotype, which was analyzed by flow cytometry. This provides evidence for a link between the BRCA2 tumor suppressor gene and a gene required for completion of the cell cycle.

Amino Acid Sequence↗
PubMed1999

Novel 6-azapyrimidine-2'-deoxy-4'-thionucleosides: synthesis, biological evaluation and conformational analysis.

We report the synthesis of novel 1-(2'-deoxy-4'-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides and the subsequent preparation of a series of N3-substituted analogues. All the novel compounds were evaluated against a range of viruses, however they lacked any measurable activity. The lack of anti-herpetic activity may be a result of the parent nucleoside having poor affinity for herpes simplex virus type 1 thymidine kinase. Conformational analysis of the parent nucleoside showed a twist (3T2) sugar conformation commonly displayed by 2'-deoxy-4'-thionucleosides and the anti-human immunodeficiency virus type 1 agents zidovudine and 3'-fluoro-ddT.

Animals↗
PubMed1999

An immunoluminometric assay for N-terminal pro-brain natriuretic peptide: development of a test for left ventricular dysfunction.

Measurement of plasma levels of brain natriuretic peptide (BNP) has been used to assess left ventricular dysfunction and prognosis. Levels of the N-terminus of the precursor of BNP (NT-proBNP) have been reported to be elevated to a greater extent than BNP in left ventricular dysfunction. We have devised a non-radioactive sensitive and specific assay for NT-proBNP based on a competitive ligand binding principle. The chemiluminescent label 4-(2-succinimidyloxycarbonylethyl)phenyl-10-methylacridinium 9-carboxylate fluorosulphonate was used to label peptides representing domains in the middle and C-terminal sections of NT-proBNP. Assay of the C-terminal section of NT-proBNP (amino acids 65-76) in patients with proven left ventricular dysfunction [left ventricular wall motion index median 0.9 (range 0.3-1.4)] revealed elevated values [median 639 (386-911) fmol/ml] compared with normal controls [left ventricular wall motion index of 2 in all, NT-proBNP median 159 (120-245) fmol/ml, P<0.001]. Measurement of the middle section of NT-proBNP (amino acids 37-49) was not a discriminating test. It is thus possible to derivatize small peptides with a methyl acridinium label and preserve immunodetection with specific antibodies. Such methodology may allow non-radioactive immunoluminometric assays to be devised.

Adult↗
PubMed1999

Effect of sampling site, repeated sampling, pH, and PCO2 on plasma lactate concentration in healthy dogs.

OBJECTIVE: To characterize the variation in plasma lactate concentration among samples from commonly used blood sampling sites in conscious, healthy dogs. ANIMALS: 60 healthy dogs. PROCEDURE: Cross-sectional study using a replicated Latin square design. Each dog was assigned to 1 of 6 groups (n = 10) representing all possible orders for 3 sites (cephalic vein, jugular vein, and femoral artery) used to obtain blood. Samples were analyzed immediately, by use of direct amperometry for pH, PO2, Pco2, glucose, and lactate concentration. RESULTS: Significant differences in plasma lactate concentrations were detected among blood samples from the cephalic vein (highest), femoral artery, and jugular vein (lowest). Mean plasma lactate concentration in the first sample obtained, irrespective of sampling site, was lower than in subsequent samples. Covariation was identified among plasma lactate concentration, pH, and PCO2, but correlation coefficients were low. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma lactate concentrations differed among blood samples from various sites. A reference range for plasma lactate concentration was 0.3 to 2.5 mmol/L. Differences in plasma lactate concentrations among samples from various sites and with repeated sampling, in healthy dogs, are small. Use of the reference range may facilitate the clinical use of plasma lactate concentration in dogs.

Animals↗
PubMed1998

The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening.

Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti-HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti-HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035; P< .00001). One baby died in utero, and of 26 HPA-1a-positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 x 10(9)/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti-HPA-1a titer >/= 1:32 (P = . 004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti-HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

Abortion, Spontaneous↗
PubMed1998

[Antibiotic resistance here to stay? Compensatory mutations restore virulence of resistant bacteria].

Bacterial antibiotic resistance has increased alarmingly because of overuse of antibiotics both in humans and animals. One way of reversing this development is to reduce the use of antibiotics, thus promoting the disappearance of the resistant bacteria already present in humans and the environment. This approach is based on the assumption that resistance is conferred at the cost of impaired survival fitness in the absence of antibiotics, as compared with sensitive strains. It seems to be generally true that resistant bacteria are less fit than the respective sensitive strains, which suggests that resistance may be reversible. However, a complicating factor is the frequent finding in resistant strains of various types of compensatory mutations that restore fitness without concomitant loss of resistance. Thus, second-site compensatory mutations may allow resistant strains to persist and compete successfully with sensitive strains even in an environment depleted of antibiotics. It is concluded in the article that, if compensatory mutations are as common in clinical settings as they are in the laboratory, many types of resistance will be irreversible.

Anti-Bacterial Agents↗
PubMed1998

Virulence of antibiotic-resistant Salmonella typhimurium.

We show that most Salmonella typhimurium mutants resistant to streptomycin, rifampicin, and nalidixic acid are avirulent in mice. Of seven resistant mutants examined, six were avirulent and one was similar to the wild type in competition experiments in mice. The avirulent-resistant mutants rapidly accumulated various types of compensatory mutations that restored virulence without concomitant loss of resistance. Such second-site compensatory mutations were more common then reversion to the sensitive wild type. We infer from these results that a reduction in the use of antibiotics might not result in the disappearance of the resistant bacteria already present in human and environmental reservoirs. Thus, second-site compensatory mutations could increase the fitness of resistant bacteria and allow them to persist and compete successfully with sensitive strains even in an antibiotic-free environment.

Animals↗