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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 127 records · Page 7Linked to original sources
PubMed1997

The effect of injection speed on the pain of lidocaine infiltration.

OBJECTIVE: To determine whether reducing the speed of injection is effective in reducing injection pain for buffered and unbuffered lidocaine solutions. METHODS: A prospective, single-blind, randomized, crossover, laboratory study was performed. Adult volunteers were recruited from ED staff at an urban teaching hospital to serve as subjects. Twenty-nine subjects each received 4 1-mL injections into the dorsum of the hands. Each subject received fast and slow injections of buffered and unbuffered lidocaine. Subjects rated the pain of each injection on a 100-mm visual analog scale (VAS). Mean pain scores for each intervention were compared using analysis of variance. RESULTS: The mean pain VAS score for fast injection of buffered lidocaine was 14.1 mm. For slow buffered injection, the mean pain score was 11.4 mm (p = 0.98). For unbuffered lidocaine, the means were 28.7 mm for fast injection and 22.2 mm for slow injection (p = 0.40). CONCLUSIONS: Reducing injection speed did not produce a statistically significant change in injection pain for either buffered or unbuffered solutions.

Adult↗
PubMed1997

Carbon starvation of Salmonella typhimurium does not cause a general increase of mutation rates.

Mutation rates in bacteria can vary depending on the genetic target studied and the specific growth conditions of the cells. Here, two different methods were used to determine how rates of mutation to antibiotic resistance, auxotrophy, and prototrophy were influenced by carbon starvation on agar plates. The rate of mutation to rifampin resistance was increased by starvation as measured by fluctuation tests, similar to what has been reported previously for Escherichia coli. In contrast, the rates of mutation to various types of auxotrophy were unaffected or decreased as measured by both fluctuation tests and a repeated-streaking procedure. Similarly, the rates of reversion to prototrophy of his and lac nonsense and missense mutations were unaffected by starvation. Thus, mutation rates of different genetic targets can be affected differently by starvation and we conclude that carbon starvation is not generally mutagenic in Salmonella typhimurium.

Drug Resistance, Microbial↗
PubMed1997

Relation between psychiatric disorder and abnormal illness behaviour in patients undergoing operations for cervical discectomy.

OBJECTIVE: To test the hypothesis that depression in patients being considered for cervical disc surgery is associated with severe organic pathology. Secondly, to test whether depression and abnormal illness attitudes recorded preoperatively would predict poorer recovery. METHODS: Seventy four patients with pain and disability from cervical arthrosis were examined during investigations before potential cervical surgery. The prevalence of psychiatric disorder was assessed using the SCAN, and attitude to illness using the illness attitude scale. RESULTS: There was a rate of depressive disorder in the sample of 37%. The depressed patients did not have more severe organic pathology, more neurological symptoms or signs, or more disablement. They reported more pain and displayed more abnormal illness behaviour. Fifty patients went on to cervical surgery. Outcome four to eight months postoperatively was not related to the presence of psychiatric disorder or illness attitude recorded preoperatively. CONCLUSION: Depressive disorder is not secondary to severe pathology; the outcome of surgery is predominantly determined by physical factors.

Adult↗
PubMed1997

The cost of depression in the elderly. Effects of drug therapy.

Depression is a widespread and debilitating illness that affects an individual's ability to carry out their usual activities. It is therefore likely to represent a considerable economic and social burden to society. The prevalence of depression in the elderly has been estimated at around 10%, although it has been suggested that the level of undetected and untreated depression may be especially high in this group. The direct and indirect costs associated with depression in the elderly are therefore likely to be considerable. The application of economic analysis to drug therapy in the treatment of depression has so far been limited. There are no economic studies of the cost effectiveness of antidepressant drug therapy that concentrate exclusively on the treatment of the elderly. Available evidence across all groups suggests that selective serotonin reuptake inhibitors may be more cost effective than tricyclic antidepressants. This is primarily attributable to the lower incidence of adverse effects with the former. Whilst these results may be replicated in the elderly, there are specific characteristics of the elderly population which suggest that it may not be possible to generalise results. These include adverse effects, the costs of detection, the costs of noncompliance, and indirect costs and benefits. Therefore, further research and careful economic evaluation of the treatment of depression in the elderly is necessary to take account of these characteristics.

Aged↗
PubMed1997

Osteoporosis. Guidelines for general practitioners. Osteoporosis Australia.

Osteoporosis and its associated problems are major health concerns in Australia, and are commonly encountered in general practice. As the population ages, the incidence of osteoporosis will continue to increase. Hence, it is important for general practitioners and healthcare professionals to remain up to date with the strategies involved in the prevention and treatment of osteoporosis. Over the last few years, there have been significant advances in our understanding and treatment of osteoporosis. It is now clear that osteoporosis is a problem for men as well as for women. Accurate and reliable measurements to diagnose osteoporosis, and effective medications to treat it, are now available. These guidelines have been prepared to help general practitioners identify people at risk of developing osteoporosis, and to inform general practitioners on the current diagnosis and treatment strategies of the condition. We commend these guidelines to you as a reference source for the treatment of people with osteoporosis.

Australia↗
PubMed1996

Effect of aluminium on expression and processing of amyloid precursor protein.

The environmental agent aluminium has been extensively investigated for a potential role in the aetiology of Alzheimer's disease. Despite many investigations there is at present no definite proof for any involvement. If aluminium is involved it is possible that its action is mediated through interaction with the synthesis or processing of amyloid precursor protein (APP). The present study compared aluminium loaded IMR-32 neuroblastoma cells and rat brains with control cells and brains to determine if aluminium affected APP expression and/or processing. In the IMR-32 model system aluminium had no effect on steady-state APP mRNA levels or on the ratio of individual isoforms. It also had no quantitative or qualitative effect on APP-immunoreactive bands detected in protein extracts from conditioned medium of these cells. In total cell extracts, aluminium reduced the intensity of APP-immunoreactive bands between 120-105 kDa but had no effect on a 9 kDa band. In rat brains, aluminium had no effect on APP-immunoreactive bands from soluble or insoluble-membranous extracts. The results, in general, provide no evidence for any effect of aluminium on APP expression or processing.

Aluminum↗
PubMed1996

Serum alpha 1-antitrypsin concentration in dogs with panniculitis.

OBJECTIVE: To measure serum alpha 1-antitrypsin (alpha 1AT) concentration in dogs with histologically confirmed panniculitis to determine whether serum deficiency could cause or exacerbate panniculitis in dogs. DESIGN: Cross-sectional, descriptive study. ANIMALS: 9 dogs (5 with multiple lesions and 4 with solitary lesions). PROCEDURE: Serum samples were obtained by means of cephalic or jugular venipuncture and frozen at -20 C until assayed. Serum alpha 1AT concentration was measured by means of radial gel immunodiffusion. RESULTS: In all dogs, serum alpha 1AT concentration was within the previously established reference range. CLINICAL IMPLICATIONS: In the small number of-dogs studied, panniculitis was not associated with serum alpha 1AT deficiency.

Adipose Tissue↗
PubMed1996

Homologous recombination between the tuf genes of Salmonella typhimurium.

The genes coding for the translation factor EF-Tu, tufA and tufB are separated by over 700 kb on the circular chromosome of Salmonella typhimurium. The coding regions of these genes have 99% identity at the nucleotide level in spite of the presumed ancient origin of the gene duplication. Sequence comparisons between S. typhimurium and Escherichia coli suggest that within each species the two tuf genes are evolving in concert. Here we show that each of the S. typhimurium tuf genes can transfer genetic information to the other. In our genetic system the transfers are seen as non-reciprocal, i.e. as gene conversion events. However, the mechanism of recombination could be reciprocal, with sister chromosome segregation and selection leading to the isolation of a particular class of recombinant. The amount of sequence information transferred in individual recombination events varies, but can be close to the entire length of the gene. The recombination is RecABCD-dependent, and is opposed by MutSHLU mismatch repair. In the wild-type, this type of recombination occurs at a rate that is two or three orders of magnitude greater than the nucleotide substitution rate. The rate of recombination differs by six orders of magnitude between a recA and a mutS strain. Mismatch repair reduces the rate of this recombination 1000-fold. The rate of recombination also differs by one order of magnitude depending on which tuf gene is donating the sequence selected for. We discuss three classes of model that could, in principle, account for the sequence transfers: (1) tuf mRNA mediated recombination; (2) non-allelic reciprocal recombination involving sister chromosomes; (3) non-allelic gene conversion involving sister chromosomes, initiated by a double-strand break close to one tuf gene. Although the mechanism remains to be determined, the effect on the bacterial cells is tuf gene sequence homogenisation. This recombination phenomenon can account for the concerted evolution of the tuf genes.

Base Sequence↗
PubMed1996

The dynamic structure of EF-G studied by fusidic acid resistance and internal revertants.

We have previously identified 20 different fusidic acid-resistant alleles of fusA, encoding mutant forms of the ribosomal translocase EF-G. One of these, P413L, is used here as the starting point in selections for internal revertants, identifying 20 different pseudo-wild-type forms of EF-G. We have also identified two alleles of fusA previously isolated as suppressors of 4.5 S RNA deficiency. All of these mutants are analysed in terms of their effects on the structural dynamics of EF-G. Most mutation conferring fusidic acid-resistance interfere with conformational changes of EF-G, but some may be located at a possible fusidic acid binding site. Revertants of the P413L mutations restore the function of EF-G with or without affecting the level of resistance to fusidic acid. The revertant mutations probably restore the balance between the GDP and GTP conformations of EF-G off the ribosome, and most of them are located close to the interface between the G domain and domain II. The procedure for the isolation of pseudo-wild-type forms of EF-G can be used to direct evolution progressively away from the wild-type while still maintaining the essential functions of EF-G.

Anti-Bacterial Agents↗
PubMed1996

Mutants of EF-Tu defective in binding aminoacyl-tRNA.

Five single amino acid substitution variants of EF-Tu from Salmonella typhimurium were tested for their ability to promote poly(U)-translation in vitro. The substitutions are Leu120 Gln, Gln124 Arg and Tyr160 (Asp or Asn or Cys). They were selected by their kirromycin resistant phenotypes and all substitutions are in domain I at the interface between domains I and III of the EF-Tu.GTP configuration. The different EF-Tu variants exhibit a spectrum of phenotypes. First, k cat/K(M) for the interaction between ternary complex and the programmed ribosome is apparently reduced by the substitutions Leu120 Gln, Gln124 Arg and Tyr160 Cys. Second, this reduction is caused by a defect in the interaction between these EF-Tu variants and aminoacyl-tRNA during translation. Third, in four cases out of five the affinity of the complex between EF-Tu.GTP and aminoacyl-tRNA is significantly decreased. The most drastic reduction is observed for the Gln124 Arg change, where the association constant is 30-fold lower than in the wild-type case. Fourth, missense errors are increased as well as decreased by the different amino acid substitutions. Finally, the dissociation rate constant (kd) for the release of GDP from EF-Tu is increased 6-fold by the Tyr160 Cys substitution, but remains unchanged in the four other cases. These results show that the formation of ternary complex is sensitive to many different alterations in the domain I-III interface of EF-Tu.

Guanosine Triphosphate↗
PubMed1996

Muller's ratchet decreases fitness of a DNA-based microbe.

Muller proposed that an asexual organism will inevitably accumulate deleterious mutations, resulting in an increase of the mutational load and an inexorable, ratchet-like, loss of the least mutated class [Muller, H.J. (1964) Mutat. Res. 1, 2-9]. The operation of Muller's ratchet on real populations has been experimentally demonstrated only in RNA viruses. However, these cases are exceptional in that the mutation rates of the RNA viruses are extremely high. We have examined whether Muller's ratchet operates in Salmonella typhimurium, a DNA-based organism with a more typical genomic mutation rate. Cells were grown asexually under conditions expected to result in high genetic drift, and the increase in mutational load was determined. S. typhimurium accumulated mutations under these conditions such that after 1700 generations, 1% of the 444 lineages tested had suffered an obvious loss of fitness, as determined by decreased growth rate. These results suggest that in the absence of sex and with high genetic drift, genetic mechanisms, such as back or compensatory mutations, cannot compensate for the accumulation of deleterious mutations. In addition, we measured the appearance of auxotrophs, which allowed us to calculate an average spontaneous mutation rate of approximately 0.3-1.5 x 10(-9) mutations per base pair per generation. This rate is measured for the largest genetic target studied so far, a collection of about 200 genes.

Adenine↗
PubMed1996

Fluorescent multiplex microsatellites used to define haplotypes associated with 75 CFTR mutations from the UK on 437 CF chromosomes.

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene contains three highly informative microsatellites: IVS8CA, IVS17bTA, and IVS17bCA. Their analysis improves prenatal/ carrier diagnosis and generates haplotypes from CF chromosomes that are strongly associated with specific mutations. Microsatellite haplotypes were defined for 75 CFTR mutations carried on 437 CF chromosomes (220 for delta F508, 217 for other mutations) from Northern Ireland and three English regions: the North-West, East Anglia, and the South. Fluorescently labelled microsatellites were amplified in a triplex PCR reaction and typed using an ABI 373A fluorescent fragment analyser. These mutations cover all the common and most of the rare CF defects found in the UK, and their corresponding haplotypes and geographic region are tabulated here. Ancient mutations, delta F508, G542X, N1303K, were associated with several related haplotypes due to slippage during replication, whereas other common mutations were associated with the one respective haplotype (e.g., G551D and R560T with 16-7-17, R117H with 16-30-13, 621 + 1G > T with 21-31-13, 3659delC with 16-35-13). This simple, fast, and automated method for fluorescent typing of these haplotypes will help to direct mutation screening for uncharacterised CF chromosomes.

Chromosomes, Human↗
PubMed1996

Predictive utility of the CSQ in low back pain: individual vs. composite measures.

Researchers have typically used factor-analytic composite measures of coping, instead of individual scales, to predict rehabilitation outcome. There are, however, both advantages and disadvantages to using individual or composite scores. This study extended the findings of Jensen et al. (1992), by prospectively comparing the individual and composite scores of the Coping Strategies Questionnaire (CSQ) in the prediction of 4 types of adjustment to low back pain. Two-hundred patients completed the CSQ, the Oswestry Index, the SCL-90R, and 4 lifting tasks at admission and discharge from a multidisciplinary pain clinic. Return to work was determined at 9-month follow-up. The CSQ scales were factor-analyzed to devise composite indices, and the 3 resultant factors were compared to the individual scales in the prediction of pain and other outcomes. The results indicated that the relative predictive utility of the composite or individual scales depended on which outcome measure was used to define adjustment.

Adaptation, Psychological↗