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Biomedical subjects

S Jones

Publications and source records attributed to S Jones.

At least 253 records · Page 14Linked to original sources
PubMed1998

The safety of topical anaesthetic and analgesic agents in a gel when used to provide pain relief at split skin donor sites.

Post operative pain from split skin donor sites is a recognised problem. This study was carried out to assess the safety of a 'depot' preparation of bupivacaine and ketoprofen when applied to denuded dermis of a split donor site. Two groups of six patients each received either bupivacaine gel (2.5 mg/ml) or ketoprofen gel (1.6 mg/ml). One patient from each group was excluded as protocol was not followed. The mean surface area for bupivacaine was 106 cm2 (range 64-160) and the mean for ketoprofen was 130 cm2 (range 64-180). Blood samples were obtained before application and at 10, 20, 30, 60, 120, 240 and 480 min after application. Serum levels were assayed using Gas Liquid Chromatography and High Pressure Liquid Chromatography. Bupivacaine levels peaked at 120 min, mean level obtained was 0.07 microgram/ml (range 0.03-0.1). Ketoprofen levels also peaked at 120 min and the mean level obtained was 0.20 microgram/ml (range 0.12-0.27). The reported toxic serum level for bupivacaine was 4 micrograms/ml and for ketoprofen is 1128 micrograms/ml. In conclusion, these preparations, when applied to denuded dermis of a split skin donor site, are unlikely to result in toxic levels.

Administration, Cutaneous↗
PubMed1998

Contemporaneous and longitudinal prediction of children's sympathy from dispositional regulation and emotionality.

The relation of 8- to 10-year-olds' teacher-reported dispositional sympathy to regulation and emotionality was examined with a longitudinal sample. In general, sympathy was correlated with adults' reports of regulation and low negative emotionality contemporaneously and, to some degree, 2 and 4 years prior. General emotional intensity interacted with some aspects of regulation in predicting sympathy; for example, attention focusing predicted sympathy but only for children low in general emotional intensity. In general, the pattern of correlations changed little from age 6-8 to age 8-10 years, although parent-reported negative emotionality was more highly negatively related to sympathy at the older age. Dispositional sympathy was associated with verbal or physiological markers of sympathy in a laboratory setting.

Arousal↗
PubMed1998

Superoxide, neuroleptics and the ubiquinone and cytochrome b5 reductases in brain and lymphocytes from normals and schizophrenic patients.

The effects of the neuroleptic flupenthixol on the expression of the genes coding for the mitochondrial ubiquinone and cytochrome b5 reductases have been studied because of the importance of these enzymes in energy metabolism, oxidative stress and also because similar but oppositely directed changes have been previously observed in the cerebral cortex from schizophrenics. The neuroleptic flupenthixol reduces the expression in rats of the gene coding for NADH-cytochrome b5 reductase as measured by in situ hybridisation and its enzymic manifestation. Flupenthixol also reduces the enzymic activity of the mitochondrial NADH-ubiquinone reductase, and it has been previously shown that mRNA from the mitochondrially coded parts of the enzyme are reduced by the drug. Both the cis- and therapeutically less active trans-flupenthixol were found to produce these changes in rats. Post-mortem brain tissue from schizophrenics who have received neuroleptic medication have reduced levels of both reductases as measured enzymically, Lymphocyte samples from schizophrenics also have reduced levels of both reductases compared with normals. The superoxide anion O2- is the principle agent of oxidative stress and both the cytochrome b5 and the ubiquinone reductase enzymes were semi-purified from sheep liver and shown to produce appreciable amounts of superoxide. Superoxide production is reduced in brain homogenates from rats treated with flupenthixol. Its production is also reduced in brain tissue and lymphocytes from schizophrenics receiving neuroleptic medication. We conclude that neuroleptic medication reduces the expression of both the ubiquinone and cytochrome b5 reductase and among the effects of this reduction is a decrease in the production of neurotoxic superoxide.

Adult↗
PubMed1998

A short questionnaire (IRQ) to assess injecting risk behaviour.

AIM: To develop a short injecting risk questionnaire (IRQ) to measure sharing of injecting equipment. DESIGN: Matrix design with quota assignment, designed to compare the questionnaire when used by interview and self-completion, in agency and community settings, by agency staff and fieldworkers, with different injectors (age < 26 vs. 26+; male vs. female, opiate vs stimulant injectors), and in different geographical areas. SETTINGS: Drug treatment and helping agencies, and community settings, in England. PARTICIPANTS: Drug users who had injected in the last 4 weeks. MEASUREMENTS: Questions measured different aspects of equipment sharing. Questionnaire performance assessed by question acceptability, test-retest (parallel forms) reliability, inter-rater reliability, inter-instrument reliability, internal reliability, construct validity and internal collateral validity. Statistical tests included product moment correlation, principal components analysis, and Cronbach's alpha. FINDINGS: The questionnaire was highly acceptable. Test-retest correlations were all high and significant, questions performed well in all conditions, with no differences by site (agency vs. out-of-contact), order (interview or self-completion first), administration (staff vs. fieldworker), elapsed time or subject characteristics. The questionnaire had high internal reliability (Cronbach's alpha > +0.86), and items measured a similar domain with all questions loading highly (> 0.32) on a single factor which accounted for > 42% of the variance. The complete IRQ elicited higher reports of equipment sharing (77%) than a single question (56%). CONCLUSIONS: IRQ performs well in a variety of settings, when administered in different ways to different kinds of IDUs. A single question on 'sharing' elicits fewer positive responses than the use of multiple questions about different sharing practices.

Adult↗
PubMed1998

Classification trees. A possible method for iso-resource grouping in intensive care.

Classification and grouping of clinical data into defined categories or hierarchies is difficult in intensive care practice. Diagnosis-related groups are used to categorise patients on the basis of diagnosis. However, this approach may not be applicable to intensive care where there is wide heterogeneity within diagnostic groups. Classification tree analysis uses selected independent variables to group patients according to a dependent variable in a way that reduces variation. In this study, the influence of three easily identified patient attributes on their length of intensive care unit stay was explored using classification analysis. Two thousand five hundred and forty-five critically ill patients from three hospitals were classified into groups so that the variation in length of stay within each group was minimised. In 23 out of 39 terminal groups, the interquartile range of the length of stay was < or = 3 days.

Critical Care↗
PubMed1998

Identification of regulators for Ypt1 GTPase nucleotide cycling.

Small GTPases of the Ypt/Rab family are involved in the regulation of vesicular transport. Cycling between the GDP- and GTP-bound forms and the accessory proteins that regulate this cycling are thought to be crucial for Ypt/Rab function. Guanine nucleotide exchange factors (GEFs) stimulate both GDP loss and GTP uptake, and GTPase-activating proteins (GAPs) stimulate GTP hydrolysis. Little is known about GEFs and GAPs for Ypt/Rab proteins. In this article we report the identification and initial characterization of two factors that regulate nucleotide cycling by Ypt1p, which is essential for the first two steps of the yeast secretory pathway. The Ypt1p-GEF stimulates GDP release and GTP uptake at least 10-fold and is specific for Ypt1p. Partially purified Ypt1p-GEF can rescue the inhibition caused by the dominant-negative Ypt1p-D124N mutant of in vitro endoplasmic reticulum-to-Golgi transport. This mutant probably blocks transport by inhibiting the GEF, suggesting that we have identified the physiological GEF for Ypt1p. The Ypt1p-GAP stimulates GTP hydrolysis by Ypt1p up to 54-fold, has a higher affinity for the GTP-bound form of Ypt1p than for the GDP-bound form, and is specific to a subgroup of exocytic Ypt proteins. The Ypt1p-GAP activity is not affected by deletion of two genes that encode known Ypt GAPs, GYP7 and GYP1, nor is it influenced by mutations in SEC18, SEC17, or SEC22, genes whose products are involved in vesicle fusion. The GEF and GAP activities for Ypt1p localize to particulate cellular fractions. However, contrary to the predictions of current models, the GEF activity localizes to the fraction that functions as the acceptor in an endoplasmic reticulum-to-Golgi transport assay, whereas the GAP activity cofractionates with markers for the donor. On the basis of our current and previous results, we propose a new model for the role of Ypt/Rab nucleotide cycling and the factors that regulate this process.

Base Sequence↗
PubMed1998

Assessing the reliability of a stage of change scale.

The purpose of this study was to assess the test-retest reliability of a scale measuring Prochaska's stages of change. Although structured questionnaire items are being increasingly used to segment target audiences according to Prochaska and DiClemente's stages of change, we could find only one report in the literature assessing the reliability of such scales. The unreliability of single-item or algorithm questionnaire scales might be why a number of studies show only minimal differences on some variables between individuals in different stages of change. A survey of the Perth metropolitan general population aged 16-69 years (N = 2629) was completed in August-September 1992 as part of a 3 year evaluation of the Western Australian Health Promotion Foundation. The consistency of respondents' responses was assessed across two questions measuring stages of change for the behaviours quitting smoking (n = 404), reducing alcohol consumption (n = 57) and doing more exercise (n = 704). Given the immediacy of the test-retest situation, the reliability results are moderately encouraging: kappa = 0.72, 0.73 and 0.52 for quitting smoking, reducing alcohol and doing more exercise, respectively. Health researchers should be aware of the probable moderate level of reliability if using the type of scale assessed in this study, when interpreting differences between individuals in different stages. In practice, several questionnaire items for classification purposes should be used so that internal reliability measures can be calculated. It is recommended that research be undertaken to devise more reliable scales for stages of change for the various health behaviours. It is noted that the attitude literature with respect to context and time specific intentions could be helpful in devising such scales.

Adolescent↗
PubMed1998

Cyst(e)ine is the transport metabolite of assimilated sulfur from bundle-sheath to mesophyll cells in maize leaves

The intercellular distribution of the enzymes and metabolites of assimilatory sulfate reduction and glutathione synthesis was analyzed in maize (Zea mays L. cv LG 9) leaves. Mesophyll cells and strands of bundle-sheath cells from second leaves of 11-d-old maize seedlings were obtained by two different mechanical-isolation methods. Cross-contamination of cell preparations was determined using ribulose bisphosphate carboxylase (EC 4.1.1.39) and nitrate reductase (EC 1.6.6.1) as marker enzymes for bundle-sheath and mesophyll cells, respectively. ATP sulfurylase (EC 2.7.7.4) and adenosine 5'-phosphosulfate sulfotransferase activities were detected almost exclusively in the bundle-sheath cells, whereas GSH synthetase (EC 6.3.2.3) and cyst(e)ine, gamma-glutamylcysteine, and glutathione were located predominantly in the mesophyll cells. Feeding experiments using [35S]sulfate with intact leaves indicated that cyst(e)ine was the transport metabolite of reduced sulfur from bundle-sheath to mesophyll cells. This result was corroborated by tracer experiments, which showed that isolated bundle-sheath strands fed with [35S]sulfate secreted radioactive cyst(e)ine as the sole thiol into the resuspending medium. The results presented in this paper show that assimilatory sulfate reduction is restricted to the bundle-sheath cells, whereas the formation of glutathione takes place predominantly in the mesophyll cells, with cyst(e)ine functioning as a transport metabolite between the two cell types.

Journal Article↗
PubMed1998

Structure-in vitro activity relationships of pentamidine analogues and dication-substituted bis-benzimidazoles as new antifungal agents.

Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against C. albicans had an MIC80 of </=0.09 microg/ml, and the most potent compound against C. neoformans had an MIC80 of 0.19 microg/ml. Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential.

Antifungal Agents↗
PubMed1998

Pharmacokinetics and inflammatory fluid penetration of clinafloxacin.

A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 microg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 microg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.

Adult↗
PubMed1998

GTP hydrolysis is not important for Ypt1 GTPase function in vesicular transport.

GTPases of the Ypt/Rab family play a key role in the regulation of vesicular transport. Their ability to cycle between the GTP- and the GDP-bound forms is thought to be crucial for their function. Conversion from the GTP- to the GDP-bound form is achieved by a weak endogenous GTPase activity, which can be stimulated by a GTPase-activating protein (GAP). Current models suggest that GTP hydrolysis and GAP activity are essential for vesicle fusion with the acceptor compartment or for timing membrane fusion. To test this idea, we inactivated the GTPase activity of Ypt1p by using the Q67L mutation, which targets a conserved residue that helps catalyze GTP hydrolysis in Ras. We demonstrate that the mutant Ypt1-Q67L protein is severely impaired in its ability to hydrolyze GTP both in the absence and in the presence of GAP and consequently is restricted mostly to the GTP-bound form. Surprisingly, a strain with ypt1-Q67L as the only YPT1 gene in the cell has no observable growth phenotypes at temperatures ranging from 14 to 37 degrees C. In addition, these mutant cells exhibit normal rates of secretion and normal membrane morphology as determined by electron microscopy. Furthermore, the ypt1-Q67L allele does not exhibit dominant phenotypes in cell growth and secretion when overexpressed. Together, these results lead us to suggest that, contrary to current models for Ypt/Rab function, GTP hydrolysis is not essential either for Ypt1p-mediated vesicular transport or as a timer to turn off Ypt1p-mediated membrane fusion but only for recycling of Ypt1p between compartments. Finally, the ypt1-Q67L allele, like the wild type, is inhibited by dominant nucleotide-free YPT1 mutations. Such mutations are thought to exert their dominant phenotype by sequestration of the guanine nucleotide exchange factor (GNEF). These results suggest that the function of Ypt1p in vesicular transport requires not only the GTP-bound form of the protein but also the interaction of Ypt1p with its GNEF.

Biological Transport↗
PubMed1998

Cardiopulmonary responses to exercise in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To examine the submaximal and maximal indices of the exercise response of patients with hypertrophic cardiomyopathy. DESIGN AND SETTING: Prospective examination of cardiopulmonary responses to ramp exercise test of a consecutive group of patients with hypertrophic cardiomyopathy attending a cardiomyopathy outpatient clinic. METHODS: 50 patients aged 12 to 76 years (mean (SD) 35 (14)) with diagnosis of hypertrophic cardiomyopathy performed incremental cycle ergometry; 22 sedentary volunteers (seven female, 15 male) aged 14 to 58 years (mean (SD) 31 (12)) served as controls. Respiratory gas was continuously sampled from the mouth-piece, and its concentration profile phase aligned to the respired air flow signals. Following analogue to digital conversion, gas exchange variables were computed breath by breath and the data were averaged every 30 seconds for graphic display. A 12 lead ECG was monitored continuously and recorded every three minutes during the exercise. RESULTS: Both the peak oxygen uptake attained on the test (VO2 peak) and anaerobic threshold were reduced in patients with hypertrophic cardiomyopathy compared with the control group (p < 0.0001). In 29 patients (59%) the VO2 peak was less than 60% and only two patients achieved a peak above 80% of their predicted values. The anaerobic threshold was below 60% of the predicted value in 31 patients and above 80% in only three patients. The slope of oxygen uptake/work rate relation (delta VO2/delta WR) was decreased in 16 patients (32%). The maximum oxygen pulse (VO2/HR) was reduced as a percentage of the predicted value, and became flat at high work rates in 32 patients. There was a significant correlation between anaerobic threshold and VO2 peak (p < 0.0001), work efficiency (p < 0.0001), and maximum oxygen pulse (p < 0.0001). The slope of change in ventilation against change in carbon dioxide output (delta VE/delta VCO2) for the subanaerobic threshold range was increased in 36 patients (72%) and was inversely correlated with anaerobic threshold (p < 0.0002). CONCLUSIONS: There were severe abnormalities in maximal and submaximal indices of pulmonary gas exchange in a cohort of hypertrophic cardiomyopathy patients attending a referral cardiovascular clinic. The pattern of the abnormalities suggests that a reduced stroke volume response, ventilation/perfusion mismatch, and abnormal peripheral oxygen utilisation are the possible mechanisms of exercise intolerance.

Adolescent↗
PubMed1998

Is forced dextrality an explanation for the fall in the prevalence of sinistrality with age? A study in northern England.

OBJECTIVES: The fall in the prevalence of left handedness with age has been attributed to either premature mortality or a cohort effect of forced dextrality. Evidence for forced dextrality was sought to differentiate between these competing theories. DESIGN: 6097 Edinburgh handedness inventories were used to calculate laterality quotients (LQ) with and without the questions relating to writing and drawing. These questions might be expected to be most influenced by forced dextrality. SETTING: The study was performed in a small industrial town in Lancashire, UK. PARTICIPANTS: Using the British family practitioner service where over 95% of the population are registered with a general practitioner a response rate of 82.17% was obtained with respect to the Edinburgh Inventory. RESULTS: Questions about writing and drawing on the Edinburgh Inventory contributed to the positivity (right handedness) of the mean LQ, but equally across the ages. When a negative LQ was used to define left handedness the prevalence of left handedness fell from 11.2% at age 15 to 4.4% at age 70. Removal of the questions about writing and drawing caused the prevalence of left handedness to fall from 10.5% at age 15 to 4.95% at age 70. CONCLUSIONS: Less than 20% of the fall in the prevalence of left handedness was accounted for by questions relating to writing and drawing. The fall in the prevalence of sinistrals in older age groups is not adequately explained by cohort effects of forced dextrality on the writing hand.

Adolescent↗
PubMed1998

Otoconia biogenesis, phylogeny, composition and functional attributes.

This work consolidates data about these interesting organic crystals of vertebrate inner ears. It addresses 5 aspects of inner ear otoliths not completely understood to date: 1) embryological data that explains the formation of the crystals, 2) the significance of the organic and the inorganic phase of the otolith and the changing patterns of otoconia formation along the evolutionary tree, 3) otoliths contribution for detecting linear acceleration, 4) the effect that altered gravity and aminoglycosides have on the development and adult shape of the crystals, and the evolutionary significance of a changing shape of the crystals from primitive forms (lamprey) to high vertebrate birds and mammals is discussed, 5) functional attributes of the otolithic organs and morphological modifications of the otoliths by physical and chemical insults are presented with an extensive discussion of the most relevant literature published and available to us.

Animals↗