A feasibility study comparing two treatment approaches for chronic fatigue syndrome in adolescents.
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Adolescent↗
Biomedical subjects
C Williams
Publications and source records attributed to C Williams.
Simple measures to reduce the rate of contamination of blood cultures in Accident and Emergency.
OBJECTIVES: To reduce the contamination rate of blood cultures taken in the Accident and Emergency (A&E) department. METHODS: The standard blood culture sampling kit was supplemented with an instruction sheet on the optimal method for drawing blood cultures and a large 62% ethyl alcohol impregnated wipe. RESULTS: There was a statistically significant reduction in the number of contaminants (p = 0.03). CONCLUSIONS: Simple measures to encourage skin disinfection and appropriate sampling technique will reduce the incidence of contamination of blood cultures in the A&E department.
Anti-Infective Agents, Local↗
G-protein coupled receptor assays: to measure affinity or efficacy that is the question.
Cell-based assays have always played an important role in the pharmaceutical industry, providing information about the functional effects of compounds. These functional assays have traditionally accompanied facile biochemical high throughput screening programmes, being applied as secondary assays in the later stages of lead development. However, with the disappointing reality that there is not likely to be a plethora of novel, druggable targets in the post-genomic era, the role of cell-based assays in drug discovery is beginning to change. Competition to develop the "best" agents for well established targets and find more effective ways of identifying "novel" agents is driving the industry towards a "quality" versus "quantity" approach. Advances in genetic engineering, automation compatible functional assay technologies and the introduction of more sophisticated robotic systems, have facilitated the application of cell-based assays to primary screening. However, despite some apparent success to move these assays into the routine "toolbox" for high throughput screening, certain preconceptions and concerns about cell-based assays persist and the subject remains a topic of much debate. Here we use examples from the screening portfolio at Pfizer, Sandwich, to discuss the practical and theoretical considerations of employing cell-based assays in HTS with a focus on G-protein coupled receptors.
Animals↗
Hospital and after: experience of patients and carers in rural and remote north Queensland, Australia.
INTRODUCTION: This article reports a study of patients and carers discharged from the Townsville General Hospital into rural and remote communities in north Queensland, Australia. The findings indicate the importance of focusing on the experiences of patients and carers in attempting to understand the impact of discharge procedures. The four stories and their implications exist within a particular healthcare context that impacts disproportionately on rural patients and their carers. Economic rationalism has shaped contemporary healthcare policy in Australia, creating a system that is encouraged to conform to market principles. The costs borne by individuals, groups and communities have been increasingly privatised. Later admission and earlier discharge from hospital is now the norm. Concern about the impact of this policy context on the lives of rural and remote patients and carers prompted the study, which aimed to: (1) examine, from the patient and carer perspective, the social, economic, cultural and emotional cost of hospitalisation away from home communities; (2) identify the needs of rural and remote patients and their carers before, during and after hospitalisation a long way from home; and (3) make recommendations for improved policies and practices concerning the continuum of care: from admission planning, through hospitalisation, discharge-planning, and post-discharge support, in the context of rural and remote location. METHODS: The experiences presented highlight the depth of the challenges faced by patients and their carers who live in rural and remote communities. Both quantitative and qualitative methodologies were used to obtain insight into the complexity of patients and carers' lives. The four vignettes presented in this paper are taken from in-depth, qualitative interviews with 12 patients and 12 carers. RESULTS: The four stories described reveal the high financial and emotional costs, for patients and carers, of negotiating a healthcare system a long way from home. Challenges faced included inadequate admission planning, excessive accommodation and transport costs, and lack of post-discharge support services in home communities, as well as business failure, marital and family strain. There was an over-reliance on carers who lacked medical caring expertise, had other major commitments (family and work) and who may have had a tenuous and uncertain relationship with the patient. CONCLUSIONS: Recognition of these complex circumstances, exacerbated by rural location, during the discharge planning process should mean that attention to ensuring patients and their carers are linked to adequate support services in their communities is of the highest priority. The communication and dissemination of information to patients and carers is also vital. Information on hospital admission, travel benefits, accommodation options, care requirements post-discharge are particular recommendations. To summarise, the experiences highlighted in this study suggest that patients and carers in rural and remote communities have not benefited from adequate discharge planning, and are struggling to cope in a policy context that encourages later admission, earlier discharge and over reliance on family and friends as carers.
Journal Article↗
Prolonged vitamin C supplementation and recovery from eccentric exercise.
We have previously shown that vitamin C supplementation affects recovery from an unaccustomed bout of demanding exercise, with the most pronounced effect being that on plasma interleukin-6 concentration. However, because of the proposed role of interleukin-6 in the regulation of metabolism, it was unclear whether this represented a reduced response to muscle damage or some form of interaction with the metabolic demands of the activity. Therefore, the aim of the present study was to investigate the effect of the same form of supplementation on a bout of exercise that initiated similar muscle damage but had a low metabolic cost. Fourteen male subjects were allocated to either a placebo (P) or a vitamin C (VC) group. The VC group consumed 200 mg of ascorbic acid twice a day for 14 days prior to a bout of exercise and for the 3 days after exercise. The P group consumed identical capsules that contained 200 mg lactose. Subjects performed 30 min of downhill running at a gradient of -18% and recovery was monitored for up to 3 days after exercise. Plasma VC concentrations in the VC group increased following supplementation. Nevertheless, downhill running provoked a similar increase in circulating markers of muscle damage (creatine kinase activity and myoglobin concentration) and muscle soreness in P and VC groups. Similarly, although downhill running increased plasma interleukin-6, there was no effect from VC supplementation. These results suggest that vitamin C supplementation does not affect interleukin-6 concentrations following eccentric exercise that has a low metabolic component.
Adult↗
Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix.
BACKGROUND: A number of randomised studies suggest hydroxyurea given alongside radiotherapy improves survival in patients with locally advanced cervix cancer. Following publication of five large randomised trials in 1999 and 2000 concomitant chemoradiotherapy has become standard treatment for these patients. In two of the studies hydroxyurea was given to patients in both control and experimental arms. The precise role of this orally administered cytotoxic drug is not known. OBJECTIVES: To assess the effectiveness (survival and toxicity) of concomitant radiation and hydroxyurea compared with radiotherapy alone in treating locally advanced cervix cancer. SEARCH STRATEGY: We searched the following:Cochrane Gynaecological Cancer Group's Specialised RegisterCENTRAL (Cochrane Library on CD ROM, issue 4, 2002) MEDLINE (Silver Platter, from 1970 to 2001) EMBASE (from 1980 to 2001) CANCERLIT (from 1970 to 2001) PDQ (search for open and closed trials) LILACSMeta-register (ongoing trials)Searches were not language or publication restricted. Investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomized controlled trials comparing concomitant radiotherapy (+/- surgery) with hydroxyurea versus radiotherapy (+/- surgery) for locally advanced cervix cancer. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for inclusion and extracted data. Discussions on all aspects of data collection and analysis took place among all the authors at regular intervals. MAIN RESULTS: Seven studies were found to be suitable for inclusion from 33 identified as relevant. None of the trials provided adequate evidence to support the use of hydroxyurea owing to small sample size, large numbers of post-randomisation exclusions and questionable rules for censoring, particularly a failure to include treatment-related deaths in the survival analysis. Details of statistical analysis were limited and often confusing, and we felt meta-analysis would lead to unreliable and invalid conclusions. Most studies appeared to be double blind placebo-controlled studies but none give details of power calculations or reasons for stopping recruitment. Only two studies had more than 50 patients. Patients were excluded from analysis in most trials for treatment-related reasons; in one, less than half those recruited were used in the analysis, the remainder having been excluded because of tumour progression or treatment-related conditions e.g. septicaemia, worsening renal/hepatic function. In another trial five out of 20 in the hydroxyurea group died of treatment-related complications but the five-year survival group was presented as 94%. REVIEWER'S CONCLUSIONS: We found no evidence to support the use of hydroxyurea in addition to radiotherapy in the routine treatment of cervix cancer.
Antineoplastic Agents↗
Regulation of mesangial cell Na+/Ca2+ exchanger isoforms.
An isoform of the Na(+)/Ca(2+) exchanger (SDNCX1.10) was cloned from mesangial cells of Sprague-Dawley rat. Regulation of this isoform was compared to two other clones that were derived from the Dahl/Rapp salt sensitive (SNCX) and salt resistant rat (RNCX). All isoforms differ at the alternative splice site and at amino acid 218 for SNCX. PKC activates RNCX but not SNCX while SDNCX1.10 was also activated by PKC. Regulation of exchanger activities by intracellular calcium ([Ca(2+)](i)), pH, and kinases was assessed using Na-dependent (45)Ca(2+) uptake assays in OK-PTH cells expressing the vector, RNCX, SNCX, or SDNCX1.10. [Ca(2+)](i) was elevated from 50 to 125 nM (n = 4) with thapsigargin (40 nM) and reduced from 50 to 29 nM (n = 4) and 18 nM (n = 4) with 10 or 20 microM BAPTA, respectively. RNCX was active at all three [Ca(2+)](i) while SNCX and SDNCX1.10 were only active at lower [Ca(2+)](i). Varying extracellular pH (pH(e), without nigericin) or pH(e) and intracellular pH (pH(i), with 10 microM nigericin) from pH 7.4 to 6.2, 6.8, or 8.0 showed that SNCX activity was attenuated at both low and high pHs. SDNCX1.10 activity was attenuated only at pH 6.2 and 6.8 (with or without nigericin) while RNCX activity was attenuated at pH 6.2 (with or without nigericin) and pH 6.8 (with nigericin). Finally, only SDNCX1.10 activity was stimulated by 250 microM CPT-cAMP or 250 microM DB-cGMP treatment. Thus the differential regulation of [Ca(2+)](i) by these exchangers is dependent upon the pattern of cellular Na(+)/Ca(2+) exchanger isoform expression.
Amino Acid Sequence↗
The acute effects of exercise and glucose ingestion on circulating angiotensin-converting enzyme in humans.
Angiotensin-converting enzyme (ACE) activity has been suggested as a determinant of some exercise phenotypes via some studies that have associated the ACE gene with exercise performance, although several studies provide conflicting evidence regarding the influence of the ACE gene. The relationships between ACE phenotype (ACE activity) and various exercise parameters should also be examined. An early step in this process is to determine whether common environmental stimuli such as exercise and diet have acute effects on ACE activity. In this study, the acute effects of aerobic exercise, resistance exercise and glucose ingestion on circulating ACE activity were examined. On three separate occasions, 20 healthy adult volunteers (9 female and 11 male) performed 20 min of submaximal cycle exercise at 70-80% of maximal heart rate, four sets of ten repetitions of unilateral leg extension resistance exercise at ten-repetition maximum load, or ingested 1 g kg(-1) glucose. Circulating ACE activity was assessed for 1 h after each intervention using a modified fluorometric method. Pre-intervention ACE activity remained remarkably stable across test days (difference < or =1.8%). Furthermore, there was no significant change in circulating ACE activity following any of the interventions (difference from pre-intervention values < or =6.8% when unadjusted for plasma volume changes, < or =4.5% when adjusted for plasma volume changes). These results suggest that acute exercise and glucose ingestion interventions as used here do not affect circulating ACE activity. These findings are an early step in illuminating the relationships between ACE activity and various exercise parameters.
Adult↗
Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix: a systematic review.
We identified eight randomised control trials of hydroxyurea and radiation versus radiotherapy alone (six published in full and two abstracts). Most concluded that outcomes were improved by use of hydroxyurea. However, methodological problems associated with these trials included small sample size, a large number of patient exclusions post randomisation, differing outcome definitions, subgroup analyses of already small numbers of patients and questionable rules for censoring, particularly a failure to include treatment related deaths in the survival analysis. All but two studies were of less than 50 patients. Patients were excluded from some analyses for treatment related reasons. The exclusion of such patients undoubtedly altered the conclusions of the studies. Even if there was a survival advantage attributed to hydroxyurea, overall survival was somewhat poor. We found the evidence regarding the use of hydroxyurea and radiotherapy to be inadequate for assessing its role in the treatment of cervical cancer.
Antineoplastic Agents↗
Validation of a new highly standardised, lab-independent whole-blood leukocyte function assay for clinical trials (ILCS).
Physical stress induced in healthy volunteers by the Loughborough intermittent shuttle test (LIST) was used to validate a newly developed whole-blood cell culture system (Instant leukocyte culture system (ILCS). Exercise induced immune modulation was investigated through measurement of cytokine levels after activating leukocytes in peripheral blood ex vivo using the physiologic stimulant lipopolysaccharide (LPS). LPS induced production of three different cytokines, interferon gamma (IFNgamma), interleukin-6 (IL-6), and interleukin-10 (IL-10). IFNgamma levels were significantly decreased (P = 0.02 and P = 0.001 ) and IL-10 levels significantly increased (P= 0.04 and 0.03) after exercise. LPS induced IL-6 production was only marginally further increased by exercise. In conclusion, the ILCS system provided a reliable ex vivo method, showing common as well as subject specific features in the time course of the immune modulation caused by the LIST protocol. This system will be useful for studies of the elderly, where cytokine standardisation is notoriously difficult.
Blood Specimen Collection↗
An outbreak of imipenem-resistant Pseudomonas aeruginosa in an intensive care unit.
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Anti-Bacterial Agents↗
Effect of season and temperature on mortality in amphibians due to chytridiomycosis.
OBJECTIVE: To investigate the distribution and incidence of chytridiomycosis in eastern Australian frogs and to examine the effects of temperature on this disease. DESIGN: A pathological survey and a transmission experiment were conducted. PROCEDURE: Diagnostic pathology examinations were performed on free-living and captive, ill and dead amphibians collected opportunistically from eastern Australia between October 1993 and December 2000. We conducted a transmission experiment in the laboratory to investigate the effects of temperature: eight great barred frogs (Mixophyes fasciolatus) exposed to zoospores of Batrachochytrium dendrobatidis and six unexposed frogs were housed individually in each of three rooms held at 17 degrees C, 23 degrees C and 27 degrees C. RESULTS: Chytridiomycosis was the cause of death or morbidity for 133 (55.2%) of 241 free-living amphibians and for 66 (58.4%) of 113 captive amphibians. This disease occurred in 34 amphibian species, was widespread around the eastern seaboard of Australia and affected amphibians in a variety of habitats at high and low altitudes on or between the Great Dividing Range and the coast. The incidence of chytridiomycosis was higher in winter, with 53% of wild frogs from Queensland and New South Wales dying in July and August. Other diseases were much less common and were detected mostly in spring and summer. In experimental infections, lower temperatures enhanced the pathogenicity of B. dendrobatidis in M. fasciolatus. All 16 frogs exposed to B. dendrobatidis at 17 degrees C and 23 degrees C died, whereas 4 of 8 frogs exposed at 27 degrees C survived. However, the time until death for the frogs that died at 27 degrees C was shorter than at the lower temperatures. Infections in survivors were eliminated by 98 days. CONCLUSION: Chytridiomycosis is a major cause of mortality in free-living and captive amphibians in Australia and mortality rate increases at lower temperatures.
Amphibians↗
Aiming towards "moral equilibrium": health care professionals' views on working within the morally contested field of antenatal screening.
OBJECTIVE: To explore the ways in which health care practitioners working within the morally contested area of prenatal screening balance their professional and private moral values. DESIGN: Qualitative study incorporating semistructured interviews with health practitioners followed by multidisciplinary discussion groups led by a health care ethicist. SETTING: Inner city teaching hospital and district general hospital situated in South East England. PARTICIPANTS: Seventy practitioners whose work relates directly or indirectly to perinatal care. RESULTS: Practitioners managed the interface between their professional and private moral values in a variety of ways. Two key categories emerged: "tolerators", and "facilitators". The majority of practitioners fell into the "facilitator" category. Many "facilitators" felt comfortable with the prevailing ethos within their unit, and appeared unlikely to feel challenged unless the ethos was radically challenged. For others, the separation of personal and professional moral values was a daily struggle. In the "tolerator" group, some practitioners sought to influence the service offered directly, whereas others placed limits on how they themselves would contribute to practices they considered immoral. CONCLUSIONS: The "official" commitment to non-directiveness does not encourage open debate between professionals working in morally contested fields. It is important that practical means can be found to support practitioners and encourage debate. Otherwise, it is argued, these fields may come to be staffed by people with homogeneous moral views. This lack of diversity could lead to a lack of critical analysis and debate among staff about the ethos and standards of care within their unit.
Attitude of Health Personnel↗
Evaluation of Binax NOW RSV as an acute point-of-care screening test in a paediatric accident and emergency unit.
Point-of-care tests (POCTs) for respiratory syncytial virus infections are a useful adjunct to reduce the risk of healthcare-associated infections in paediatric wards. A new test based on immunochromatography, Binax NOW RSV, was introduced in the winter of 2002-03. It has user friendly features making it particularly suitable for non-laboratory personnel in a paediatric accident and emergency unit. A prospective study comparing the POCT with laboratory-based direct immunofluorescence (DIF) showed sensitivity of 87% specificity of 94%, positive predictive value of 89% and negative predictive value 92%. The simplicity of Binax NOW RSV should not detract from training staff and maintaining consistent vigilance on quality control.
Cross Infection↗
Acute administration of nutritionally sourced tryptophan increases fear recognition.
RATIONALE: The serotonin precursor tryptophan (TRP) has been widely used as a nutritional supplement and antidepressant. Recently, however, the use of TRP has been severely restricted due to its association with the eosinophilic myalgic syndrome, an autoimmune disorder probably caused by ingestion of a contaminant produced in certain TRP manufacturing processes. OBJECTIVES: To determine the bioavailability of a nutritional source of TRP obtained from milk protein and to assess whether administration of this material produced neuroendocrine and neuropsychological effects consistent with increased brain serotonin activity. METHODS: We studied 24 healthy subjects who ingested approximately 1.8 g of nutritionally-sourced TRP or placebo in a double-blind, parallel group, design. We carried out venous sampling for amino acid and hormone estimation and performed a test of emotional processing using a facial expression recognition task. RESULTS: The nutritionally-sourced TRP caused a substantial increase in the availability of TRP in plasma. Relative to placebo the TRP material produced some evidence of an increase in plasma cortisol, and enhanced the perception of fearful and happy facial expressions. CONCLUSIONS: A nutritional source of TRP increased the availability of TRP for brain serotonin synthesis and produced endocrine and neuropsychological changes consistent with increased brain serotonin function. The effect of TRP on emotional processing may be relevant to its reported activity in primate studies of social behaviour.
Adult↗
Post-exercise vitamin C supplementation and recovery from demanding exercise.
The aim of this study was to investigate whether post-exercise vitamin C supplementation influences recovery from an unaccustomed bout of exercise. Sixteen male subjects were allocated to either a placebo (P; n=8) or vitamin C (VC) group ( n=8). Subjects performed a prolonged (90-min) intermittent shuttle-running test, and supplementation began after the cessation of exercise. Immediately after exercise the VC group consumed 200 mg of VC dissolved in a 500 ml drink, whereas the subjects in the P group consumed the drink alone. Later on the same day and then in the morning and evening of the following 2 days, subjects consumed additional identical drinks. Plasma VC concentrations in the VC group increased above those in the P group 1 h after exercise and remained above P values for the 3 days after exercise. Nevertheless, post-exercise VC supplementation was not associated with improved recovery. Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation. Muscle soreness and the recovery of muscle function in the leg flexors and extensors were not different in VC and P groups. Furthermore, although plasma concentrations of interleukin-6 and malondialdehyde increased following exercise, there was no difference between VC and P groups. These results suggest that either free radicals are not involved in delaying the recovery process following a bout of unaccustomed exercise, or that the consumption of VC wholly after exercise is unable to deliver this antioxidant to the appropriate sites with sufficient expediency to improve recovery.
Adaptation, Physiological↗
The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.
BACKGROUND: Dieting in healthy women results in a decrease in the availability of tryptophan (TRP), the amino-acid precursor of serotonin (5-HT), for brain 5-HT synthesis. This is associated with increases in the prolactin response to 5-HT drug challenge suggesting a 'supersensitivity' of 5-HT neuroendocrine responses. The aim of the study was to assess whether increased TRP intake during dieting would prevent the changes in TRP availability and 5-HT neuroendocrine function. METHOD: Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced TRP (1.8 g daily) or placebo in a double-blind, parallel group, design. RESULTS: TRP supplementation failed to modify the dieting-induced reduction in fasting TRP availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional TRP did not show enhanced prolactin responses to intravenous TRP challenge. CONCLUSIONS: The decrease in TRP availability produced by dieting may be due to increased TRP metabolism rather than decreased TRP intake. While TRP treatment did not increase fasting TRP availability it may have modified the effect of dieting on brain 5-HT function. Further studies will be needed to see if this effect of TRP has consequences for the effectiveness of dieting as means of weight control.
Administration, Oral↗
Effect of carbohydrate feeding during recovery from prolonged running on muscle glycogen metabolism during subsequent exercise.
This study examined the effect of carbohydrate (CHO) intake during a 4 h recovery from prolonged running on muscle glycogen metabolism during subsequent exercise. On 2 occasions, 7 male subjects ran for 90 min at 70 % maximum oxygen uptake VO(2 max) on a motorized treadmill (R1) followed by a 4 h rest period (REC) and a 15 min run (R2) consisting of 5 min at 60 % and 10 min at 70 % VO(2 max) During REC, each subject ingested a total of 2.7 l of an isotonic solution containing either 50 g of CHO (LOW) or 175 g of CHO (HIGH). Biopsy samples were obtained from the vastus lateralis immediately after R1, REC and R2. During REC, a higher muscle glycogen resynthesis was observed in HIGH when compared with LOW trial (75 +/- 20 vs. 31 +/- 11 mmol x kg dry matter (dm) -1, respectively; p < 0.01). Muscle glycogen utilization during R2 was similar between the HIGH and LOW trials (39 +/- 10 vs. 46 +/- 11 mmol x kg dm -1, respectively). These results suggest that ingestion of a large amount of CHO at frequent intervals during recovery from exercise does not affect the rate of muscle glycogen utilization during subsequent exercise.
Adult↗