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Biomedical subjects

L Griffiths

Publications and source records attributed to L Griffiths.

At least 19 recordsLinked to original sources
PubMed2000

Survival of bacteria during oxygen limitation.

Regulatory mechanisms that enable bacteria associated with food, drinks and the human body to adapt to changes in the availability of oxygen are reviewed. Excess oxygen induces two adaptive responses to oxidative stress. Five or more control circuits enable enteric bacteria to generate energy and grow well in anaerobic environments. Two sets of enzymes catalyse both nitrate and nitrite reduction, and dual two-component regulatory systems sense and respond to the available nitrate and nitrite in the environment. The periplasmic nitrate reductase enables bacteria to scavenge low concentrations of nitrate: similar systems are found in food-borne and other pathogens.

Anaerobiosis↗
PubMed2000

Talking contracts and taking care: managers and professionals in the British National Health Service internal market.

This paper draws on audio-recordings of a Health Authority's contract monitoring meetings with hospital providers to examine the nature of interactions between managers and clinical professionals in the British National Health Service internal market. It describes how managers and professionals arrive at a working division of labour, which acknowledges their respective spheres of expertise, but also leaves a space where definitions are contested. There is an interplay of competing managerial and professional discourses which construct problems and proposed solutions in fundamentally non-commensurable ways. Yet only rarely do managers or professionals mount challenges in ways that bring them on to the territory of the other group; rather each group seeks to frame problems to mesh with its special domain of competence. Managers seek to push back the boundaries of professional control by constructing a language and set of practices which will govern the contracting process. But they remain reliant on professionals to mediate between the requirements of contracting and the realities of clinical work. Clinical arguments continue to have high perceived legitimacy for managers, and will often be taken up by hospital managers in negotiations with their Health Authority counterparts. It is argued that the dependency of managers on professionals to make the contracting system work, taken together with the continued social and cultural authority of senior medical consultants, limits managers' ability to control professionals.

Contract Services↗
PubMed2000

Patellar tendinopathy in junior basketball players: a controlled clinical and ultrasonographic study of 268 patellar tendons in players aged 14-18 years.

Anterior knee pain is a common presenting complaint amongst adolescent athletes. We hypothesised that patellar tendinopathy may occur at a younger age than is generally recognised. Thus, we studied the patellar tendons in 134 elite 14- to 18-year-old female (n=64) and male (n=70) basketball players and 29 control swimmers (17 female, 12 male) clinically and with ultrasonography. We found that of 268 tendons, 19 (7%) had current patellar tendinopathy on clinical grounds (11% in males, 2% in females). Twenty-six percent of the basketball players' patellar tendons contained an ultrasonographic hypoechoic region. Ultrasonographic abnormality was more prevalent in the oldest tertile of players (17-18 years) than the youngest tertile (14-15.9 years). Of tendons categorised clinically as 'Never patellar tendinopathy', 22% had an ultrasonographic hypoechoic region nevertheless. This study indicates that patellar tendinopathy can occur in 14- to 18-year-old basketball players. Ultrasonographic tendon abnormality is 3 times as common as clinical symptoms.

Adolescent↗
PubMed2000

The macrophage - a novel system to deliver gene therapy to pathological hypoxia.

The use of activated macrophages in the treatment of cancer has been largely ineffectual. By 'arming' these cells with the ability to express a therapeutic gene we demonstrate significant advances in the efficacy of this approach. We have used a hypoxia-regulated adenoviral vector to transduce human macrophages with either a reporter or a therapeutic gene encoding human cytochrome P4502B6 (CYP2B6). Infiltration of transduced macrophages into a tumour spheroid results in induction of gene expression. We demonstrate significant tumour cell killing only in the presence of cyclophosphamide via activation by P4502B6 and show that this can be further targeted to tumours through hypoxia regulated gene expression. Gene Therapy (2000) 7, 255-262.

Adenoviridae↗
PubMed2000

Opening Pandora's box? Freedom of information and health services research.

The introduction, or extension, of freedom of information legislation in Britain and other Western countries seems certain to influence the climate for health services research. However, researchers should be clear that, although such legislation may improve access to certain types of data, it will also create new problems and dilemmas. Statutory freedom of information regimes are likely to raise difficult issues of adaptation and compliance for health service bodies. Researchers may find that this translates into reluctance to agree access and accentuates difficulties in managing field relationships. They may, inter alia, face difficult dilemmas in deciding whether, or how, to report non-compliance, judging whether to extend research into areas where consent has not been obtained and weighing the benefits of using the official rules to insist on disclosure against the dis-benefits of jeopardising relationships. Health services researchers should regard freedom of information legislation, not simply as a resource, but a topic deserving study in its own right.

Confidentiality↗
PubMed2000

Prospective imaging study of asymptomatic patellar tendinopathy in elite junior basketball players.

To evaluate the ability of ultrasonography to predict eventual symptoms in an at-risk population, 52 elite junior basketball players' patellar tendons were studied at baseline and again 16 months later. The group consisted of 10 study tendons (ultrasonographically hypoechoic at baseline) and 42 control tendons (ultrasonographically normal at baseline). By design, all tendons were asymptomatic at baseline. No differences were noted between subjects and controls at baseline for age, height, weight, training hours, and vertical jump. Functional (P < 0.01) and symptomatic outcome (P < 0.05) were poorer for subjects' tendons than for controls. Relative risk for developing symptoms of jumper's knee was 4.2 times greater in case tendons than in control tendons. Men were more likely to develop ultrasonographic changes than women (P < 0.025), and they also had significantly increased training hours per week (P < 0.01) in the study period. Half (50%) of abnormal tendons in women became ultrasonographically normal in the study period. Our data suggest that presence of an ultrasonographic hypoechoic area is associated with a greater risk of developing jumper's knee symptoms. Ultrasonographic patellar tendon changes may resolve, but this is not necessary for an athlete to become asymptomatic. Qualitative or quantitative analysis of baseline ultrasonographic images revealed it was not possible to predict which tendons would develop symptoms or resolve ultrasonographically.

Adolescent↗
PubMed1999

Competition between Escherichia coli strains expressing either a periplasmic or a membrane-bound nitrate reductase: does Nap confer a selective advantage during nitrate-limited growth?

The physiological role of the periplasmic nitrate reductase, Nap, one of the three nitrate reductases synthesized by Escherichia coli K-12, has been investigated. A series of double mutants that express only one nitrate reductase were grown anaerobically in batch cultures with glycerol as the non-fermentable carbon source and nitrate as the terminal electron acceptor. Only the strain expressing nitrate reductase A grew rapidly under these conditions. Introduction of a narL mutation severely decreased the growth rate of the nitrate reductase A strain, but enhanced the growth of the Nap(+) strain. The ability to use nitrate as a terminal electron acceptor for anaerobic growth is therefore regulated primarily by the NarL protein at the level of transcription. Furthermore, the strain expressing nitrate reductase A had a substantial selective advantage in competition with the strain expressing only Nap during nitrate-sufficient continuous culture. However, the strain expressing Nap was preferentially selected during nitrate-limited continuous growth. The saturation constants for nitrate for the two strains (which numerically are equal to the nitrate concentrations at half of the maximum specific growth rate and therefore reflect the relative affinities for nitrate) were estimated using the integrated Monod equation to be 15 and 50 microM for Nap and nitrate reductase A respectively. This difference is sufficient to explain the selective advantage of the Nap(+) strain during nitrate-limited growth. It is concluded that one physiological role of the periplasmic nitrate reductase of enteric bacteria is to enable bacteria to scavenge nitrate in nitrate-limited environments.

Anaerobiosis↗
PubMed1999

Detecting child sexual abuse in general practice: a retrospective case-control study from Wales.

OBJECTIVE: To investigate if routine medical contacts provide indicators that would assist general practitioners in detecting male child abuse. DESIGN: A case-control study of the general practice records of male victims of a major episode of school-based child abuse and matched controls. SETTING: General practices serving cases and controls from two South Wales schools. SUBJECTS: 107 abused boys and 107 aged-matched controls. RESULTS: No boys had disclosed sexual abuse to general practitioners. Somatic and behavioural symptoms were reported by small numbers in both groups (18 cases/25 controls). Odds ratios showed no significant positive association between abuse and numbers of boys presenting with symptoms (odds ratio 0.66; 95% confidence interval 0.32-1.37), and no difference could be found in the nature of the symptoms complained of by boys from the two groups. However, abused boys were more likely than controls to present with symptoms that persisted for more than a year (eight cases compared with one control). The two-tailed p-value calculated using the Fisher exact test was 0.035, suggesting a statistically significant association between abuse and persistent symptoms. CONCLUSIONS: Sexually-abused boys are unlikely to visit general practitioners with open requests for help, and do not appear to present with behavioural or somatic symptoms different from those presented by non-abused boys. However, where boys complain of persistent, inexplicable, somatic or behaviour problems over a period of time, the possibility of abuse should be considered.

Case-Control Studies↗
PubMed1999

Antipronation taping and temporary orthoses. Effects on tibial rotation position after exercise.

Abnormal lower-limb biomechanics--in particular, abnormal pronation of the subtalar joint with concomitant increased internal rotation of the tibia--is one of the major causes of overuse injuries of the lower limb. A randomized, controlled, within-subjects research design (N = 14) was used to investigate the effect of a temporary felt orthosis and an antipronation taping technique to control the transverse tibial rotation position immediately after application and after each of two 10-minute periods of exercise. The results showed that the taping technique was superior to both the orthosis and no intervention in controlling tibial rotation position immediately after application and after 10 minutes of exercise. After 20 minutes of exercise, neither the tape nor the orthosis was significantly superior to the control; however, the trends suggested that some residual control was maintained. Future studies are needed to determine the amount of foot pronation control required to relieve symptoms in a symptomatic population in order to determine the clinical effectiveness of these treatment methods.

Adolescent↗
PubMed1998

The influence of elevated levels of platelet-derived endothelial cell growth factor/thymidine phosphorylase on tumourigenicity, tumour growth, and oxygenation.

PURPOSE: Investigation of the effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on various aspects of tumour growth in a xenograft model, including growth rate, tumourigenicity and oxygenation levels. METHODS AND MATERIALS: MDA 231 breast cancer cells overexpressing PD-ECGF/TP protein were made by retroviral transduction. These cells were grown in vitro and in vivo as xenografts. Direct measurement of tumours was used to record growth parameters, while the comet assay with the bioreductive drug RSU 1069 was used to assess tumour cell oxygenation. RESULTS: We report that MDA 231 breast tumour cell lines expressing an increased range of levels of PD-ECGF/TP have increased tumourigenicity positively related to the level of PD-ECGF/TP when implanted in nude mice. As previously reported, tumours grown from these overexpressing cell lines grew faster than the parental line. These tumours expressed higher levels of TP activity and showed increased immunocytochemical staining for PD-ECGF. In addition, the rate of growth was found to be positively related to the level of PD-ECGF/TP expressed by the tumour cells. When the comet assay was used to compare the oxygenation status of cells between the parental and PD-ECGF/TP overexpressing tumours, the latter were found to have a larger proportion of well oxygenated cells. This is consistent with these tumours having an increased and functionally competent vascular supply in response to the expression of PD-ECGF/TP. CONCLUSION: PD-ECGF/TP appears to be capable of influencing tumourigenicity, angiogenesis and tumour growth in a proportional manner and can directly influence tumour oxygenation levels via its role in formation of functional vasculature.

Animals↗
PubMed1998

Patellar tendon ultrasonography in asymptomatic active athletes reveals hypoechoic regions: a study of 320 tendons. Victorian Institute of Sport Tendon Study Group.

OBJECTIVE: To compare patellar tendon sonographic findings in active, currently asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: The Victorian Institute of Sport Tendon Study Group, an institutional elite athlete study group in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female athletes from the sports of basketball, cricket, netball, and Australian rules football. Forty athletes who had current symptoms of jumper's knee were excluded from analysis, leaving 320 subject tendons in athletes who were currently asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the dimensions of subject tendons and noted the presence or absence of hypoechoic regions and tendon calcification. Dimensions of hypoechoic regions were measured, and approximate cross-sectional areas were calculated. Chi-squared analysis was used to test the prevalence of hypoechoic regions in subjects and controls and men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions were more prevalent in athlete tendons (22%) than in controls (4%), in male subject tendons (30%) than in female subjects (14%), and in basketball players (32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities were equally prevalent in men and women but more prevalent in basketball players (15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were present in 35 of 250 (14%) patellar tendons in athletes who had never had anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas were present in asymptomatic patellar tendons of a proportion of elite athletes but rarely present in controls. This has implications for clinicians managing athletes with anterior knee pain.

Adult↗
PubMed1997

The influence of oxygen tension and pH on the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast tumor cells grown in vitro and in vivo.

We report that hypoxia regulates and influences the level of the angiogenic enzyme platelet-derived endothelial cell growth factor (PD-ECGF), also called thymidine phosphorylase, in vitro and in vivo. Levels of PD-ECGF protein increased 6-fold in the breast cancer cell line MDA 231 after 16 h of growth in 0.3% oxygen. A simultaneous increase in enzyme activity was observed. Immunohistochemical staining of MDA 231 tumors grown in nu/nu mice showed increased expression of PD-ECGF in those parts of the tumor that are proximal to the areas of necrosis. In addition, increased and widespread staining for PD-ECGF protein was obtained when the tumor vascular supply was occluded for 2 h by clamping. Lowering the media pH to 6.3-6.7 in vitro also resulted in an increase in PD-ECGF protein levels. This study demonstrates that tumor microenvironmental factors can result in the specific up-regulation of an angiogenic enzyme that can also activate 5-fluorouracil prodrugs and hence is exploitable therapeutically.

Animals↗
PubMed1997

Characterisation of Escherichia coli K-12 mutants defective in formate-dependent nitrite reduction: essential roles for hemN and the menFDBCE operon.

Three Escherichia coli mutants defective in formate-dependent nitrite reduction (Nrf activity) were characterised. Two of the mutants, JCB354 and JCB356, synthesized all five c-type cytochromes previously characterised in anaerobic cultures of E. coli. The third mutant, JCB355, was defective for both cytochrome b and cytochrome c synthesis, but only during anaerobic growth. The insertion sites of the transposon in strains JCB354 and JCB356 mapped to the menFDBCE operon; the hemN gene was disrupted in strain JCB355. The mutation in strain JCB354 was complemented by a plasmid encoding only menD; strain JCB356 was complemented by a plasmid encoding only menBCE. A mutant defective in the methyltransferase activity involved in both ubiquinone synthesis and conversion of demethylmenaquinone to menaquinone expressed the same Nrf activity as the parental strain. The effects of men, ubiA and ubiE mutations on other cytochrome-c-dependent electron transfer pathways were also determined. The combined data establish that menaquinones are essential for cytochrome-c-dependent trimethylamine-N-oxide reductase (Tor) and Nrf activity, but that either menaquinone or ubiquinone, but not demethylmenaquinone, can transfer electrons to a third cytochrome-c-dependent electron transfer chain, the periplasmic nitrate reductase.

Anaerobiosis↗
PubMed1997

"Ruling in" and "ruling out": two approaches to the micro-rationing of health care.

Much of the implicit rationing said to characterise British health care occurs as doctors decide what resources to allocate to individual patients. This paper examines this process using data from case studies of selection of patients for cardiac surgery and admission to a specialist neurological rehabilitation centre. The analysis focuses on cardiac catheterisation conferences in which cardiologists present surgical candidates to a cardiac surgeon, and neuro-rehabilitation admissions conferences in which a multidisciplinary team assess the suitability of head injury and stroke patients referred by hospital doctors. For much of the time participants in both settings discuss patients within a clinical discourse that relies on technical assessments of coronary anatomy, ADL scores and the like. However, there are many examples where the discourse "frame" shifts to address patient characteristics of a social or moral nature. Information of this kind tends to be deployed in two ways: it can be used to signal the patient's unsuitability, usually on the basis that past behaviour implies poor prognosis ("ruling out"), or it can be used to suggest that a patient is especially deserving of help ("ruling in"). Analysis of the data suggests that "ruling out" is more salient within the cardiac catheterisation conferences, and "ruling in" within the neuro-rehabilitation admissions conferences. The authors suggest that this reflects differences in the work organisation of the two specialties, including the division of labour, the organisation of waiting lists as a queue or a pool, and the putative significance of patient agency in the genesis of disease and recovery.

Adult↗
PubMed1997

Platelet-derived endothelial cell growth factor thymidine phosphorylase in tumour growth and response to therapy.

Angiogenesis plays an important role in the growth and metastasis of solid tumours. Platelet-derived endothelial cell growth factor (PD-ECGF) is known to be chemotactic for endothelial cells in vitro and angiogenic in vivo. It is also known as gliostatin, a factor promoting neuronal survival, and thymidine phosphorylase (dThdPase), which catalyses the reversible phosphorylation of thymidine to thymine and 2-deoxyribose-1-phosphate. This enzymatic activity is critical for angiogenic activity. PD-ECGF protein is highly expressed in tumours compared with most normal tissues and has been correlated with tumour growth, invasion and metastasis in clinical studies. In addition, dThdPase activity (by inference PD-ECGF) has been found to be a major determinant of the toxicity of 5-fluorouracil and its prodrugs, which are extensively studied clinically as anti-cancer agents. This review attempts to summarize recent gains in understanding the nature, location and action of PD-ECGF and its specific relevance to tumour biology.

Antineoplastic Agents↗