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Biomedical subjects

N James

Publications and source records attributed to N James.

At least 37 records · Page 2Linked to original sources

Role of MAP kinase signalling pathways in the mode of action of peroxisome proliferators.

Peroxisome proliferators (PPs) are a class of non-genotoxic chemicals that cause rodent liver enlargement and hepatocarcinogenesis. In primary rat hepatocytes, PPs cause cell proliferation, suppression of apoptosis and peroxisome proliferation. We have investigated the role of different families of mitogen-activated protein (MAP) kinases in the mode of action of PPs. Addition of 50 microM nafenopin to primary rat hepatocyte cultures caused weak activation of extracellular signal regulated kinases and p38 MAP kinase. However, incubation of primary hepatocytes with the p38 MAP kinase inhibitor SB203580 or the MAP kinase kinase (MEK) inhibitor PD098059 prevented the induction of DNA synthesis and the suppression of transforming growth factor beta(1)-induced apoptosis by the PP nafenopin. In contrast, in the presence of these MAP kinase inhibitors, nafenopin still induced palmitoyl CoA oxidation, a measure of peroxisome proliferation. We have shown previously that PPs such as nafenopin require tumour necrosis factor alpha (TNF-alpha) to exert their effects on cellular proliferation and apoptosis. Here we show that treatment of primary rat hepatocyte cultures with nafenopin causes an increase in bioactive TNF-alpha and that this process requires p38 MAP kinase activity.

Animals↗

Preferences for different sources of information about cancer.

A wide range of cancer information resources is available to patients and their relatives, who are increasingly acting as independent learners. In order to examine preferences for different types of information and to establish the appropriateness of providing a Web-based cancer information resource (CancerHelp UK) a questionnaire survey was undertaken. Of 258 questionnaires distributed to patients attending for oncology outpatient or general practice appointments, 205 (80%) were suitable for analysis. 74% (95% confidence interval 68% to 80%) of participants wanted as much information as possible. All participants cited people most frequently as a future source of cancer information. All participants frequently cited television as a source of both general and cancer-specific information. Despite a lack of computer experience patients were significantly more likely than other groups to say that they would like to use the Web-based resource. It is suggested that such resources are likely to be increasingly well used, particularly by cancer patients, given the growth in health information on the Web and developments in delivery of digital information into the home via television.

Adult↗

Effects of regular exercise in management of chronic idiopathic constipation.

Regular physical exercise has long been considered in the management of chronic constipation. This recommendation is probably based on the assumption that exercise shortens the transit time through the gastrointestinal tract. However, on the basis of previous studies, the effect of exercise on the transit remains controversial at best. Therefore, it was the goal of the present study to assess the influence of regular physical exercise, what average people may consider routine exercise, in the management of chronic idiopathic constipation. The study population consisted of eight patients, seven women and a man, with chronic idiopathic constipation. They were studied for six weeks, including two weeks of rest and four weeks of regular exercise. Patients had a submaximal exercise test, before and after the exercise period, to determine their rate of perceived exertion (RPE), the target heart rate, and the intensity of exercise they can perform. In addition to their routine daily activities, they exercised 1 hr a day, five days a week according to their performance at the initial exercise tolerance test. They kept a daily activity log and maintained their normal dietary intake during this period. The patients overall physical activity was assessed by a pedometer. They also maintained a diary of the number and consistency of their bowel movements and the amount of straining required for defecation. The impact of exercise on constipation was assessed by utilizing an index that took into consideration all three parameters of bowel function. Results of the study revealed that patients covered 1.8+/-0.33 and 3.24+/-0.28 miles/day in the rest period and during the exercise period, respectively (P = 0.007). The intensity of exercise may have improved the level of training as reflected on the mean maximum time before and after exercise period (P = 0.039). This level of exercise did not improve their constipation indices, which were 9.11+/-0.65 and 8.57+/-1.08 in the rest and exercise periods, respectively (P = 0.68). In conclusion, physical activity, to the extent that people consider "regular exercise," does not play a role in the management of chronic idiopathic constipation.

Adult↗

Development of ganglioneuroma following successful treatment for orbital rhabdomyosarcoma.

A female infant presented with a left orbital embryonal rhabdomyosarcoma at the age of 3 months. She was successfully treated for this tumour with chemo- and radiotherapy. Eight years later she developed a ganglioneuroma in the same area which was treated surgically, but recurred at the age of 19. Re-examination of all of the specimens using immunohistochemistry confirmed that the initial and successive diagnoses had been correct. Two further explanations for this rare sequence of events are considered: whether the initial biopsy had been unrepresentative of the whole tumour, or whether there had indeed been two separate tumours arising in the same area. The theories of this previously undocumented occurrence are discussed further.

Adult↗

Almost simultaneous measurement of cardiovascular and gas exchange variables during maximal exercise.

We measured gas exchange variables such as oxygen uptake, carbon dioxide output, and lung diffusing capacity using noninvasive techniques almost simultaneous with assessment of cardiovascular variables such as pulmonary blood flow at several levels of treadmill exercise up to and including maximal capacity. We utilized a single breath exhalation technique for measurement of diffusing capacity and cardiac output and breath by breath methodology for evaluating oxygen uptake. The equipment required for these measurements--rapid gas analyzers, oximeters, on-line computation, and pneumatic valves--are well within the capabilities of many exercise laboratories and are not difficult to use with subjects even at the heaviest levels of exercise. The results agreed well with values reported in the literature. From these entirely noninvasive measures, we calculated mixed venous oxygen saturation and maximal tissue oxygen diffusing capacity.

Adult↗

Improving the acceptability of high-dose radiotherapy by reducing the duration of treatment: accelerated radiotherapy in high-grade glioma.

Radiotherapy, although clearly beneficial in patients with high-grade glioma, is largely palliative, and a protracted course of treatment may not be the most appropriate approach in the context of limited survival. We therefore assessed the feasibility, toxicity and survival results of a short accelerated radiotherapy regimen given twice daily over a period of 3 weeks. A total of 116 patients with high-grade glioma were treated with radiotherapy in a prospective study using an accelerated fractionation regimen. The total dose of 55 Gy was given in 32-36 fractions of 1.72-1.53 Gy, twice daily 5 days a week, with a minimum 6 h interval between fractions. Toxicity was assessed using Karnofsky performance status scale and in the later part of the study with the Barthel index. Survival data were compared with a control group treated with 60 Gy in 30 daily fractions in a previous MRC study, matched for known prognostic factors. The median survival of 116 patients treated with accelerated radiotherapy was 10 months. Survival comparison of accelerated patients with matched controls treated with conventional fractionation demonstrated a hazard ratio of 1.13 (95% confidence interval 0.85-1.51; P = 0.39). Early treatment toxicity was acceptable, with only seven patients developing transient decrease in performance status. The accelerated radiotherapy regimen was logistically feasible and acceptable to patients, carers and staff. Treatment time was reduced without apparent increase in early toxicity and there was no loss of survival benefit. The effectiveness and convenience of a short accelerated regimen makes this a suitable alternative to a 6 week course of radiotherapy in patients with high-grade glioma. However, a full randomised trial comparing conventional and accelerated radiotherapy may be required as proof of equivalence.

Actuarial Analysis↗

Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma.

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.

Activities of Daily Living↗

Developing and implementing a user-driven departmental database system--implications for the Royal College of Radiologists' COIN proposal.

With the increasing availability of computers, more departments are using word processors in place of typewriters. In the course of typing patient discharge summaries and letters, a large amount of information of potential use for audit or research purposes is entered into the computer but in a form inaccessible for analysis. We have developed a data-base system, based on information entered by departmental staff in the course of their work, rather than by designated data managers. The aim of the system is to replace word-processed clinical summaries. We describe the design, implementation and possible advantages and disadvantages of such a system and implications for the COIN proposal of the Royal College of Radiologists.

Computer Communication Networks↗

Determining nurse staffing levels: a critical review of the literature.

This paper presents an overview of current methods for determining nurse staffing requirements. A range of methods is described and the strengths and drawbacks of each are discussed. There follows an examination of some of the wider issues raised by the use of particular methods for determining nurse staffing. The paper concludes that since a perfect workload measurement system is unlikely ever to exist, such systems can be used to facilitate, but not to dictate, decisions about nurse staffing.

Activities of Daily Living↗

Acidosis stimulates beta-endorphin release during exercise.

Elevated blood levels of beta-endorphin have been associated with high-intensity exertion, but the stimulus for beta-endorphin release is unknown. Some studies of exercise have associated beta-endorphin release with increased exertion levels, but other evidence suggests that acidosis may stimulate the release of beta-endorphin. This study examines acidosis as a possible stimulus for beta-endorphin release by examining the effects of arterial blood gases, whole blood lactate, and respiratory changes on beta-endorphin levels and by examining the effects of buffering during exercise on these levels. Initially, seven healthy adult males were evaluated during incremental exercise. During incremental exertion, indicators of acidosis correlated with endorphin levels: pH (r = -0.94), PCO2 (r = -0.85), HCO3- (r = -0.88), base excess (r = -0.94), and lactate (r = 0.89). A multivariate model showed that beta-endorphin levels were predicted best by the change in base excess. A time course analysis showed that beta-endorphin responses peaked postexercise and paralleled blood acid levels. Subsequently, subjects were compared after alkali loading and placebo during constant-intensity exercise at 85% of maximal exertion to determine whether acidosis is necessary for endorphin release. Treatment with a buffer, which effectively maintained pH above 7.40, significantly suppressed endorphin release (F = 3.07; P < 0.0001). The results of this study indicate that acidosis rather than any other physiological change associated with high-intensity exertion is the primary stimulus for beta-endorphin release.

Acidosis↗

Melatonin and gonadotropin secretion after acute exercise in physically active males.

Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone, testosterone (T) and melatonin were measured in seven physically active male volunteers after exercise on a treadmill using the Bruce protocol. Measurements were made on blood samples obtained before exercise, within 30 s after exercise, at 15 min after exercise, and subsequently at 30-min intervals after exercise for a total duration of 180 min. Serum LH concentration fell from a peak post-exercise level of 15.7 (4.7) IU.l-1 [mean (SD)] to a nadir of 10.3 (2.4) IU.l-1 (P < 0.004). Nadir values in individual volunteers were seen between 60 and 150 min after exercise. This fall in serum LH was paralleled by a similar fall in the concentration of serum T. Serum melatonin concentrations did not change significantly after exercise. It is concluded that melatonin, despite is reported anti-gonadotropic properties, does not play a role in the depression of serum LH after acute strenuous exercise in physically active males.

Adult↗

Effects of exercise on total and segmental colon transit.

To investigate the effect of aerobic exercise on total gastrointestinal and segmental colon transit, 16 male health care workers with a sedentary life-style were studied during 1 week of rest and 1 week of exercise. The exercise phase consisted of walking 4.5 km on a level treadmill for 1 h on each of 3 days. Total gastrointestinal and segmental colon transit times were measured using radiopaque markers ingested on each of 3 consecutive days with an abdominal radiograph obtained on the fourth day. With exercise, total gastrointestinal transit time decreased in 5, increased in 6, and did not change in 5 subjects. Using a paired t test, total transit did not show a significant change from rest (24.5 +/- 21.8 h) to exercise (20.9 +/- 16.8 h), p = 0.50. These observations support our previous findings that physical activity to the extent that average people consider routine exercise does not necessarily improve gastrointestinal transit. Therefore, the role of such exercise in the management of chronic constipation can be seriously questioned.

Adult↗

The routinization of hospice: charisma and bureaucratization.

In 25 years the number of hospices in Britain has multiplied from under 15 in 1965 to over 430 in 1991. During this period, often working out with the mainstream health system, the hospices actively sought to transform terminal care. More recently a process of diversification and legitimation has meant that hospices have become increasingly subject to mainstream influence. Using Weber's concept of charisma we examine the development of the hospice movement during this period of expansion. We suggest there are a number of factors leading to the routinization of hospice care including the ways in which it was sponsored and developed at the local level, and pressures toward bureaucratization and professionalization. We make links with recent developments in the health services. Finally we consider whether it is possible for the hospice movement to sustain its founding ideals.

Hospices↗