Placing an upper limit on cryptic marine sulphur cycling.

A quantitative understanding of sources and sinks of fixed nitrogen in low-oxygen waters is required to explain the role of oxygen-minimum zones (OMZs) in controlling the fixed nitrogen inventory of the global ocean. Apparent imbalances in geochemical nitrogen budgets have spurred numerous studies to measure the contributions of heterotrophic and autotrophic N2-producing metabolisms (denitrification and anaerobic ammonia oxidation, respectively). Recently, 'cryptic' sulphur cycling was proposed as a partial solution to the fundamental biogeochemical problem of closing marine fixed-nitrogen budgets in intensely oxygen-deficient regions. The degree to which the cryptic sulphur cycle can fuel a loss of fixed nitrogen in the modern ocean requires the quantification of sulphur recycling in OMZ settings. Here we provide a new constraint for OMZ sulphate reduction based on isotopic profiles of oxygen ((18)O/(16)O) and sulphur ((33)S/(32)S, (34)S/(32)S) in seawater sulphate through oxygenated open-ocean and OMZ-bearing water columns. When coupled with observations and models of sulphate isotope dynamics and data-constrained model estimates of OMZ water-mass residence time, we find that previous estimates for sulphur-driven remineralization and loss of fixed nitrogen from the oceans are near the upper limit for what is possible given in situ sulphate isotope data.

The role of thymidine phosphorylase and uridine phosphorylase in (fluoro)pyrimidine metabolism in peripheral blood mononuclear cells.

Thymidine phosphorylase (TP) and uridine phosphorylase (UP) catalyze the (in)activation of several fluoropyrimidines, depending on their catalytic activity and substrate specificity. Blood cells are the first compartment exposed to most anticancer agents. The role of white blood cells in causing toxic side effects and catalyzing drug metabolism is generally underestimated. Therefore we determined the contribution of the white blood cell compartment to drug metabolism, and we investigated the activity and substrate specificity of TP and UP for the (fluoro)pyrimidines thymidine (dThd), uridine (Urd), 5'-deoxy-5-fluorouridine (5' dFUrd) and 5-fluorouracil (5FU) in peripheral blood mononuclear cells (PBMC) and undifferentiated monocytes and differentiated monocytes: macrophages and dendritic cells. PBMC had an IC50 of 742 microM exposed to 5'dFUrd, increasing to > 2000 microM when both TP and UP activities were inhibited. Total phosphorolytic activity was higher with dThd than with Urd, 5'dFUrd or 5FU. Using a specific TP inhibitor (TPI) and UP inhibitor (BAU) we concluded that dThd and Urd were preferentially converted by TP and UP, respectively, while 5'dFUrd and 5FU were mainly converted by TP (about 80%) into 5FU and FUrd, respectively. 5FU was effectively incorporated into RNA. dThd conversion into thymine was highest in dendritic cells (52.6 nmol thymine/h/10(6) cells), followed by macrophages (two-fold) and undifferentiated monocytes (eight-fold). TPI prevented dThd conversion almost completely. In conclusion, PBMC were relatively insensitive to 5'dFUrd, and the natural substrates dThd and Urd were preferentially converted by TP and UP, respectively. TP and UP were both responsible for converting 5'dFUrd/5FU into 5FU/FUrd, respectively.

Co-expression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42.

Variants of the human ovarian carcinoma cell line, OAW42, exhibiting low-level intrinsic resistance (OAW42-SR) and drug-induced higher-level resistance (OAW42-A1 & OAW42-A), were studied along with a sensitive clonal population (OAW42-S) which was isolated from OAW42-SR. Expression of the MDR-associated protein P-170, the more recently discovered LRP (lung resistance-related protein) and MRP (multidrug resistance-associated protein), topoisomerase II alpha and beta, GST pi and the cytoskeletal proteins, cytokeratin 8 and vimentin, were studied (using immunocytochemistry and Western blotting techniques) in conjunction with drug (doxorubicin) accumulation and subcellular distribution. Expression of mRNA for P-170, MRP, topoisomerase 11 alpha and beta and GST pi was studied using RT-PCR (reverse transcriptase polymerase chain reaction). Results indicate differential co-expression of four MDR-associated parameters (P-170, MRP, LRP and reduced topoisomerase II alpha and beta) in the OAW42-SR and OAW42-A1 variants, whereas resistance in the OAW42-A variant appeared to be mainly P-170 mediated. Comparable amounts of MRP and greater amounts of LRP were detected in the OAW42-S cells compared to the OAW42-SR variant (which showed increased resistance compared to the OAW42-S cells), but all cell lines expressed similar low-level amounts of MRP mRNA (by RT-PCR). GST pi levels did not differ markedly between variants. Increased levels of the cytoskeletal proteins were observed with increasing levels of resistance. The relative resistance of the variants, OAW42-SR and OAW42-A1, compared with OAW42-S was seen to change during increased serial passaging of the cells. There was greater drug accumulation by the sensitive OAW42-S cell line compared with that of the resistant variants, particularly the most highly resistant OAW42-A cells. Both verapamil and cyclosporin A effectively restored the accumulation defects seen in the resistant variants, cyclosporin A being the more effective of the two. Sub-cellular location of drug was predominantly in the nucleus with maximum levels seen in the sensitive OAW42-S variant and minimum levels in the most resistant OAW42-A clone.

Pathology and clinical relevance of radial scars: a review.

Radial scar (RS) is a benign, well recognised, radiological and pathological entity. Histologically, it is characterised by a fibroelastotic core with entrapped ducts and surrounding radiating ducts and lobules. Postmortem studies indicate that these lesions are present commonly in the population, especially in association with benign breast disease. In recent years, their clinical relevance has assumed more importance with the introduction of population based screening programmes. The exact pathogenesis of RS is unknown. Accumulating evidence indicates that they are associated with atypia and/or malignancy and, in addition, may be an independent risk factor for the development of carcinoma in either breast. In view of the association with atypia and malignancy, excision biopsy is justified in RS, although it has been argued that core biopsy evaluation and surveillance may be appropriate in selected patients.

Health promotion versus disease and care: failure to establish "blissful clarity" in British nurse education and practice.

An evaluation which involved documentary analysis, observation and interviews with teachers, students and nurses in four educational institutions, revealed that the interpretation and implementation of a philosophy of health in nursing in the UK has been variable. A small but influential group of teachers saw health as the basis for the curriculum and the way forward for nursing. The new Project 2000 health-based curriculum led some participants to reassess their conception of nursing, but disease and care of the sick remained uppermost. Trained hospital nurses in particular continued to view nursing as primarily concerned with disease treatment. The care model associated with 'New Nursing', rooted in communication and interpersonal relationships, was also apparent particularly among pre- and post-registration students. Health was operationalised as both health education and health promotion ranging from individualised information giving and disease prevention to more participatory forms based on equity and empowerment. Participants' responses to the introduction of health in the curriculum were categorised in one of four ways: pessimism, partisanship, fanschen (to turn over) or marketisation. Their response depended on whether they viewed health as the central nursing philosophy rather than disease or care. On the basis of our findings we propose that these responses give rise to four policy choices for nurses at an individual and group level.

Health and the curriculum: an illuminative evaluation--Part I: Methodology.

A six-month exploratory study commissioned in 1993 by the English National Board for Nursing, Midwifery and Health Visiting (ENB) is described in this two-part paper. The research evaluated the integration of a philosophy of health within pre- and post-registration curricula in England (Lask et al 1994). In Part I of the paper, a philosophy of health as a basis for the curriculum is discussed. This is followed by an outline of the project aims, methodology and the literature that informed our theoretical understanding of a philosophy of health. In Part 2(1) of the paper we present our main findings and discuss their implications for professional preparation and continuing education.

Action research: a suitable method for promoting change in nurse education.

This paper arose from a research study and its follow-up in four schools of nursing and midwifery. The study was concerned with evaluating the extent to which a philosophy of health had been integrated into the educational curricula of nurses, midwives and health visitors. The purpose of the follow-up was to disseminate and implement the study findings in the four centres. The findings showed that the interpretation and implementation of a philosophy of health in nursing had been variable. Health was operationalized as both health education and health promotion ranging from individualized information giving and disease prevention. Action research was chosen as the appropriate methodology for the follow-up because of its emphasis on participation and partnership. As the follow-up study progressed a number of issues emerged which were indicative of the changes taking place in nurse education as its institutional base shifted into higher education. Other issues were associated with the gap between the rhetoric and reality of action research and the expectations and needs of the key partners. The authors conclude that the follow-up study presented both challenges and opportunities to nurse educators in their endeavour to undertaken research and implement educational change.

Tomlinson: a social policy perspective (Part 1).

This article is the first of two which explore the Report of the Inquiry into London's Health Service, Medical Education And Research (1) (the Tomlinson Report), and consider its origins and implications from a social policy perspective. In this article, the Tomlinson Report will be placed within its historical context and the key events leading up to its commissioning and publication examined. To facilitate the analysis, a 'policy as process model' will be adopted throughout to articulate and emphasise the relationships between the phenomena involved (2). Part two appears next week.

Practising at a higher level.

New nursing roles are continually being developed. Nurses working at higher levels of practice are only partially regulated at present. More formal regulation by the UKCC would help protect nurses working at higher levels, as well as their employers and patients.

Managing the unmanageable? Nurse Executive Directors and new role developments in nursing.

This paper offers a unique insight into the factors affecting the functioning of the Nurse Executive Director(s) and their views on the realities of nursing management in the new National Health Service in England. It is based on the findings of the Exploring New Roles in Practice (ENRiP) project which was carried out for the Department of Health. As part of this project interviews were undertaken with Nurse Executive Directors from a 20% sample of acute hospital trusts in England. The interviews were designed to explore the Nurse Executive's perceptions of the process of new role development. The findings highlight a tension between the drive for professional development and the pragmatics of service delivery in a health care system which lacks dedicated funding for nursing development. It was evident that most Nurse Executives vacillated between responding either in an ad hoc way to internal and external pressures or leading and supporting managed development.

Continuing care: developing a policy analysis for nursing.

Continuing care: developing a policy analysis for nursing Many authors have commented on the invisibility of nursing in policy development, implementation and analysis. Some of this invisibility may be attributed to the lack of an easily accessible framework to assist analysis of policy from a nursing perspective. In this paper we offer a framework for nursing policy analysis based on the domain concepts of nursing. We use continuing care for older people, a topical policy issue and fundamental nursing specialty, as a case study to demonstrate the utility and potential of such a framework in action. The resulting analysis helps identify areas of potential policy interest to nurses, raises questions for further policy analysis and offers a coherent position statement for action.

Value of MR pancreatography in the evaluation of patients with chronic pancreatitis.

AIM: To determine the diagnostic accuracy of magnetic resonance (MR) pancreatography and to define its role in the imaging work-up of patients with severe chronic pancreatitis. MATERIAL AND METHODS: Thirty-two patients (13 men and 19 women; 15-84 years old; mean age, 48 years) with severe chronic pancreatitis diagnosed using cross-sectional imaging, examination using contrast medium (endoscopic retrograde cholangiopancreatography, pseudocyst injection) and/or surgical findings underwent MR pancreatography performed using a two-dimensional multi-slice fast spin echo technique. All patients underwent transabdominal pancreatic sonography and computed tomography (CT) was performed in 12 patients. Two observers independently assessed the MR pancreatograms for pancreatic duct dilatation and pancreatic duct abnormalities. Compared to the final diagnosis, the accuracy of MR pancreatography in revealing complications of chronic pancreatitis was calculated and its role in the radiological work-up of patients with chronic pancreatitis evaluated. RESULTS: When compared to the final diagnosis, MR pancreatography showed the following sensitivity, specificity and diagnostic accuracy: for filling defects in pancreatic duct, 56-78%, 100% and 87-94%, respectively; for strictures, 75-88%, 92-96% and 88-94%, respectively; and for pseudocysts 100%, 100% and 100%, respectively. Filling defects were correctly diagnosed in all patients when MR pancreatography was interpreted in combination with cross-sectional imaging. Contrast pancreatography was required for the complete evaluation of strictures and communication with pseudocysts. CONCLUSION: MR pancreatography is poorly sensitive but specific in revealing pancreatic duct filling defects and strictures. However, when MR pancreatography is interpreted in combination with sonography and CT, it provides sufficient information to plan therapy in the majority of patients.

Randomisation in clinical trials.

BACKGROUND: Several studies of papers published in non-psychiatric medical journals that report on randomised controlled trials (RCTs) indicate that there is inadequate reporting of the process by which randomisation is carried out. AIMS: To examine the adequacy of the reporting of the procedure of randomisation in clinical trials of parallel design published in the British Journal of Psychiatry (BJP) and the American Journal of Psychiatry (AJP). METHODS: All issues of the BJP and the AJP published between January 1990 and December 1998 were surveyed, and papers that reported on RCTs were examined to judge the adequacy of the reporting of the process of randomisation. RESULTS: We found 183 papers which claimed to report on RCTs (73 in the BJP and 110 in the AJP). Nine (8.2%) of those in the AJP and six (8.2%) in the BJP described the technique of creating the randomisation sequence. Two (1.8%) of those in the AJP and 11 (15.1%) of those in the BJP described the mechanism of allocating treatment. One paper in the AJP and five papers in the BJP described both the generation of random numbers and allocation. CONCLUSIONS: Adequate reporting of the method of randomisation was uncommon. The RCT status of some of the papers must therefore be in doubt.

Nomifensine maleate in adult attention deficit disorder.

The authors studied 18 adults (8 men and 10 women) in an open trial of nomifensine maleate for the treatment of attention deficit disorder (ADD). All patients met DSM-III criteria and the Utah criteria for ADD, residual type (RT). Medication effect was measured at week 1 and week 4 of treatment using the Structured Interview for ADD-H Symptoms. Data from week 4 showed that all eight men and seven of the women responded well to nomifensine, showing a significant decrease in ADD with hyperactivity symptoms. Side effects were minimal, consisting of drowsiness, dry mouth, headache, and nausea. One responder (5%) was taken off the medicine after developing an allergic reaction. Results showed that short-term use of nomifensine was relatively free from side effects and was remarkably effective in the treatment of ADD-RT. The authors discussed the implications of the use of nomifensine and related drugs in the treatment of ADD-RT.

Random blood glucose estimation in type 2 diabetes: does it reflect overall glycaemic control?

The relationship between clinic-measured random blood glucose and glycated haemoglobin was investigated in 204 non-insulin-dependent diabetic patients to determine the value of random blood glucose on management decisions in these patients. Treatment was with diet alone in 104 patients (51%: Group 1), and diet and oral hypoglycaemic agents in 100 patients (49%: Group 2). Random blood glucose and glycated haemoglobin were lower in Group 1 than Group 2 (10.9 +/- 4.0 vs 13.0 +/- 4.0 mmol l-1, p < 0.001, and 8.5 (7.8-10.2) vs 9.6 (8.1-11.0)%, p < 0.01, respectively), and there was a positive correlation between random blood glucose and glycated haemoglobin in both groups (rGroup1 = 0.76, and rGroup2 = 0.54, both p < 0.001). In Group 1, 48 (46%) patients had a random blood glucose < 10 mmol l-1 and all but 2 of these had a glycated haemoglobin of < 10%. Thus, random blood glucose < 10 mmol l-1 was 96% sensitive for glycated haemoglobin < 10%. In Group 2 the same sensitivity was 92%. These data suggest that clinic-measured random blood glucose levels below 10.0 mmol l-1 predict acceptable overall glycaemic control in non-insulin-dependent diabetic patients, particularly in those on diet alone. However, a clinic-measured random blood glucose above 10 mmol l-1 was of limited value in predicting glycated haemoglobin values above 10% and a blood glucose cut-off of 14 mmol l-1 appeared more useful. Where resources are limited, clinic random blood glucose estimation may allow clinicians to use glycated haemoglobin measurements more discriminately.

The development of advanced practice roles: implications in the international nursing community.

This article examined the critical elements that have been identified in the development of advanced practice roles of nurses in four countries: Brazil, Thailand, the United Kingdom and the United States of America. Several sociopolitical and professional forces were examined for possible insights and ways in which they may have shaped the development and evolution of the roles of advanced practice nurses (APNs). These forces were: the socio-political environment; the health needs of society; the health workforce supply and demand; governmental policy and support; intra- and interprofessional collaboration; the development of nursing education; and documentation of effectiveness of the advanced role. The development of APN roles in the four social systems was reviewed to illustrate how socio-political and professional forces may have shaped nursing roles in each health care delivery system. Commonalities and distinguishing features across the four health and social systems were analysed to assess the predictive forces that may be identified as advanced roles in nursing have evolved in the global community.

Low-dose twice-daily fractionated X-irradiation of ovarian tumor cells in vitro generates drug-resistant cells overexpressing two multidrug resistance-associated proteins, P-glycoprotein and MRP1.

Failure of chemotherapy is frequently observed in patients previously treated with radiotherapy. To establish a cellular model for examining this resistance phenotype a series of mammalian tumor cell lines were exposed in vitro to fractionated X-irradiation and were then shown to express resistance to multiple antitumor drugs, including vincristine, etoposide and cisplatin. In these experiments the radiation was delivered as 10 fractions of 5 Gy (dose resulting in 1 log cell kill) given intermittently over several months. We now report that a comparable multidrug-resistance profile is expressed by human SK-OV-3 human ovarian tumor cells exposed in vitro to low dose (2 Gy) twice-daily fractions of X-rays given for 5 days on two consecutive weeks, essentially mimicking clinical practice, involving an overexpression of two MDR-associated proteins, P-glycoprotein and the multidrug resistance protein 1 (MRP1), with the latter being readily detectable by immunocytochemistry.