bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of inhibitors to FVIII with an ELISA in congenital and acquired haemophilia A
Authors: Lindgren A. , Wadenvik H. , Tengborn L.
Published: March 2003

Summary.  Different methods can be used for the detection and quantification of inhibitors or antibodies to coagulation factor VIII (FVIII). Traditionally, clotting assays have been used, in particular the Bethesda assay. These assays have, however, several shortcomings, due to the complex reaction kinetics of some inhibitors and a low sensitivity to low‐titre antibodies. In addition, a universal FVIII inhibitor standard is lacking. Furthermore, clotting assays do not detect noninhibitory antibodies. Use of ELISAs has been described and FVIII from various commercially available FVIII concentrates has been used as target antigen in the assays. In the present study, we systematically explored the influence of different FVIII concentrates on the performance of an ELISA for detection of FVIII antibodies. The described ELISA was also used for further characterization of FVIII inhibitors in patients with acquired and congenital haemophilia A. We found that the source of FVIII had a substantial impact on the frequency of antibody detection. Albumin‐free recombinant FVIII as target antigen gave the highest sensitivity for the assay, whereas plasma‐derived concentrates containing a high level of von Willebrand factor (vWF) gave the lowest sensitivity. Presumably vWF interferes with the binding of antibodies to FVIII. We suggest that albumin‐free recombinant FVIII should be used as target antigen when ELISAs are used for detection of FVIII antibodies.
Successful percutaneous transluminal coronary angioplasty for acute myocardial infarction in von Willebrand's disease
Authors: James P. R. , De Belder A. J. , Kenny M. W.
Published: March 2003

Summary. An elderly woman with mild von Willebrand's disease presented with acute myocardial infarction. Percutaneous transluminal coronary angioplasty, to mechanically disrupt the thrombus without anticoagulation, was successfully undertaken. Haemostatic cover was also avoided.
Nanofiltration of plasma‐derived biopharmaceutical products
Authors: Burnouf T. , Radosevich M.
Published: March 2003

Summary. This review presents the current status on the use and benefits of viral removal filtration systems – known as nanofiltration – in the manufacture of plasma‐derived coagulation factor concentrates and other biopharmaceutical products from human blood origin.

Nanofiltration of plasma products has been implemented at a production scale in the early 1990s to improve margin of viral safety, as a complement to the viral reduction treatments, such as solvent–detergent and heat treatments, already applied for the inactivation of human immunodeficiency virus, hepatitis B and hepatitis C virus. The main reason for the introduction of nanofiltration was the need to improve product safety against non‐enveloped viruses and to provide a possible safeguard against new infectious agents potentially entering the human plasma pool.

Nanofiltration has gained quick acceptance as it is a relatively simple manufacturing step that consists in filtering protein solution through membranes of a very small pore size (typically 15–40 nm) under conditions that retain viruses by a mechanism largely based on size exclusion. Recent large‐scale experience throughout the world has now established that nanofiltration is a robust and reliable viral reduction technique that can be applied to essentially all plasma products. Many of the licensed plasma products are currently nanofiltered.

The technology has major advantages as it is flexible and it may combine efficient and largely predictable removal of more than 4 to 6 logs of a wide range of viruses, with an absence of denaturing effect on plasma proteins. Compared with other viral reduction means, nanofiltration may be the only method to date permitting efficient removal of enveloped and non‐enveloped viruses under conditions where 90–95% of protein activity is recovered. New data indicate that nanofiltration may also remove prions, opening new perspectives in the development and interest of this technique. Nanofiltration is increasingly becoming a routine step in the manufacture of biopharmaceutical products.
Optimization of storage conditions for diluted working solutions of porcine factor VIII and performance of the Bethesda assay for the determination of antiporcine FVIII inhibitor titres
Authors: Winikoff R. , Boulanger A. , Robinson P. , ST‐Louis J. , Lacroix S. , Rivard G.‐É.
Published: March 2003

Summary. The use of porcine factor VIII (FVIII) (Hyate:C, Ipsen) has proven to be very successful in treating patients with FVIII inhibitors. The best way to predict the usefulness of porcine FVIII therapy, and/or to estimate the appropriate treatment dose in a given patient, is to measure the patient inhibitor titre against porcine FVIII with the Bethesda assay, using porcine FVIII as the source of FVIII in the assay. The goals of the present study were to (1) find the optimal storage temperature, diluent and concentration for a working solution of porcine FVIII to be used as the source of FVIII for the porcine Bethesda assay, (2) assess the reliability of the labelled FVIII units in the preparation of such working solutions of porcine FVIII and (3) compare the inhibitor titres determined by the Bethesda assay using both porcine and human standard reference curves for measuring residual FVIII. The results of the present study demonstrate that a ready‐to‐use working solution of 1 U mL−1 of Hyate:C diluted in human FVIII deficient plasma, either containing or deficient in von Willebrand factor antigen, is stable for up to 12 months, at −20 °C. The preparation of the 1 U mL−1 working solution could be reliably calculated based on the units indicated on the vial label. Finally, using the human standard curve yields similar results to using the porcine standard curve for measuring any titre of allo‐ or auto‐antibody against FVIII in the Bethesda assay, using Hyate:C as the source of FVIII. These findings are of practical value when performing a porcine FVIII‐based Bethesda assay.
Analgesic use and pain coping among patients with haemophilia
Authors: Elander J. , Barry T.
Published: March 2003

Summary.  Pain is an important consequence of bleeding episodes in haemophilia. Previous research has included pain frequency and severity among measures of illness‐related disability and quality of life in haemophilia, but little systematic evidence exists about analgesic use and pain coping in haemophilia. This paper reports cross‐sectional findings from a national survey of patients with severe haemophilia type A and type B. Respondents provided information about pain frequency, pain coping strategies (using the haemophilia‐adapted CSQ), use of analgesics and other drugs, and described any concerns they had about their drug use. Participants registered with comprehensive care haemophilia centres did not differ from the rest of the sample on any of the factors recorded. Over one‐third of participants expressed concerns about their drug use, the most frequent of which were about dependence on prescribed analgesics. Pain frequency was the most important predictor of analgesic use, but pain coping, and specifically negative thoughts about pain, was associated with concerns about drug use independently of other factors, including analgesic use and pain frequency. Further research will be needed to evaluate possible interventions to promote more effective pain coping in haemophilia, and to examine the possible effects of pain coping on illness outcomes beyond analgesic use, such as well‐being and quality of life.
Potential of agroforestry techniques in mitigating CO2emissions in Nigeria: some preliminary estimates
Authors: Adesina F. A. , Siyanbola W. O. , Oketola F. A. , Pelemo D. A. , Momodu S. A. , Adegbulugbe A. O. , Ojo L. O.
Published: March 2003

This paper attempts some preliminary evaluation of the potential of agroforestry techniques as a forestry strategy for controlling atmospheric CO2—a critical greenhouse gas. Theend‐usescenario that attempts to meet the wood and related needs of the nation while mitigating climate change was adopted. The net emission estimate for the Forestry Sector in 1990—the base year for the study—was 9.5 million tonnes of carbon (MtC). Based on this figure, projections into the year 2030 gave cumulative net emissions of 427.4 and 580.5 MtC at 1.3% and 2.6% deforestation rates respectively. However, mitigating with agroforestry techniques, assuming that about 76% of the estimated 39.5 million ha of farmland in the country is committed to a variety of agroforestry systems, the results show that a total of 1530 MtC can be withdrawn from the atmosphere by the year 2030. The paper concludes that there is a reasonable case for the use of agroforestry techniques in the country, both as a means of sustaining soil productivity and as a strategy for mitigating climate change.
Phytophagous insect assemblages and the regional species pool: patterns and asymmetries
Authors: Frenzel M. , Brandl R.
Published: March 2003

We describe three models predicting relationships between: (a) the taxonomic composition of the regional species pool of phytophagous insects and the composition of the phytophagous insect fauna on a host taxon; and (b) the faunal composition of two host taxa. The predictions of these models were compared with empirical data representing the regional pool of phytophages in Central Europe and the faunas of two plant taxa: the cabbage plants (Brassicaceae) and the thistles (Asteraceae: Cardueae). Three important findings emerge at a general level. (1) Different taxonomic levels of insects (orders, families, genera) of the regional pool and on the investigated host taxa are well correlated in terms of species richness, but there is no consistent trend in the variance explained by this correlation across taxonomic levels. (2) The model considering evolutionary interactions and speciation processes is consistent with patterns found in the empirical data. (3) Asymmetries in sampled species numbers of insect families on both host taxa may be accounted for by reference to the biology of these insects. We conclude that the faunas of single host taxa can provide the basis for extrapolating to the regional pool, at least at high taxonomic levels.
Toward error analysis of large‐scale forest carbon budgets
Authors: Phillips Donald L. , Brown Sandra L. , Schroeder Paul E. , Birdsey Richard A.
Published: March 2003

Quantification of forest carbon sources and sinks is an important part of national inventories of net greenhouse gas emissions. Several such forest carbon budgets have been constructed, but little effort has been made to analyse the sources of error and how these errors propagate to determine the overall uncertainty of projected carbon fluxes. We performed an error analysis for estimates of tree volume and volume change determined by repeated measurements of permanent sample plots for the South‐eastern United States as a step toward assessing errors in the carbon budget constructed by the USDA Forest Service. Error components recognized were: sampling error for sample plot selection; measurement error for tree height and diameter; and regression error for tree volume. Most of the propagated error in volume and volume change estimation was due to sampling error. Error estimates depended on the size of the area examined (single state to region) and the degree to which tree growth and recruit‐ment balanced mortality and harvesting. Approximate regional 95% confidence intervals were 3 455 073 000 ± 39 606 000 (1.1%) m3 for current growing‐stock volume, and 10 616 000 ± 4210 000 (39.7%) m3 years−1 for growing‐stock volume change. These methods should be useful in further analysis of the sources of error and overall uncertainty in national efforts to quantify carbon fluxes associated with forests and land cover dynamics.
The role of the terrestrial biosphere in Holocene carbon cycle dynamics
Authors: Beerling D. J.
Published: March 2003

Measurements of atmospheric CO2 concentration, and its stable carbon isotope composition, from gas samples trapped in ice at Taylor Dome, Antarctica, indicate that the global carbon cycle has not been in steady state during the Holocene epoch. Inverse carbon cycle modelling has led to the hypothesized cumulative release from the terrestrial biosphere of 195 Gt C between 7 and 1 kyr before present (bp). Here, three independent lines of evidence testing this hypothesis are critically examined: global reconstructions of terrestrial carbon reservoirs, vegetation–climate modelling, and high latitude subfossil plant stable carbon isotope records. Despite inherent uncertainties associated with each approach, it emerges that none strongly upholds the suggestion that terrestrial ecosystems released large amounts of carbon between 7 and 1 kyr bp. Consequently, our understanding of the processes involved in the exchange of CO2 between the atmosphere, oceans and land biota continues to remain incomplete and to require further investigation.
The littoral fish assemblage of the Desventuradas Islands (Chile) has zoogeographical affinities with the Western Pacific
Authors: Pequeño Germán , Lamilla Julio
Published: March 2003

A systematic account of fish species inhabiting waters surrounding the Desventuradas Islands, off Chile, is presented. The 61 species recognized belong to 33 families of Osteichthyes, and one of Chondrichthyes (Squalidae). It was found that the icthyofaunal links were stronger to the Western Pacific (90.7%) than to the Eastern Pacific (6.9%), despite the fact that these islands are much closer to the South American coast than to the coasts of Oceania. Hydrographic and physical barriers are postulated as explaining this pattern.
Floristics and environmental relations in two extreme desert zones of western Egypt
Authors: Abd El‐Ghani Monier M.
Published: March 2003

The present study provides quantitative estimates of soil, vegetation structure and species distribution in 144 stands along two transects in two extreme desert zones of western Egypt. This study had two aims: (1) to describe the floristic composition of the accidental type of vegetation growing in parts of the Western Desert of Egypt; and (2) to analyse the distribution of species in relation to certain environmental factors by multivariate data analysis.

Eight environmental variables were recorded: salinity, pH, calcium carbonate, soil moisture, organic matter content, and percentages of sand, silt and clay. A total of 60 species belonging to 19 families of the angiosperms and Ephedra alata was recorded. Chamaephytes and therophytes were the most frequent, denoting a typical desert life‐form spectrum, mainly of Saharo‐Arabian distribution.

The samples were classified into eight twinspan groups. Detrended correspondence analysis (DCA) showed that these groups could be distinguished by the first two DCA axes. They could also be effectively interpreted and explained with canonical correspondence analysis (CCA). Based on forward regression, salinity, fine sediments, organic matter and soil moisture content related closely to the first three canonical axes, and accounted for 84.1% of the species–environment relationship among the stands.

Both classification and ordination resulted in a clear demonstration of the vegetation pattern in the study area. Other twinspan groups were characterized in addition to those identified previously. In conclusion, the study area has a transitional character where the Nubian Desert and the Northern Mediterranean vegetation meet.
The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing
Authors: Hansson MD, PhD Carita ,   The Cadexomer Iodine Study Group
Published: March 2003

Background The aim was to examine cadexomer iodine paste in a comparative clinical trial.

Methods A 12‐week, randomized, open, controlled, multicenter, multinational trial in patients with exudating, venous leg ulcers of cadexomer iodine paste (Iodosorb®/Iodoflex®), hydrocolloid dressing (Duoderm E®, Granuflex E®), or paraffin gauze dressing (Jelonet®) was carried out. All patients used short‐stretch compression bandages (Comprilan®) throughout the study. The primary efficacy variable was a reduction in ulcer size (%), and the secondary end‐point was the time taken to stop exudation, when the patient had completed the study according to the protocol. A total of 153 patients entered the study and were treated for 12 weeks or until cessation of exudation.

Results The mean reduction in ulcer size in all patients was 62% with cadexomer iodine vs. 41% and 24% for hydrocolloid and paraffin gauze (ns). Of those treated for 12 weeks (n =51), ulcer area reduction was 66% for cadexomer iodine and 18% for hydrocolloid (p =0.0127). For the whole material, the rate of healing (ulcer area reduction per week) was significantly higher for cadexomer iodine than for paraffin gauze (0.64 cm2/week vs. 0.19 cm2/week, p = 0.0353). The treatment costs were similar in all groups; however, when the costs were correlated with healing over a 12‐week period, cadexomer iodine paste was found to be more cost effective than hydrocolloid dressing or paraffin gauze dressing.

Conclusions This study shows that cadexomer iodine paste is an efficient, cost‐effective and safe alternative to hydrocolloid dressing and paraffin gauze dressing for the treatment of venous leg ulcers.
Once‐daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double‐blind, placebo‐controlled study
Authors: Ring Johannes , Hein Rüdiger , Gauger Anke , Bronsky Edwin , Miller Bruce ,   and the Desloratadine Study Group
Published: March 2003

Abstract

Background  Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first‐line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first‐generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second‐generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile.

Methods  This was a multicenter, randomized, double‐blind, placebo‐controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate‐to‐severe CIU. A total of 190 patients, aged 12–79 years, with at least a 6‐week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment‐emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals.

Results  Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6‐week study. No significant adverse events occured.

Conclusions  Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period.
Minority ethnic community participation in needs assessment and service development in primary care: perceptions of Pakistani and Bangladeshi people about psychological distress
Authors: Kai Joe , Hedges Clive
Published: March 2003

Objectives To promote community participation in exploring perceptions of psychological distress amongst Pakistani and Bangladeshi people, in order to develop appropriate services.

Design Training and facilitation of resident community members (as community project workers), to define and conduct qualitative research involving semistructured interviews in their own communities, informing primary care led commissioning and service decision making.

Setting A socio‐economically disadvantaged inner‐city locality in the UK.

Participants One‐hundred and four South Asian people (49 of Pakistani and 55 of Bangladeshi origin), interviewed by 13 resident community members.

Results All community project workers completed training leading to a National Vocational Qualification, and successfully executed the research. Most study respondents located their main sources of stress within pervasive experience of racism and socio‐economic disadvantage. They were positive about `talking' and neutral listening as helpful, but sought strategies beyond non‐directive counselling services that embraced practical welfare advice and social support. The roles of primary health care professionals were believed to be restricted to physical ill health rather than personal distress. The importance of professionals' sex, age, ethnicity and social status were emphasized as affecting open communication. Practical recommendations for the re‐orientation and provision of services were generated and implemented in response to the findings, through dialogue with a primary care commissioning group, Health and Local Authority, and voluntary agencies.

Conclusions The work illustrates the feasibility and value of a community participation approach to research and service development in addressing a challenging and neglected area of minority ethnic health need. It offers one model for generating responsive service change in the context of current health policy in the UK, whilst also imparting skills and empowering community members. The study findings emphasize the need to recognize the social contexts in which distress is experienced and have implications for effective responses.
What do people with MS want and expect from health‐care services?
Authors: Somerset Maggie , Campbell Rona , Sharp Deborah J. , Peters Tim J.
Published: March 2003

Objective To determine the health‐care preferences of people with Multiple Sclerosis (MS).

Design Cross‐sectional survey using a postal questionnaire comprising standardized measures of health related quality of life (SF‐36) and of depression (BDI) and original questions about issues linked to health‐care, prioritized by people with MS during an earlier qualitative phase.

Participants A stratified sample of 318 people with MS in Scotland and England.

Results Questionnaires were sent to 471 people with multiple sclerosis. The 318 respondents (68%) reported a wide variation in quality of life, but on average scored significantly lower than normative values in all dimensions of the SF‐36. The most commonly used home treatment during the previous year was evening primrose oil, taken by almost half of the sample (47%). Use of cannabis was acknowledged by 8%. There was evidence that many preferences concerning health services were not satisfied. For instance lack of advice about at least one MS related issue was reported lacking for three‐quarters of the sample and 17% lacked advice in at least five areas. Advice about exercise was the single most requested area. The most frequently consulted health professional was the GP (78%) followed by the hospital consultant (50%). The professional that respondents most commonly said they would like to have seen was a specialist MS nurse (30%). Forty‐three percent of the sample said they had attended a special meeting for people with MS or disabilities. They were equally divided between those who did and who did not find their last attendance helpful.

Conclusions People with MS display a wide variation in their preference for services and unmet needs. Information about management (both conventional and unconventional), relevant tailored advice and access to appropriately skilled professionals should be feasible components of high quality care. This work has highlighted the value of involving people with MS in the identification of their preferences; further research is needed to show how these might be provided most effectively.
Women’s preferences for discussion of prognosis in early breast cancer
Authors: Lobb Elizabeth A. , Kenny Dianna T. , Butow Phyllis N. , Tattersall Martin H.N.
Published: March 2003

Objectives To determine preference for prognostic information in women with early breast cancer.

Design Cross sectional survey.

Participants 100 women with early stage breast cancer attending six teaching hospitals in Sydney, Australia.

Main outcome measures Women’s preference for prognostic information.

Results This study identifies new elements to consider in the prognostic consultation. Whilst 91% of women wanted to know their prognosis prior to commencing adjuvant treatment, 63% wanted their cancer specialist to check with them first before giving it. Seventy‐seven percent wanted to be asked if they would like a second opinion. Seventy‐five percent wanted to know about complementary therapies. Most wanted their cancer specialist to check their understanding, provide an opportunity to ask questions, and explain medical terms (98%). The majority wanted information summarized (94%), supported by published information (88%) and written down (79%). Ninety‐seven percent wanted their fears and concerns listened to and 79% wanted emotional support. In addition 80% of women wanted their cancer specialist to tell them where they could go to get additional emotional support for themselves and their families. Seventy‐two percent of women wanted their cancer specialist to make sure they had a relative or friend with them.

Conclusions Data from this study suggests that a variety of techniques are needed to communicate prognosis. Whilst acknowledging individual women’s preferences, and not wanting to appear prescriptive, recommendations emerge for effective discussion of prognosis with women with early stage breast cancer.
Conversation analysis: a method for research into interactions between patients and health‐care professionals
Authors: Drew Paul , Chatwin John , Collins Sarah
Published: March 2003

Background It is clear that much of the success of health‐care provision depends on the quality of interactions between health professionals and patients. For instance, it is widely recognized that patients are more likely to take medication effectively if they have been involved in discussions about treatment options, and understand and support the decision about what is prescribed (patient concordance). Hence, patient participation is important for the success of medical outcomes. The key is to explore how communicative choices made by health professionals impact on the quality of interactions in general, and of patient participation in particular. However, to date there has not been an appropriate method for investigating this connection or impact.

Objective To outline the perspective and method of Conversation Analysis (CA). Developed within sociology and linguistics, CA offers a rigorous method (applicable to large data sets) to the study of interaction in health settings.

Strategy The method of CA is illustrated through a review of CA studies of doctor–patient interactions. Two such studies, one from the US and the other from Finland, are reviewed, in order to show how CA can be applied to identifying both forms of patient participation, and the interactional conditions which provide opportunities for patient participation. These studies focus principally on the medical examination and diagnostic stages of the consultation. Further research will examine the forms and conditions of patient participation in decision‐making.
A qualitative exploration of treatment decision‐making role preference in adult asthma patients
Authors: Caress Ann‐Louise , Luker Karen , Woodcock Ashley , Beaver Kinta
Published: March 2003

Objectives  To explore preferred treatment decision‐making roles, and rationales for role preference, and to identify perceived facilitators to and barriers from attaining preferred role.

Design  Qualitative design.

Setting and Participants  One secondary care and four primary care sites in North‐west England. Purposive sample of 32 adult asthma patients with varied socio‐economic backgrounds and disease severity.

Methods  Tape‐recorded focused‐conversation style interviews. Interview topic guide derived from the literature. Sort cards employed to provide the focus for exploration of role preferences.

Results  Active (n = 7), collaborative (n = 11) and passive (n = 14) decisional role preferences were identified. Respondents cited level of knowledge; trust; duration of condition; severity of condition at the decisional juncture; lifelong nature of asthma; a perception that ‘it is my body’; characteristics of the individual and their response to health professionals as influencing role preference. Perceived facilitators and barriers to participation included condition‐related knowledge, practical issues (e.g. lack of time during consultation) and clinicians' interpersonal skills.

Conclusions  Most respondents wished to contribute to or feel involved in treatment decision‐making, but not necessarily to control it. Some hindrances to participation would be amenable to intervention. The quality of the provider–patient relationship is central to facilitating participation.
Responding to the active and passive patient: flexibility is the key
Authors: Brown Rhonda F. , Butow Phyllis N. , Henman Michael , Dunn Stewart M. , Boyle Francis , Tattersall Martin H.N.
Published: March 2003

Background  Patients vary widely in their preferences and capacity for participation in medical decision‐making. This study aimed to document oncologist responses to more extreme presentations and identify helpful and unhelpful strategies for clinicians.

Patients and methods  A trained actor played the role of a patient with early stage breast cancer who was attending her first consultation with a medical oncologist. She adopted in random order two different consultation participation styles: that of a very anxious, active patient, and that of a depressed, passive patient. Medical consultations between the actor and 16 medical oncologists were videotaped and then analysed qualitatively by two trained raters.

Results  Strategies that facilitated shared decision‐making with both patient types and were positively endorsed by the actor/patient included explicit agenda‐setting, active listening, checking understanding, endorsing question‐asking, offering decisional delay, and non‐verbal behaviours conveying empathy and warmth. Oncologists successfully negotiated with the active patient to share control of the consultation, and responded to emotional cues from the passive patient. Unhelpful strategies were also identified.

Conclusions  Few clinicians receive training in responding to differing communication styles in their patients that could potentially cause conflict and hinder optimal treatment decision‐making. This study suggests some useful strategies for oncologists to consider, to widen their behavioural repertoire in the cancer consultation.
‘Well, have I got cancer or haven't I?’ The psycho‐social issues for women diagnosed with ductal carcinoma in situ
Authors: De Morgan Simone , Redman Sally , White Kate J , Cakir Burcu , Boyages John
Published: March 2003

Objectives  To explore women's experience of being diagnosed with ductal carcinoma in situ (DCIS) in relation to the following: response to the diagnosis; understanding about the diagnosis; satisfaction with information; satisfaction with the level of involvement in treatment decision‐making and satisfaction with support services.

Design  An explorative descriptive qualitative design was used to facilitate an in‐depth exploration of women's experiences.

Setting and participants  Five focus group interviews were conducted in New South Wales (NSW), Australia, involving 26 women diagnosed with DCIS.

Results  DCIS is a non‐invasive breast disease, that in most cases will not recur if treated, and cannot of itself metastasize to other parts of the body. However, this study found that women were confused about whether or not they had cancer that could result in death. Women's confusion was compounded by the use of the term ‘carcinoma’ and by the recommendation of treatments such as mastectomy. Women's confusion was not alleviated by appropriate information, with most women reporting dissatisfaction with the information they received specifically about DCIS.

Conclusions  This study identifies that a diagnosis of DCIS has a significant psychological impact on women. The communication challenges highlighted in this study are not only relevant to DCIS but to any other disease in which the natural history is uncertain and the evidence about treatment effectiveness is still emerging. Further research is needed in areas such as DCIS to explore the difficulties experienced in doctor–patient communication and their impact on patient outcomes, and how to optimize doctor–patient communication.
Induction of (2′−5′)oligoadenylate synthetase in the marine sponges Suberites domuncula and Geodia cydonium by the bacterial endotoxin lipopolysaccharide
Authors: Grebenjuk Vladislav A. , Kuusksalu Anne , Kelve Merike , Schütze Joachim , Schröder Heinz C. , Müller Werner E. G.
Published: March 2003

Recent studies have shown that the Porifera, with the examples of the demosponges Suberites domuncula and Geodia cydonium, comprise a series of pathways found also in the immune system of Deuterostomia, such as vertebrates, but are absent in Protostomia, with insects or nematodes as examples. One pathway is the (2′−5′)oligoadenylate synthetase [(2–5)A synthetase] system. In the present study we show that crude extracts from tissue of S. domuncula collected from the sea display a considerable amount of (2–5)A synthetase activity; 16% of the ATP substrate is converted to the (2–5)A product, while tissue from specimens which were kept for 6 months in an aquarium shows only 1% of conversion. As aquarium animals show a lower bacterial load, those specimens were treated for the experiments with the bacterial endotoxin lipopolysaccharide (LPS); they responded to LPS with a stimulation of the (2–5)A synthetase activity. To monitor if this effect can be obtained also on the in vitro level, primmorphs which comprise proliferating and differentiating cells, were incubated with LPS. Extracts obtained from LPS‐treated primmorphs also convert ATP to the (2–5)A products mediated by the synthetase. In parallel to this effect on protein level, LPS causes after an incubation period of 12 h also an increase in the steady‐state level of the transcripts encoding the putative (2–5)A synthetase. It is postulated that in sponges the (2–5)A synthetase is involved in antimicrobial defense of the animals.
The mitochondrial‐lysosomal axis theory of aging
Authors: Brunk Ulf T. , Terman Alexei
Published: March 2003

Cellular manifestations of aging are most pronounced in postmitotic cells, such as neurons and cardiac myocytes. Alterations of these cells, which are responsible for essential functions of brain and heart, are particularly important contributors to the overall aging process. Mitochondria and lysosomes of postmitotic cells suffer the most remarkable age‐related alterations of all cellular organelles. Many mitochondria undergo enlargement and structural disorganization, while lysosomes, which are normally responsible for mitochondrial turnover, gradually accumulate an undegradable, polymeric, autofluorescent material called lipofuscin, or age pigment. We believe that these changes occur not only due to continuous oxidative stress (causing oxidation of mitochondrial constituents and autophagocytosed material), but also because of the inherent inability of cells to completely remove oxidatively damaged structures (biological ‘garbage’). A possible factor limiting the effectiveness of mitochondial turnover is the enlargement of mitochondria which may reflect their impaired fission. Non‐autophagocytosed mitochondria undergo further oxidative damage, resulting in decreasing energy production and increasing generation of reactive oxygen species. Damaged, enlarged and functionally disabled mitochondria gradually displace normal ones, which cannot replicate indefinitely because of limited cell volume. Although lipofuscin‐loaded lysosomes continue to receive newly synthesized lysosomal enzymes, the pigment is undegradable. Therefore, advanced lipofuscin accumulation may greatly diminish lysosomal degradative capacity by preventing lysosomal enzymes from targeting to functional autophagosomes, further limiting mitochondrial recycling. This interrelated mitochondrial and lysosomal damage irreversibly leads to functional decay and death of postmitotic cells.
The effects of low pH on the properties of protochlorophyllide oxidoreductase and the organization of prolamellar bodies of maize (Zea mays)
Authors: Selstam Eva , Schelin Jenny , Brain Tony , Williams W. Patrick
Published: March 2003

Prolamellar bodies (PLB) contain two photochemically active forms of the enzyme protochlorophyllide oxidoreductase POR‐PChlide640 and POR‐PChlide650 (the spectral forms of POR‐Chlide complexes with absorption maxima at the indicated wavelengths). Resuspension of maize PLB in media with a pH below 6.8 leads to a rapid conversion of POR‐PChlide650 to POR‐PChlide640 and a dramatic re‐organization of the PLB membrane system. In the absence of excess NADPH, the absorption maximum of the POR complex undergoes a further shift to about 635 nm. This latter shift is reversible on the re‐addition of NADPH with a half‐saturation value of about 0.25 mm NADPH for POR‐PChlide640 reformation. The disappearance of POR‐PChlide650 and the reorganization of the PLB, however, are irreversible. Restoration of low‐pH treated PLB to pH 7.5 leads to a further breakdown down of the PLB membrane and no reformation of POR‐PChlide650. Related spectral changes are seen in PLB aged at room temperature at pH 7.5 in NADPH‐free assay medium. The reformation of POR‐PChlide650 in this system is readily reversible on re‐addition of NADPH with a half‐saturation value about 1.0 µm. Comparison of the two sets of changes suggest a close link between the stability of the POR‐PChlide650, membrane organization and NADPH binding.

The low‐pH driven spectral changes seen in maize PLB are shown to be accelerated by adenosine AMP, ADP and ATP. The significance of this is discussed in terms of current suggestions of the possible involvement of phosphorylation (or adenylation) in changes in the aggregational state of the POR complex.
Detailed characterization of polydnavirus immunoevasive proteins in an endoparasitoid wasp
Authors: Tanaka Kohjiro , Matsumoto Hitoshi , Hayakawa Yoichi
Published: March 2003

Polydnaviruses are a unique group of insect viruses in terms of their obligate and symbiotic associations with some parasitic wasps. The Cotesia kariyai polydnavirus (CkPDV) replicates only in ovarian calyx cells of C. kariyai female wasps and is injected into the wasp's host, the armyworm Pseudaletia separata, along with the eggs. A previous study indicated the possibility that one of the CkPDV surface proteins mediates immunoevasion by the wasp from the encapsulation reaction of the host insect's hemocytes. This protein was named immunoevasive protein (IEP). The present studies substantially confirmed the previous observation by showing that an anti‐IEP IgG neutralizes immunoevasive activity on the wasp eggs. Further, we isolated the IEP homologue (IEP‐2) cDNA and IEP (IEP‐1) cDNA, sequenced them and found that both are cysteine‐rich proteins, each containing epidermal growth factor (EGF)‐like repeats. IEP genes were not found to reside in the CkPDV genome, but in the wasp chromosomal DNA. IEPs are synthesized in the female reproductive tract and their expression was detected from 4 days after pupation, 1 day later than expression of the virus capsid proteins. In situ hybridization and immunocytochemistry indicated that the lateral oviduct cells of the reproductive tracts produce IEP‐1/IEP‐2 mRNAs and secrete the proteins into the oviduct. These data suggest that the expression pattern and localization of IEPs are different from other components of CkPDV virions.
Interaction between p21‐activated protein kinase and Rac during differentiation of HL‐60 human promyelocytic leukemia cell induced by all‐trans‐retinoic acid
Authors: Nisimoto Yukio , Ogawa Hisamitsu
Published: March 2003

Undifferentiated human promyelocytic leukemia HL‐60 cells show little or no superoxide production, but generate a very low O2– concentration upon incubation with all‐trans‐retinoic acid (ATRA). Its production reaches a maximum within 20 h, and thereafter is maintained at an almost constant level. The differentiated cells show phorbol 12‐myristate 13‐acetate (PMA)‐stimulated NADPH oxidase activity consistent with the amount of gp91phox (phagocytic oxidase) expressed in the plasma membrane. Three isoforms of p21‐activated serine/threonine kinases, PAK68, PAK65 and PAK62, were found in both cytosolic and membrane fractions, and their contents were significantly increased during induced differentiation. The amount of Rac identified in the two fractions was also markedly enhanced by ATRA‐ induced differentiation. In contrast, neither PAK nor Rac was seen in the plasma membrane of undifferentiated HL‐60 or human neutrophil, but they were abundant in the cytoplasmic fraction. Binding of Rac with PAK isoforms was shown in the membrane upon induced differentiation of HL‐60 cells. Direct binding of purified Rac1 to PAK68 was quantified using a fluorescent analog of GTP (methylanthraniloyl guanosine‐5′‐[β,γ‐imido]triphosphate) bound to Rac as a reporter group. Rac1 bound to PAK68 with a 1 : 1 stoichiometry and with a Kd value of 6.7 nm.
EPR characterization of the mononuclear Cu‐containing Aspergillus japonicus quercetin 2,3‐dioxygenase reveals dramatic changes upon anaerobic binding of substrates
Authors: Kooter Ingeborg M. , Steiner Roberto A. , Dijkstra Bauke W. , van Noort Paula I. , Egmond Maarten R. , Huber Martina
Published: March 2003

Quercetin 2,3‐dioxygenase (2,3QD) is a copper‐containing dioxygenase that catalyses the oxidation of the flavonol quercetin to 2‐protocatechuoylphloroglucinol carboxylic acid with concomitant production of carbon monoxide. In contrast to iron dioxygenases, very little is known about copper dioxygenases. We have characterized 2,3QD from the fungus Aspergillus japonicus by electron paramagnetic resonance spectroscopy (EPR). At pH 6.0, 2,3QD shows a mixture of two EPR species. The major form has parameters typical of type 2 Cu sites (g// = 2.330, A// = 13.7 mT), the minor one has a more distorted geometry (g// = 2.290, A// = 12.5 mT). Anaerobic addition of the substrate quercetin results in a different, single species EPR spectrum with g// = 2.336, A// = 11.4 mT, parameters, which are in‐between those of the type 2 and type 1 Cu sites in the Peisach–Blumberg (g// vs. A//) plot. After turnover, a new EPR signal is observed, which is ascribed to the carboxylic acid ester product complex. This spectrum is similar to that of the native enzyme at pH 10.0 and has g‐tensor parameters suggesting a trigonal bipyramidal site. Of a variety of flavonoids studied, only flavonols are able to bind to the copper centre of 2,3QD. Nine flavonols with different hydroxylation patterns at the A‐ and B‐ring have been analysed. They cluster in two different regions of the Peisach–Blumberg plot and show that the presence of a 5‐OH group has a large effect on the A// parameter. Several differences are noted between A. japonicus 2,3QD and the enzyme from A. niger German Collection of Microorganisms 821.
Glycation and glycoxidation of low‐density lipoproteins by glucose and low‐molecular mass aldehydes
Authors: Knott Heather M. , Brown Bronwyn E. , Davies Michael J. , Dean Roger T.
Published: March 2003

Patients with diabetes mellitus suffer from an increased incidence of complications including cardiovascular disease and cataracts; the mechanisms responsible for this are not fully understood. One characteristic of such complications is an accumulation of advanced glycation end‐products formed by the adduction of glucose or species derived from glucose, such as low‐molecular mass aldehydes, to proteins. These reactions can be nonoxidative (glycation) or oxidative (glycoxidation) and result in the conversion of low‐density lipoproteins (LDL) to a form that is recognized by the scavenger receptors of macrophages. This results in the accumulation of cholesterol and cholesteryl esters within macrophages and the formation of foam cells, a hallmark of atherosclerosis. The nature of the LDL modifications required for cellular recognition and unregulated uptake are poorly understood. We have therefore examined the nature, time course, and extent of LDL modifications induced by glucose and two aldehydes, methylglyoxal and glycolaldehyde. It has been shown that these agents modify Arg, Lys and Trp residues of the apoB protein of LDL, with the extent of modification induced by the two aldehydes being more rapid than with glucose. These processes are rapid and unaffected by low concentrations of copper ions. In contrast, lipid and protein oxidation are slow processes and occur to a limited extent in the absence of added copper ions. No evidence was obtained for the stimulation of lipid or protein oxidation by glucose or methylglyoxal in the presence of copper ions, whereas glycolaldehyde stimulated such reactions to a modest extent. These results suggest that the earliest significant events in this system are metal ion‐independent glycation (modification) of the protein component of LDL, whilst oxidative events (glycoxidation or direct oxidation of lipid or proteins) only occur to any significant extent at later time points. This ‘carbonyl‐stress’ may facilitate the formation of foam cells and the vascular complications of diabetes.
The unorthodox histidine kinases BvgS and EvgS are responsive to the oxidation status of a quinone electron carrier
Authors: Bock Andreas , Gross Roy
Published: March 2003

The purified soluble forms of the histidine kinases BvgS and EvgS of Bordetella pertussis and Escherichia coli, respectively, are shown to be responsive to oxidized ubiquinone‐0 (Q‐0) in vitro. The oxidized ubiquinone is a strong inhibitor of kinase activity of both enzymes with half maximal inhibition occurring at 11 µm (BvgS) and 4 µm (EvgS). Reduced Q‐0 has no effect on the histidine kinases. Kinase activity can reversibly be switched off and on by changing the oxidation status of the quinone. This inhibitory effect is due to a decrease of the kinase activity of BvgS rather than an increase of intrinsic phosphatase activities. Other electron carriers such as menadione (MK‐3), NAD or FAD did not have a significant effect on the kinase activities of BvgS and EvgS. Nicotinic acid and sulfate ions, known to inhibit the histidine kinases in vivo, did not affect the purified truncated sensor proteins lacking their periplasmic domains in vitro. Mutations introduced by site‐directed mutagenesis into the putative PAS domain of BvgS caused a weak decrease of qui‐ none‐dependent inhibition of autophosphorylation. These data suggest that BvgS and EvgS are connected with the oxi‐ dation status of the cell via the link to the ubiquinone pool.