bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotopic synovectomy with P‐32 in paediatric patients with haemophilia
Authors: Mathew  , Talbut  , Frogameni  , Singer  , Chrissos  , Khuder  , Ohler  , Farley  , Michael  , Robinson
Published: March 2003

Isotopic synovectomy is being proposed as an option in the treatment of patients with haemophilic arthropathy. We present our experience with 11 paediatric patients who underwent 17, P‐32 isotopic synovectomies for chronic haemophilic arthropathy. P‐32 was injected into the joint per protocol, approved by the institutional review board. All our patients were male. Nine were factor VIII and two were factor IX deficient. The following joints were treated: ankle (n=10 procedures), elbow (n=5) and knee (n=2). The first procedure was performed on December 1993. None were human immunodeficiency virus positive. Mean age at the first procedure was 10.8 years (range, 5.2–15.2 years). Mean pretreatment joint clinical scores using the World Federation of Hemophilia guidelines for the ankle was 5.5 (SD ± 2.3), the elbow 4.2 (±2.5), and knee 5.5 (±3.5); the corresponding post‐treatment scores were 2.6 (±2.0), 1.4 (±0.5) and 2.5 (±3.5) respectively. Presynovectomy mean radiological scores using the Pettersson method were: ankle 1.8, elbow 1.8, and knee 1.5. A scoring system used in our centre for evaluating joints using magnetic resonance imaging (MRI) gave the following mean pretreatment scores: ankle 9.5, elbow 8.4, and knee 5.0. A marked decrease (an 80–100% decrease) in bleeding was seen in 13 of 17 procedures, and a moderate decrease (51–79% decrease) in two procedures, accounting for 85% reduction in bleeding into the target joints. The procedure was well tolerated and no untoward side‐effects were noted as of May 1999, with a median follow‐up of 40 months (range 19–65 months). None had any clinical evidence of cancer. Three patients had their joints retreated [elbow (one), ankle (two)]. These procedures were also well tolerated. In conclusion, in our study, isotopic synovectomy using P‐32 appears to be feasible, safe and efficacious in the treatment of haemophilic arthropathy in paediatric patients who have been followed for a median of 40 months. As previously shown, MRI appears to give more detailed information about joint arthropathy than plain radiographs.
Acquired haemophilia in recipients of depot thioxanthenes
Authors: Stewart A. J. , Manson L. M. , Dasani H. , Beddall A. , Collins P. , Shima M. , Ludlam C. A.
Published: March 2003

We present two cases in which the occurrence of acquired haemophilia is associated with the use of depot preparations of the thioxanthenes zuclopenthixol and flupenthixol. These drugs have not previously been implicated in the aetiology of acquired haemophilia.
Chemical synovectomy in haemophilia: status and challenges
Authors: Rivard G.‐É.
Published: March 2003

Chemical synovectomy has been used for the last three decades as an alternative for surgical synovectomy in the treatment of chronic haemophilic synovitis. Comparable results have been obtained with the many different radionuclides used: decreased bleeding, decreased pain and stable range of motion, in more than 50% of treated patients. Yttrium 90Y and Phosphorus 32P seem to be the isotopes of choice. Osmic acid and rifampicine have been used in a relatively small number of subjects. Global result of treatment with these two pro‐ducts seems to be less favourable than with radionuclides. Late effects of chemical synovectomy are not known.
Utility of the PFA‐100® for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations
Authors: Favaloro E. J.
Published: March 2003

The PFA‐100® (platelet function analyser) is a relatively new tool for the investigation of primary haemostasis. Recent studies have shown its utility in monitoring antiplatelet therapy (including aspirin) and as a screening tool for investigating possible von Willebrand disease (vWD) and various platelet disorders. More recently, the PFA‐100® has been shown to be of value in monitoring DDAVP therapy in both vWD and platelet disorders. This paper reviews current findings, details the utility of the PFA‐100® for some of these purposes, as well as reviewing analytical variables that may complicate the interpretation of results. The author highlights the benefits, as well as noting the limitations, of its use. Ultimately, the greatest strengths of the PFA‐100® are its simplicity in use and excellent sensitivity to particular haemostatic disturbances such as vWD, platelet disorders and platelet‐affecting medication. However, because it is thus a ‘global’ test system, this also creates a significant limitation, as the PFA‐100® is not specific for, nor predictive of, any particular disorder. However, utilized appropriately, the PFA‐100® can be considered a worthwhile addition to any haemostasis laboratory involved in the diagnosis or therapeutic‐monitoring of bleeding disorders including vWD and platelet‐dysfunctions. This review should be of value to both haemostasis scientists and clinical specialists.
Mild bleeding diathesis in a boy with combined severe haemophilia B (C10400→T) and heterozygous factor V Leiden
Authors: Vianello F. , Belvini D. , Dal Bello F. , Tagariello G. , Zanon E. , Lombardi A‐M. , Zerbinati P. , Girolami A.
Published: March 2003

Haemophilia B patients with factor IX (FIX) activity < 1% are usually characterized by severe bleeding episodes early in life. We report a case of sporadic severe haemophilia B, clinically characterized by mild bleeding diathesis. The presence of anamnestic thrombophlebitis in the patient’s mother prompted us to investigate a possible associated hypercoagulable condition. Resistance to activated protein C due to factor V R506Q mutation was present in the mother and in the propositus, in the homozygous and heterozygous form, respectively. Molecular analysis of the FIX gene led to the identification of a nonsense mutation resulting in a stop codon at position 50, previously described and usually responsible for a severe pattern of haemophilia B. The implications of this unusual association are discussed.
Acquired inhibitor to factor VIII in a patient with Hodgkin’s disease following treatment with interferon‐alpha
Authors: Regina S. , Colombat P. , Fimbel B. , Guerois C. , Gruel Y.
Published: March 2003

We describe a young woman who developed acquired haemophilia after 18 months of interferon (IFN‐)‐α therapy. This patient had been monitored since 1992 for Hodgkin’s disease initially treated by chemotherapy. After two relapses, she received intensive chemotherapy followed by an autologous peripheral progenitor cell graft. IFN‐α was then administered for 18 months. Bleeding of the limbs and tongue occurred 1 month after withdrawal of IFN‐α and high titres (123 Bethesda units) of autoantibody to factor VIII (FVIII):C were measured. Prednisone (1 mg kg−1 day−1) achieved rapid cessation of the bleeding and FVIII autoantibodies were undetectable 5 months later. This case report suggests that the activated partial thromboplastin time should be regularly checked in every patient treated with IFN‐α in cases of unexplained bleeding, together testing for antibodies to FVIII if the bleeding is prolonged.
Safety of factor VIII inhibitor bypass activity (FEIBA®): 10‐year compilation of thrombotic adverse events
Authors: EHRLICH H. J. , HENZL M. J. , GOMPERTS E. D.
Published: March 2003

Published and unpublished spontaneously reported thrombotic adverse events (AEs) in factor VIII inhibitor bypass activity (FEIBA®) recipients were compiled for the most recent 10‐year period during which FEIBA® units equivalent to 3.95 × 105 typical infusions were distributed worldwide. A total of 16 thrombotic AEs were documented over the 10‐year period, corresponding to an incidence of 4.05 per 105 infusions (95% CI, 2.32–6.58 per 105 infusions). Disseminated intravascular coagulation (n=7) and myocardial infarction (n=5) were the most frequent thrombotic AEs. One fatality occurred in an 87‐year‐old metastatic cancer patient. In 13/16 (81%) patients known risk factors were present, most commonly FEIBA® overdose in 8/16 (50%), obesity in 3/16 (19%) and serum lipid abnormalities in 2/16 (12%). These findings indicate that thrombotic AEs in FEIBA® recipients are very rare. Recognition of risk factors and avoidance of FEIBA® overdosage may avert thrombotic AEs.
Thrombotic stroke associated with the use of porcine factor VIII in a patient with acquired haemophilia
Authors: ASHRANI A. A. , REDING M. T. , GREENO E. W. , SHET A. , KEY N. S.
Published: March 2003

Porcine factor VIII (pFVIII), which is used to control bleeding in patients with congenital or acquired haemophilia who have high‐titre neutralizing antibodies to human FVIII, is not known to increase the risk of arterial or venous thrombosis. We have recently encountered a patient with acquired haemophilia who developed a thrombotic left middle cerebral artery distribution stroke while being treated with pFVIII. To our knowledge, this is the first such reported thrombotic event. We speculate that platelet activation induced by pFVIII may have contributed to thrombosis and suggest that pFVIII be used with caution in elderly patients with pre‐existing cardiovascular risk factors.
Conduct of clinical trials in developing countries
Authors: KASPER C. K.
Published: March 2003

Research subjects in developing countries may be especially vulnerable to exploitation. Scrupulous care should be taken to maintain the basic principles of ethical trial conduct: the right of participants to make their own informed decisions, a favorable balance of benefit to risk, good trial design, candour about results, and, above all, use of honourable investigators. Involvement of local participants in planning a trial helps ensure both culturally‐sensitive protocols and consents and also maximum benefit to patients and to local research infrastructure.
Factors predictive of death among HIV‐uninfected persons with haemophilia and other congenital coagulation disorders
Authors: Diamondstone L. S. , Aledort L. M. , Goedert J. J. ,   MULTICENTRE HEMOPHILIA COHORT STUDY
Published: March 2003

Summary. Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high‐titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all‐cause mortality among HIV‐uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end‐stage liver disease and sepsis. Among the 387 HIV‐uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all‐cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age‐adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4–6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97–17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV‐uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.
Female haemophiliac homozygous for the factor VIII intron 22 inversion mutation, with transcriptional inactivation of one of the factor VIII alleles
Authors: David D. , Morais S. , Ventura C. , Campos M.
Published: March 2003

Summary.  Phenotypic expression of X‐linked recessive disorders, including haemophilia A, is rare in females. This report describes a female with sporadic severe haemophilia A. The female patient and her family members were evaluated by coagulation assays. Visible detectable disturbance of X chromosome structure or number, as well as 2N von Willebrand disease, were excluded as possible explanations of the haemophilia A phenotype. Molecular studies, factor VIII (FVIII) intron 22 inversion mutation analysis showed that the severe haemophilia A phenotype is the result of a maternally inherited, distal, FVIII gene inversion and a paternally inherited de novo, also distal, FVIII gene inversion. Furthermore, comparative single‐stranded conformation polymorphism analysis revealed the absence of detectable maternally inherited abnormal FVIII gene transcript in the patient's peripheral blood lymphocytes. X chromosome methylation analysis indicates that this could be explained by preferential inactivation of the maternally inherited X chromosome carrying the distal FVIII gene inversion.
Continuous intravenous infusion of a plasma‐derived factor IX concentrate (Mononine®) in haemophilia B
Authors: Hoots W. K. , Leissinger C. , Stabler S. , Schwartz B. A. , White G. , Dasani H. , Massion C. , Negrier C. , Schindel F. , Schulman S.
Published: March 2003

Summary.  This prospective, multicentre, open‐label study evaluated the efficacy and safety of a plasma‐derived factor IX concentrate [Mononine®, Coagulation Factor IX (Human) Monoclonal Antibody Purified] administered by continuous intravenous (CIV) infusion to patients with haemophilia B. Admission criteria included documented diagnosis of haemophilia B (mild, moderate, or severe). Twenty‐eight patients (25 surgery, two trauma, one severe spontaneous haemorrhage) were enrolled to receive a therapeutic bolus dose followed by CIV infusion of factor IX (FIX) to maintain FIX:C plasma levels of 0.4–1.0 IU mL−1 (i.e. 40–100%). A median intravenous bolus dose of 54.2 IU kg−1 FIX was administered to a subset of 13 non‐emergency patients 7–21 days prior to CIV infusion to determine pharmacokinetic parameters in order to guide the dosing for CIV. For treatment, a bolus injection (median FIX dose; 89.6 IU kg−1) (range, 12.4–108.3), followed by a median total CIV infusion dose of 396.4 IU kg−1 (range, 44.9–785.5) was administered at a median rate of 3.84 IU kg−1 h−1 (range, 1.74–7.33) for 107.17 h (range, 31.75–144). Twenty‐four patients completed 72–120 h of FIX CIV infusion. Overall, ‘excellent’ (i.e. achievement of normal haemostasis) efficacy was reported in 23 of 24 (96%) evaluable patients, and ‘good’ (i.e. slight oozing) efficacy was reported in one (4%) patient. Median FIX:C was 72–86% for all patients receiving FIX by CIV on all days. Nine patients reported 13 adverse events that were possibly related to study medication but were not deemed serious by the investigator and were mainly because of local irritation at the infusion site. FIX CIV infusion therapy is safe and effective in the treatment of haemophilia B patients undergoing surgery, exposed to trauma, or experiencing severe spontaneous haemorrhage.
Genotype and phenotype of haemophilia A in Thai patients
Authors: Yenchitsomanus P. , Akkarapatumwong V. , Pung‐Amritt P. , Intorasoot S. , Thanootarakul P. , Oranwiroon S. , Veerakul G. , Mahasandana C.
Published: March 2003

Summary.  To study genotype and phenotype correlation of haemophilia A in Thai patients, molecular defects of the factor VIII (FVIII) gene were examined and their correlation with clinical phenotypes were evaluated. The molecular pathologies of FVIII in Thai patients were found to be heterogeneous. The most common mutation was FVIII intron 22 inversion accounting for about 30% of the severe cases while gene deletion was rare. Sixteen point mutations were identified, comprising two nonsense mutations (R‐5X and R1966X), five missense mutations (T233I, D542Y, G1850V, W2229S and G2325C), five nucleotide deletions (1145delT, 1187–8delACAC, 1191–4delA, 1458delGA and 1534delA), three nucleotide insertions (1439–41insA, 1934insTA and 2245insACTA) and one splicing defect (IVS15+1G>T). Nine mutations (T233I, D542Y, 1145delT, 1458delGA, 1534delA, 1934insTA, W2229S, 2245insACTA and G2325C) were novel, firstly identified in Thai patients. The genotypes were found to correlate with clinical phenotypes in a majority of cases. However, in five patients the molecular defects did not correlate with clinical severity and FVIII:C level. Cellular and molecular mechanisms were proposed to be responsible in amelioration of clinical severity caused by deleterious mutations. Carrier detection by direct mutation analysis was also demonstrated.
Severe spontaneous intracranial haematoma in a HIV‐negative 66‐year‐old mild haemophiliac. Complete recovery with the use of 1‐month factor VIII replacement
Authors: Bauduer F. , Delpy P. , Borde C. , Ducout L. , Boutin J. B.
Published: March 2003

Summary.  Intracranial haemorrhage is the most feared manifestation of haemophilia and is usually seen in severe forms. We report herein the case of a 66‐year‐old HIV‐negative patient with mild haemophilia (factor VIII: 7%) who presented with a spontaneous and massive intracranial haematoma causing hemiplegia and aphasia. We discuss the management of this peculiar situation emphasizing the need for rapid and adapted FVIII replacement. A complete recovery was obtained using this strategy combined with initial resuscitation measures and subsequent physical therapy.
Monitoring and modelling open savannas using multisource information: analyses of Kalahari studies
Authors: Dougill Andrew , Trodd Nigel
Published: March 2003

In the Kalahari of Botswana, as in many other open savannas, the main ecological change following cattle‐based agricultural intensification is one of grass removal and bush encroachment. Changes to vegetation communities in Kalahari rangelands have been expressed in terms of a state‐and‐transition model. However, there remain uncertainties as to the mechanisms and conditions for ecological change. In part, this is due to previous (inadequate) spatial and temporal scales of data collection. This paper describes the results of ongoing ecological studies in the Makoba ranches and analyses the contribution that fine‐scale ground‐based surveys and interpretation of Earth observation data can make to reducing uncertainties in state‐and‐transition models. This detailed case study provides a mechanism for evaluating the role of multi‐source information for monitoring and modelling open savannas.
Global land cover characterization from satellite data: from research to operational implementation?
Authors: Defries R. S. , Townshend J. R. G.
Published: March 2003

Satellite data provide the basis for geographically referenced global land cover characterization that is internally consistent, repeatable over time, and potentially more reliable than ground‐based sources. During the last 20 years considerable research efforts have been devoted to the extraction of land cover information from these data. Only during the last few years have these methods begun to be applied in operational contexts. Such applications have thus far primarily addressed key global change issues such as the global carbon balance. Examples of the successful quasi‐operational implementation of remote sensing include NASA's Humid Tropical Landsat Pathfinder project, where high resolution data are being used at subcontinental scales to measure change in the areal extent of tropical rain forests throughout the world, and the Tropical Ecosystem Environment observation by Satellite (TREES) project to assess forest cover in the tropics. At coarser resolutions, a number of land cover products suitable for incorporation in global and regional models have been developed. Alternatives to traditional land cover classifications have also been developed to describe gradients and mosaics in the vegetation more realistically. These land cover products offer the possibility for applications in ecological and human dimensions research at regional and global scales, as well as for implementation of international agreements that require land cover information. Recently launched and future satellites will carry sensors that provide data with greatly improved capabilities for land cover characterization and advancements in computing environments make it feasible to take advantage of these new data. However, several challenges must be overcome in making a transition from research to operational land cover monitoring, including automation of methods to analyse the satellite data, more effective techniques for validation, and assurance of long‐term continuity in the availability of satellite measurements.
Biodiversity, conservation and development in Mkomazi Game Reserve, Tanzania
Authors: Homewood Katherine , Brockington Daniel
Published: March 2003

Savanna woodlands and their associated species diversity and endemism are widely seen as declining through human impacts. Alternative views suggest that savanna ecosystems vary with a large number of biophysical factors, among which human impacts may be of relatively minor importance. This paper examines the debate with respect to Mkomazi Game Reserve in Northern Tanzania, where biodiversity has been inventoried and local resource use studied. It sets out the history of land use in Mkomazi and examines the available data on the area's plant, bird and invertebrate diversity. Comparative analysis is complicated by the paucity of data for other savannas in the same biogeographic zone, and by differences in sampling effort and methodology. Conservation literature and Tanzanian government documents present Mkomazi as one of the richest savannas in Africa, as a centre of endemism, and as threatened by deleterious impacts of human land use. Available data do not substantiate such statements. The paper examines implications of those perceptions for management, particularly eviction of resident pastoralists from the Reserve in 1988, and subsequent exclusion of reserve‐adjacent dwellers. Conservation relies increasingly on reserve‐adjacent people, and on prioritizing the allocation of scarce resources. There is an urgent need for rigorous studies of the implications of human land use in savannas, for better data on biodiversity, and for rigorous standards in the way those data are applied.
Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild‐type in patients with allergic rhinitis
Authors: Van Hage‐Hamsten M. , Johansson E. , Roquet A. , Peterson C. , Andersson M. , Greiff L. , Vrtala S. , Valenta R. , Grönneberg R.
Published: March 2003

Background Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE‐binding capacity, but with retained T cell activating ability.

Objective To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild‐type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction.

Methods Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge‐sessions in a randomized, double‐blind, and cross‐over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild‐type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge‐series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively.

Results All 10 patients tolerated the highest accumulated dose, 8.124 µg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild‐type. No late phase reactions were observed. The change in tryptase levels (pre‐challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild‐type. The change in EPO/ECP concentration pre‐challenge versus 4 h post‐challenge was lower for rBet v 1 trimer and the change was significantly lower when pre‐challenge versus 24 h post‐challenge to rBet v 1 fragments and rBet v 1 wild‐type was examined.

Conclusion The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild‐type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.
Xeroderma pigmentosum in Libya
Authors: Khatri Mishri Lal , Bemghazil Mohammed , Shafi Mohammed , Machina Alhashmi
Published: March 2003

Background A preliminary study of 24 cases of xeroderma pigmentosum (XP) was presented in 1990 and later published in 1992. Since then we have seen 18 further cases.

Objective To study the clinical profile of Libyan cases of XP.

Methods With the help of a special protocol, all 42 cases (23 girls and 19 boys from 29 families) treated and followed between 1981 and 1994 were subjected to detailed analysis.

Results A history of consanguinity was present in the parents of 39 patients. XP in Libya is characterized by a relatively high incidence (approximately 15–20 per million of the population), early onset of initial manifestations (median age, 12 months) and malignant tumors (median age, 8 years), severe ocular and oral lesions in a high percentage of patients, and early death (median age, 15.5 years). The malignant skin tumors seen were squamous cell carcinoma (SCC) in 23 patients, basal cell carcinoma (BCC) in 17 patients, and basosquamous carcinoma in two patients. Malignant melanoma was not seen, but lentigo maligna was found in one case. SCC of the tongue, carcinoma of the thyroid, and lymphatic leukemia affected individual patients. Subnormal physical growth was observed in six patients, but none of the patients had significant neurologic abnormalities. The results of etretinate therapy in nine patients revealed that it is an effective preventive agent against carcinogenesis, but not a curative one.

Conclusions Severe ophthalmic manifestations affected a higher percentage of patients at an early age. Malignant melanoma did not develop in any case, except for lentigo maligna in one patient.
Development of a patient decision aid for choice of surgical treatment for breast cancer
Authors: Sawka Carol A. , Goel Vivek , Mahut Catherine A. , Taylor Glen A. , Thiel Elaine C. , O'Connor Annette M. , Ackerman Ida , Burt Janet H. , Gort Elaine H.
Published: March 2003

Purpose A patient decision aid for the surgical treatment of early stage breast cancer was developed and evaluated. The rationale for its development was the knowledge that breast conserving therapy (lumpectomy followed by breast radiation) and mastectomy produce equivalent outcomes, and the current general agreement that the decision for the type of surgery should rest with the patient.

Methods A decision aid was developed and evaluated in sequential pilot studies of 18 and 10 women with newly diagnosed breast cancer who were facing a decision for breast conserving therapy or mastectomy. Both qualitative (general reaction, self‐reported anxiety, clarity, satisfaction) and quantitative (knowledge and decisional conflict) measures were assessed.

Results The decision aid consists of an audiotape and workbook and takes 36 min to complete. Based on qualitative comments and satisfaction ratings, 17 of 18 women reported a positive reaction to the decision aid, and all 18 reported that it helped clarify information given by the surgeon. Women did not report an increase in anxiety and 17 of 18 women were either satisfied or very satisfied with the decision aid.

Conclusion This pilot study supports the hypothesis that this decision aid may be a helpful adjunct in the decision for surgical management of early stage breast cancer. We are currently conducting a randomized trial of the decision aid versus a simple educational pamphlet to evaluate its efficacy as measured by knowledge, decisional conflict, anxiety and post‐decisional regret.
A randomized controlled trial of information‐giving to patients referred for coronary angiography: effects on outcomes of care
Authors: Bernstein Steven J. , Skarupski Kimberly A. , Grayson Carla E. , Starling Mark R. , Bates Eric R. , Eagle Kim A.
Published: March 2003

ObjectiveTo assess the impact of providing an educational videotape, `Treatment Choices for Ischaemic Heart Disease: a Shared Decision‐Making Program Videotape,' to patients referred for coronary angiography compared with standard patient‐physician decision making (usual care).

Study designRandomized controlled clinical trial.

SettingUniversity Hospital and Veterans Affairs Hospital.

PatientsA consecutive sample of 217 patients referred for coronary angiography were randomized to receive `usual care' or to receive the videotape in addition to standard patient physician decision making (videotape): 109 completed the study (50% completion rate).

Main outcome measuresKnowledge of coronary artery disease, satisfaction, self‐reported physical and mental health functioning, and the proportion of patients who were referred for coronary revascularization.

ResultsCompared with patients who received `usual care,' those who received the videotape were more knowledgeable (mean score 83 vs. 58%; P < 0.0001) but less satisfied with their treatment (79 vs. 88%; P = 0.038). There were no significant differences between the videotape and `usual care' groups with respect to satisfaction with the decision making process (mean score 73 vs. 77%; P = 0.37), satisfaction with the decision made (mean score 73 vs. 78%; P = 0.28), physical functioning (38 vs. 38%; P = 0.76), mental health functioning (49 vs. 49%; P = 0.94), or in referral for coronary revascularization (OR 0.60; 95% CI 0.22–1.65; P = 0.33).

ConclusionAlthough the educational videotape increased patients' knowledge level, it was associated with a decrease in their level of satisfaction with treatment. Before there is wide‐spread dissemination of this technology, advocates should demonstrate its effectiveness in everyday practice.
Implementing shared decision‐making in routine practice: barriers and opportunities
Authors: Holmes‐Rovner Margaret , Valade Diane , Orlowski Catherine , Draus Catherine , Nabozny‐Valerio Barbara , Keiser Susan
Published: March 2003

Objective

Determine feasibility of shared decision‐making programmes in fee‐for‐service hospital systems including physicians’ offices and in‐patient facilities.

Design

Survey and participant observation. Data obtained during Phase 1 of a patient outcome study.

Settings and participants

Three hospitals in Michigan: one 299‐bed rural regional hospital, one 650‐bed urban community hospital, one 459‐bed urban and suburban teaching hospital. All nurses and physicians who agreed to use the programmes participated in the evaluation (n = 34).

Intervention

Two shared decision‐making® (SDP) multimedia programmes: surgical treatment choice for breast cancer and ischaemic heart disease treatment choice.

Main outcome measures

(1) clinicians’ evaluations of programme quality; (2) challenges in hospital settings; and (3) patient referral rates.

Results

SDP programmes were judged to be clear, accurate and about the right length and amount of information. Programmes were judged to be informative and appropriate for patients to see before making a decision. Clinicians were neutral about patients’ desire to participate in treatment decision‐making. Referral volume to SDPs was lower than expected: 24 patients in 7 months across three hospitals. Implementation challenges centred on time pressures in patient care.

Conclusions

Productivity and time pressure in US health care severely constrain shared decision‐making programme implementation. Physician referral may not be a reliable mechanism for patient access. Possible innovations include: (1) incorporation into the informed consent process; (2) provider or payer negotiated requirement in the routine hospital procedure to use the SDP as a quality indicator; and (3) payer reimbursement to professional providers who make SDP programmes available to patients.
Whose interests do lay people represent? Towards an understanding of the role of lay people as members of committees
Authors: Hogg Christine , Williamson Charlotte
Published: March 2003

Increasingly, lay people are appointed as members to health service committees. The term ‘lay’ is used loosely and the reasons for involving lay people are seldom clearly defined. This paper argues that the different roles that lay people play need to be explicitly defined in order for their contributions to be realized. Although lay members of health service committees are generally assumed to be working for patients’ interests, our observations lead us to think that some lay people tend to support professionals’ or managers’ interests rather than patients’ interests as patients would define them. We suggest that lay people fall into three broad categories: supporters of dominant (professional) interests, supporters of challenging (managerial) interests and supporters of repressed (patient) interests. These alignments should be taken into account in appointments to health service bodies. Further research is needed on the alignments and roles of lay members.
Information about screening – is it to achieve high uptake or to ensure informed choice?
Authors: Raffle Angela E.
Published: March 2003

For many years, public information about screening has been aimed at achieving high uptake but concerns are now being raised about this approach. There are several problems that have prompted these concerns. By giving information that emphasizes only the positive aspects of screening the autonomy of individuals is ignored, individuals feel angry when they perceive that they are let down by screening, symptoms may be disregarded because of the belief that screening gives full protection, health service staff carry the blame for problems that are in fact inherent in screening, and sound debate about policy and investment in screening is hampered by misunderstanding about the benefits and costs of screening.

If we adopt instead an approach that makes explicit the limitations and adverse effects then a different set of problems will be encountered. We risk a reduction in uptake of screening and thus population benefits may reduce, those most likely to be deterred from accepting screening may be the most socially disadvantaged, there will be a cost in terms of staff time to explain screening more fully to participants, and cost‐effectiveness could be reduced if uptake falls so low as to make services barely viable.

In the UK current General Medical Council (GMC) advice1 to doctors about informed consent for screening makes it clear that full information should be given. The UK National Screening Committee has also signalled the need for a changed approach to information2 giving so that individuals are offered a choice based on appreciation of risks and benefits. It will take time for this approach to be fully reflected across the full range of UK screening programmes. New national information will be needed to assist staff in giving full information, and some aspects of policy, such as screening coverage targets for Health Authorities and General Practitioners, will need to be altered.

There are many questions still to be answered about the kind of information needed to achieve informed participation, and about how it should be framed and communicated. These questions can begin to be addressed when there is clarity at national level about the purpose of information about screening.
The potential contribution of decision aids to screening programmes
Authors: Entwistle Vikki
Published: March 2003

Decision aids for health service users facing decisions about screening have been developed for controversial tests (such as that for prostate specific antigen as a screen for prostate cancer) and tests in which outcomes are value laden (as in some prenatal tests). The potential usefulness of decision aids in established screening programmes (such as those offering mammography to women over 50 in the United Kingdom) remains to be explored. In principle any decision about screening test acceptance may be sensitive to individual preferences and could be supported by an appropriate decision aid. Decision aids might also help reduce some of the problems currently associated with public misconceptions about screening. Objections to the promotion of individual choice regarding screening tests usually take the form of concern that this will lead to unacceptable losses in terms of population health gain and health system efficiency, or of fear that individuals will choose options that are wrong for them. The introduction of decision aids could alleviate both of these objections to some extent. Decision aids could encourage people to consider the social as well as the individual consequences of their choices and they should promote choices consistent with personal values. Although there are strong arguments in principle for introducing decision aids into established screening programmes, their potential needs to be confirmed in empirical evaluations and there may be many contentious decisions and practical challenges to be overcome in order to implement them.
Evaluation of the quality of patient information to support informed shared decision‐making
Authors: Godolphin William , Towle Angela , McKendry Rachael
Published: March 2003

Objectives (a) To find out how much patient information material on display in family physicians’ offices refers to management choices, and hence may be useful to support informed and shared decision‐making (ISDM) by patients and (b) to evaluate the quality of print information materials exchanged during the consultation, i.e. brought in by patients or given out by family physicians.

Design All print information available for patients and exchanged between physicians and patients was collected in a single complete day of the office practices of 21 family physicians. A published and validated instrument (DISCERN) was used to assess quality.

Setting and participants Community office practices in the greater Vancouver area, British Columbia, Canada. The physicians were purposefully recruited by their association with the medical school Department of Family Practice, their interest in providing patients with print information and their representation of a range of practice types and location.

Main variables studied The source of the pamphlets and these categories: available in the physicians’ offices; exchanged between physician and patient; and produced with the explicit or apparent intent to support evidence‐based patient choice.

Main outcome measures The quality of the print information to support ISDM, as measured by DISCERN and the ease of use and reliability of the DISCERN tool.

Results and conclusions Fewer than 50% of pamphlets available in these offices fulfilled our minimum criteria for ISDM (mentioned more than one management option). Offices varied widely in the proportion of pamphlets on display that supported ISDM and how particular the physician was in selecting materials. The DISCERN tool is quick, valid and reliable for the evaluation of patient information. The quality of patient information materials used in the consultation and available in these offices was below midpoint on the DISCERN score. Major deficiencies were with respect to the mention of choices, risks, effect of no treatment or uncertainty and reliability (source, evidence‐base). Good quality information can be produced; some is available locally.
Principles of distributive justice used by members of the general public in the allocation of donor liver grafts for transplantation: a qualitative study
Authors: Wilmot Stephen , Ratcliffe Julie
Published: March 2003

Objective  To investigate the nature of public preferences in the allocation of donor liver grafts for transplantation.

Design  A qualitative study based upon the transcripts of four focus groups.

Setting  Derby, Derbyshire, UK.

Participants  Twenty‐two members of the public in the Derby locality, recruited to one of four focus groups through local community groups.

Main outcome measures  The views of focus group members as to the importance (or otherwise) of several potential discriminating factors which could be used in the prioritization of patients on the waiting list for liver transplantation were ascertained. The factors included were expected post‐transplant prognosis, the age of the patient, whether the patient was personally responsible for their illness, the time spent on the waiting list, re‐transplantation or primary transplant and the social background of the patient.

Results and conclusions  Group members explored the criteria from a number of perspectives, and made some unexpected linkages between the criteria and wider moral principles. They did not come to firm conclusions about the relative desirability of the criteria, but their approach was notably flexible and thoughtful, with the exception of a few instances where they appeared to resort to arguments based on what is ‘obvious’ and ‘natural’. The results of these discussions suggest that members of the public would be able and willing to respond positively to a more open and consultative system of donor liver prioritization than exists presently within the UK.
The effect of amino‐acid substitutions I112P, D147E and K152N in CYP11B2 on the catalytic activities of the enzyme
Authors: Bechtel Stephanie , Belkina Natalya , Bernhardt Rita
Published: March 2003

By replacing specific amino acids at positions 112, 147 and 152 of the human aldosterone synthase (CYP11B2) with the corresponding residues from human, mouse or rat 11β‐hydroxylase (CYP11B1), we have been able to investigate whether these residues belong to structural determinants of individual enzymatic activities. When incubated with 11‐deoxycorticosterone (DOC), the 11β‐hydroxylation activity of the mutants was most effectively increased by combining D147E and I112P (sixfold increase). The two substitutions displayed an additive effect. The same tendency can be observed when using 11‐deoxycortisol as a substrate, although the effect is less pronounced. The second step of the CYP11B2‐dependent DOC conversion, the 18‐hydroxylation activity, was not as strongly increased as the 11β‐hydroxylation potential. Activity was unaffected by D147E, whereas the single mutant I112P displayed the most pronounced activation (70% enhancement), thus causing different increasing effects on the first two enzymatic reaction steps. A slightly enhanced aldosterone synthesis from DOC could be measured due to increased levels of the intermediates. However, the 18‐oxidation activity of all the mutants, except for I112S and D147E, was slightly reduced. The strongly enhanced 18‐hydroxycorticosterone and aldosterone formation observed in the mutants provides important information on a possible role of such amino‐acid replacements in the development of essential hypertension. Furthermore, the results indicate the possibility of a differential as well as independent modification of CYP11B2 reaction steps. The combination of functional data and computer modelling of CYP11B2 suggests an indirect involvement of residue 147 in the regulation of CYP11B isoform specific substrate conversion due to its location on the protein surface. In addition, the results indicate the functional significance of amino‐acid 112 in the putative substrate access channel of human CYP11B2. Thus, we present the first example of substrate recognition and conversion being attributed to the N‐terminal part of human CYP11B2.
Divergent members of a soybean (Glycine max L.) 4‐coumarate:coenzyme A ligase gene family
Authors: Lindermayr Christian , Möllers Britta , Fliegmann Judith , Uhlmann Annette , Lottspeich Friedrich , Meimberg Harald , Ebel Jürgen
Published: March 2003

4‐Coumarate:CoA ligase (4CL) is involved in the formation of coenzyme A thioesters of hydroxycinnamic acids that are central substrates for subsequent condensation, reduction, and transfer reactions in the biosynthesis of plant phenylpropanoids. Previous studies of 4CL appear to suggest that many isoenzymes are functionally equivalent in supplying substrates to various subsequent branches of phenylpropanoid biosyntheses. In contrast, divergent members of a 4CL gene family were identified in soybean (Glycine max L.). We isolated three structurally and functionally distinct 4CL cDNAs encoding 4CL1, 4CL2, and 4CL3 and the gene Gm4CL3. A fourth cDNA encoding 4CL4 had high similarity with 4CL3. The recombinant proteins expressed in Escherichia coli possessed highly divergent catalytic efficiency with various hydroxycinnamic acids. Remarkably, one isoenzyme (4CL1) was able to convert sinapate; thus the first cDNA encoding a 4CL that accepts highly substituted cinnamic acids is available for further studies on branches of phenylpropanoid metabolism that probably lead to the precursors of lignin. Surprisingly, the activity levels of the four isoenzymes and steady‐state levels of their transcripts were differently affected after elicitor treatment of soybean cell cultures with a β‐glucan elicitor of Phytophthora sojae, revealing the down‐regulation of 4CL1 vs. up‐regulation of 4CL3/4. A similar regulation of the transcript levels of the different 4CL isoforms was observed in soybean seedlings after infection with Phytophthora sojae zoospores. Thus, partitioning of cinnamic acid building units between phenylpropanoid branch pathways in soybean could be regulated at the level of catalytic specificity and the level of expression of the 4CL isoenzymes.
Formation of aberrant phosphotau fibrillar polymers in neural cultured cells
Authors: Pérez Mar , Hernández Félix , Gómez‐Ramos Alberto , Smith Mark , Perry George , Avila Jesús
Published: March 2003

Here we show, for the first time, the in vitro formation of filamentous aggregates of phosphorylated tau protein in SH‐SY5Y human neuroblastoma cells. The formation of such aberrant aggregates, similar to those occurring in vivo in Alzheimer's disease and other tauopathies, requires okadaic acid, a phosphatase inhibitor, to increase the level of phosphorylated tau, and hydroxynonenal, a product of oxidative stress that selectively adducts and modifies phosphorylated tau. Our findings suggest that both phosphorylation and oxidative modification are required for tau filament formation. Importantly, the in vitro formation of intracellular tau aggregates could be used as a model of tau polymerization and facilitate the development of novel therapeutic approaches.
The sodium pump
Authors: Scheiner‐Bobis Georgios
Published: March 2003

The sodium pump (Na+/K+‐ATPase; sodium‐ and potassium‐activated adenosine 5′‐triphosphatase; EC 3.6.1.37) has been under investigation for more than four decades. During this time, the knowledge about the structure and properties of the enzyme has increased to such an extent that specialized groups have formed within this field that focus on specific aspects of the active ion transport catalyzed by this enzyme. Taking this into account, this review, while somewhat speculative, is an attempt to summarize the information regarding the enzymology of the sodium pump with the hope of providing to interested readers from outside the field a concentrated overview and to readers from related fields a guide in their search for gathering specific information concerning the structure, function, and enzymology of this enzyme.