bluuebunny/crossref_metadata_2025 huggingface dataset:
The expression of P‐glycoprotein in AML cells with FLT3 internal tandem duplications is associated with reduced apoptosis in response to FLT3 inhibitors
Authors: Hunter Hannah M. , Pallis Monica , Seedhouse Claire H. , Grundy Martin , Gray Claire , Russell Nigel H.
Published: September 2004

P‐glycoprotein (pgp), a membrane efflux pump, is recognized to have an anti‐apoptotic function. Internal tandem duplications (ITDs) of the Fms‐like tyrosine kinase 3 (FLT3) receptor are the most common mutations in acute myeloid leukaemia (AML). Both ITDs and pgp positivity confer an adverse clinical prognosis. FLT3 inhibitors induce variable apoptosis in cell lines transfected with FLT3 ITDs. We studied the effect of herbimycin A, AG1296 and PKC412 on primary AML blasts. All compounds showed significantly higher cell kill after 48‐h incubation in samples with an ITD compared with wild type (Herbimicin P < 0·001; AG1296 P = 0·001, PKC412, P = 0·002). Pgp‐positive samples were significantly less sensitive to herbimycin and AG1296 than pgp‐negative samples, although neither molecule inhibited the efflux function of pgp. The concurrent incubation with the pgp inhibitor PSC833 resulted in an enhanced cell kill in 4/5 ITD pgp‐positive samples versus two of nine ITD pgp‐negative samples. PKC412 inhibited pgp function and induced cell death in FLT3 ITD/pgp‐positive samples. We conclude that AML samples with a FLT3 ITD are more susceptible to these inhibitors than wild‐type samples. However, the expression of pgp in cells with FLT3 ITDs can reduce their sensitivity to FLT3 inhibitors and therefore pgp expression should be assessed in clinical trials of FLT3 inhibitors.
Loss of heterozygosity, a frequent but a non‐exclusive mechanism responsible for HLA dysregulation in non‐Hodgkin's lymphomas
Authors: Drénou Bernard , Tilanus Marcel , Semana Gilbert , Alizadeh Mehdi , Birebent Brigitte , Grosset Jean‐Marc , Dias Patricia , Van Wichen Dick , Arts Yvonne , De Santis Dianne , Fauchet Renée , Amiot Laurence
Published: September 2004

The frequent alteration of human leucocyte antigen (HLA) class I molecule expression observed in non‐Hodgkin's lymphomas (NHL), similarly to solid tumours, has been reported to favour tumoral escape from the immune system. In order to identify the underlying mechanisms, we analysed 15 HLA defective NHL including partial (n = 10) and total class I (n = 5) loss, as well as HLA class II defects (n = 5). The HLA defect concerned HLA‐A and ‐B antigens in 14 of 15 cases. In the cases with partial defect, the use of specific allelic monoclonal antibodies detected a defect of both alleles of A or B loci in six of seven tested cases. Allelic reverse transcription polymerase chain reaction (RT‐PCR) demonstrated defects in six of nine cases, including four alterations of both A and B mRNA alleles. Real‐time quantitative RT‐PCR (RQ‐PCR) did not detect the HLA‐DR transcript in the two negative HLA‐DR lymphomas, contrasting with the presence of CMH II transactivator (CIITA) transcript. Loss of heterozygosity (LOH) was detected in nine of 14 cases through variable pattern of nine microsatellites markers of the HLA locus. Taken together, these findings demonstrate the complexity and the variability of the mechanisms underlying HLA protein deficiencies with a high frequency of LOH. The diversity of these mechanisms indicates the importance of positive selection of HLA altered clones in the development of these NHL cases.
Flow cytometric analysis of BCL‐2 can distinguish small numbers of acute lymphoblastic leukaemia cells from B‐cell precursors
Authors: Hartung Leah , Bahler David W.
Published: September 2004

Flow cytometric identification of small numbers of precursor B‐cell acute lymphoblastic leukaemia (B‐ALL) cells in post‐treatment marrow specimens could benefit from the identification of additional, easily detectable markers that could be used in most cases. In this study, we evaluate whether bcl‐2 expression quantified by four‐colour flow cytometry can be effectively used to discriminate precursor B‐ALL blasts from normal B‐cell precursors (haematogones) and function as a leukaemia‐specific marker. Levels of bcl‐2 in the 22 precursor B‐ALL cases studied were found to be significantly higher (over sixfold higher on average) than those present in haematogone populations from 22 control marrow specimens. Higher relative levels of bcl‐2 expression in the B‐ALL cases were maintained with respect to both immature CD34+ and more mature CD34− haematogone subsets, and appeared stable. Dilutional studies indicated that multiparameter flow cytometry analysis using bcl‐2 could identify precursor B‐ALL blasts representing as few as 1% of CD19+ cells or 0·01% of total leucocytes in bone marrow specimens containing substantial numbers of haematogones. This study suggests that bcl‐2 may be an important marker for flow cytometric detection and quantification of small numbers of residual precursor B‐ALL cells in bone marrow specimens.
The risk of overanticoagulation in patients with heart failure on coumarin anticoagulants
Authors: Visser Loes E. , Bleumink Gysèle S. , Trienekens Paul H. , Vulto Arnold G. , Hofman Albert , Stricker Bruno H. Ch.
Published: September 2004

Heart failure has been identified as a risk factor for increased coumarin anticoagulant responsiveness in several small‐scale experiments. Epidemiological studies quantifying the risk of overanticoagulation by heart failure in a non‐selected population on coumarins are scarce. Therefore, we investigated whether patients with heart failure have an increased risk of overanticoagulation and determined the effect of incidental heart failure on coumarin dose requirements. A cohort study of all patients was performed from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon between 1 January 1990 and 1 January 2000. All cohort members were followed until the first occurrence of an international normalized ratio (INR) ≥6·0, the last INR assessment, death, loss to follow‐up, or end of the study period. Of the 1077 patients in the cohort, 396 developed an INR ≥6·0. The risk of overanticoagulation was 1·66 [95% confidence interval (CI): 1·33–2·07] for cases of prevalent heart failure and 1·91 (95%CI: 1·31–2·79) for incidental cases. The decrease in dose requirements in patients with incidental heart failure showed a significant trend from the fifth INR measurement preceding the date of incidental heart failure to the third measurement after this date. Heart failure is an independent risk factor for overanticoagulation. Therefore, patients with heart failure should be closely monitored to prevent potential bleeding complications.
Oxidised‐HDL3 induces the expression of PAI‐1 in human endothelial cells. Role of p38MAPK activation and mRNA stabilization
Authors: Norata Giuseppe D. , Banfi Cristina , Pirillo Angela , Tremoli Elena , Hamsten Anders , Catapano Alberico L. , Eriksson Per
Published: September 2004

Modified lipoproteins have been suggested to modulate endothelial expression of plasminogen activator inhibitor‐1 (PAI‐1). As oxidized high‐density lipoprotein (Ox‐HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of Ox‐HDL3 on the expression of PAI‐1. Ox‐HDL3 but not native HDL3, increased PAI‐1 mRNA expression in endothelial cells. Furthermore, PAI‐1 antigen expression and activity increased in the supernatant of cells incubated with Ox‐HDL3. The intracellular pathways involved in this effect were investigated. Ox‐HDL3 activated both extracellular signal‐regulated kinases (ERK) 1/2 and p38 mitogen‐activated protein kinase (MAPK). Moreover, incubation with specific inhibitors of these kinases showed that p38MAPK was mainly involved in the Ox‐HDL3‐dependent PAI‐1 induction. Transient transfection experiments suggested that none of the response elements in the proximal promoter (−804 to 17) were involved in Ox‐HDL3‐mediated PAI‐1 expression. mRNA stability experiments showed that Ox‐HDL3 increased the PAI‐1 mRNA half‐life. In summary, Ox‐HDL3 induced PAI‐1 mRNA expression and antigen release through a molecular mechanism involving MAPK activation and mRNA stabilization. Thus, oxidative modification converts HDL to a prothrombotic lipoprotein species.
FEIBA®: mode of action
Authors: Turecek P. L. , Váradi K. , Gritsch H. , Schwarz H. P.
Published: September 2004

Summary.  FEIBA®(factor eight inhibitor bypassing activity) has a history of more than 30 years of successful use in controlling bleeding in haemophilic patients who have developed inhibitory antibodies against factor (F)VIII or FIX. Recently it was shown that FEIBA® contains the proenzymes of the prothrombin complex factors, prothrombin, FVII, FIX and FX, but only very small amounts of their activation products, with the exception of FVIIa, which is contained in FEIBA® in greater amounts. FEIBA® controls bleeding by induction and facilitation of thrombin generation, a process for which FV is crucial. A number of biochemical in vitro and in vivo studies have shown that FXa and prothrombin play a critical role in the activity of FEIBA®. Consequently, they are considered to be key components of this product. The prothrombinase complex has been found to be a major target site for FEIBA®. Apart from prothrombin and FXa, FEIBA® contains other proteins of the prothrombin complex, which could also facilitate haemostasis in haemophilia patients with inhibitors.
FEIBA® safety profile in multiple modes of clinical and home‐therapy application
Authors: Luu H. , Ewenstein B.
Published: September 2004

Summary.  The development of neutralizing antibodies to factor VIII or IX therapeutic concentrates remains the most serious and challenging complication in the management of patients with haemophilia A and B. FEIBA®, Anti‐Inhibitor Coagulant Complex, is an activated prothrombin complex concentrate that has been used to treat patients with such complications for almost 30 years. The mechanism of action of FEIBA® has been proposed to involve simultaneous FVIII/FIX inhibitor bypassing action in the common, intrinsic and extrinsic coagulation pathways. FEIBA® is derived from human plasma that undergoes stringent viral screening followed by significant viral inactivation and removal. To date, there have been no confirmed reports of transmission of hepatitis A, B or C, or of human immunodeficiency viruses associated with the use of the current, vapour‐heat‐treated FEIBA® concentrate. The incidence of thrombotic adverse events recorded in the Baxter pharmacovigilance database for the 10‐year postmarket period (1990–99) was approximately 4 : 100 000 infusions of FEIBA®. Almost all documented thrombotic events with FEIBA® occurred with doses that exceeded dosing recommendations, and known risk factors for cardiovascular disease were evident in more than 80% of the patients involved. Overall, clinical data have shown FEIBA® to be safe and well‐tolerated for use in a wide variety of clinical settings, including treatment of bleeding episodes, management of surgical procedures, home therapy, long‐term prophylaxis, and prophylaxis during immune tolerance induction, when used according to dosing guidelines.
Thrombin generation assay and other universal tests for monitoring haemophilia therapy
Authors: Váradi K. , Turecek P. L. , Schwarz H. P.
Published: September 2004

Summary.  Factor VIII bypassing agents have different multiple modes of action, but share the common feature of inducing or facilitating thrombin generation. The information obtained from most overall assays to measure the haemostatic response to inhibitor‐bypassing agents is limited to the initial phase of blood coagulation (clotting time measurement) or the formation of a solidifying clot followed by fibrinolysis (thrombelastography), and excludes the real endpoint of thrombin generation. Thrombin generation assays (TGAs) measure the whole kinetics of thrombin generation even after the clot formation, and thus assess all activating and inactivating systems of coagulation. Therefore, TGAs are not only becoming a universal tool to improve understanding of haemostasis and to investigate biochemical principles of the haemostatic system, but are also evolving as a powerful prognostic and monitoring tool for inhibitor bypassing therapies.
Surgery in haemophilic patients with inhibitor: 20 years of experience
Authors: Quintana‐Molina M. , Martínez‐Bahamonde F. , González‐García E. , Romero‐Garrido J. , Villar‐Camacho A. , Jiménez‐Yuste V. , Fernández‐Bello I. , Hernández‐Navarro F.
Published: September 2004

Summary.  Surgery in haemophilic patients with inhibitor against factor (F)VIII or FIX is high risk. Surgery may be performed with the administration of sufficiently high dose of FVIII in patients with low‐response inhibitor or who, despite having a high response, present a low inhibitor titre at the time of surgery. The use of high doses of FX is more complicated in patients with a low‐titre FIX inhibitor, as there is a high risk of anaphylactic reactions. In the case of patients with high‐titre inhibitors, several treatments have been proposed, such as porcine FVIII, recombinant FVIIa (rFVIIa), and activated prothrombin complex concentrate (APCC). We present our 20 years' experience in the treatment and subsequent management of haemophilic patients with inhibitor in surgery and evaluate the results obtained with the products available for haemostatic control in 64 surgical procedures. The efficacy we obtained with FVIII is good in 100% of the cases described; we had no haemorrhagic complication (HC) in the 18 procedures in which it was used (three major and 15 minor surgery). With APCC we obtained excellent results with only one HC in a synoviorthesis in the form of bleeding and haematomas out of 32 procedures. Good results were obtained with rFVIIa with few haemorrhagic episodes. Thus, in major surgery there was one HC out of three cases. In minor surgery, greater efficacy was observed using extremely large doses of rFVIIa (≥ 120 mg kg−1 2h−1) because of the shorter half‐life of this factor in this type of patients.
Activated prothrombin complex concentrate (FEIBA®) treatment during surgery in patients with inhibitors to FVIII/IX: the updated Norwegian experience
Authors: Tjønnfjord G. E.
Published: September 2004

Summary.  Non‐activated and activated prothrombin complex concentrates have been used successfully to treat bleeds in haemophilia patients with inhibitors, but most physicians do not consider these products as effective as factor VIII/IX concentrates in non‐inhibitor patients. Thus, surgical procedures in inhibitor patients have been performed reluctantly. We have performed 15 minor and six major surgical and invasive diagnostic or therapeutic procedures in eight inhibitor patients with congenital haemophilia A and in two patients with acquired haemophilia. Administration of a loading dose of 100 U kg−1 of FEIBA® followed by 200 U kg −1 day−1 in three doses every 8 h for 3 days and then tapering the daily dose to 150–100 U kg−1, resulted in no severe or unexpected bleeding complications. One adverse event was observed. A 69‐year‐old man suffered a myocardial infarction the third postoperative day following sigmoidectomy. He was managed safely with opiate analgesia, nitrates and diuretics and the continued use of FEIBA®.
Cases of surgery in high‐responder haemophilia patients
Authors: Goudemand J. , Tagariello G. , Lopaciuk F.
Published: September 2004

Summary.  We present 11 cases of surgery in haemophilia patients with inhibitors (high responders). They were: one haemorroidectomy, one vesical surgery in a high responder, one adenoidectomy, seven orthopaedic procedures (one bone fixation of a femoral neck fracture, four total knee arthroplasties, two total knee arthroplasties), and one retroperitoneal haematoma that required emergency surgery. We conclude that surgery in haemophilia patients with inhibitor can be considered feasible but nevertheless remains difficult. When applied to high‐responding patients the treatment must take into account both the haemorrhagic risk and the risk of anamnestic response. Use of activated fractions as first‐line therapy makes it possible (if the titre of the antibody allows it) to resort to conventional replacement therapy with FVIII or FIX concentrates. NovoSeven® or FEIBA® can be equally used as first‐line therapy including therapy for major surgeries. It can be useful to alternate one with the other in case of occurrence of haemorrhagic complications.
Consensus perspectives on surgery in haemophilia patients with inhibitors: summary statement
Authors: Rodriguez‐Merchan E. C. , Rocino A. , Ewenstein B. , Bartha L. , Batorova A. , Goudemand J. , Gringeri A. , Joao‐Diniz M. , Lopaciuk S. , Negrier C. , Quintana M. , Tagariello G. , Tjonnfjord G. E. , Villar V A. , Vorlova Z.
Published: September 2004

Summary.  Participants in an international workshop on surgery in haemophilia patients with inhibitors developed a consensus summary of the findings and conclusions of the meeting. In the consensus, participants agreed upon revised definitions for minor and major surgery, including an intermediate degree of surgery. An evaluation system of intraoperative and postoperative bleeding was developed. Recommended doses of FEIBA® and rFVIIa (both in bolus injections and in continuous infusion) for surgery were agreed. Participants also agreed on the main blood tests to be performed peri‐operatively. They also suggested the need of a prospective evaluation in the future. Finally, the approximate number of surgical procedures and costs performed on haemophilia patients with inhibitors were analysed.
Computerized cognitive–behaviour therapy for anxiety and depression: a practical solution to the shortage of trained therapists
Authors: VAN DEN BERG S. , SHAPIRO D. A. , BICKERSTAFFE D. , CAVANAGH K.
Published: September 2004

Computerized cognitive–behaviour therapy (CCBT) programmes have been developed to help meet the enormous need for evidence‐based psychological treatment of common mental health problems in the context of a severe shortage of trained therapists to meet that need. Randomized controlled trials have confirmed the efficacy of such programmes. We present the experience of a community mental health team (CMHT) resource centre with one such programme, Beating the Blues, together with outcome data on a small sample of its clients. We conclude that experience and data, taken together, demonstrate the practical benefits of CCBT in routine practice.
Primary health care practitioners’ tools for mental health care
Authors: HYVÖNEN S. , NIKKONEN M.
Published: September 2004

The purpose of this study was to describe and analyse the content of mental health care from the practitioner's point of view. The specific aim of this paper was to outline the types of mental health care tools and the ways in which they are used by primary health care practitioners. The data were derived from interviews with doctors and nurses (n = 29) working in primary health care in six different health care centres of the Pirkanmaa region in Finland. The data were analysed by using qualitative content analysis. The tools of mental health care used in primary health care were categorized as communicative, ideological, technical and collaborative tools. The interactive tools are either informative, supportive or contextual. The ideological tools consist of patient initiative, acceptance and permissiveness, honesty and genuineness, sense of security and client orientation. The technical tools are actions related to the monitoring of the patient's physical health and medical treatment. The collaborative tools are consultation and family orientation. The primary health care practitioner him/herself is an important tool in mental health care. On the one hand, the practitioner can be categorized as a meta‐tool who has control over the other tools. On the other hand, the practitioner him/herself is a tool in the sense that s/he uses his/her personality in the professional context. The professional skills and attitudes of the practitioner have a significant influence on the type of caring the client receives. Compared with previous studies, the present informants from primary health care seemed to use notably versatile tools in mental health work. This observation is important for the implementation and development of mental health practices and education.
A comparison of the work and values of community mental health nurses in two mental health NHS Trusts
Authors: NOLAN P. , HAQUE M. S. , BOURKE P. , DYKE R.
Published: September 2004

With the reconfiguration of health services in both the primary and secondary sectors, the role of community mental health nurses (CMHNs) has become a highly contested one within mental health care. There would be great variability in the skills that CMHNs possess, the contexts in which they work and the nature of the work they do. This study sought to explore aspects of the work of those nurses who provide services at the interface between policy and practice. Two groups of CMHNs were compared, one working in an urban setting (Trust A) and the other in a rural (Trust B), focusing particularly on caseloads and client mix, the values held by CMHNs, the models of care they utilize and what they consider would improve care in the future. A specially designed 39‐item questionnaire was employed, with a mix of open and closed questions, and statements to which participants were asked to respond on a three‐point Likert scale. The findings raised interesting issues around collaborative working, whether CMHNs are happy to take on clients previously on their caseload, bureaucratization, autonomy, role definition within a culture of working with primary care, lack of specific models utilized by CMHNs, and the demand for greater training and educational support. The implications of the study are discussed with the aim of assisting mental health nurses determine their future roles.
‘Finding the person the disease has’– the case for multisensory environments
Authors: HOPE K. W. , EASBY R. , WATERMAN H.
Published: September 2004

Education about, and exposure to, the utilization of a multisensory environment (MSE) was provided to clinical staff as a response to findings from the problem identification stage of an action research study. Feedback was obtained about their experience and perceptions of its use. Through the auspices of focus groups and one‐to‐one interviews, respondents commented on the impact that using the MSE had on their perception of their clients and on subsequent care. The case is made that MSEs afford an opportunity to impact on care through their mediating influence on formal carers’ perceptions of their clients and, as such represent a significant but as yet unrealized potential for improving the quality of care of older people with dementia.
The effectiveness of two interventions in the management of patient violence in acute mental inpatient settings: report on a pilot study
Authors: NEEDHAM I. , ABDERHALDEN C. , MEER R. , DASSEN T. , HAUG H. J. , HALFENS R. J. G. , FISCHER J. E.
Published: September 2004

Systematic risk assessment and training courses have been suggested as interventions to deal with patient violence in psychiatric institutions. A dual centre prospective feasibility study was conducted on two Swiss psychiatric admission wards to test the hypothesis that such interventions will reduce the frequency and severity of violent events and coercion. A systematic aggression risk assessment, in combination with a standardized training course in aggression management was administered and the frequency and severity of aggressive incidents and the frequency of coercive measures were registered. The incidence rates of aggressive incidents and attacks showed no significant reduction from the baseline through risk prediction and staff training, but the drop in coercive measures was highly significant. A ‘ward effect’ was detected with one ward showing a decline in attacks with unchanged incidence rates of coercion and the other ward showing the opposite. The severity of the incidents remained unchanged whilst the subjective severity declined after the training course. We conclude that a systematic risk assessment and a training course may assist in reducing the incidence rate of coercive measures on psychiatric acute admission wards. Further testing of the interventions is necessary to measure the effect of the training alone and to counteract ‘ward effects’.
Family burden and participation in care: differences between relatives of patients admitted to psychiatric care for the first time and relatives of re‐admitted patients
Authors: ÖSTMAN M.
Published: September 2004

Studies on emotional and physical strain imposed on family members in connection with their responsibility of caring for a person with a severe mental illness have focused on the chronic patients. The situation of family members with patients who are at an early stage of illness and admitted for the first time may illuminate different patterns. In this Swedish multi‐centre study, 162 relatives of patients in acute psychiatric wards, both those admitted for the first time and those re‐admitted, were interviewed concerning their experience of family burden and their participation in care. There were relatively few differences found in burden measures and participation in care between the two subgroups of relatives. However, relatives who were in a career of being a relative to a person with severe mental illness earlier, more often viewed the psychiatric services to be of good quality, although they had had less contact with the staff of the psychiatric services during the last year. The relatives of re‐admitted patients experience more often psychological aspects of burden, equivalent to associated stigma. The future task of maintaining the relatives’ good opinion of psychiatric services, as well as the issue of giving informationare discussed.
Education and training in psychosocial interventions: a survey of Thorn Initiative course leaders
Authors: O'CARROLL M. , RAYNER L. , YOUNG N.
Published: September 2004

The Thorn Initiative is a prominent education and training programme for psychosocial interventions. The course originated in two centres in the UK in 1992, 10 years on the programme had expanded to 13 centres across England and Wales. A survey of course content and structure was sent out to all 13 sites by email of which eight responded by post. The survey results showed that since 1999 there has been a rapid growth in the number of Thorn sites. There remains a high degree of fidelity to the original courses in mode of delivery, service user and carer participation, and core content. All of the sites were progressing towards providing degree courses, usually in a modular format and with an expanded curriculum. In conclusion, the Thorn Steering Group has been successful in Thorn site expansion and curriculum development. Such success has taken activity away from audit and research in psychosocial interventions, education, training, implementation and fidelity to taught skills. Implementation remains a cause for concern and it is recommended that a focus for Thorn sites should be on creating and evaluating novel solutions to this pervasive problem.
Pool‐fills: a window to palaeoflood history and response in bedrock‐confined rivers
Authors: Jansen John D. , Brierley Gary J.
Published: September 2004

Channel‐scale sedimentary units associated with bedrock‐controlled riffle‐pool morphology are examined in detail along Sandy Creek gorge, an ephemeral stream in arid south‐eastern central Australia. Pool‐fills comprise cut‐and‐fill assemblages of poorly sorted sediments ranging in texture from muds to boulders. Five unit types are defined based on particle size, sedimentary structures, geometry and bounding surface character: (1) coarse‐grained bar platform; (2) fine‐grained bar supraplatform; (3) fine‐grained pool‐fill; (4) fine‐grained bench; and (5) modern pool‐fill. The last coarse‐grained unit currently lining the pools suggests an altered sedimentation style over the post‐settlement period (post‐ad 1860s). Situated at bedrock valley constrictions, pool‐fills are compared with other sedimentary units associated with recirculating currents: eddy bars and slackwater deposits. But only the fine‐grained bench units reflect eddy recirculation; the pool‐fills are principally forced‐bars associated with bedrock‐controlled or ‘forced’ riffle‐pool morphology. A late Holocene palaeoflood history is proposed based on radiocarbon ages from the pool‐fills: multiple phases of cut‐and‐fill activity were preceded by a superflood 3400–1900 years ago that eroded the pool‐fills to bedrock. The resilience of the pool‐fills was illustrated by the passage of a 1‐in‐100‐year flood in 1992, which caused only minor erosion. The presence of pool‐fills may provide a window to past phases of river activity that cannot be extracted from either historical records/observations or palaeoflood slackwater sediment analyses. The formation and sedimentary preservation potential of these landforms reflect a combination of hydraulic and structural influences, but the occurrence of high‐magnitude floods exerts the dominant control.
Textural trends in turbidites and slurry beds from the Oligocene flysch of the East Carpathians, Romania
Authors: Sylvester Zoltán , Lowe Donald R.
Published: September 2004

Deep‐water sandstone beds of the Oligocene Fusaru Sandstone and Lower Dysodilic Shale, exposed in the Buzău Valley area of the East Carpathian flysch belt, Romania, can be described in terms of the standard turbidite divisions. In addition, mud‐rich sand layers are common, both as parts of otherwise ‘normal’ sequences of turbidite divisions and as individual event beds. Eleven units, interpreted as the deposits of individual flows, were densely sampled, and 87 thin sections were point counted for grain size and mud content. S3/Ta divisions, which form the bulk of most sedimentation units, have low internal textural variability but show subtle vertical trends in grain size. Most commonly, coarse‐tail normal grading is associated with fine‐tail inverse grading. The mean grain size can show inverse grading, normal grading or a lack of grading, but sorting tends to improve upward in most beds. Fine‐tail inverse grading is interpreted as resulting from a decreasing effectiveness of trapping of fines during rapid deposition from a turbidity current as the initially high suspended‐load fallout rate declines. If this effect is strong enough, the mean grain size can show subtle inverse grading as well. Thus, thick inversely graded intervals in deep‐water sands lacking traction structures do not necessarily imply waxing flow velocities. If the suspended‐load fallout rate drops to zero after the deposition of the coarse grain‐size populations, the remaining finer grained flow bypasses and may rework the top of the S3 division, forming well‐sorted, coarser grained, current‐structured Tt units. Alternatively, the suspended‐load fallout rate may remain high enough to prevent segregation of fines, leading to the deposition of significant amounts of mud along with the sand. Mud content of the sandstones is bimodal: either 3–13% or more than 20%. Two types of mud‐rich sandstones were observed. Coarser grained mud‐rich sandstones occur towards the upper parts of S3/Ta divisions. These units were deposited as a result of enhanced trapping of mud particles in the rapidly deposited sediment. Finer grained mud‐rich units are interbedded with ripple‐laminated very fine‐grained sandy Tc divisions. During deposition of these units, mud floccules were hydraulically equivalent to the very fine sand‐ and silt‐sized sediment. The mud‐rich sandstones were probably deposited by flows that became transitional between turbidity currents and debris flows during their late‐stage evolution.
Pliocene sedimentation in a shallow, cool‐water, estuarine gulf, Murray Basin, South Australia
Authors: Pufahl Peir K. , James Noel P. , Bone Yvonne , Lukasik Jeff J.
Published: September 2004

The Pliocene Norwest Bend Formation is a well‐preserved succession of terrestrial and shallow‐marine deposits in the Murray Basin, South Australia. Sediments in this unit consist of two discrete terrigenous clastic‐rich, decametre‐scale sequences, or informal members, which record episodes of marine incursion during the Early and Late Pliocene respectively. The base of each sequence is a transgressive lag and/or strandline deposit that is transitional upwards into a highstand, subtidal, terrigenous clastic and cool‐water carbonate sediment accumulation. The top of each sequence is incised by fluvial channels that are filled by river deposits which formed as relative sea‐level fell and terrestrial environments prograded basinward. Sedimentological data suggest that gross stratigraphic architecture was primarily determined by glacioeustasy. Differences in sedimentary style between these two sequences, however, reflect a major climatic change that took place in southern Australia during the mid‐Pliocene. The lower quartzose sand member is formed of siliciclastic sediment derived from prolonged, deep, subaerial weathering and contains a bivalve‐dominated, cool‐temperate, open‐marine mollusc assemblage. These sediments accumulated under an equitable, relatively warm, humid climate. The Murray Basin during this time, because of high fluvial discharge, was a salt‐wedge estuary with typical estuarine circulation. In contrast, the upper, oyster‐rich member is typified by large monospecific oyster buildups that grew in restricted coastal environments. Strandline deposits contain a warm‐temperate skeletal assemblage. Contemporaneous aeolian sediments accumulated under warm, semi‐arid climatic conditions. Well‐developed ferricrete, silcrete and calcrete horizons reflect cyclic conditions of rainwater infiltration and evaporation in the seasonally dry climate that typifies southern Australia today. Highly seasonal rainfall produced an estuary that fluctuated annually from being well to partially mixed. These Pliocene sediments support the notion that mollusc‐rich facies are the signature of cool‐water carbonate accumulations in inboard neritic environments. Unlike bryozoans that dominate the outer parts of Cenozoic cool‐water carbonate shelves, molluscs evolved to exploit an array of coastal ecosystems with wide salinity variations and variable sedimentation rates.
The formation and environmental significance of calcite rafts in tropical tufa‐depositing rivers of northern Australia
Authors: Taylor M. P. , Drysdale R. N. , Carthew K. D
Published: September 2004

Spring‐fed rivers of the Barkly karst in tropical northern Australia form an array of tufa and related freshwater carbonate deposits. One of these deposits, calcite rafts, is precipitated at the water–air interface principally as a consequence of CO2 degassing and evaporation. Calcite rafts have been reported in cave environments but have not been described in detail from fluvial systems. Observations using scanning electron microscopy coupled with water chemistry data reveal that they form by a combination of physical, chemical and biological processes. They grow downwards into the water column and form a dentate lower surface, while a flat upper surface occurs at the water–air interface. The rafts are readily inhabited by microorganisms, particularly diatoms, which frequently become entombed by calcite as the rafts develop. The decay of the biological material leaves voids, creating a pock‐marked texture. The rafts are subject to secondary calcite growth along the crystal edges. Once they become submerged in the water column after disturbance of the water surface, they may become completely covered by this overgrowth, creating a homogeneous veneer. The rafts form in quiescent settings, principally behind tufa dams in large, lake‐like water bodies along each river. Therefore, they can be used in conjunction with adjacent exposures of other tufa facies to decipher palaeohydrological conditions. Although the rafts are extremely thin and fragile, they are readily preserved within fossil waterhole facies, and their occurrence has been identified in rocks from the Quaternary to the Tertiary.
Mudrock‐dominated fills formed in avulsion splay channels: examples from the Willwood Formation, Wyoming
Authors: Kraus Mary J. , Davies‐Vollum K. Sian
Published: September 2004

Mudrock‐dominated channel fills are common features of the fluvial Palaeogene Willwood Formation of Wyoming. These fills are small, on average 30 m wide and 3 m deep, and they vary from simple plugs to more lithologically complex fills with internal scour surfaces. Some fills preserve plant material, and others show pedogenic modification. All fills are located within metre‐thick intervals of weakly pedogenically modified mudstones that surround ribbon sandstones. The intervals have previously been attributed to channel avulsion; the fine‐grained channel fills are interpreted as crevasse‐splay feeder channels within these avulsion deposits.Variation in fill type, particularly the presence of pedogenic features, appears to be related to floodplain drainage. Possible factors that influenced drainage were basin position of the fills and Palaeogene climate fluctuations, although the role of either is not unequivocal. In general, channel fills with sombre colours and preserved plant detritus, indicating poorly drained conditions, dominate locations that were proximal to the Palaeogene basin axes. Fills that contain root traces, red and yellow‐brown matrix colours and mottling, which indicate pedogenic modification and episodic subaerial exposure of the sediment, dominate locations that were more distal to the Palaeogene basin axes. Eocene climate fluctuations, particularly episodes of global warming, may have been a secondary control on the kind of fill that developed. Mudrock‐dominated channel fills have not been described previously from ancient avulsion deposits. Their common presence in the Willwood Formation suggests that they are a typical component of avulsion belts and that similar channel fills in other stratigraphic units should be considered with regard to channel avulsion. The variety of fills observed in the Willwood Formation indicates that avulsion belt channels can experience very different fill histories. The descriptive details of fills provided here should help in their recognition elsewhere. In addition, the nature of the channel fill provides important information on ancient drainage conditions in the avulsion belt. Pedogenically modified channel fills have been recognized only rarely from the stratigraphic record. Their presence throughout the Willwood Formation suggests that they should exist in other alluvial successions and may have been overlooked previously. They indicate that periods of sediment exposure alternated with episodic influxes of water and sediment in an active avulsion belt.
Adjunctive stimulant use in patients with bipolar disorder: treatment of residual depression and sedation
Authors: Carlson Paul J. , Merlock Megan C. , Suppes Trisha
Published: September 2004

Background:  Residual depression and medication‐induced sedation remain significant problems for many patients with bipolar disorder (BD). Some evidence indicates that bipolar depression may be more responsive to dopaminergic agents, suggesting that adjunctive stimulant medication may be an effective treatment for bipolar depression as well as for medication‐induced sedation. However, there are few data regarding the use of these medications in BD, likely due in part to concerns regarding potential stimulant‐induced switching and stimulant abuse.

Methods:  In order to evaluate the effectiveness and safety of psychostimulants in BD, we retrospectively reviewed the cases of eight consecutive individuals from our clinic (five with bipolar I and three with bipolar II) who received adjunctive stimulants (either methylphenidate or amphetamine) within the last 2 years. Primary target symptoms of stimulant therapy included residual depression and medication‐induced sedation. The degree of clinical change in target symptoms was estimated, and the Clinical Global Impression‐BP Version scale (CGI‐BP) was used to evaluate the overall severity of illness at baseline, 6 months after stimulant initiation, and at last visit.

Results:  The eight patients generally showed moderate clinical improvement in their target symptoms and substantial improvement of overall bipolar illness (mean change in CGI‐BP overall score 2.9). There was no evidence of stimulant‐induced switching or abuse. The stimulants were well tolerated.

Conclusion:  The present case series suggests that adjunctive stimulants may be a reasonable therapeutic option for treating residual depression and medication‐induced sedation in some patients. Controlled trials are needed to assess the safety and effectiveness of stimulant augmentation in BD.
A pilot study of visual backward masking performance among affected versus unaffected offspring of parents with bipolar disorder
Authors: MacQueen Glenda M , Grof Paul , Alda Martin , Marriott Michael , Young L Trevor , Duffy Anne
Published: September 2004

Background:  Cognitive dysfunction is evident in some euthymic patients with established bipolar disorder (BD), including deficits in visual backward masking (VBM) tasks which map to a specific neural pathway. A high‐risk paradigm would clarify the temporal relation of cognitive dysfunction to clinical course.

Method:  We compared euthymic offspring (age range: 18–32 years) of lithium‐responsive bipolar parents with and without a previous lifetime history of psychiatric illness to healthy comparison subjects with a negative family history, on a VBM task that requires target location.

Results:  High‐risk offspring with no lifetime psychiatric history performed the VBM task at levels of healthy controls. High‐risk offspring with a previous history of a mood disorder, in complete remission, made significantly more errors at short target‐mask intervals than control or never ill offspring. These higher error rates were not a consequence of faster response times.

Conclusions:  There is preliminary evidence of specific cognitive dysfunction early in the course of illness in affected offspring of parents with lithium responsive BD. VBM is ideal for future longitudinal studies addressing whether cognitive dysfunction in BD is a trait marker or a consequence of illness manifestation.
Quality of life in patients with bipolar I depression: data from 920 patients
Authors: Yatham Lakshmi N , Lecrubier Yves , Fieve Ronald R , Davis Kimberly H , Harris Soyna D , Krishnan Anupama A
Published: September 2004

Objective:  To determine the impact of acute depression on quality of life (QOL) in patients with bipolar I disorder and to compare these results with published data on QOL in patients with unipolar depression.

Methods:  Quality of life was assessed using the SF‐36 in bipolar patients (n = 958) who had recently experienced an episode of acute bipolar depression and participated in a large randomized, double‐blind, safety and efficacy trial. Seven studies that included SF‐36 data from patients with unipolar depression were identified in the published literature and descriptive comparisons of SF‐36 scores were made between the unipolar depression trials and this bipolar depression trial.

Results:  There were 920 patients who completed the SF‐36. Mean transformed scores, which could range from 0 to 100, were very low in bipolar depressed patients for the role‐physical (36.7), vitality (22.4), social functioning (29.9), role‐emotion (11.4), and mental health (31.0) subscales. Mean SF‐36 scores for all subscales were significantly and inversely correlated (p < 0.0001) with the HAM‐D indicating that patients with milder depressive symptoms had better QOL. Further, the mean SF‐36 scores for the bipolar sample were consistently lower compared with published data on QOL in unipolar depression on four of the eight subscales: general health; social functioning; role‐physical, and role‐emotional.

Conclusions:  While both unipolar and bipolar depression have serious detrimental effects on patient QOL, our results suggest that some aspects of QOL may be worse in bipolar depression.
Gender differences in the phenomenology of bipolar disorder
Authors: Kessing Lars Vedel
Published: September 2004

Objectives:  To investigate gender differences in the phenomenology of episodes in bipolar disorder as according to ICD‐10.

Methods:  All patients who got a diagnosis of a manic episode/bipolar disorder in a period from 1994 to 2002 at the first outpatient treatment ever or at the first discharge from psychiatric hospitalization ever in Denmark were identified in a nationwide register.

Results:  Totally, 682 outpatients and 1037 inpatients got a diagnosis of a manic episode/bipolar disorder at the first contact ever. Significantly more women were treated as outpatients than as inpatients. Women were treated for longer periods as inpatients but not as outpatients. In both settings, the prevalence of depressive versus manic/mixed episodes was similar for men and women and the severity of manic episodes (hypomanic /manic without psychosis/manic with psychosis) and the severity of depressive episodes (mild/moderate/severe without psychosis/severe with psychosis) did not differ between genders. The prevalence of psychotic symptoms at first contact was the same for both genders. Among patients treated in outpatient settings more men than women presented with comorbid substance abuse and among patients treated during hospitalization more women than men presented with mixed episodes.

Conclusions:  Besides differences in the prevalence of mixed episodes and comorbid substance abuse few gender differences are found among patients presenting with a manic episode/bipolar disorder at first contact in psychiatric inpatient or outpatient hospital settings.
Burden of general medical conditions among individuals with bipolar disorder
Authors: Kilbourne Amy M , Cornelius Jack R , Han Xiaoyan , Pincus Harold A , Shad Mujeeb , Salloum Ihsan , Conigliaro Joseph , Haas Gretchen L
Published: September 2004

Objective:  Treatment of coexisting medical comorbidities may reduce the risk of adverse outcomes among patients with bipolar disorder. We determined the prevalence of general medical conditions in a population‐based sample of patients diagnosed with bipolar disorder in the Veterans Administration (VA).

Methods:  We conducted a cross‐sectional study of patients (n = 4310) diagnosed with bipolar disorder in fiscal year 2001 receiving care at VA facilities located within the mid‐Atlantic region. General medical conditions were assessed using ICD‐9 codes, and we compared the prevalence of each condition in our bipolar sample with national data on the VA patient population.

Results:  The mean age was 53 (SD = 13), 10% were women, and 12% African‐American. The mean age of the VA national patient population was higher (58 years). The most prevalent conditions among patients with bipolar disorder included cardiovascular (e.g. hypertension, 35%), endocrine (e.g. hyperlipidemia, 23%; diabetes, 17%), and alcohol use disorder (25%). When compared with national data, the prevalence of diabetes was higher in the bipolar cohort than in the national cohort (17.2% versus 15.6%; p = 0.0035). Hepatitis C was more common in the bipolar group than the national cohort (5.9% versus 1.1%; p < 0.001). Lower back pain (15.4% versus 10.6%; p < 0.0001) and pulmonary conditions (e.g. COPD: 10.6% versus 9.4%; p = 0.005) were also more prevalent among the bipolar cohort than the VA national cohort.

Conclusions:  Individuals with bipolar disorder possess a substantial burden of general medical comorbidity, and are occurring at an earlier age than in the general VA patient population, suggesting the need for earlier detection and treatment for patients with bipolar disorder.