bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation
Authors: KENYON C. J. , NARDI R. V. , WONG D. , HOOPER G. , WILDING I. R. , FRIEND D. R. 
Published: October 2003

Background: Colonic delivery of corticosteroids may reduce the side‐effects commonly associated with their use. Therefore, we tested the ability of the naturally occurring polysaccharide guar gum to deliver a corticosteroid, dexamethasone, to the colon using pharmacoscintigraphy. Guar gum is metabolized in the colon by resident bacterial enzymes to trigger drug release. Materials: Each subject (eight per group, parallel study design) was administered one of four dexamethasone (9 mg) tablet formulations, radiolabelled with 153Sm using neutron activation, under fasted conditions. One formulation was designed to release drug rapidly following ingestion while the other three formulations were designed to delay release of dexamethasone to varying degrees. Progression of the formulations down the gastrointestinal tract was followed by gamma scintigraphy. Serum concentrations were measured over time to relate disintegration profiles of the tablets with pharmacokinetic observations. Results: The immediate release formulation disintegrated in the stomach, on average, within 20 min of dosing. One of the three delayed release preparations (CD1) began to disintegrate in the small intestine 1.7±1.0 h after dosing. The second and third delayed release preparations (CD2 and CD3) did not begin to disintegrate until 5.8±2.3 and 3.6±1.6 h after dosing, respectively. All three colonic delivery preparations completely disintegrated in the colon ranging from 7.8±2.7 h (CD1) to 12.4±3.2 h (CD2) following oral administration. Pharmacoscintigraphic data indicated that 72–82% of the dexamethasone was delivered into the colon although not all the dexamethasone delivered into the colon was absorbed. Conclusions: Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.
Emergency admissions for upper gastrointestinal disease and their relation to NSAID use
Authors: BLOWER A. L. , BROOKS A. , FENN G. C. , HILL A. , PEARCE M. Y. , MORANT S. , BARDHAN K. D. 
Published: October 2003

Background: There are considerable variations in estimates of the number of emergency upper gastrointestinal admissions per annum which are attributable to nonsteroidal anti‐inflammatory drug (NSAID) use.Aim: To obtain a more accurate estimate of the number of these emergency admissions per annum in UK.Methods: A retrospective survey of the case notes of all emergency admissions for upper gastrointestinal disease (‘Cases’) to two English District General Hospitals with a combined catchment population of 550000. Records of all community deaths attributed to upper gastrointestinal diagnoses (with the same ICD codes) were also surveyed. Matched controls were identified from emergency admissions not caused by upper gastrointestinal diagnoses. The proportions of patients taking NSAIDs on admission to hospital (or at the time of death at home) and the outcome following admission to hospital were analysed.Results: 620 emergency upper gastrointestinal admissions were identified and matched with 460 controls. Cases were more likely to be NSAID users than Controls (31% vs. 16%, OR 2.4, 95% CI: 1.8, 3.3; P<0.001). Case NSAID use was higher in females and with increasing age. As severity of mode of presentation worsened, the probability of NSAID use increased (e.g. OR relative to controls for peptic pain 1.9, for perforation 5.9). Blood transfusion requirements were significantly higher (P<0.0001) in Cases taking NSAIDs, although NSAID use did not influence mortality. Extrapolation from these data indicate that there are 65000 emergency upper gastrointestinal admissions per annum in UK; 12000 of these admissions (including 2230 deaths) are attributable to NSAID use. A further 330 attributable deaths occur in the community.Conclusions: There is a strong association between NSAID use and propensity for upper gastrointestinal emergency admission; NSAID use is associated with significant morbidity and mortality each year in UK.
Expression of rhombotin 2 in normal and leukaemic haemopoietic cells
Authors: Dong W‐F. , Billia F. , Atkins H. L. , Iscove N. N. , Minden M. D. 
Published: October 2003

The rhombotin 2 gene was identified by its association with a recurrent chromosome translocation (11;14)(p13;q11), occurring in T‐cell acute lymphoblastic leukaemias (ALLs). High levels of RBTN2 have been found in T‐cell leukaemias carrying the translocation and in some T‐cell ALLs that lack, by cytogenetic and molecular techniques, translocations involving 11p13. In normal murine tissues RBTN2 has been found to be widely expressed, with high levels present in brain and early B cells. Studies carried out in mice lacking RBTN2 have demonstrated the importance of this gene in erythropoiesis.We have investigated the expression of RBTN2 in human leukaemic cells, and in human and murine normal myeloid progenitor cells. RBTN2 is expressed in the leukaemic cells of patients with pre‐B ALL, T‐ALL and acute myeloblastic leukaemia (AML). By cytogenetic and molecular techniques no abnormalities were noted in 11p13. Using clonogenic assays and single cell PCR we found that RBTN2 is expressed strongly in the precursors of mixed erythrocyte/macrophage/mast, erythrocyte, megakaryocyte, neutrophil and macrophage colonies. In contrast, RBTN2 message was low to undetectable in the mature progeny. These findings indicate that RBTN2 is expressed in leukaemias of both the myeloid and lymphoid lineages. Further, these studies show that in normal myeloid and lymphoid cells the expression of RBTN2 is present in progenitor cells and is lost as the cells terminally differentiate. This latter finding further illustrates that the detection of a RNA in a population of cells should not be interpreted to mean that all of the cells in that population express the RNA.
ORAL CONTRACEPTIVES ENHANCE THE RISK OF CLINICAL MANIFESTATION OF VENOUS THROMBOSIS AT A YOUNG AGE IN FEMALES HOMOZYGOUS FOR FACTOR V LEIDEN
Authors: Rintelen Claudia , Mannhalter Christine , Ireland Helen , Lane David A. , Knöbl Paul , Lechner Klaus , Pabinger Ingrid 
Published: October 2003

In 29 patients (17 females) homozygous Arg 506 Gln mutation (FV Leiden) was identified. 25 had been investigated because of venous thromboembolism (VTE); four asymptomatic patients were found during family studies.The first VTE had occurred significantly earlier in females (median age [m] 26 years, range 17–49) than in males (m=38 years, range 21–82) (P = 0.01). 12 females (80%) had taken oral contraceptives (OC, oestrogen content 0.02–0.1 mg) for 6–150 months prior to thrombosis. Further triggering conditions in females were hormone replacement (n = 1) and pregnancy (n = 2). In 8/10 males the first VTE had occurred spontaneously — in two after surgery. The sites of VTE were deep vein thrombosis, pulmonary embolism, caval vein thrombosis and superficial thrombophlebitis.From our data we conclude that OC medication is the most important precipitating factor for VTE in females with homozygous FV Leiden.
Hepatitis C virus and non‐Hodgkin's lymphomas
Authors: Mazzaro Cesare , Zagonel Vittorina , Monfardini Silvio , Tulissi Patrizia , Pussini Elisabetta , Fanni Massimiliano , Sorio Roberto , Bortolus Roberto , Crovatto Marina , Santini Gianfranco , Tiribelli Claudio , Sasso Franco , Masutti Roberto , Pozzato Gabriele 
Published: October 2003

Hepatitis C virus (HCV) seems to be the aetiologic agent of mixed cryoglobulinaemia, and as this ‘benign’ lymphoproliferative disorder can frequently develop into more aggressive haematological disorders, this study was undertaken to determine the prevalence of HCV infection in non‐Hodgkin's lymphomas. 199 unselected subjects treated by three haematological centres in Northeast Italy were investigated for the presence of HCV infection. As controls, the prevalence of HCV infection was determined in a group of patients affected by other haematological malignancies (153 subjects) and in the general population of the same geographical area in the cohort study called the Dyonisos project (6917 subjects).The presence of anti‐HCV antibodies was determined by a commercial kit and, in positive cases, by PCR amplification of the 5′ untranslated region of the virus. The HCV genotype was also obtained by PCR amplification of the Core region with type‐specific primers. The presence of serum cryoglobulins was determined in each case of NHL.HCV infection was significantly (P<0.00000001) higher in patients with non‐Hodgkin's lymphomas (28.0%) when compared with that of the general population (2.9%), and with the group of patients affected by other malignancies (3.1%). The prevalence is particularly high in low‐grade (38.4%), as compared with intermediate (11.4%), or high‐grade (15.2%) lymphomas. The presence of the virus is significantly (P<0.000001) associated with the presence of detectable levels of cryoglobulins. On the basis of these findings, HCV seems to play an important role in the development of low‐grade non‐Hodgkin's lymphomas.
Acquired von Willebrand factor deficiency during high‐dose infusion of recombinant factor VIII
Authors: ROCK G. , Adamkiewicz T. , Blanchette V. , Poon A. , Sparling C. 
Published: October 2003

Constant infusion of factor VIII (FVIII) into patients with haemophilia A after major surgery has been recommended as optimal treatment to avoid peaks and valleys in the circulating levels of FVIII and to allow the use of much lower doses of FVIII than are historically required.One of our young patients with severe (<0.01 U/ml FVIII) haemophilia suffered a subdural haematoma for which he received treatment with 815 190 recombinant FVIII (rFVIII) units over a period of 52 d. 2 weeks after admission, because of low FVIII levels and the presence of FVIII inhibitors, the infusion rate was increased to >100 U/kg/h for 14 d. During this time the FVIII level fluctuated between 0.6 and 4.2 U/ml. For some period it was not possible to detect ristocetin co‐factor activity in this patient’s plasma and the von Willebrand factor (VWF) level and VWF multimer pattern resembled those of a patient with von Willebrand’s disease. Subsequently, when the rFVIII dose was increased 2‐fold, this was not reflected by the plasma level of FVIII although antibodies were not detected.The data suggest that the prolonged infusion of very high levels of rFVIII which is deficient in von Willebrand factor can result in depletion of VWF from existing stores, producing a laboratory picture which is consistent with the diagnosis of von Willebrand’s disease. Further, in the absence of complexing with VWF, FVIII appears to be cleared from the circulation at an increased rate. This is expensive and potentially compromising. Therefore, when administering very high doses of FVIII concentrates devoid of VWF for prolonged periods of time, ristocetin cofactor and VWF levels should be monitored.
Activated protein C resistance: a comparison between two clotting assays and their relationship to the presence of the factor V Leiden mutation
Authors: Legnani C. , Palareti G. , Biagi R. , Coccheri S. , Bernardi F. , Rosendaal F. R. , Reitsma P. H. , De Ronde H. , Bertina R. M. 
Published: October 2003

Resistance to the anticoagulant effect of activated protein C (APC resistance), a frequent abnormality in patients with a history of venous thrombosis, is known to be due, in the large majority of cases, to the presence of an abnormal factor V: the factor V Leiden. It is reasonable to surmise that screening for this abnormality should be performed with a clotting method for APC resistance, before submitting the patients with abnormal results to DNA analysis. The present study was performed on 216 individuals enrolled at the Bologna centre, of which 189 were unrelated patients with a history of juvenile venous thromboembolism and 27 were relatives with or without thrombosis. APC resistance was first measured in Bologna by a standard commercial method and then, in Leiden, by an in‐house method; DNA analysis was performed in those cases in which at least one of the clotting methods was abnormal. The data obtained confirm the good performance and the optimal positive predictive value for the Leiden mutation (100%) of the Leiden in‐house clotting method. Performance of the commercial method was less satisfactory but markedly improved by expressing the data in relation to the values simultaneously obtained with a normal plasma pool. Even with optimal data expression, however, the positive predictive value of the commercial method, versus DNA analysis, did not exceed 88%.It is concluded that further standardization of the commercial method here evaluated is necessary before it can be widely adopted for the screening of APC resistance and prediction of the presence of factor V Leiden.
The genetic basis of a new partial D antigen: DDBT
Authors: BECKERS E. A. M. , FAAS B. H. W. , SIMSEK S. , OVERBEEKE M. A. M. , VAN RHENEN D. J. , WALLACE M. , VON DEM BORNE A. E. G. KR , VAN DER SCHOOT C. E. 
Published: October 2003

The Rh system, the most polymorphic system on red cells, is genetically controlled by two different but highly homologous genes on chromosome 1. The RHCE gene encodes different RhCcEe polypeptides and the RHD gene encodes D antigens. It is well established that in D negative individuals the RHD gene is either absent or grossly deleted. The D antigen comprises at least nine serologically defined D epitopes. The D antigen can be divided into different partial D categories, reflecting a different pattern of specific D epitopes.In this study a newly defined partial D antigen, DDBT, was studied. D epitope mapping revealed the presence of D epitopes 6/7 and 8 and the absence of the other D epitopes. The molecular basis of this phenotype was studied by Southern blotting, by RHD typing using the polymerase chain reaction (RHD‐PCR) and by sequence analysis of Rh transcripts. The DBT phenotype appeared to be encoded by a hybrid RHD gene, in which exons 5, 6 and 7 (and possibly the identical exon 8) were replaced by the corresponding exons of the RHCE gene.From this study it may be concluded that D epitopes 1, 2, 3, 4, 5 and 9 are dependent on the presence of RHD exons 5, 6, and 7.
Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients
Authors: TROUSSARD X. , VALENSI F. , DUCHAYNE E. , GARAND R. , FELMAN P. , TULLIEZ M. , HENRY‐AMAR M. , BRYON P. A. , FLANDRIN G. 
Published: October 2003

The diagnosis of splenic lymphoma with villous lymphocytes (SLVL) was assessed by a panel of cytologists in a series of 100 patients. Clinical and biological characteristics were analysed in relation to prognosis.SLVL is a chronic B‐cell lymphoproliferative disorder characterized by splenomegaly and the presence, in peripheral blood, of lymphocytes with ‘villous’ projections. The cytological diagnosis can be difficult in patients without an absolute lymphocytosis which was observed in 24% of cases. B‐cells expressed CD19+, CD20+, CD22+, CD24+ and DBA44+, whereas the expression of CD5, CD10 and CD25 was usually negative.SLVL is a disease of the elderly with a relatively benign clinical course. In the present series the 5‐year overall survival was 78%. Deaths in 15 patients were related to disease progression or treatment (nine cases). Patients with a leucocyte count >30 × 109/l or lymphocyte count <4 × 109/l or initially treated with chemotherapy had significantly (P < 0.001) lower overall survival than other patients. From these findings, treatment abstention should be considered in patients with favourable prognostic factors; on the other hand, the efficacy of conventional chemotherapy remains to be evaluated in patients with unfavourable prognostic factors.
Pretransplant cytotoxic donor T‐cell activity specific to patient HLA class I antigens correlating with mortality after unrelated BMT
Authors: Speiser D. E. , Löliger C.‐C. , Siren M.‐K. , Jeannet M. 
Published: October 2003

Unrelated bone marrow transplantation (BMT) is associated with increased post‐transplant complication rates, partly because more transplantation antigens are mismatched than in HLA‐identical related BMT. We have shown previously that the cytotoxic T‐lymphocyte precursor (CTLp) test performed before transplantation specifically detects HLA class I mismatches demonstrating its usefulness for the identification of new HLA class I alleles. In this study we analysed the clinical relevance of the CTLp test in 41 patients who underwent unrelated BMT between 1990 and 1994. All patient–donor pairs were HLA‐A, ‐B, ‐DR compatible as defined by AB‐serology and oligotyping for DR1‐14. The host‐reactive CTLp test was performed using previously frozen peripheral blood mononuclear cells (PBMC) as stimulators and PHA blasts as target cells. We found 10 CTLp‐positive and 31 CTLp‐negative patient–donor pairs. Between the two groups there were no significant differences for age, diagnosis, sex, preconditioning and GvHD prophylaxis. The clinical results for the CTLp positive and the CTLp negative transplants were: severe acute GvHD III–IV 67% and 26% (P = 0.0315), transplant‐related mortality 60% and 26% (P = 0.0085), and patient survival at 3.5 years 10% and 54% (P = 0.0006).Seven patient–donor pairs were mismatched for HLA‐DR and/or ‐DQ subtypes. Only one of these seven class II mismatched pairs had a positive CTLp test. In the remaining nine CTLp positive pairs the CTL reactivity was directed against HLA‐A, ‐B or ‐C antigens, revealing a statistically significant (P < 0.005) correlation between the CTLp frequency and HLA class I matching. In conclusion, the CTLp test helped to select optimally matched bone marrow donors and was particularly useful in association with high resolution oligotyping for DR‐ and DQ‐subtypes for precise matching of both classes of HLA antigens.
The use of rh‐G‐CSF in chronic autoimmune neutropenia: reversal of autoimmune phenomena, a case history
Authors: Kuijpers Taco W. , DeHaas Masja , DeGroot CeesJ. , Von Dem Borne Albert E. G. Kr , Weening Ron S. 
Published: October 2003

An 8‐year‐old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high‐dose steroids and intravenous (either low‐ or high‐dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of autoimmune haemolytic anaemia did, however, respond to high‐dose prednisone. Other signs of immune dysregulation in this patient consisted of insulin‐dependent diabetes mellitus type I (IDDM) and an acquired hypogammaglobulinaemia, most compatible with common variable immunodeficiency (CVI). Prior to rhG‐CSF therapy the child had suffered for more than 2 years from recurrent life‐threatening bacterial infections.Anti‐neutrophil autoantibodies had pan‐FcγRIII (CD16, NA1/NA2) specificity. The neutropenia as well as the anti‐neutrophil autoantibodies disappeared when subcutaneous rhG‐CSF therapy was started. Upon tapering rhG‐CSF, anti‐FcγRIII antibodies reappeared together with an absolute neutropenia. Renewed administration resulted again in the normalization of symptoms.Soluble FcγRIII (sFcγRIII) antigen levels in plasma increased dramatically during rhG‐CSF treatment. These high levels of sFcγRIII together with increased numbers as well as decreased apoptotic reactions of neutrophils apparently result in adsorption of the autoantibodies in vivo, contributing to the normalization of autoimmune‐mediated neutropenia upon rhG‐CSF treatment. Long‐term administration of rhG‐CSF represents an alternative in the treatment of autoimmune neutropenia.
Mainstream or margin? The current use of family group conferences in child welfare practice in the UK
Authors: Brown Louise 
Published: October 2003

ABSTRACTA decade has passed since family group conferences were initially introduced into the UK by Family Rights Group. Ten years on, this paper examines the extent to which family group conferences have developed and become embedded into current social work practice. Despite the initial interest by social work practitioners and the picture often painted of a growing radical movement, the degree to which family group conferencing has become part of mainstream practice has until now remained fairly anecdotal. A number of difficulties have been identified with implementing the model, including fitting it into an existing system and the challenge it poses to professionals to hand over power. Two surveys, the first undertaken in 1999 and the second in 2001, describe the current use of the model in the UK by Councils with Social Services Responsibilities (Councils). The surveys reveal the areas of practice within which family group conferences are being used, the size and capacity of projects and why some Councils have adopted the model whilst others remain hesitant. It concludes by considering why family group conferences remain on the margins of practice.
Services for troubled adolescents: exploring user variation
Authors: Berridge David , Beecham Jennifer , Brodie Isabelle , Cole Ted , Daniels Harry , Knapp Martin , MacNeill Virginia 
Published: October 2003

ABSTRACTThis paper outlines some of the main findings from an exploratory study of a sample of 257 adolescents living in children's homes, foster homes and residential special schools ‘for pupils with emotional and behavioural difficulties’ (‘EBD’). It focuses on the characteristics of service users, particularly contrasting the looked after and EBD groups. Though there are some similarities, there are also important differences between the populations in terms of age, gender, ethnicity, reasons for separation, legal status, family background and education. An attempt was made systematically to compare groups by creating a subsample of ‘difficult’ adolescents, based on involvement in anti‐social behaviour. Unexpectedly, this revealed that half of the teenagers were not ‘difficult’. Factors associated with being identified as ‘difficult’ were explored.