bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful adoptive immunotherapy for relapse of AML 9 years after T‐cell‐depleted BMT
Authors: Bertz Hartmut , Kunzman Regine , Bunjes Donald , Finke JÜrgen 
Published: March 2003

Relapse is one of the main problems which can occur following allogeneic transplantation for haematological malignancies. In this situation the enhancement of the graft‐versus‐leukaemia effect by transfusion of donor buffy coats with or without cytokines may lead to complete remission especially in myeloid leukaemias. FISH (fluorescence in situ hybridization) is a sensitive method to monitor chimaerism in gender‐different transplantation.We report a case of successful buffy coat transfer therapy > 9 years after bone marrow transplanation. This is the longest interval reported, to our knowledge, between transplantation to relapse, which was treated by adoptive immunotherapy. Complete donor chimaerism was confirmed by FISH.
Kinetic analysis of 52Fe‐labelled iron(III) hydroxide–sucrose complex following bolus administration using positron emission tomography
Authors: Beshara Soheir , Lundqvist Hans , Sundin Johanna , Lubberink Mark , Tolmachev Vladimir , Valind Sven , Antoni Gunnar , Långström Bengt , Danielson Bo G. 
Published: March 2003

Kinetic analysis of a single intravenous injection of 100 mg iron(III) hydroxide–sucrose complex (Venofer®) mixed with 52Fe(III) hydroxide–sucrose as a tracer was followed for 3–6 h in four generally anaesthetized, artificially ventilated minipigs using positron emission tomography (PET). The amount of injected radioactivity ranged from 30 to 200 MBq.Blood radioactivity, measured by PET in the left ventricle of the heart, displayed a fast clearance phase followed by a slow one. In the liver and bone marrow a fast radioactivity uptake occurred during the first 30 min, followed by a slower steady increase. In the liver a slight decrease in radioactivity uptake was noted by the end of the study. A kinetic analysis using a three‐compartment (namely blood pool, reversible and irreversible tissue pools) model showed a fairly high distribution volume in the liver as compared with the bone marrow.In conclusion, the pharmacokinetics of the injected complex was clearly visualized with the PET technique. The organs of particular interest, namely the heart (for blood kinetics), liver and bone marrow could all be viewed by a single setting of a PET tomograph with an axial field of view of 10 cm. The half‐life (T1/2) of 52Fe (8.3 h) enables a detailed kinetic study up to 24 h. A novel method was introduced to verify the actual 52Fe contribution to the PET images by removing the interfering radioactive daughter 52mMn positron emissions. The kinetic data fitted the three‐compartment model, from which rate constants could be obtained for iron transfer from the blood to a pool of iron in bone marrow or liver to which it was bound during the study period. In addition, there was a reversible tissue pool of iron, which in the liver slowly equilibrated with the blood, to give a net efflux from the liver some hours after i.v. administration. The liver uptake showed a relatively long distribution phase, whereas the injected iron was immediately incorporated into the bone marrow. Various transport mechanisms seem to be involved in the handling of the injected iron complex.
The erythrocyte effects of haemoglobin OARAB
Authors: Nagel Ronald L. , Krishnamoorthy Rajagopal , Fattoum Slaheddine , Elion Jacques , Genard Nathalie , Romero Jose , Fabry Mary E. 
Published: March 2003

To test the hypothesis that HbOARAB induces an increase in red cell mean corpuscular haemoglobin concentration (MCHC), we studied members of four Tunisian families who were either homo‐ or heterozygous for HbOARAB or were double heterozygotes for HbS and HbOARAB. The α‐gene status was also tested. The findings included: (1) Distinctive variation in red cell density (MCHC) as determined by separation of red cells on isopycnic gradients: (a) All red cells from patients homozygous for HbOARAB were denser than normal red cells, as is observed for homozygous HbC patients. (b) In patients heterozygous for HbOARAB, red cell density was strongly influenced by the presence of α‐thalassaemia. The coexistence of −α/αα resulted in an average red cell density slightly greater than normal (AA) red cells. Patients heterozygous for HbOARAB with a normal complement of four α genes had denser red cells similar to sickle cell disease with some cells of normal density but with most cells very dense. (c) Finally, the double heterozygotes for HbS and HbOARAB had significant haemolytic anaemia and red cells denser than normal with some as dense as the densest cells found in sickle cell anaemia. (2) Reticulocytes in patients homozygous for HbOARAB were found in the densest density fraction of whole blood. (3) Cation transport in patients homozygous for HbOARAB was abnormal, with K:Cl cotransport activity similar to that of HbS‐Oman and only somewhat lower than in sickle cell anaemia red cells. The activity of the Gardos channel was indistinguishable from that found in HbS, HbC and HbS‐Oman cells.We conclude that the erythrocytic pathogenesis of HbOARAB involves the dehydration of red cells due, at least in part, to the K:Cl cotransport system. The similarity of the charge and consequences of the presence of both HbC and HbOARAB, which are the products of mutations at opposite ends of the β‐chain, raises the possibility that this pathology is the result of a charge‐dependent interaction of these haemoglobins with the red cell membrane and/or its cytoskeleton and that this abnormality is present early in red cell development.
Extraordinary bone involvement in a Gaucher disease type I patient
Authors: Barone R. , Pavone V. , Nigro F. , Chabàs A. , Fiumara A. 
Published: March 2003

We report on a 63‐year‐old patient with Gaucher disease type I who developed severe bone involvement with destructive lesions and huge soft tissue extension in both humeri that appeared to evolve slowly. The clinical course and histopathological findings in our patient suggested a progressive extraosseous extension of the storage cells into the soft tissue, accompanied by a striking increase of fibrotic tissue and resulting in an impressive deformity.The extraordinary bone involvement in this patient expands our knowledge on the most severe skeletal complications of untreated Gaucher disease.
Characterization of lineage‐specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse
Authors: Bader P. , Stoll K. , Huber S. , Geiselhart A. , Handgretinger R. , Niemeyer C. , Einsele H. , Schlegel P. G. , Niethammer D. , Beck J. , Klingebiel T. 
Published: March 2003

Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused by the reappearance of normal recipient haematopoiesis or by the reoccurrence of malignant cells, we purified different leucocyte subpopulations and analysed these subfractions with regard to their donor–recipient ratio by a PCR‐based method for the analysis of minisatellite DNA regions. In 14 patients [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leukaemia (AML) and three MDS] subfractions were analysed when increasing MC was first noted upon serial analysis of the peripheral blood. In seven of these 14 patients (four ALL, two AML and one MDS), subfractions were characterized at the time of frank haematological relapse. In all 14 patients investigated with increasing MC, recipient cells were detected in different mononuclear cell subpopulations. In patients characterized during frank relapse, two distinct distribution patterns were found. Patients who relapsed before day +300 (one ALL, two AML and one MDS) showed recipient‐derived (normal) cells in addition to blast populations in different mononuclear subsets as well as granulocytes. In patients with acute leukaemias who relapsed after day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were donor derived.These data show that persistent MC in the early post‐transplant period is caused predominantly by normal recipient haematopoietic cells. This finding further supports the hypothesis that a state of mixed haematopoietic chimaerism may reduce the clinical graft‐versus‐leukaemia (GVL) effect of alloreactive donor‐derived effector cells in patients with acute leukaemias and MDS, and thus facilitate the proliferation of residual malignant cells that may have survived the preparative regimen.
Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long‐term follow‐up of a randomized clinical trial
Authors: Finazzi Guido , Ruggeri Marco , Rodeghiero Francesco , Barbui Tiziano 
Published: March 2003

We have previously demonstrated that hydroxyurea (HU) reduces the rate of vascular complications in patients with essential thrombocythaemia (ET) at high risk of thrombosis. However, the relatively short follow‐up (median 27 months) did not enable the evaluation of the risk of developing secondary malignancies. In this study, we report the long‐term outcome of the 114 patients included in the trial: 56 patients randomized to receive HU and 58 patients to receive no cytoreductive therapy. Before randomization, 15 patients had been treated with busulphan. During the observation period, 29 patients (50%) shifted from the control to the HU group mainly because of thrombosis. Median follow‐up was 73 months (range 3–94). Analysis was by intention to treat and, when indicated, by treatment.When analysed by intention to treat, 46 out of 54 patients (85%) originally randomized in the HU group are alive, compared with 49 of 58 patients (84%) in the control group [not significant (n.s.)]. Five patients (9%) in the HU group and 26 patients (45%) in the control group had thrombosis (P < 0·0001). Seven patients (13%) in the HU group developed secondary acute leukaemia, myelodysplastic syndromes or solid tumours, compared with only one of the control group patients (1·7%) (P = 0·032). The occurrence of secondary malignancies was also analysed by treatment: none of the 20 patients who had never been treated with chemotherapy developed neoplasia vs. three of the 77 patients given HU only (3·9% n.s.) and five of the 15 patients given busulphan plus HU (33% P < 0·0001).This study showed that: (a) HU reduced the risk of thrombosis in ET patients; (b) the sequential use of busulphan and HU significantly increased the risk of second malignancies; and (c) overall survival was not affected by HU therapy.
Novel mutations in the Factor VII gene of Taiwanese Factor VII‐deficient patients
Authors: Shen Ming‐Ching , Lin Jen‐Shiou , Lin Shu‐Wha , Yang Wei‐Shin , Lin Bodo 
Published: March 2003

The genetic defects of four Taiwanese patients with factor VII (FVII) deficiency were studied. FVII activity and antigen levels were < 1 u/dl and 125·7 u/dl (patient I), < 1 u/dl and < 1 u/dl (patient II), 3·4 u/dl and 5·9 u/dl (patient III), and 1·2 u/dl and 30·4 u/dl (patient IV) respectively. The 5′ flanking region, and all exons and junctions were amplified using polymerase chain reaction and sequenced. Patient I was homozygous for a 10824C→A transversion with Pro303→Thr mutation in exon 8. In patient II, a heterozygous transversion, 9007+1G→T at the IVS6, a heterozygous decanucleotide insertion polymorphism at −323 (both mutations present in his father) and a heterozygous deletion, del TC (26–27) in exon 1A (originating from his mother) were identified. Patient III had a homozygous 10961T→G transversion with His348→Gln mutation in exon 8. Patient IV had a heterozygous 10902T→G transversion with Cys329→Gly mutation in exon 8 (transmitted to her second son) and a heterozygous decanucleotide insertion polymorphism at −323 (transmitted to her third son). All but one of the FVII gene mutations detected in the four patients have not been previously reported. In conclusion, four novel mutations of the FVII gene in Taiwanese, including two missense mutations in exon 8, one point mutation at the exon 6 splice site and one deletion in exon 1A, were identified.
Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment‐related mortality in stem cell transplantation from unrelated donors using pretransplantin vivoT‐cell depletion with anti‐thymocyte globulin
Authors: Kröger Nicolaus , Zabelina Tatjana , Krüger William , Renges Helmut , Stute Norbert , Schrum Johanna , Kabisch Hartmut , Schafhausen Philippe , Jaburg Nicole , Löliger Cornelius , Schäfer Peter , Hinke Axel , Zander Axel R. 
Published: March 2003

We evaluated the cytomegalovirus (CMV) serostatus as a risk factor for survival and treatment‐related mortality (TRM) in 125 patients allografted from an unrelated donor between 1994 and 1999. All patients received pretransplantin vivoT‐cell depletion using rabbit anti‐thymocyte globulin (ATG). Only one patient had primary graft failure and severe grade III/IV graft‐versus‐host disease occurred in 14% of the patients. The overall survival (OS) at 3 years was 70% for CMV‐negative patients (n = 76) and 29% in the seropositive cohort (n = 49) (P > 0·001). In multivariate analyses, CMV seropositivity remained an independent negative prognostic factor for OS (RR: 2·1; CI: 1·2–3·8;P = 0·014), apart from age > 20 years (RR: 2·74; CI: 1·2–3·8;P = 0·004) and late leucocyte engraftment (RR: 2·4; CI: 1·2–4·9;P = 0·015). The TRM for all patients was 27%. Despite monitoring for CMV antigenaemia and preemptive therapy with ganciclovir when reactivation occurred, seropositive patients had a three times higher risk of fatal treatment‐related complications than seronegative patients. In multivariate analyses, CMV seropositivity remained the strongest independent negative factor for TRM (RR: 5·3; CI: 1·9–14·6;P = 0·002), followed by age > 20 years (RR: 4·8; CI: 1·3–18·1;P = 0·02) and delayed leucocyte engraftment (RR: 3·6; CI: 1·2–11;P = 0·02). The TRM was identical in seropositive patients with (n = 27) or without (n = 22) CMV reactivation (44% versus 50%). We conclude that CMV seropositivity, despite preemptive ganciclovir therapy and even without reactivation, is a major negative prognostic factor for survival as well as for TRM in unrelated stem cell transplantation using pretransplantin vivoT‐cell depletion with ATG.
Mutations of the cationic trypsinogen gene in patients with hereditary pancreatitis
Authors: Creighton J E , Lyall R , Wilson D I , Curtis A , Charnley R M 
Published: March 2003

Abstract

Background
Hereditary pancreatitis has been shown to be caused by one of two mutations (R117H and N21I) of the cationic trypsinogen gene (PRSS1). Families with hereditary pancreatitis in the north of England were investigated for these mutations. The clinical features associated with each mutation were compared.

Methods
In individuals from nine families with hereditary pancreatitis, DNA was screened for the R117H and N21I mutations. All five exons of the cationic trypsinogen gene were also sequenced to search for additional mutations. Haplotype analysis was carried out to identify common ancestors. Clinical data were collected.

Results
The R117H mutation was identified in three families and N21I in a further five. The R117H mutation was associated with a more severe phenotype than N21I in terms of mean(s.d.) age of onset of symptoms (8·4(7·2) versus 16·5(7·1) years; P = 0·007) and requirement for surgical intervention (eight of 12 versus four of 17 patients respectively; P = 0·029). Haplotype analysis suggested that each mutation had arisen more than once.

Conclusion
Two mutations in the cationic trypsinogen gene cause hereditary pancreatitis in eight of nine families originating in this region. The R117H mutation is associated with a more severe form of the disease in terms of age at onset of symptoms and requirement for surgical intervention.
Lymphocyte activation after non-thermal trauma
Authors: Walsh D S , Siritongtaworn P , Pattanapanyasat K , Thavichaigarn P , Kongcharoen P , Jiarakul N , Tongtawe P , Yongvanitchit K , Komoltri C , Dheeradhada C , Pearce F C , Wiesmann W P , Webster H K 
Published: March 2003

Abstract

Background
Severe injury causes immunological changes that may contribute to a poor outcome. Longitudinal characterization of lymphocyte response patterns may provide further insight into the basis of these immunological alterations.

Methods
Venous blood obtained seven times over 2 weeks from 61 patients with injury severity scores above 20 was assessed for lymphocyte phenotypic and activation markers together with serum levels of interleukin (IL) 2, IL-4, soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8) and interferon γ.

Results
Severe injury was associated with profound changes in the phenotypic and activation profile of circulating lymphocytes. Activation was indicated by increased numbers of T cells expressing CD25, CD69 and CD71, and raised serum levels of IL-2, sIL-2R, sCD4 and sCD8. Relatively higher levels of sIL-2R and sCD4 were found in patients with sepsis syndrome.

Conclusion
Polytrauma is associated with dramatic alterations in the phenotypic and activation profile of circulating lymphocytes which are generally independent of clinical course. In contrast, several lymphocyte soluble factors, including sCD4 and sIL-2R, paralleled the clinical course. These data provide new insight into lymphocyte responses after injury and suggest that further assessment of soluble factors as clinical correlates, including those related to lymphocyte activation or generalized inflammation, may be warranted.
Xenotransplantation
Authors: Soin B , Vial C M , Friend P J 
Published: March 2003

Abstract

Background
The success of clinical transplantation has led to a large discrepancy between donor organ availability and demand; considerable pressure exists to develop an alternative source of organs. The use of animal organs for donation is a possible solution that is not yet clinically applicable.

Methods and results
A literature review was performed based on a Medline search to find articles on xenotransplantation. Keywords included hyperacute, acute vascular, xenograft rejection combined with concordant and discordant. Additional references cited in these articles from journals not included in Medline were obtained from the British Library. Limited information on unpublished, preliminary work has been included from sources known to the authors, based on their research work in the field. One hundred and forty-six references and four personal communications have been included in this review article.

Conclusion
A greater understanding of the pathogenesis of xenograft rejection is developing rapidly. Strategies to abrogate hyperacute rejection have proved successful, but control of antibody-driven acute vascular rejection has not yet been achieved. The safety and viability of xenotransplantation as a therapeutic modality are still unproven.
Apolipoprotein E genotype is associated with differential expansion rates of small abdominal aortic aneurysms
Authors: Gerdes L U , Lindholt J S , Vammen S , Henneberg E W , Fasting H 
Published: March 2003

Abstract

Background
The common polymorphism of the apolipoprotein E (APOE) gene is associated with differential risk of atherosclerosis; the gene could be a candidate gene in abdominal aortic aneurysms (AAA).

Methods
APOE genotypes were determined in 57 men aged 65–73 years with a small AAA (30–50 mm). The patients were included in a population ultrasonographic screening programme and were followed with at least two examinations during an interval of 2–4·5 years. The AAA expansion rates in patients with four different APOE genotypes were studied, with adjustment for initial AAA size and smoking.

Results
APOE genotype was a significant determinant of AAA expansion rate (P = 0·001). The adjusted mean (95 per cent confidence interval) rate was 2·1 (1·7–2·6) mm/year in 31 men with genotype E3E3, 1·3 (0·7–1·9) mm/year in 17 men with E3E4, 3·1 (2·0–4·1) mm/year in six men with E2E3 and 4·2 (2·7–5·6) mm/year in three men with E2E4. The mean expansion rate was 2·2 (1·5–2·8) mm/year in non-smokers and 3·0 (2·5–3·6) mm/year in smokers (P = 0·014).

Conclusion
APOE genotype seems to influence AAA expansion rate, but the effects of the individual genotypes, in particular E3E3 and E3E4, are contradictory when compared with the effects of the genotypes on risk of atherosclerosis.
Systematic review of antimicrobial agents used for chronic wounds
Authors: O'Meara S M , Cullum N A , Majid M , Sheldon T A 
Published: March 2003

Abstract

Background
This paper is one of a series of eight systematic reviews that aim to identify effective interventions for chronic wounds. Here, antimicrobial agents are evaluated.

Methods
Electronic databases and other relevant sources were accessed to identify published and unpublished material. Studies were eligible for inclusion if they used concurrent controls, recruited participants with chronic wounds, evaluated an intervention designed to prevent or treat chronic wounds, and incorporated an objective assessment of wound healing. All included studies were assessed against a comprehensive checklist for methodological quality. A narrative overview was conducted.

Results
Thirty trials were included, 25 of randomized design. Small sample size and other methodological problems meant that findings were often difficult to interpret. Results do not support the routine use of systemic antibiotics for leg ulcers or diabetic foot ulcers without acute infection, but they may be useful as an adjunct to surgery for pilonidal sinuses. Several topical preparations may be helpful, including dimethyl sulphoxide, silver sulphadiazine, benzoyl peroxide, oxyquinoline and gentamicin.

Conclusion
Most of this research requires replication in larger, well designed studies to establish both clinical and cost effectiveness.
Nitric oxide prevents intestinal mitochondrial dysfunction induced by surgical stress
Authors: Thomas S , Anup R , Susama P , Balasubramanian K A 
Published: March 2003

AbstractBackgroundThe intestine is highly susceptible to free radical-induced damage and earlier work has shown that surgical stress induces generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with changes in mitochondrial structure and function. Nitric oxide is an important mediator of gastrointestinal function and this study looked at the effect of nitric oxide on surgical stress-induced intestinal mitochondrial alterations.MethodsControls and rats pretreated with the nitric oxide donor l-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine. Enterocytes were isolated, mitochondria prepared and the protection offered by l-arginine against damage due to surgical stress was determined. Protection to structural as well as functional aspects of mitochondria was examined.ResultsMild handling of the intestine affected the enterocyte mitochondrial structure as assessed by lipid composition and electron microscopy. Mitochondria were also functionally impaired with altered calcium flux and decreased respiratory control ratio. Pretreatment with the nitric oxide synthase substrate l-arginine prevented these damaging effects of surgical stress. Protection with arginine was abolished by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester, indicating the role of nitric oxide.ConclusionSurgical stress in the small intestine can affect enterocyte mitochondrial structure and function. These damaging effects can be prevented by nitric oxide, an important modulator of cellular function.