bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction
Authors: Farrahi Farinaz , Egbert Barbara M. , Swetter Susan M. 
Published: June 2005

Background: Lentigo maligna (LM) can histologically simulate dysplastic nevus (DN). Partial biopsy of LM may lead to misdiagnosis.Methods: One hundred and fourteen cases of LM and LM melanoma (LMM) were diagnosed at the Veterans Affairs Palo Alto Health Care System (1993–2002). Biopsy and excision specimens for 68in situand 28 invasive melanomas were classified as having predominant classical LM features, predominant DN‐like morphology, or a mixed pattern.Results: Biopsy specimens demonstrated a predominant classical pattern in 38% (25/65) LM and 36% (10/28) LMM, predominant DN‐like features in 43% (28/65) LM and 25% (7/28) LMM, and mixed pattern in 15% (10/65) LM and 29% (8/28) LMM. Most LM and LMM biopsies were partial. Significant DN‐like features were present in 51% LM and 57% LMM excision specimens. Median age was 72 years for LM and 73 years for LMM, mean lesion diameters were 1.3 and 1.7 cm for LM and LMM, respectively, and 85% of LM and 75% of LMM cases were located on heavily sun‐exposed sites.Conclusions: Misdiagnosis of LM or LMM as DN could have devastating results. Large pigmented lesions on sun‐damaged skin in elderly individuals should warrant consideration of LM/LMM diagnosis, even in the setting of DN‐like features histologically. Excisional biopsy may help to avoid misdiagnosis.
Lymphoepithelioma‐like carcinoma of the skin with spindle cell differentiation
Authors: Clarke Loren E. , Ioffreda Michael D. 
Published: June 2005

Background:  Primary cutaneous LELC is a cutaneous neoplasm with histopathologic features identical to those seen in the undifferentiated subtype of nasopharyngeal carcinoma. It is extremely rare, with only approximately 30 cases reported in the literature.Methods:  We report a case of primary cutaneous LELC arising on the forehead of a 72 year‐old male in which a proportion of the neoplastic cells demonstrated distinctive spindle cell morphology.Results:  Microscopic examination showed a dense lymphoplasmacytic infiltrate admixed with large spindle‐shaped cells with vesicular nuclei, prominent nucleoli, and frequent mitotic figures. These cells were negative for an extensive panel of immunohistochemical markers and positive only for broad‐spectrum cytokeratins and epithelial membrane antigen. There was no connection between the tumor and the epidermis and no epidermal dysplasia. In situ hybridization for Epstein‐Barr virus was negative.Conclusions:  The spindle cell differentiation in this case is unusual and suggests that in some cases the differential diagnosis of cutaneous spindle cell neoplasms might include primary cutaneous LELC.
Tectonic modification of the Australian North‐West Shelf: episodic rejuvenation of long‐lived basin divisions
Authors: Harrowfield Mat , Keep Myra 
Published: June 2005

AbstractNeogene collision between Australia and the Banda Arc modified two adjacent depocentres within Australia's North‐West Shelf, the Browse and Bonaparte Basins. We identify two components of this modification: (1) continuous long‐wavelength amplification of Permo‐Carboniferous basement topography, and (2) flexure and normal faulting of Triassic–Recent sedimentary cover. Although this deformation was continuous across the Browse and Bonaparte Basins, the degree of basement architectural control, mechanisms of fault linkage and distribution of syntectonic accommodation space varied significantly between the two basins. These variations reflect fundamental differences in the structural relief, amplitude and depth of rifted basement on either side of a rupture‐barrier‐style accommodation zone, the Browse/Bonaparte Transition. This long‐lived architectural divide, of which there is no discrete structural expression, was amplified by Neogene collision. We examine tectonic rejuvenation of the Browse/Bonaparte Transition and describe a mechanism for actively sustaining long‐lived segmentation of the continental shelf.
Aqueous and petroleum fluid flow associated with sand injectites
Authors: Jonk Rene , Parnell John , Hurst Andrew 
Published: June 2005

AbstractField, petrographic and fluid inclusion characteristics of sand injectites from five outcrop localities and from the subsurface of the Tertiary of the south Viking Graben are described. Although the case studies are from a wide variety of sedimentological, stratigraphic and tectonic settings, and hence their diagenetic evolutions differ significantly, it is possible and useful to assign diagenetic events to three distinct phases of fluid flow associated with sand injectites in sedimentary basins. Firstly, there is fluid flow associated with the injection of the fluid–sediment mix during shallow burial. Early diagenetic imprints in sand injectites reveal that basinal fluids, which may be released during movement along deeper‐seated faults, can be associated with this process and thus the injection process may reveal information on the timing of basin‐scale movement of fluids. Secondly, following the injection process, basinal fluids continue to migrate through uncemented injectites and mix with the ambient meteoric and/or marine pore fluids that invade injectites from the overlying and surrounding host sediments. Early, often pervasive, carbonate cementation is common within sand injectites and rapidly turns sand injectites into flow barriers during shallow (<1 km) burial. If early carbonate cementation is not pervasive, fluid inclusions in late quartz cement (∼>2 km of burial) reveal additional information on fluid flow associated with sand injectites during deeper burial. The latest phase of fluid flow occurs when sand injectites are reactivated as preferential fluid conduits during phases of deformation, when well‐cemented subvertical sand injectites become sites of focussed brittle deformation (fracturing). This study shows that sand injectites are a common and volumetrically important type of structural heterogeneity in sedimentary basins and that long‐lived fluid flow associated with sand injectites in very different settings can be assessed and compared systematically using a combination of petrography and fluid inclusion studies.
Burial and exhumation history of Pennsylvanian strata, central Appalachian basin: an integrated study
Authors: Reed Jason S. , Spotila James A. , Eriksson Kenneth A. , Bodnar Robert J. 
Published: June 2005

AbstractAn inferred burial and exhumation history of Pennsylvanian strata in the central Appalachian foreland basin is constrained by integrating palaeothermometers, geochronometers and estimated palaeogeothermal gradients. Vitrinite reflectance data and fluid inclusion homogenization temperatures indicate that burial of Lower and Upper Pennsylvanian strata of the Appalachian Plateau in West Virginia exceeded ∼4.4 km during the late Permian and occurred at a rate of ∼100 m Myr−1. Exhumation rates of ∼10 m Myr−1 from the late Permian to the early Cretaceous are constrained using maximum burial conditions and published apatite fission track (AFT) ages. AFT and radiogenic helium ages indicate exhumation rates of ∼30–50 m Myr−1 from the early to late Cretaceous. Radiogenic helium dates and present day sampling depths indicate that exhumation rates from the late Cretaceous to present were ∼25 m Myr−1. Exhumation rates for Upper and Lower Pennsylvanian strata within the Appalachian Plateau are remarkably similar. Early slow exhumation was possibly driven primarily by isostatic rebound associated with Triassic rifting. The later, more rapid exhumation can be attributed to thermal expansion followed by lithospheric flexure related to sediment loading along the passive margin.
Susceptibility to infection in patients with neutropenia: the role of the innate immune system
Authors: Neth O. W. , Bajaj‐Elliott M. , Turner M. W. , Klein N. J. 
Published: June 2005

SummaryChemotherapy‐induced neutropenia increases the risk of infection. There appears to be a wide variability in the severity and length of infective episodes. Susceptibility to infections is determined by the underlying malignant disease and its treatment, environmental factors (e.g. nutritional state of the patient and hygiene) and genetically determined variations of the immune system. The majority of primary immunodeficiencies are rare (c. frequency one in 10 000), whereas some genetic polymorphisms in the innate immune system, such as profound mannose‐binding lectin deficiency, are much more common (c. frequency one in 10). Here, we review the potential role of the innate immune system in determining susceptibility to infections in patients with neutropenia.
Psychological complications in sickle cell disease
Authors: Anie Kofi A 
Published: June 2005

SummaryThis review examines the evidence for some of the common psychological complications found across the life span of patients with sickle cell disease (SCD), which are likely to be encountered by haematologists responsible for their medical management. Electronic searches of medical and psychological databases were conducted with a focus on three main areas: psychological coping, quality of life and neuropsychology. Psychological complications were identified in both children and adults with SCD, and included inappropriate pain coping strategies; reduced quality of life owing to restrictions in daily functioning, anxiety and depression; and neurocognitive impairment. There were wide variations in design and consistency of the studies, therefore, some caution needs to be observed in the findings. Moreover, interventional studies were lacking in some areas such as neuropsychology. Utilization of psychological interventions including patient education, cognitive behavioural therapy, and special educational support to help improve the quality of life of patients are recommended.
Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial
Authors: Mitchell C. D. , Richards S. M. , Kinsey S. E. , Lilleyman J. , Vora A. , Eden T. O. B. ,   the Medical Research Council Childhood Leukaemia Working Party
Published: June 2005

SummaryCorticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event‐free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0·0007). Event‐free survival was significantly improved with dexamethasone (84·2% vs. 75·6% at 5 years; P = 0·01), with no evidence of differing effects in any subgroup of patients. The use of 6·5 mg/m2 dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk‐groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.
SHP1 expression in bone marrow biopsies of myelodysplastic syndrome patients: a new prognostic factor
Authors: Mena‐Duran Armando V. , Togo Summanuna H. , Bazhenova Lyudmila , Cervera Jose , Bethel Kelly , Senent Maria L. , Nieva Jorge , Sanz Guillermo F. , Sanz Miguel A. , Saven Alan , Mustelin Tomas 
Published: June 2005

SummaryMyelodysplastic syndrome (MDS) progresses into acute leukaemia with a variable time course. We analysed 45 newly diagnosed patients and found that the expression of the Src homology 2 domain‐containing tyrosine phosphatase 1 (SHP1) had a significant impact on disease severity, progression and overall prognosis. Global or lineage‐specific loss of SHP1 was observed by immunohistochemistry in bone marrow biopsies of MDS patients who progressed rapidly (P = 0·0021) and had shorter survival (P < 0·001). Cox regression analysis demonstrated that SHP1 expression in megakaryocytes had prognostic relevance for time to progression (P = 0·009) and overall survival (P = 0·001).
PAD combination therapy (PS‐341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma
Authors: Oakervee Heather E. , Popat Rakesh , Curry Nicola , Smith Pat , Morris Curly , Drake Mary , Agrawal Samir , Stec Jim , Schenkein David , Esseltine Dixie‐Lee , Cavenagh Jamie D. 
Published: June 2005

SummaryBortezomib (formerly PS‐341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21‐d cycles of PAD, comprising bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1–4, 8–11 and 15–18 during cycle 1 and days 1–4 during cycles 2–4. During days 1–4, patients also received 0, 4·5 or 9 mg/m2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high‐dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention‐to‐treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.
Red cell pyruvate kinase deficiency: 17 new mutations of the PK‐LR gene
Authors: Fermo Elisa , Bianchi Paola , Chiarelli Laurent R. , Cotton Frederic , Vercellati Cristina , Writzl Karin , Baker Kerry , Hann Ian , Rodwell Robin , Valentini Giovanna , Zanella Alberto 
Published: June 2005

SummaryThe PK‐LR gene was studied in 23 patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase (PK) deficiency. Twenty‐seven different mutations were detected among the 42 mutated alleles identified: 19 missense mutations, four splice site mutations and one nonsense, one single base deletion and two large deletions. Seventeen of them (107G, 278T, 403T, 409A, 661A, 859C, 958A, 1094T, 1190T, 1209A, 1232C, 1369G, 507A, IVS9 −1c, IVS9 +43t, del C224, del 5006bp IVS3→ nt 1431) were new. Although all the exons, the flanking regions and the promoter were sequenced in all cases, we failed to detect the second expected mutation in four subjects. To correlate genotype to phenotype, the molecular results were related to the biochemical properties of the mutant enzymes by an analysis of the three‐dimensional structure of erythrocyte PK. The new mutant 409A, found in association with the large deletion of 5006 bp in a newborn baby who died soon after birth, was functionally characterized by mutagenesis and in vitro expression of the protein to investigate its contribution in the severity of the clinical pattern. However, the biochemical data obtained for the mutant enzyme cannot explain the severe anaemia found in the PK‐deficient patient hemizygous for this mutation.
Genetic analysis of the 2q33 region containing CD28–CTLA4–ICOS genes: association with non‐Hodgkin's lymphoma
Authors: Piras G. , Monne M. , Uras A. , Palmas A. , Murineddu M. , Arru L. , Bianchi A. , Calvisi A. , Curreli L. , Gaviano E. , Lai P. , Murgia A. , Latte G. C. , Noli A. , Gabbas A. 
Published: June 2005

SummaryThere is strong evidence that altered immunological function entails an increased risk of lymphoma, although the current knowledge of aetiological factors for lymphomas is limited. The CTLA4 gene encodes a receptor that provides a negative signal to the T‐cell once an immune response is initiated and completed. We analysed the 2q33 chromosomal region harbouring CD28, CTLA4 and ICOS genes, which are closely linked and have related functions in immune regulation, for association in 100 non‐Hodgkin's lymphoma (NHL) patients and in 128 healthy controls; both groups originated from Sardinia. There was a strong association of the CTLA4 49A and the 3′‐untranslated region (AT)82 alleles with NHL [odds ratio (OR) = 2, 95% confidence interval (CI) = 1·2–3·2, and OR = 1·6, 95% CI = 1·1–2·4 respectively]. CTLA4‐318C:49A:(AT)82 was the most represented haplotype in the studied population and was associated with NHL (P = 0·0029, OR = 1·76, 95% CI = 1·2–2·5). Strong linkage disequilibrium was detected between CD28, CTLA4 and ICOS and a ‘common’ haplotype was found very frequently among NHLs. However, no independent association between CD28, ICOS, D2S72 markers and NHL was observed. Our findings enable CTLA4 from adjacent functionally related genes as the true causative risk gene for NHL susceptibility at least in Sardinian patients.
Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study
Authors: Cortelezzi Agostino , Moia Marco , Falanga Anna , Pogliani Enrico M. , Agnelli Giancarlo , Bonizzoni Erminio , Gussoni Gualberto , Barbui Tiziano , Mannucci Pier Mannuccio ,   the CATHEM Study Group
Published: June 2005

SummaryThis prospective, observational and multicentre study assessed the incidence of, and risk factors for, symptomatic venous thrombotic complications after central venous catheter (CVC) positioning in patients with haematological malignancies. A total of 458 consecutive CVC insertions were registered in 416 patients (81·2% of whom had severe thrombocytopenia). Over the observation period (3 months or up to catheter removal), the incidence of events was: CVC‐related deep vein thrombosis (DVT), 1·5%; lower limb DVT, 0·4%; pulmonary embolism (PE), 1·3%; fatal PE, 0·6%; CVC‐related superficial thrombophlebitis, 3·9%; CVC‐occlusion/malfunction of thrombotic origin, 6·1%; major arterial events, 1·1%. Severe bleeding and CVC‐related infections were observed in 3·5% and 4·6% of cases respectively. A composite end point (any venous thromboembolism or superficial thrombophlebitis or CVC occlusion/malfunction) was defined in order to consider venous thrombotic events with a significant impact on clinical practice. With this criterion, the overall incidence was 12·0% (2·54 cases/1000 catheter days). No factor helped to predict venous thrombotic complications: only thrombocytopenia was associated with a weak trend for a reduced risk (odds ratio 0·52; 95% confidence interval 0·26–1·07). No severe bleeding was observed in those patients who received antithrombotic prophylaxis. This study shows that the impact on clinical practice of symptomatic CVC‐related thrombotic complications is not negligible in patients with haematological malignancies.
Outcomes of patients with acute leukaemia who relapsed after reduced‐intensity stem cell transplantation from HLA‐identical or one antigen‐mismatched related donors
Authors: Kobayashi Kazuhiko , Kami Masahiro , Murashige Naoko , Kusumi Eiji , Kishi Yukiko , Hamaki Tamae , Hori Akiko , Matsumura Tomoko , Yuji Koichiro , Masuo Shigeru , Mori Shinichiro , Miyakoshi Shigesaburo , Tanosaki Ryuji , Mitamura Tadayuki , Takaue Yoichi , Taniguchi Shuichi ,   the Tokyo SCT Consortium Institution
Published: June 2005

SummaryThe characteristics of relapse following reduced‐intensity stem‐cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine‐analogue‐based regimens. Their median age was 55 years (range, 29–65 years). Median interval between RIST and relapse was 4·9 months (range, 1·8–24·9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow‐up of 27·6 months (range, 16·0–28·9 months); three in remission and one in relapse. The 2‐year overall survival after relapse was 28·9%. Causes of death in 15 patients included progressive disease (n = 7), graft‐versus‐host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse‐related and non‐relapse‐related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0·017; hazard ratio (HR), 1·16; 95% confidence interval (CI), 1·03–1·32], and ALL as underlying disease (P = 0·011; HR, 10·4; 95% CI, 1·73–62·4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy‐based interventions; however they carry a significant risk of non‐relapse mortality.
Genetic analysis in FXI deficiency: six novel mutations and the use of a polymerase chain reaction‐based test to define a whole gene deletion
Authors: Hill Marian , McLeod Fiona , Franks Hester , Gordon Ben , Dolan Gerry 
Published: June 2005

SummaryThe genetic basis of factor XI (FXI) deficiency was investigated in 30 patients from 13 different families of non‐Jewish origin. Twelve different mutations were detected (including six novel changes), seven missense mutations and three mutations leading to null alleles. Haplotype analysis suggested a large gene deletion in one family. We confirmed the presence of a recently reported Alu‐mediated FXI gene deletion. An unrelated patient with severe deficiency was shown to be compound heterozygous for A412V and this whole gene deletion. We suggest that this recurrent gene deletion should be included in the genetic analysis of FXI deficiency.
Cryoglobulin‐induced cytokine production via FcγRIIa: inverse effects of complement blockade on the production of TNF‐α and IL‐10. Implications for the growth of malignant B‐cell clones
Authors: Mathsson Linda , Tejde Andreas , Carlson Kristina , Höglund Martin , Nilsson Bo , Nilsson‐Ekdahl Kristina , Rönnelid Johan 
Published: June 2005

SummaryMonoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC‐induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or FcγRIIa, FcγRIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme‐linked immunosorbent assay. CG‐induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via FcγRIIa‐ and complement‐dependent mechanisms. Complement blockade resulted in increased IgG CG‐induced interleukin (IL)‐10 production that was inversely correlated with decreased production of tumour necrosis factor‐α. CG‐induced IL‐10 might be a growth factor for malignant B‐lymphocytes in CG‐associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG‐induced cytokine production can be useful for designing treatments for type I CG‐associated pathology in lymphoproliferative diseases.