bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syntectonic subaqueous mass flows of the Neoproterozoic Otavi Group, Namibia: where is the evidence of global glaciation?
Authors: Eyles Nick , Januszczak Nicole 
Published: April 2007

ABSTRACTThe thick (>1 km) Neoproterozoic Otavi Group of Namibia accumulated after ca. 760 Ma along >700 km of the faulted margin of the Congo Craton. The margin shows a north to south, downbasin transition from a shallow‐water carbonate shelf (Otavi Platform) to offshore deepwater slope (Outjo Basin). Within the latter, the Abenab and Tsumeb Subgroups contain large volumes of poorly sorted breccias, conglomerates and diamictites composed principally of locally derived carbonate. Diamictite facies were reported in the 1930s as tillites left by an ice sheet (although the absence of striated clasts and other key glacial indicators was viewed as problematic). Later workers rejected a glacial origin concluding that Outjo basin facies were deposited as parts of prograding submarine wedges built by mass flows during active rifting. Recently, the Snowball Earth hypothesis has returned to the earlier glacial interpretation; arguing that these strata represent a record of extraordinary late Neoproterozoic glacial and interglacial climates when global temperatures fluctuated by up to 100°C. Facies analysis of breccias, diamictites, conglomerates and sandstone strata of the Otavi Group identifies them as genetically related, subaqueously deposited sediment gravity flows. They lack diagnostic indicators of any one specific climate in source areas. These facies were all deposited in deepwater at the foot of landslide‐prone scarp blocks where debris flows and turbidity currents moved large volumes of coarse, freshly broken carbonate debris produced by faulting. Breccias, diamictites, conglomerates and sandstones occur in composite fining‐ and thinning‐upward bundles that are directly analogous to those reported from many other faulted margins in the Phanerozoic stratigraphic record. These rocks provide no clear sedimentological signature of a glacial source or catastrophic Snowball Earth‐type temperature fluctuations. Instead, they point to a dominant tectonic control on sedimentation related to faulting along the margin of the Congo Craton.
World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes
Authors: Bernasconi Paolo , Klersy Catherine , Boni Marina , Cavigliano Paola M. , Calatroni Silvia , Giardini Ilaria , Rocca Barbara , Zappatore Rita , Caresana Marilena , Dambruoso Irene , Lazzarino Mario , Bernasconi Carlo 
Published: April 2007

SummaryThis study correlated chromosomal defects with French–American–British (FAB)/World Health Organization (WHO) classification subtypes, proposed a revised International Prognostic Scoring System (IPSS) cytogenetic grouping; and established which classification, when used with the IPSS cytogenetic categories, best predicted clinical outcome in the myelodysplastic syndromes (MDS). A higher prevalence of chromosomal defects and distinct defects were observed in patients with multi‐lineage dysplasia and a blast cell percentage >10%. Abnormalities of the long arm of chromosome 3, del(7)(q31q35), trisomy 8, del(11)(q14q23), del(12p) and 20q‐ could be segregated from their respective IPSS cytogenetic categories and used to develop new cytogenetic subgroups. Clinical parameters, FAB/WHO classification, IPSS score and standard or revised cytogenetic categories were statistically relevant for overall survival (OS) and progression‐free intervals (PFI) and were included within five distinct multivariate models compared by the Akaike Information Criterion. To predict OS, the best models included age, WHO classification and standard or revised IPSS cytogenetic categories; to predict PFI, the best model included the same variables and revised cytogenetic categories. In conclusion, (i) the WHO classification was associated with a more homogeneous cytogenetic pattern than the FAB classification, (ii) WHO classification and standard/revised IPSS cytogenetic categories were much more effective than IPSS for predicting MDS clinical outcome, (iii) revised cytogenetic subgroups predicted PFI more effectively than standard categories.
Stage I/II follicular lymphoma: spread of bcl‐2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy
Authors: Pulsoni Alessandro , Starza Irene Della , Frattarelli Natalia , Ghia Emanuela , Carlotti Emanuela , Cavalieri Elena , Matturro Angela , Tempera Settimio , Rambaldi Alessandro , Foà Robin 
Published: April 2007

SummaryStage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl‐2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66·6%). After treatment, in 9/15 Bcl‐2/IgH positive evaluable patients, a disappearance of Bcl‐2/IgH+ cells was observed, which persisted after a median follow‐up of 43·5 months (range 11–70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl‐2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl‐2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl‐2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR.
Vaccination with autologous non‐irradiated dendritic cells in patients with bcr/abl+ chronic myeloid leukaemia
Authors: Westermann Jörg , Kopp Joachim , Van Lessen Antje , Hecker Ann‐Christine , Baskaynak Gökben , Le Coutre Philipp , Döhner Konstanze , Döhner Hartmut , Dörken Bernd , Pezzutto Antonio 
Published: April 2007

SummaryIn chronic myeloid leukaemia (CML), dendritic cells (DC) and leukaemic cells share a common progeny, leading to constitutive expression of putative tumour antigens, such as bcr/abl, in DC. In this phase‐I/II study, autologous DC were used as a vaccine in patients with chronic phase bcr/abl+ CML, who had not achieved an adequate cytogenetic response after treatment with α‐interferon or imatinib. Ten patients were enrolled, DC were generated from peripheral blood monocytes and vaccination consisted of four subcutaneous injections of increasing numbers of DC (1–50 × 106 cells per injection) on days 1, 2, 8 and 21. Vaccination was feasible and safe. Improvement of the cytogenetic/molecular response, as detected by fluorescence in situ hybridization of peripheral blood mononuclear cells (PBMC), was possibly related to vaccination in four of 10 patients. In three of these patients, T cells recognizing leukaemia‐associated antigens became detectable. The proliferative capacity of PBMC in response to autologous DC increased after vaccination in all evaluable patients. We conclude that vaccination with autologous, non‐irradiated ‘leukaemic’ DC is feasible, safe and induces anti‐leukaemic T‐cell responses in some CML patients. DC vaccination might be useful in CML as postremission therapy, i.e. after treatment with tyrosine kinase inhibitors.
Establishment of a novel childhood acute myeloid leukaemia cell line, KOPM‐88, containing partial tandem duplication of the MLL gene and an in vivo model for childhood acute myeloid leukaemia using NOD/SCID mice
Authors: Hayashi Mutsumi , Kondoh Kensuke , Nakata Yuji , Kinoshita Akitoshi , Mori Taijiro , Takahashi Takao , Sakamoto Michi‐ie , Yamada Taketo 
Published: April 2007

Summary MLL gene rearrangement is common in both adult and childhood acute myeloid leukaemia (AML), and its role in oncogenesis has been investigated. While over 50 translocated‐partner genes have been identified so far, few studies have detailed the molecular mechanism of partial tandem duplication (PTD) of the MLL gene. The prognostic impact and contribution to leukaemogenesis of MLL‐PTD, especially in childhood cases, remain unknown. We have established a novel cell line containing MLL‐PTD derived from an 11‐year‐old patient with AML and designated as KOPM‐88. KOPM‐88 cells exhibited certain characteristics associated with the myeloid lineage including abundant primary granules in the cytoplasm and the expression of myeloperoxidase. The cell growth of KOPM‐88 was cytokine independent but was accelerated by granulocyte colony‐stimulating factor and granulocyte‐macrophage colony‐stimulating factor. MLL‐PTD of exon 2 to exon 6 and exon 2 to exon 8 was revealed using Southern blotting, fluorescence in situ hybridisation, and reverse transcription polymerase chain reaction/DNA sequencing. Furthermore, non‐obese diabetic/severe combined immunodeficient mice inoculated with KOPM‐88 cells exhibited leukaemic infiltrations in the bone marrow and hemiparalysis because of compression myelopathy. This is the first report of an in vivo animal model exhibiting the systemic involvement of childhood AML containing MLL‐PTD. KOPM‐88 cells and our murine model may be useful for investigating the pathogenesis of childhood AML associated with MLL gene rearrangement.
Genetic polymorphisms associated with priapism in sickle cell disease
Authors: Elliott Laine , Ashley‐Koch Allison E. , Castro Laura De , Jonassaint Jude , Price Jennifer , Ataga Kenneth I. , Levesque Marc C. , Brice Weinberg J. , Eckman James R. , Orringer Eugene P. , Vance Jeffery M. , Telen Marilyn J. 
Published: April 2007

SummaryPriapism occurs in 30–45% of male patients with sickle cell disease (SCD), but the possible influence of genetic risk factors on the incidence of priapism is not well understood. We examined genetic polymorphisms in 199 unrelated, adult (>18 years), male patients with Hb SS and Hb Sβ0‐thalassaemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation and cell signalling. Additionally, we examined genes involved in nitric oxide biology (NOS2, NOS3, SLC4A1), as well as polymorphisms in the klotho (KL) gene, which has previously been associated with priapism. Strong evidence of association was found for single nucleotide polymorphisms in transforming growth factor‐β receptor, type III (TGFBR3) (rs7526590; P = 0·00058), aquaporin (AQP1) (rs10244884; P = 0·00068), integrin αv (ITGAV) (rs3768780; P = 0·00090), and the A1 subunit of coagulation factor XIII (F13A1) (hcv1860621; P = 0·00156). Associations with TGFBR3, AQP1, and ITGAV remained significant after adjusting for multiple testing, using the Benjamini–Hochberg procedure. Our data suggest that genes involved in the TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.
The expression of the novel cytotoxic protein granzyme M by large granular lymphocytic leukaemias of both T‐cell and NK‐cell lineage: an unexpected finding with implications regarding the pathobiology of these disorders
Authors: Morice William G. , Jevremovic Dragan , Hanson Curtis A. 
Published: April 2007

SummaryGranzyme M (GrM) is a novel cytotoxic protein normally exclusively expressed by natural killer (NK)‐cells and cytotoxic T‐cells with innate immune function. As most T‐cell granular lymphocytic leukaemias (T‐LGL) are thought to be derived from the adaptive immune system it was predicted that T‐LGL would be GrM negative. Contrary to this hypothesis, bone marrow biopsy immunohistochemistry revealed that GrM was frequently expressed in both T‐LGL (16 / 18) and NK‐LGL (6 / 9). These unexpected results suggest commonality between T‐ and NK‐LGL, providing further support to the notion that T‐LGL is a disorder of dysregulated, chronically stimulated, adaptive cytotoxic T‐cells.
Anaemia characterises patients with myelofibrosis harbouring MplW515L/K mutation
Authors: Guglielmelli Paola , Pancrazzi Alessandro , Bergamaschi Gaetano , Rosti Vittorio , Villani Laura , Antonioli Elisabetta , Bosi Alberto , Barosi Giovanni , Vannucchi Alessandro M. ,   for the GIMEMA‐Italian Registry of Myelofibrosis and the MPD Research Consortium, Chicago, IL, USA
Published: April 2007

SummaryThe clinical and haematological phenotype of patients with myelofibrosis harbouring MPLW515L/K mutation has not been thoroughly investigated. Of 217 myelofibrosis subjects, 18 (8·2%) had an MPL mutation, four of which (22%) co‐existed with JAK2V617F mutation. When compared with MPL wild‐type patients, irrespective of JAK2V617F status, those with MPLW515L/K, were more frequently female, were older (61 years vs. 57 years; P = 0·02), presented with more severe anaemia (haemoglobin, 101 g/l vs. 121 g/l; P = 0·002) and were more likely to require regular transfusional support (P = 0·012). These data indicate that MPL mutation in myelofibrosis characterises patients with more severe anaemic phenotype.
Benign cortisol‐secreting adrenocortical adenomas produce small amounts of androgens
Authors: Kamenicky Peter , Houdoin Laurence , Ferlicot Sophie , Salenave Sylvie , Brailly Sylvie , Droupy Stéphane , Meduri Geri , Sasano Hironobu , Suzuki Takashi , Young Jacques , Chanson Philippe 
Published: April 2007

SummaryBackground  Serum androgen levels are below normal in patients with benign cortisol‐secreting adrenocortical adenomas, owing to ACTH suppression. Associated androgen secretion is usually considered as indicative of malignancy. The objective of the study was to analyse the androgen‐producing ability of cortisol‐secreting adrenocortical adenomas.Design  Retrospective data collection in a single referral hospital centre.Methods  Dehydroepiandrosterone sulfate (DHEAS), Δ4androstenedione and testosterone concentrations were measured before and after adrenalectomy and then at 6‐month intervals in 20 women (eight cortisol‐secreting adrenocortical adenomas, six subclinical cortisol‐secreting adrenocortical adenomas, and six nonfunctional adenomas).Results  Before adrenalectomy, serum androgen concentrations were measurable in all women with clinically apparent and subclinical cortisol‐secreting adrenocortical adenomas. DHEAS levels were either at the lower end of the normal range or below normal, but were always clearly detectable. Postoperatively, during adrenocortical insufficiency, DHEAS, Δ4androstenedione and testosterone concentrations fell to near the detection limit in all patients with cortisol‐secreting adrenocortical adenomas (P = 0·008 for each marker) and showed a similar tendency to fall in all patients with subclinical cortisol‐secreting adrenocortical adenomas. Pre‐ and post‐treatment androgen concentrations did not differ in patients with nonfunctional adenomas. Immunohistochemical analysis confirmed CYP17, HSD3B2, SULT2A1 and CYB5 expression by all cortisol‐producing tumours. The intensity of CYP17 and SULT2A1 expression was stronger in cortisol‐secreting adenomas than in their adjacent normal adrenal tissue.Conclusion  Both clinically apparent and subclinical cortisol‐secreting adrenocortical adenomas appear to show moderate autonomous androgen production. Thus, weak androgen secretion in patients with adrenocortical tumours should not necessarily be considered as a sign of malignancy.
Oxytocin is not important for the control of gonadotrophin secretion in the late follicular phase of the cycle
Authors: Vanakara P. , Dafopoulos K. , Papastergiopoulou L. , Kallitsaris A. , Papageorgiou I. , Messinis I. E. 
Published: April 2007

SummaryObjective  To study the role of oxytocin in basal and GnRH‐induced gonadotrophin secretion in normal women.Design  Normal women were studied in three cycles. When the diameter of the leading follicle was 15–16 mm, the women were infused intravenously (i.v.) for 3 h with normal saline (cycle 1), atosiban (cycle 2) or oxytocin (cycle 3).Patients  The study included 12 normally cycling women aged 23–38 years.Measurements  After cessation of treatment, two injections of GnRH, 10 µg each, were administered i.v. 2 h apart and blood samples were collected every 30 min for a total of 240 min. The 30‐min pituitary response (sensitivity) to a single GnRH injection (10 µg i.v.) was investigated thereafter every 12 h from the end of the 3‐h infusion until the day of LH surge onset.Results  No significant differences in LH and FSH response to GnRH (sensitivity and reserve) during the 240‐min experiment were found between the three cycles. The time of LH surge onset from the initiation of the infusion was similar in the three cycles. Also similar in the three cycles were oestradiol (E2) and gonadotrophin levels as well as the 30‐min response to GnRH for 48 h following the 3‐h infusion.Conclusions  The present study demonstrates that neither exogenous oxytocin administration nor blockage of endogenous oxytocin action influences pituitary sensitivity to GnRH in cycling women.
Differential inflammatory mediator response in vitro from murine macrophages to lactobacilli and pathogenic intestinal bacteria
Authors: Marcinkiewicz J. , Ciszek M. , Bobek M. , Strus M. , Heczko P. B. , Kurnyta M. , Biedroń R. , Chmielarczyk A. 
Published: April 2007

SummaryChronic active colitis (including inflammatory bowel disease – IBD) is maintained by a variety of pro‐inflammatory mediators. Certain intestinal bacterial strains may induce colitis, whereas some strains (e.g. Lactobacillus spp.) show a protective effect in colitis owing to their anti‐inflammatory activity. In this study, we have examined the production of selected inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO) and the expression of haeme oxygenase‐1 (HO‐1) by murine peritoneal macrophages stimulated in vitro by the intestinal bacterial strains, isolated from mice with colitis. Lactobacillus strains (Lactobacillus reuteri, L. johnsonii, L. animalis/murinus) and two potentially pathogenic bacteria (Escherichia coli and Enterococcus faecalis) induced the production of substantial amounts of cytokines with a strain specific profile. Despite some interstrain differences, all lactobacilli induced production of anti‐inflammatory cytokines (IL‐10high, IL‐6low, IL‐12p70low). Conversely, E. faecalis and E. coli induced the production of proinflammatory cytokines (TNF‐α, IL‐12p70), the cytokines essential for chronic IBD. Macrophages released comparably substantial amounts of ROS in response to all Lactobacillus strains tested, while E. coli and E. faecalis ability to induce generation of ROS was negligible. In contrast to ROS, the production of NO/NO2− by macrophages activated with all bacterial strains tested was similar. Moreover, for the first time, it has been shown that intestinal bacteria differed in their ability to induce expression of HO‐1, a stress‐inducible enzyme with antioxidant and anti‐inflammatory properties. The beneficial immunoregulatory properties of candidate probiotic bacteria for the treatment of IBD are discussed.
The role and potential contribution of clinical research nurses to clinical trials
Authors: Spilsbury Karen , Petherick Emily , Cullum Nicky , Nelson Andrea , Nixon Jane , Mason Su 
Published: April 2007

Aims and objectives.  This study explores the scope and potential contribution of the Clinical Research Nurse (CRN) role to clinical trials of a nursing‐specific topic.Background.  Over the past two decades, there have been increases in the numbers of nurses working as CRNs because of the increasing global demand for clinical trials. CRNs can influence the quality of clinical trials but the scope and contribution of the role to clinical trials is not known.Design.  Qualitative focus group study.Methods.  A focus group interview was carried out with CRNs (n = 9) employed on a large, multi‐centre (six NHS Trusts) randomized controlled trial of pressure area care. The focus group interview was recorded, alongside field notes of participant interactions and behaviours, and transcribed verbatim. Data were analysed for thematic content and process.Findings.  CRNs described their transition to a clinical research role. They reported a lack of confidence, role conflict as researcher and nurse, the challenges of gaining cooperation of clinical nursing staff to comply with trial protocols and difficulties maintaining their own motivation. CRNs provided their perceptions and observations of pressure area care and prevention. They identified areas of inadequate treatment, management and care, influenced by organizational and clinical aspects of care delivery.Conclusions.  The study reveals challenges associated with training and management of CRNs. CRNs are usually associated with trial recruitment and data collection. This study highlights the additional contributions of CRNs for the study of topics specific to nursing as the result of their unique placement in the research centres as informal ‘participant observers.’ Such observations enhance understanding of the contexts being studied.Relevance to clinical practice.  These findings are relevant to the design and conduct of research studies of nursing care and practice and present ways for investigators to optimize the skills and knowledge of nurses working as CRNs.
Splanchnic blood flow and oxygen consumption: effects of enteral nutrition and dopexamine in the elderly cardiac surgery patient
Authors: Rapp‐Kesek D. , Joachimsson P.‐O. , Karlsson T. 
Published: April 2007

Background:  After cardiac surgery, patients are at risk of organ dysfunction because of decreased perfusion. Different measures have been used to increase the splanchnic blood flow. We compared the effects of enteral nutrition and dopexamine on the cardiac output, splanchnic blood flow and oxygen consumption.Methods:  Sixteen patients undergoing cardiac surgery were included. Indocyanine green extraction and thermodilution were used for repeated measurements of the splanchnic blood flow and cardiac output. On the first post‐operative day, indocyanine green infusion was started. Patients were randomized to start with dopexamine (Dpx group) or enteral nutrition (EN group). After 180 min, both groups received a combination of dopexamine and enteral nutrition. Blood gases from the hepatic vein and pulmonary and radial arteries were analysed repeatedly.Results:  In the Dpx group, the cardiac index increased with dopexamine infusion, but not when enteral nutrition was added. In the EN group, enteral nutrition alone did not increase the cardiac index, but dopexamine addition increased the cardiac index in this group. The splanchnic blood flow increased initially in the Dpx group, but then returned to baseline and remained constant on addition of enteral nutrition. In the EN group, the splanchnic blood flow initially remained at baseline, but increased after dopexamine addition. There was no difference between the groups with regard to systemic or splanchnic oxygen consumption or the oxygen extraction ratio. In the Dpx group, lactate increased from baseline with no further increase on addition of enteral nutrition. Lactate was unchanged in the EN group.Conclusions:  Dopexamine and enteral nutrition caused no adverse effects on oxygen consumption or the oxygen extraction ratio. Enteral nutrition did not increase the splanchnic blood flow or cardiac index. Dopexamine increased the systemic blood flow with only a transient effect on the splanchnic blood flow. Dopexamine increased the lactate concentration, possibly indicating a more ischaemic condition.