bluuebunny/crossref_metadata_2025 huggingface dataset:
Classical and molecular cytogenetic abnormalities and outcome of childhood acute myeloid leukaemia: report from a referral centre in Israel
Authors: Stark Batia , Jeison Marta , Gabay Leticia Glazer , Mardoukh Jacques , Luria Drorit , Bar‐Am Irit , Avrahami Gali , Kapeliushnik Yossef , Sthoeger Dalia , Herzel Gavriel , Steinberg David M. , Cohen Ian J. , Goshen Yacov , Stein Jerry , Zaizov Rina , Yaniv Isaac
Published: July 2004

The incidence of cytogenetic abnormalities in childhoodde novoacute myeloid leukaemia (AML) and its prognostic significance was assessed in an Israeli paediatric referral centre. Cytogenetic analysis was successful in 86 of 97 children (<20 years of age) diagnosed between 1988 and 2002 withde novoAML. Fluorescencein situhybridization analysis detected new information in 11 of them, leading to reassignment in cytogenetic group classification. The incidence of the various cytogenetic subgroups was as follows: normal – 9%; t(11q23) – 22%; t(8;21) – 13%; t(15;17) – 8%; inv(16) – 3·4%; abn(3q) – 4·6%; 7/7q‐(sole or main) – 5·8%; del(9q)(sole) and +21(sole) – 4·6% each; t(8;16) – 2·3%; t(6;9), t(1;22), +8(sole) – 1·1% each; and miscellaneous – 18%. The overall survival (OS) and event‐free survival (EFS) (4 years) for 94 patients treated with the modified Berlin‐Frankfürt‐Münster (BFM) AML protocols (non‐irradiated) were 59·9% (SE = 5%) and 55·7% (SE = 5%), respectively, and for the favourable t(8;21), t(15;17) and inv(16), OS was 60% (SE = 15%), 83% (SE = 15%) and 100% respectively. For the normal group it was 62% (SE = 17%), miscellaneous 64% (SE = 12%), t(11q23) 44·6% (SE = 11%) and of the −7/7q‐, del(9q)(sole) or t(6;9), none had survived at 4 years. The incidence of cytogenetic subgroups in the Israeli childhood AML population and their outcome were similar to other recently reported paediatric series. Cytogenetic abnormalities still carry clinical relevance for treatment stratification in the context of modern chemotherapy.
Functional analysis of apoptosis induction in acute myeloid leukaemia‐relevance of karyotype and clinical treatment response
Authors: Braess Jan , Schneiderat Peter , Schoch Claudia , Fiegl Michael , Lorenz Isolde , Hiddemann Wolfgang
Published: July 2004

Deficiencies or structural defects of the apoptotic machinery have been postulated as a potential mechanism for a broad resistance of acute myeloid leukaemia (AML) blasts towards cytotoxic therapy comprising chemotherapeutic agents with diverse pharmacodynamic principles but also cell‐mediated cytotoxicity of the graft‐versus‐leukaemia effect, for example, in the setting of allogeneic transplantation. This hypothesis was systematically tested by functionally analysing the early, intermediate and late events of the apoptotic process in primary AML (n = 31) blasts following activation of the intrinsic and extrinsic pathway of apoptosis (etoposide and cytarabine as DNA damaging agents, FAS‐ligand as an activator of the death receptor pathway). Activation of the extrinsic pathway by FAS‐ligand did not induce apoptosis in primary AML, instead the proapoptotic signal was shown to ‘fade’, even in the early phase of the apoptotic sequence. However, activation of the intrinsic pathway induced severe cytotoxicity in all samples that showed the characteristic features of typical apoptosis, with a prominent apoptotic volume decrease (blebbing) in the early phase, significant increases in caspase 3 activity (intermediate or effector phase) and breakdown of cellular energy production in the late phase of apoptosis. These characteristics did not differ between prognostically favourable versus unfavourable AML karyotypes or between clinically responding versus refractory AML – indicating that a functional apoptotic apparatus is present even in the unfavourable AML subgroups . Our data indicate that the mechanism for a broad clinical resistance is not a dysfunctional apparatus per se but rather the consequence of anti‐apoptotic regulation impeding otherwise functional apoptotic machinery.
Haploidentical donor T cells fail to facilitate engraftment but lessen the immune response of host T cells in murine fetal transplantation
Authors: Chen Jeng‐Chang , Chang Ming‐Ling , Lee Hanmin , Muench Marcus O.
Published: July 2004

The effects of donor T cells, or their CD8+ subset, on engraftment and tolerance induction in fetal transplantation were evaluated using an F1‐into‐parent mouse‐model that does not permit a graft‐versus‐host effect. Gestational day 13 C57BL/6 (H‐2Kb) fetuses were transplanted with B6D2F1 (H‐2Kb/d) light density bone marrow cells (LDBMC) containing 1–2% T cells, T‐cell depleted bone marrow cells (TDBMC, <0·1% T cells), or TDBMC with enriched CD8+ T cells (CD8). Chimaerism levels in the peripheral blood, spleen and bone marrow were usually below 0·2% in all groups, indicating that T cells do not improve engraftment without a graft‐versus‐host effect. A significant, but transient, wave of donor cells was seen in the peripheral blood at 1 month of age in the CD8 and LDBMC groups. Relatively high levels of chimaerism (<17%) were sometimes detected in the peritoneal cavities of recipients. T‐cell tolerance specific to donor cells was evaluated in mixed lymphocyte cultures. The CD8 and LDBMC groups had significantly lower T‐cell responses than untransplanted controls. These findings indicate that in utero transplantation of haploidentical donor CD8+ or CD3+ cells can help to lessen the immune response of host T cells towards donor cells. The persistence of donor cells in the peritoneal cavity also correlated with tolerance induction.
Evidence of parvovirus B19 infection in patients of pre‐eclampsia and eclampsia with dyserythropoietic anaemia
Authors: Yeh Su‐Peng , Chiu Chang‐Fang , Lee Chien‐Chung , Peng Ching‐Tien , Kuan Chih‐Yu , Chow Kuan‐Chih
Published: July 2004

Parvovirus B19 (PVB19) infection can induce transient anaemia in patients with increased erythropoiesis. However, the dynamic change within the bone marrow after PVB19 infection is not well understood. Increased erythropoiesis is a physiological phenomenon in puerperital women. Nevertheless, anaemia as a result of PVB19 infection in puerperital women has never been reported. We report one patient with eclampsia and two patients with pre‐eclampsia who had transient, severe anaemia during the puerperital period because of PVB19 infection. Viral genomes were detected in the peripheral blood during the anaemic period by polymerase chain reaction and became undetectable after the anaemia was resolved. Viral genomes and protein could also be detected in bone marrow by in situ hybridization and immunohistochemical staining, respectively. Serial aspiration cytology of bone marrow showed severe dysplastic change involving erythroid precursors with a few apoptotic cells at the initial onset of anaemia, markedly increased apoptotic cells that was confirmed by the increased expression of activated caspase 3, around the nadir of anaemia, and a normal marrow picture without features of apoptosis after recovery from anaemia. Our data indicates that PVB19 infection can induce transient, severe dyserythropoietic anaemia in puerperital women with pre‐eclampsia/eclampsia and the pathogenetic mechanism may probably involve the induction of apoptosis following PVB19 infection.
Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE
Authors: Frazer David M , Wilkins Sarah J , Millard Kirstin N , McKie Andrew T , Vulpe Christopher D , Anderson Gregory J
Published: July 2004

The effect of HFE inactivation on iron homeostasis during an acute phase response was investigated in mice. HFE knockout, β2‐microglobulin knockout and C57BL/6J mice were injected with Freund's Complete Adjuvant to induce an acute phase response and hepatic hepcidin expression and serum transferrin saturation was determined 16 h later. Hepcidin mRNA increased in all strains in response to an acute phase stimulus when compared with untreated control animals. Hypoferraemia also occurred in all strains, indicating that both the upregulation of hepcidin and the decrease in transferrin saturation associated with an acute phase response is not dependent on HFE function.
Aberrant expression of β‐catenin discriminates acute myeloid leukaemia from acute lymphoblastic leukaemia
Authors: Serinsöz Ebru , Neusch Michael , Büsche Guntram , von Wasielewski Reinhard , Kreipe Hans , Bock Oliver
Published: July 2004

The role of β‐catenin in epithelial neoplasms has been widely studied whereas current knowledge regarding β‐catenin gene and protein expression in bone marrow cells derived from normal haematopoiesis and clonal haematological disorders is lacking. β‐Catenin gene expression was quantitatively investigated in bone marrow cells derived from clonal haematological disorders [acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Philadelphia chromosome‐positive chronic myeloid leukaemia (Ph+ CML], Ph− myeloproliferative disorders, n = 96) compared with non‐neoplastic haematopoiesis (n = 33) by real‐time reverse transcription polymerase chain reaction. Cellular localization of β‐catenin protein was detected by immunocytochemistry. β‐Catenin gene expression was significantly increased in AML compared with ALL cases (P < 0·0001), Ph+ CML (P < 0·0001) and non‐neoplastic haematopoiesis (P = 0·019). Immunocytochemistry revealed that, in non‐neoplastic haematopoiesis, the granulopoietic lineage as well as megakaryocytes showed membranous and cytoplasmic staining to various degrees along with unlabelled nuclei. Besides haematopoiesis, β‐catenin prominently marked bone marrow vascularity and diverse stroma cells. β‐Catenin gene was inversely expressed in AML and ALL with a lack of protein expression in neoplastic cells in ALL. In contrast, the other haematological disorders under study, except for Ph+ CML, did not show significant alterations of overall β‐catenin gene expression compared with normal bone marrow. These data suggest different regulatory mechanisms in the expression and function of β‐catenin in haematopoietic cells.
Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form
Authors: Khaiboullina Svetlana F. , Maciejewski Jaroslaw P. , Crapnell Kirsten , Spallone Patricia A. , Dean Stock A. , Pari Gregory S. , Zanjani Esmail D. , Jeor Stephen St
Published: July 2004

CD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro‐infected and latently‐infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV‐infected cells was lower in naturally‐infected cells than in in vitro‐infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte‐macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently‐infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently‐infected cells.
Disturbed flow promotes deposition of leucocytes from flowing whole blood in a model of a damaged vessel wall
Authors: Skilbeck Christopher A. , Walker Peter G. , David Tim , Nash Gerard B.
Published: July 2004

Departure from simple laminar flow in arteries may promote the local attachment of leucocytes either to intact endothelium or platelet thrombi. We perfused blood through a chamber with a backward facing step, to observe whether adhesion from whole blood to P‐selectin was indeed localized to a region of recirculating flow, and whether platelets binding to collagen in such a region could capture leucocytes. Blood flowing over the step established a stable vortex, a reattachment point where forward and backward flow separated, and a simple laminar flow with wall shear rate c. 400/s further downstream. Fluorescently labelled leucocytes were observed to attach to P‐selectin immediately upstream or downstream of the reattachment point, and to roll back towards the step or away from it, respectively. There was negligible adhesion further downstream. When a P‐selectin‐Fc chimaera was used to coat the chamber, stable attachment occurred, again preferentially in the disturbed flow region. Numerous platelets adhered to a collagen coating throughout the chamber, although there were local maxima either side of the reattachment point. The adherent platelets captured flowing leucocytes in these regions alone. Leucocytes may adhere from flowing blood in vessels with high shear rate if the flow is disturbed. While platelets can adhere over a wider range of shear rates, their ability to capture leucocytes may be restricted to regions of disturbed flow.
HDL metabolic activities in a boy with lipoprotein lipase deficiency and his family
Authors: Brites F. , Verona J. , Fernández K. , Henriksen F. , Fruchart J. , Cesar M. , Castro G. , Wikinski R.
Published: July 2004

Background Lipoprotein lipase (LPL) deficiency is a rare autosomal recessively inherited disease characterized by elevated triglyceride, low total cholesterol and quantitative and qualitative alterations of high‐density lipoprotein (HDL). The aim of the present study was to explore HDL metabolic activities in a patient with LPL deficiency and in his family (n = 11).

Materials and methods Subjects were divided into four groups: proband (Ser447Stop/Arg170Leu carrier), Ser447Stop carriers, Arg170Leu carriers and silent mutation/wild‐type carriers (controls). Cholesterol efflux from Fu5AH cells, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), paraoxonase 1 (PON1) and platelet‐activating factor acetylhydrolase (PAF‐AH) activities were evaluated.

Results Comparison between the proband and the control group revealed that the boy had significantly reduced cholesterol efflux (P < 0·001), conserved LCAT activity (P > 0·05) and increased CETP activity (P < 0·001). As regards antioxidant enzymes, while PON1 activity was higher in the proband than in the controls (P < 0·0001), PAF‐AH activity was reduced (P < 0·05). The other groups did not show relevant differences in comparison with controls.

Conclusions The presence of one mutation was not enough to introduce important modifications in HDL functions. Markedly reduced HDL levels can keep certain normal enzymatic activities, which probably tend to counteract the deleterious effects of LPL deficiency.
Selenium supplementation decreases nuclear factor‐kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients
Authors: Faure P. , Ramon O. , Favier A. , Halimi S.
Published: July 2004

Objective  The role of selenium in preventing cardiovascular diseases has been largely described. Oxidative stress and the subsequent activation of nuclear factor‐kappa B (NF‐κB) have been linked to the development of vascular complications. We investigated the effects of selenium supplementation in type 2 diabetic patients on several oxidative stress parameters and NF‐κB activity.

Methods  We enrolled 56 type 2 diabetic patients with similar glycaemic control: 21 were supplemented by selenium (960 µg d−1, 3 months) and 27 received a placebo, and 10 nondiabetic subjects formed the control group. To determine NF‐κB activation, we used an electrophoretic mobility shift assay followed by a semi‐quantitative determination of NF‐κB in peripheral blood mononuclear cells.

Results  Selenium treatment resulted in a significant increase in plasma selenium and red‐cell Se GSH px activity. It had no effect on lipid peroxidation measured by malone‐dialdehyde (MDA) or on red‐cell Cu/Zn SOD. NF‐κB activity was increased by 80% in diabetic patients. In patients receiving selenium supplementation, selenium NF‐κB activity was significantly reduced, reaching the same level as the nondiabetic control group.

Conclusion  In type 2 diabetic patients, activation of NF‐κB measured in peripheral blood monocytes can be reduced by selenium supplementation, confirming its importance in the prevention of cardiovascular diseases.
Cholecystokinin‐1 receptor protein up‐regulation during pancreatic regeneration after acute haemorrhagic pancreatitis in rats
Authors: Yoshikawa H. , Nakamura H. , Tashiro M. , Yamaguchi T. , Taguchi M. , Fukumitsu K. , Otsuki M.
Published: July 2004

Background  Cholecystokinin (CCK) plays an important role in regeneration after acute pancreatitis in rats. The present study was aimed to elucidate the role of CCK‐1 receptor (CCK‐1R) in acute pancreatitis. We investigated the serial changes in CCK‐1R mRNA and protein levels and their immunolocalization after acute haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal infusion of 4% sodium taurocholate (100 µL 100 g−1 body weight).

Methods  Histological changes were evaluated by haematoxylin and eosin staining. Pancreatic CCK‐1R mRNA was determined by Northern blot analysis. Pancreatic CCK‐1R protein was evaluated by immunoblot analysis and immunohistochemistry with a polyclonal antibody against rat CCK‐1R protein.

Results  Histological findings revealed that newly formed acinar cells were detected at the periphery of tubular complexes on day 14, and normal architecture of lobules was observed focally on day 21. Pancreatic CCK‐1R mRNA peaked on day 3 and thereafter gradually decreased. Cholecystokinin‐1R protein rapidly increased after induction of pancreatitits, reaching a maximal level on day 3. On day 3, intense immunoreactivity for CCK‐1R protein was observed in both the cytoplasm of vacuolized acinar cells and the tubular complexes. In the regenerative process after acute haemorrhagic pancreatitis in rats, the expression of pancreatic CCK‐1R mRNA and protein increased, and intense immunoreactivity for CCK‐1R protein was observed in tubular complexes in the cytoplasm of regenerated acinar cells.

Conclusion  These results suggest that CCK‐1R contributes to pancreatic regeneration after acute haemorrhagic pancreatitis and that tubular complexes are involved in the process of acinar cell regeneration following pancreatic injury.
Effects of low‐dose dopamine on ventilation in patients with chronic obstructive pulmonary disease
Authors: Ciarka A. , Rimacchi R. , Vincent J.‐L. , Velez‐Roa S. , Dumonceaux M. , Leeman M. , Van De Borne P.
Published: July 2004

Background  Dopamine plays an important role in the regulation of respiration and low‐dose dopamine infusion is associated with a decreased respiratory drive response to hypoxia in animals and humans. The effects of dopamine on ventilation in patients with chronic obstructive pulmonary disease (COPD) is unknown. We tested the hypothesis that dopamine inhibits ventilation in patients with COPD.

Materials and methods  In a double‐blinded, cross‐over, placebo‐controlled, randomized study we studied nine patients with decompensated COPD, ventilated in the pressure support mode in the intensive care unit (ICU) and five ambulatory patients with stable COPD. All patients received 5 µg kg−1 min−1 of dopamine or an equivalent volume of 5% glucose solution.

Results  In the mechanically ventilated COPD patients, there was no difference in the effects of dopamine compared with placebo on blood pressure, heart rate, minute ventilation (−0·5 ± 1·1 vs. −0·2 ± 0·9 L min−1, P = 0·46, respectively), respiratory rate (−0·4 ± 2·7 vs. −0·3 ± 2·1 min−1, P = 0·96), PaO2 (−5 ± 4 vs. −5 ± 10 mmHg, P = 0·90, respectively), or PaCO2 (−0·7 ± 1·4 vs. −1·0 ± 3·4 mmHg, P = 0·83, respectively). In spontaneously breathing stable patients, dopamine increased systolic blood pressure (P = 0·02) but did not influence other haemodynamic and respiratory variables.

Conclusion  Although low‐dose dopamine has been shown to depress ventilation in a variety of conditions, it does not compromise ventilation in COPD patients either breathing spontaneously or when weaned using pressure support ventilation.
8‐isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP‐1 macrophages, resulting in long‐lived foam cells
Authors: Scholz H. , Aukrust P. , Damås J. K. , Tonstad S. , Sagen E. L. , Kolset S. O. , Hall C. , Yndestad A. , Halvorsen B.
Published: July 2004

Background  Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8‐isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F2‐isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8‐isoprostane to modulate oxidized (ox)LDL‐induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation.

Methods and results  8‐isoprostane (10 µM) augmented the oxLDL‐induced (20 µg mL−1) lipid accumulation of THP‐1 macrophages evaluated by Oil‐Red‐O staining and lipid mass quantification (colourimetric assay). Additionally, 8‐isoprostane induced the expression of the scavenger receptor A type 1 (MSR‐1) [mRNA and protein level], assessed by RT‐PCR and Western blotting, respectively. Moreover, 8‐isoprostane counteracted the oxLDL‐induced apoptosis of these cells, involving both mitochondrial‐protective and caspase‐suppressive mechanisms. Along with these changes, 8‐isoprostane increased the oxLDL‐induced gene expression of matrix metalloproteinase (MMP)‐9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)‐1] accompanied by enhanced total MMP activity.

Conclusions  We show that 8‐isoprostane increases foam cell formation at least partly by enhancing MSR‐1 expression and by inhibiting apoptosis of these cells, inducing long‐lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8‐isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization.
Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide
Authors: Borke W. B. , Munkeby B. H. , Halvorsen B. , Bjornland K. , Tunheim S. H. , Borge G. I. A. , Thaulow E. , Saugstad O. D.
Published: July 2004

Background  Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia–reoxygenation injury.

Objective  To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O2 at different PaCO2‐levels.

Methods  Newborn pigs (12–36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O2 at different PaCO2 levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix‐degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay.

Results  Matrix metalloproteinase‐2 more than doubled from baseline values (P < 0·001), and was higher in piglets resuscitated with 100% O2 than with ambient air (P = 0·012). The ORAC value was considerably decreased (P < 0·001). In piglets with elevated PaCO2, total MMP‐activity in the right ventricle was more increased than in the left ventricle (P = 0·008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO2 than in the piglets with elevated PaCO2 (P = 0·013).

Conclusion  In hypoxaemia‐reoxygenation injury the MMP‐2 level was highly increased and was most elevated in the piglets resuscitated with 100% O2. Antioxidant capacity was considerably decreased. Assessed by total MMP‐activity, elevated PaCO2 during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.
Tobacco and myocardial infarction in middle‐aged women: a study of factors modifying the risk
Authors: Janzon E. , Hedblad B. , Berglund G. , Engström G.
Published: July 2004

Background.  Although myocardial infarction (MI) is strongly related to smoking, few have studied why some smokers are more vulnerable than others. This study explored how the risk of MI in current and former smokers is modified by other cardiovascular risk factors.

Methods.  Incidence of MI (fatal and nonfatal) amongst 10619 women, 48.3 ± 8.2 years old, were studied in relation to smoking, hypertension, hypercholesterolaemia, diabetes, marital status and occupational level over a mean follow‐up of 14 years.

Results.  Of the 3738 smokers, one‐third had at least one major biological risk factor besides smoking; 228 women had MI during follow‐up. Smoking and hypertension showed a synergistic effect on incidence of MI. The adjusted relative risks (RR) were 12.2 (95% CI: 7.5–19.8) for smokers with hypertension, 5.3 (CI:3.3–8.1) for smokers with normal blood pressure and 2.4 (CI:1.4–4.3) for never‐smokers with hypertension (reference: normotensive never‐smokers). The corresponding RRs for diabetic smokers and diabetic never‐smokers were 19.0 (CI: 10.2–35.4) and 8.8 (CI: 4.4–17.4), respectively (reference: nondiabetic never‐smokers). In terms of attributable risks, hypertension, hypercholesterolaemia and diabetes accounted for 12.9, 11.5 and 7.2%, respectively, of MI in female smokers. Low socio‐economic level and being unmarried accounted for 19.6 and 1.6%, respectively.

Conclusions.  Although smoking is a major risk factor for MI, the risk varies widely between women with similar tobacco consumption. The results illustrate the need of a global risk factor assessment in female smokers and suggest that female smokers should be targets both for intensified risk factor management and programmes to stop smoking.
Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin‐1β‐511 promoter gene and raised levels of interleukin‐1β and interleukin‐18
Authors: Maury C. P. J. , Liljeström M. , Laiho K. , Tiitinen S. , Kaarela K. , Hurme M.
Published: July 2004

Objective.  In amyloid A (AA) amyloidosis the receptor for advanced glycation end products is a target for the circulating amyloid precursor protein (SAA) resulting in upregulation of the proinflammatory cytokine pathway. Besides inducing hepatic SAA synthesis the interleukin‐1 cytokine family is involved in the regulation of haematopoiesis. We therefore studied the relationship between the circulating levels of interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18), a new member of the IL‐1 complex, as well as polymorphisms within the IL‐1 cluster with the occurrence of anaemia in patients with AA amyloidosis.

Design, setting and subjects.  The study included 54 adult patients with biopsy‐proven reactive amyloidosis allocated into three groups on the basis of haemoglobin (Hb) level: group I included all patients with Hb < 110 g L−1 (n = 16); group II patients (Hb > 110 g L−1, n = 16) were selected to match group I patients with respect to sex, age, underlying disease (seropositive, erosive rheumatoid arthritis) and renal function; and group III patients (n = 38) represented all patients (unselected) with Hb ≥ 110 g L−1. Gene polymorphisms were studied by polymerase chain reaction restriction length assay and included the base exchange at position‐889 of the IL‐1α gene, the polymorphic region at position‐511 and the polymorphic locus at exon 5, position +3954 of the IL‐1β gene, as well as the IL‐1 receptor antagonist (IL‐1Ra) exon 2 polymorphism caused by the 86‐bp tandem repeats. Plasma IL‐1β, IL‐1α, IL‐18, IL‐1 Ra, SAA, ferritin, soluble transferrin receptor and erythropoietin levels were studied by enzyme immunoassays.

Results.  Circulating IL‐β and IL‐18 were significantly raised in the anaemic patients with AA amyloidosis when compared with group II patients (matched, Hb > 110 g L−1) as well as group III patients (nonmatched, Hb ≥ 110 g L−1). A significant inverse relationship was found between IL‐1β and haemoglobin levels, as well as between IL‐18 and haemoglobin levels. The frequency of allele 2 (T) of the IL‐1β‐511 promoter gene was significantly increased and that of allele 1 (C) decreased in anaemic amyloid patients (group I) when compared with group II and III patients. Circulating IL‐1β levels tended to be higher amongst the IL‐1β‐511 allele 2 carriers than amongst the noncarriers, as well as amongst the anaemic amyloid patients filling all criteria of anaemia of chronic disease.

Conclusion.  The occurrence of anaemia in patients with AA amyloidosis is associated with allele 2 (T) of the IL‐1β‐511 promoter gene and elevated levels of circulating IL‐1β and IL‐18. In AA amyloidosis the raised cytokine levels may generate a vicious cycle leading to accelerated amyloidogenesis, suppression of erythropoiesis and aggravation of the underlying inflammatory disorder.
Suspicion of pulmonary embolism in outpatients: nonspecific chest pain is the most frequent alternative diagnosis
Authors: Bernard Bagattini S. , Bounameaux H. , Perneger T. , Perrier A.
Published: July 2004

Objectives.  Several recent studies have focused on identifying clinical predictors of embolism. However, although pulmonary embolism is ruled out in 70–85% of the patients in whom it is suspected, data on the clinical characteristics and discharge diagnosis of such patients are scarce. Our aim was to evaluate whether clinical characteristics would allow predicting alternative diagnoses other than pulmonary embolism thereby ruling out venous thromboembolism.

Design.  Retrospective analysis.

Setting.  Emergency centres of two teaching and general hospitals.

Subjects.  A total of 1090 consecutive outpatients admitted for clinically suspected pulmonary embolism and a diagnosis established by a validated algorithm and a 3‐month follow‐up.

Outcomes.  Discharge diagnoses of patients in whom pulmonary embolism was ruled out were identified and regrouped into two categories: (i) nonspecific chest pain and (ii) diagnosis other than pulmonary embolism. Predictive accuracy of clinical and laboratory variables for diagnosing nonspecific chest pain was assessed by univariate and multivariate analysis.

Results.  In patients without pulmonary embolism, nonspecific chest pain (parietal chest pain, chest pain of unknown origin and pleuritis) was the most frequent discharge diagnosis (n = 334, 31% of the entire cohort, 43% of the patients without pulmonary embolism). Other patients without pulmonary embolism had a wide variety of diagnoses, of which the most frequent were bronchopneumonia (6.0% of the entire cohort) and heart failure (5.2%). In the multivariate analysis, seven variables were strongly associated with nonspecific chest pain: younger age (below 40 years), female gender, respiratory rate below 20 min−1, heart rate below 100 min−1, and absence of recent immobilization, dyspnoea and haemoptysis. Two of the 24 patients in whom all those characteristics were present had pulmonary embolism (8%, 95% CI 3–22%).

Conclusions.  The most frequent discharge diagnosis in emergency ward patients in whom pulmonary embolism is ruled out is nonspecific chest pain. A clinical model did not allow to predict nonspecific chest pain with enough accuracy to rule out pulmonary embolism without further testing. Whether a more precise characterization of chest pain might allow an accurate identification of such patients deserves further study.
The effect of psychological and educational counselling in reducing anxiety in nursing students
Authors: SHARIF F. , ARMITAGE P.
Published: July 2004

A quasi‐experimental pre‐, post‐test, follow‐up and control group design was used to investigate the effect of psychological and educational counselling in reducing anxiety in nursing students. The research study used methodological triangulation, involving the use of structured data collection techniques such as standardized questionnaires and semi‐structured focus groups. Focus groups were used to provide greater insight regarding the student's opinions. The sample consisted of 100 second‐ and fourth‐year baccalaureate nursing students from the Faculty of Nursing at Shiraz University of Medical Sciences, Iran. They were randomly assigned to either an experimental group (n = 50) or a control group (n = 50). The experimental group received a 12‐week intervention programme. Quantitative analysis of data was undertaken using t‐test and analysis of variance for repeated measures to test differences between and within groups. The results indicated that from pre‐ to post‐test there was no statistically significant reduction in anxiety between groups, but there was a statistically significant reduction in anxiety after one semester (in the follow‐up). Student self‐esteem was increased significantly from pre‐ to post‐test. This increase was statistically significant and remained the same in follow‐up. A statistically significant difference was seen in the student grade point average from pre‐test to follow‐up in the experimental group but not for the control group. The implementation of an intervention programme reduced their anxiety, increased their self‐esteem and improved their grade point average over time.
The Nurses’ Global Assessment of Suicide Risk (NGASR): developing a tool for clinical practice
Authors: CUTCLIFFE J. R. , BARKER P.
Published: July 2004

Contemporary and established literature indicates that people with mental health problems are at a higher risk of suicide than the general population. Because suicide is a multifaceted, complex phenomenon, risk assessment within the mental health care system requires a pluralistic, multidimensional and multiprofessional response. While assessment tools may provide useful guidance, especially guarding against complacency and over confidence, the fundamental basis of risk assessment must involve a thorough examination of the personal, interpersonal and social circumstances of each individual. Such thorough and rigorous assessments, the authors of this paper would add, require a degree of ‘clinical judgement’. As a rule, inexperienced members of mental health care staff should not be charged with the responsibility of conducting suicide risk assessments without sound mentorship. However, with the right support and assessment tool, the novice practitioner might develop the kind of clinical judgement necessary for this critical task. Accordingly, this paper traces the development of the Nurses’ Global Assessment of Suicide Risk (NGASR). It illustrates the practice development context out of which the need for the tool arose; it outlines the key evidence that underpins the construction of the tool and it is described. It is important to point out that as yet, no wide scale, quantitative validation of the tool has been conducted. Therefore, at this point, the tool should be treated with a degree of appropriate caution. Nevertheless, the preliminary attempts that have been made to ‘validate’ or ‘rate’ the tool in practice are included. While acknowledging that any risk assessment tool represents only one aspect of the necessarily broader assessment of risk, the NGASR appears to provide a useful template for the nursing assessment of suicide risk, especially for the novice.
Short shrift for the sane? The hospital management of self‐harm patients with and without mental illness
Authors: BARR W. , LEITNER M. , THOMAS J.
Published: July 2004

In recent years the British government has sought to target service provision both on people with severe enduring mental illness and on those considered to be at risk of suicide. The study reported here suggests these policies may have had unforeseen repercussions on services for people who self‐harm but have no identifiable mental illness. This paper compares the hospital management of self‐harm patients with and without mental illness. Over the years 1996–2000, a total of 4329 self‐harm patient attendances were recorded at the accident and emergency department of a British hospital. Whilst patients in 63.7% of attendances could reasonably have been considered to have some form of mental illness, we found that in the remaining 36.3% of attendances (where patients had no indicator of mental illness) a particularly poor standard of service was given. We suggest that if government targets for a reduction in the suicide rate are to be met, it is crucial that there should be marked improvements in services for all self‐harm patients presenting at accident and emergency departments. However, in improving services we must be vigilant to the danger that targeting those with a mental illness may mean we fail to provide even basic levels of care for others.
‘Therapy as well as the tablets’: an exploratory study of service users’ views of community mental health nurses’ (CMHNs) responses to hearing voices
Authors: COFFEY M. , HIGGON J. , KINNEAR J.
Published: July 2004

Mental health nurses have traditionally been discouraged from engaging with service users’ experiences of hearing voices and to reinforce reality. However, this may not be a helpful way of intervening in what can be a very distressing symptom. There is little evidence of service users’ experiences of community mental health nurses’ (CMHNs) responses to their voices. This paper presents the findings of an exploratory interview study of a sample (n = 20) of service users to ascertain their perception of CMHN responses to their experience of hearing voices. Data are both quantitative and qualitative in nature. Content analysis of the qualitative elements of the study suggests responses can be conceptualized as facilitators, barriers and attributions. CMHNs are considered to be allies and the quality of the relationship is deemed important. The therapeutic repertoire of CMHNs, however, is seen as limited and rarely extends beyond facilitating access to the psychiatrist for review of medication.
Smoking and mental health nurses: a survey of clinical staff in a psychiatric hospital
Authors: DICKENS G. L. , STUBBS J. H. , HAW C. M.
Published: July 2004

There is a lack of evidence on the prevalence of smoking among mental health nurses, and the beliefs and attitudes they hold about smoking at work. This paper describes results from a cross‐sectional survey of clinical staff working in a UK specialist charitable‐status psychiatric hospital and focuses on the responses of registered mental health nurses. Questionnaires specifically developed for this study were sent to all 1371 clinical employees. Completed questionnaires were returned by 167 of 429 (38.9%) registered nurses (RNs), 300 of 842 (35.6%) nursing assistants (NAs), and 123 of 200 (61.5%) other health professionals (OHPs). Twenty‐nine (17.4%) RNs, 93 (31%) NAs and eight (6.5%) OHPs reported themselves as current smokers. Differences in response to attitudinal questions between groups could not be attributed to age. RN smokers were significantly more likely than RN non‐smokers to state that staff should be allowed to smoke with patients, and to report therapeutic value for patients in this activity. RN smokers were less likely than RN non‐smokers to report that patients should be encouraged to stop smoking. RNs were significantly more likely than OHPs to report therapeutic value for patients in smoking with staff, even after controlling for the possible confounding effect of smoking status. Implications of the survey are discussed in the context of the international literature, including the disproportionately high smoking prevalence among patients living in psychiatric institutions and current guidelines to move towards no ‘smoking allowed’ areas for staff working in them.
Assertive outreach nurses’ experience of engagement
Authors: ADDIS J. , GAMBLE C.
Published: July 2004

There are currently no studies available in the literature to highlight nurses’ experiences of the assertive outreach (AO) engagement process. This study aimed to understand how AO nurses experience this process and what can be learned from it. The participants were five nurses working in a rural AO service in one county. Methodological considerations were rooted in the work of Martin Heidegger and the data analysed using the hermeneutic phenomenological thematic method. The data‐gathering tool was semi‐structured interviews. Seven major themes emerged to construct the nurses’ understanding of their experience of assertive engagement. These were: (1) having time; (2) anticipatory persistence and tired dejection; (3) pressure, relief and satisfaction; (4) being the human professional confluence; (5) accepting anxiety and fear; (6) working and learning together; and (7) bringing the caring attitude. This paper focuses on the seven emerging themes and discusses the implications and recommendations for nurses practising in the AO setting.
The development and evaluation of a telepsychiatry service for prisoners
Authors: LEONARD S.
Published: July 2004

The introduction of increasingly sophisticated telecommunication systems seems to offer opportunities to respond to some of the key problems around structural and spatial inequalities in access to health care. There is evidence which suggests that serious mental health problems are common among prisoners and psychiatric comorbidity is the norm. Many prisoners have complex mental health needs, but more often than not these remain unaddressed. Telepsychiatry is one strategy to improve the accessibility and quality of mental health care in the prison setting. This paper firstly reviews the current prison health care system and then describes a research study which is focused on the development and evaluation of a telepsychiatry service for prisoners. This study has investigated what is lost or gained in a psychiatric assessment when it is conducted via telepsychiatry. The researcher compared the inter‐rater reliability between two raters interviewing 80 participants in an observer/interviewer split configuration in telepsychiatry and same room settings. The measure used was the Comprehensive Psychopathology Rating Scale. Prisoners and prison staff also took part in semi‐structured interviews which focused on their satisfaction and acceptability of the telepsychiatry service. A cost comparison of the telepsychiatry service with the existing visiting service was conducted. This paper outlines the study design and focuses on the potential impact that telepsychiatry may have upon the practice setting.
A staff perspective of early warning signs intervention for individuals with psychosis: clinical and service implications
Authors: SCOTT S. R. , REID I. , SMITH J. , NATYNCZUK S. , ROBSON‐WARD M. , VAUGHAN J.
Published: July 2004

Research has established the benefits of early warnings signs monitoring in the prevention of relapse for individuals with psychosis. This study explored staff views (n = 8) of the implementation of an early warning signs clinic within a day hospital of an adult mental health service. A qualitative methodology using focus groups was adopted and content analysis was used to discover themes arising from the data. Overall, the data indicated a positive view of the early warning signs clinic, with benefits for clients, staff and their relationship; and for service delivery and resources. The clinical and service implications are discussed.
Putative common origin of two MLH1 mutations in Italian‐Quebec hereditary non‐polyposis colorectal cancer families
Authors: Thiffault I , Foulkes WD , Marcus VA , Farber D , Kasprzak L , MacNamara E , Wong N , Hutter P , Radice P , Bertario L , Chong G
Published: July 2004

Hereditary non‐polyposis colorectal cancer (HNPCC) is one of the most common inherited cancer syndromes, accounting for 3–5% of all cases of colorectal cancer. In most HNPCC families, the disease is caused by a germline mutation in MLH1 or MSH2. In some populations, founder mutations appear to explain a substantial fraction of HNPCC. We report here the identification and preliminary characterization of two putative MLH1 founder mutations. The mutation MLH1c.1831delAT was shown to segregate in two Quebec families of Italian origin who fulfilled the Amsterdam criteria for HNPCC. Haplotype analysis using five intragenic microsatellite/single nucleotide polymorphism markers spanning MLH1 on chromosome 3 showed that these two unrelated families share an identical haplotype. In addition, two other Italian kindred whose affected members carry MLH1g.IVS6 + 3A>G also share a common haplotype, suggesting that, similarly, the latter mutation has a common origin. These mutations are the first putative founder MLH1 mutations to be identified in HNPCC kindred of Italian origin.
Spectrum and frequencies of mutations in the GJB2 (Cx26) gene among 156 Czech patients with pre‐lingual deafness
Authors: Seeman P , Malíková M , Rašková D , Bendová O , Groh D , Kubálková M , Sakmaryová I , Seemanová E , Kabelka Z
Published: July 2004

Mutations in the gene gap junction beta 2 (GJB2), the gene for the connexin 26, are the most common cause of pre‐lingual deafness worldwide. The mutation 35delG within GJB2 is prevalent in Europe. To date, there are no data about GJB2 mutation spectrum and frequencies from the Czech population. We investigated and report here the spectrum and frequencies of mutations in the GJB2 gene among 156 unrelated, congenital deafness Czech patients. Allele‐specific polymerase chain reaction, together with fluorescent fragment analysis, were used for the detection of the 35delG mutation. The entire coding region of the GJB2 was directly sequenced in all patients who were not homozygous for the 35delG. No pathogenic mutation was detected in 51.9% of patients. At least one pathogenic mutation was found in 48.1% of patients, and both pathogenic mutations were detected in 37.8% of patients. Single mutations in a heterozygous state were detected in 10.3% of patients. The mutation 35delG accounts for 82.8% of detected disease mutations, Trp24stop accounts for 9.7% of pathogenic alleles and was found in patients with gypsy heritage. Mutation 313del14 accounts for 3.7% of pathogenic alleles. The frequency of 35delG heterozygotes in the Czech Republic is 1 : 29.6. Testing for only the three most common mutations would detect over 96% of all pathogenic alleles in the Czech Republic.
Social workers in the new human services marketplace: Trends, challenges and responses
Authors: Healy Karen
Published: July 2004

This paper examines employment trends in social welfare occupations and challenges to the industrial and cultural recognition of professional social work in the new human services market place. Following examination of the threats posed by market reform and the crisis in public confidence in some domains of human services work, I focus on three key concerns. First, through analysis of Census data from 1996 to 2001, I compare trends in the employment of social workers, welfare workers and community workers. Second, drawing on the work of Nancy Fraser (1997), I argue that the challenges facing social workers can be understood as problems of ‘recognition’. Using this framework, I examine the external contests to the valuing of professional social work and also the internal challenges, that is, threats from within the social work profession to the industrial and cultural recognition of social work. Finally, I will consider how social workers, particularly new graduates, can respond to the challenges facing them in the new human services marketplace. I propose that social workers should claim a position as practice leaders and I outline practical strategies for achieving this goal.