bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemolink™, an o‐raffinose cross‐linked haemoglobin‐based oxygen carrier, does not affect activation and function of human platelets in whole blood in vitro
Authors: Leytin Valery , Mazer David , Mody Meera , Garvey Bernadette , Freedman John
Published: March 2003

Summary. Haemoglobin‐based oxygen carriers (HBOCs) are anticipated to be safe and efficient alternatives to RBC transfusions. Haemoglobin (Hb) raffimer (Hemolink™; Hemosol, Toronto, ON, Canada) is polymerized human Hb, cross‐linked with o‐raffinose. As administration of cell‐free Hb may affect blood cells and tissues, this study was focused on evaluating effects of Hb raffimer on human platelets in whole blood in vitro. Citrated blood from healthy donors was incubated with Hb raffimer to achieve raffimer concentrations of 2–50 vol percentage (2–50 g/l). Platelet activation, phosphatidylserine exposure and microparticle generation were measured by flow cytometry. Aperture closure time on collagen/ADP‐ and collagen/epinephrine‐coated membranes was determined by a platelet function analyser (PFA‐100®). We found that addition of Hb raffimer to blood samples up to 50 vol % did not affect human platelets as measured by various markers of platelet activation (CD42b, CD41, PAC‐1, CD62, CD63), procoagulant activity (annexin V) and microparticle formation; differences between Hb raffimer‐ and lactated Ringer's‐diluted blood were not significant. Similarly, no adverse effect of Hb raffimer on closure time was observed at concentrations up to 50 vol %, in comparison with Ringer's solution. These data indicate that exposure of human blood to high concentrations of Hb raffimer in vitro did not cause platelet activation nor affect platelet function.
Imatinib mesylate (STI571) treatment in patients with chronic‐phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation
Authors: Cervantes Francisco , Hernández‐Boluda Juan‐Carlos , Odriozola Jesús , Camós Mireia , Villalón Lucía , Martínez‐Climent José‐Angel , Del Campo Raquel , García‐Conde Javier , Montserrat Emilio
Published: March 2003

Summary. Imatinib mesylate (STI571) is a highly effective and well‐tolerated treatment for patients with chronic‐phase chronic myeloid leukaemia (CML), but information on its efficacy and tolerance in intensively pretreated patients is scarce. Thirty‐three chronic‐phase CML patients who were resistant or intolerant to interferon (IFN) and had been previously submitted to autologous stem cell transplantation were treated with imatinib for a median of 14 months (range: 6–19 months). Seven patients were in haematological response (HR) at the start of treatment; the remaining 26 attained a HR at a median of 3 weeks (range: 1–4 weeks). Major cytogenetic response rates at 3, 6 and 12 months were 42%, 45% and 55%, respectively, including 21%, 24% and 33% complete responses. Grade 3–4 neutropenia, thrombocytopenia and anaemia developed in 33%, 27% and 12% of patients respectively. Non‐haematological toxicity included superficial oedema (21% of patients), gastrointestinal symptoms (18%), muscle cramps (15%), skin rash and liver enzyme increase (3% each). These results were not significantly different from those in 65 chronic‐phase CML patients, resistant or intolerant to interferon without a previous ASCT, who were included in the same protocol. Imatinib mesylate is effective and safe in chronic‐phase CML patients with a previous history of intensive treatment.
Complete remission of tumour with interleukin 2 therapy in a patient with non‐Hodgkin's lymphoma post allogeneic bone marrow transplant associated with polyclonal T‐cell bone marrow lymphocytosis
Authors: Kiss Thomas L. , Spaner David , Daly Andrew S. , Hasegawa Wanda S. , Lipton Jeffrey H. , Messner Hans A. , Chang Hong
Published: March 2003

Summary. A patient with low‐grade non‐Hodgkin's lymphoma (NHL) who relapsed shortly after an allogeneic bone marrow transplant (BMT) is reported. The patient was treated with interleukin 2 (IL‐2), which resulted in a flare‐up of graft‐versus‐host disease followed by disease control, with disappearance of peripheral lymphadenopathy. Sequential bone marrow testing showed the disappearance of bone marrow involvement with disease but occurrence of T‐cell aggregates post IL‐2 that were identified as polyclonal by molecular methods. The patient remains in complete remission 37 months following allogeneic BMT.
Absence of SCL mutations in myeloid malignancies
Authors: Delabesse Eric , Li Juan , Schnittger Susanne , Hiddemann Wolfgang , Green Anthony R.
Published: March 2003

Summary. Transcription factors play a central role in the pathogenesis of acute leukaemia. Genes encoding transcription factors are frequently perturbed by chromosome rearrangements. More recently acquired point mutations have been described in a number of important genes for normal haematopoiesis. The stem cell leukaemia (SCL) gene encodes a basic helix–loop–helix transcription factor and is upregulated by chromosome rearrangements in T‐acute lymphoblastic leukaemia. SCL function is essential for the development of both primitive and definitive haematopoiesis. We searched for SCL mutations in myeloid leukaemias and chronic myeloproliferative disorders. Our data demonstrated that SCL point mutations were rare in acute myeloid leukaemia and myeloproliferative disorders.
Paradoxical association between the 316 Trp to Ser beta 2‐glycoprotein I (Beta2GPI) polymorphism and anti‐Beta2GPI antibodies
Authors: Nash Michael J. , Camilleri Raymond S. , Liesner Ri , Mackie Ian J. , Machin Samuel J. , Cohen Hannah
Published: March 2003

Summary. We report a woman with an obstetric history ofa stillbirth at 28 weeks, associated with hypertension and severe intrauterine growth restriction and a miscarriage at 9 weeks. She was persistently positive for immunolgobulin G (IgG) anticardiolipin antibodies and IgG anti‐Beta‐2‐glycoprotein I (anti‐Beta2GPI) antibodies. She has delivered three healthy babies when managed antenatally with aspirin and low‐molecular‐weight heparin prophylaxis. Genotyping revealed that she was homozygous for the 316 Trp to Ser Beta2GPI polymorphism. Studies examining the binding of her plasma Beta2GPI to purified cardiolipin showed markedly reduced binding in comparison with Beta2GPI in pooled normal plasma.
Angiogenesis occurs in hairy cell leukaemia (HCL) and in NOD/SCID mice transplanted with the HCL line Bonna‐12
Authors: Pruneri Giancarlo , Bertolini Francesco , Baldini Luca , Valentini Stefano , Goldaniga Maria , Soligo Davide , Carboni Nadia , Viale Giuseppe , Lambertenghi‐Deliliers Giorgio
Published: March 2003

Summary. Microvessel density (MVD), a surrogate marker for angiogenesis, was evaluated by anti‐CD34 and CD105 monoclonal antibodies (Abs), and found to be increased in the bone marrow (BM) of hairy cell leukaemia (HCL) patients and in a preclinical model of non‐obese diabetice/severe combined immunodeficient mice transplanted with the HCL line Bonna‐12. The anti‐CD105 Ab was significantly more sensitive than anti‐CD34 Ab in identifying blood vessels. The BM tumour burden significantly decreased in patients treated with interferon‐α, but the mean value of MVD remained unchanged. These data suggest that angiogenesis may be involved in the pathogenesis of HCL.
Different levels of p38 MAP kinase activity mediate distinct biological effects in primary human erythroid progenitors
Authors: Somervaille Tim C. P. , Linch David C. , Khwaja Asim
Published: March 2003

Summary. There have been conflicting reports regarding the role of p38 mitogen‐activated protein kinase (MAPK) in the regulation of differentiation, proliferation and apoptosis in erythroid cell lines. We have, therefore, examined the functions of this kinase in primary human erythroid progenitors. Cells in steady‐state culture showed low‐level p38 MAPK activity, which decreased further within 1 h of growth factor withdrawal and increased over a limited range within minutes of re‐exposure of cells to erythropoietin or stem cell factor, demonstrating the link between low‐level p38 MAPK activity and the prevailing growth factor milieu. Use of the p38 MAPK‐specific inhibitor SB203580 demonstrated that this level of activity was necessary for (1) optimal proliferation, (2) erythroid burst‐forming unit migration and (3) full upregulation of E‐cadherin and CD36 expression, but not haemoglobin A or glycophorin A expression, during human erythroid differentiation. In contrast, cells deprived of growth factors for an 8‐h period, following a transient decrease in p38 MAPK activity, demonstrated sustained, substantial and caspase‐independent increases in p38 MAPK activity, and its blockade using SB203580 reduced the proportion of erythroblasts undergoing apoptosis by 40 ± 7%, demonstrating a role for p38 MAPK in apoptosis induction in human erythroblasts. Thus, in primary human erythroblasts, different environmental conditions induce different levels of p38 MAPK activity, which have distinct functions.
Abnormal telomere metabolism in Fanconi's anaemia correlates with genomic instability and the probability of developing severe aplastic anaemia
Authors: Li Xiaxin , Leteurtre François , Rocha Vanderson , Guardiola Philippe , Berger Roland , Daniel Marie‐Therese , Noguera Maria Helena , Maarek Odile , Roux Gwenaëlle L. E. , De La Salmonière Pauline , Richard Patrice , Gluckman Eliane
Published: March 2003

Summary. Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by progressive bone marrow failure and a susceptibility to cancer. Haematopoietic stem cell transplantation is the only curative method for restoring normal haematopoiesis, and survival is improved if the transplant is carried out before severe complications occur. However, the evolution of FA is difficult to predict because of the absence of known prognostic factors and the unknown function of the genes involved. In studying 71 FA patients, a correlation was found between severe aplastic anaemia (SAA) and the individual annual telomere‐shortening rate (IATSR) in peripheral blood mononuclear cells (P < 10−3). Spontaneous apoptosis was highest in SAA patients or patients with high IATSR (> 200 bp/year) (P < 0·01, n = 18). Univariate and multivariate analyses showed that significant relative risks for evolution towards SAA were high IATSR (P < 10−4), and that a high number of chromosome breakages occurred in the presence of nitrogen mustard (P < 0·001). A high IATSR was also associated with an increased frequency of malignancy (P < 0·01). Thus, these biological parameters were related to the spontaneous evolution of FA and could be used as prognostic factors. These data indicated that telomeres might play a role in the evolution of bone marrow failure and malignant transformation in FA.
Potential role of endothelin 1 in ischaemia-induced angiogenesis in critical leg ischaemia
Authors: Tsui J C S , Baker D M , Biecker E , Shaw S , Dashwood M R
Published: March 2003

Background

Ischaemia-induced angiogenesis occurs in critical leg ischaemia (CLI) and endothelin (ET) 1 may be involved in this process. The aim of this study was to quantify microvessels and study ET receptor expression and distribution in critically ischaemic leg muscle.

Methods

Leg muscle biopsies were taken from 12 patients with CLI and 12 patients with no leg ischaemia. Microvessels were identified immunohistochemically on muscle sections, and the number of immunopositive cells was quantified. ETAand ETB receptor messenger RNA (mRNA) expression was studied using real-time quantitative reverse transcriptase–polymerase chain reaction, and receptor binding was localized and assessed by in vitro autoradiography.

Results

The number of microvessels in CLI muscle biopsies was 2·6 times higher than that in controls (P < 0·01). ETB receptor mRNA expression and binding were significantly increased in CLI tissue (P < 0·05), while ETA receptor levels were not significantly raised. High-resolution autoradiography showed that ET receptor binding was associated with microvessels.

Conclusion

Angiogenesis occurs in CLI and raised ETB receptors within the muscle were associated with microvessels, suggesting that ET-1 may mediate angiogenesis via these receptors in critically ischaemic muscle.
Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours
Authors: Ohlsson B , Nilsson J , Stenram U , Åkerman M , Tranberg K-G
Published: March 2003

Background

The aim of the study was to investigate the value of percutaneous fine-needle aspiration cytology (FNAC) in the diagnosis and management of liver tumours.

Methods

FNAC followed by histopathological examination was carried out in 216 patients with suspected liver tumours. The final diagnosis was primary liver cancer in 106, colorectal metastases in 51, non-colorectal metastases in 46, benign tumour in nine and no tumour in four patients.

Results

Cytology resulted in correct classification of the lesion as benign or malignant in 87 per cent of patients, correct discrimination between primary and secondary malignancy in half of the patients, and a correct diagnosis of tumour type in one-third of patients. The tumour was erroneously classified as benign or malignant in 22 patients (11 per cent) and four patients (2 per cent) respectively. When FNAC showed malignancy, the predictive value was 98 per cent, whereas the predictive value was 27 per cent when it did not. FNAC guided investigations and treatment in one-quarter of patients. Implantation metastases were recorded in seven patients (3 per cent), including five (10 per cent) of 51 patients with colorectal liver metastases, and caused major local problems and death in four patients.

Conclusion

FNAC was valuable in about a quarter of patients with liver tumour. The risks of implantation metastases and a false-negative finding do not justify its use in candidates for curative therapy of liver tumours.
Late results concerning feasibility and compliance from a randomized trial of ultrasonographic screening for abdominal aortic aneurysm
Authors: Vardulaki K A , Walker N M , Couto E , Day N E , Thompson S G , Ashton H A , Scott R A P
Published: March 2003

Background

The study was an update at 10 years of a randomized trial of the efficacy of screening for abdominal aortic aneurysm (AAA). The extent of benefit, feasibility and compliance were examined, and reasons why this intervention may fail a proportion of those screened were identified.

Methods

A total of 6058 men aged 65 years and over were randomized to a group invited to attend ultrasonographic screening or to a control group. The mortality rate from AAA in the two arms of the trial was compared using a Poisson model. Analyses were by intention to treat.

Results

There was a 21 per cent reduction in mortality rate from AAA over the 10-year follow-up (relative risk 0·79 (95 per cent confidence interval 0·53 to 1·40)). The observed relative mortality reduction peaked at 4 years with a 52 per cent reduction in the study group. Eighteen of 24 AAA deaths in the study group were among those who did not attend the first screen, or failed to comply with the follow-up protocol.

Conclusion

A greater awareness of the benefits of full participation in a screening programme could provide a larger and sustained mortality reduction.
Liver fluke-associated cholangiocarcinoma
Authors: Watanapa P , Watanapa W B
Published: March 2003

Background

Infection with liver flukes has been reported to be associated with bile duct malignancy.

Methods

The review is based on a literature search (Medline) and, in some cases, direct contact with authors or principal investigators.

Results

A large body of evidence indicates that Opisthorchis viverrini is a definite cause of human cholangiocarcinoma, whereas Clonorchis sinensis is a probable cause. The evidence regarding Opisthorchis felineus is insufficient to assess its role in carcinogenesis. Possible mechanisms of carcinogenesis include chronic irritation, nitric oxide formation, intrinsic nitrosation and activation of drug-metabolizing enzymes. Early detection of bile duct malignancy is difficult and not clinically available at present, although cholangiocarcinoma-associated soluble antigen has been reported in an experimental study to be a useful early marker of cancer development. Long-term survival after surgical treatment of liver fluke-associated cancer is similar to that reported in patients without liver fluke infestation.

Conclusion

Liver fluke-associated cholangiocarcinoma is still a health problem in developing countries. Mechanisms of carcinogenesis should be explored further in order to reduce the impact of this disease.
Size of lesion is not a criterion for resection during management of giant liver haemangioma
Authors: Terkivatan T , Vrijland W W , den Hoed P T , de Man R A , Hussain S M , Tilanus H W , IJzermans J N M
Published: March 2003

Background

The unknown natural history and risk of complications of large haemangiomas may pose therapeutic dilemmas. The authors describe their experience with the management of giant haemangiomas.

Methods

Patients with a giant haemangioma were identified by a survey of the hospital database. Forty-nine patients with a haemangioma of at least 4 cm in diameter presented between January 1990 and December 2000. Medical records were analysed retrospectively.

Results

Eleven patients had surgical treatment and 38 were managed conservatively. The median diameter of the tumours was 8·0 cm in surgically treated patients and 6·0 cm in the group managed by observation. Surgery-related morbidity occurred in three patients, and abdominal complaints persisted in three of ten patients with a symptomatic lesion. During a median follow-up of 52 months, 12 non-operated patients had mild abdominal complaints, considered to be unrelated to the lesion. In these patients symptoms either diminished or became minimal during follow-up. Complications did not occur.

Conclusion

Observation of giant haemangiomas can be performed safely. The authors advocate resection of cavernous liver haemangiomas only in patients with persistent severe symptoms.
Comparison of methods based on annexin‐V binding, DNA content or TUNEL for evaluating cell death in HL‐60 and adherent MCF‐7 cells
Authors: Del Bino G. , Darzynkiewicz Z. , Degraef C. , Mosselmans R. , Fokan D. , Galand P.
Published: March 2003

Abstract. HL‐60 and MCF‐7 cells were treated with 0.15 μM camptothecin (CPT) or with the solvent dimethylsulfoxide (DMSO) for the controls, for 2, 3 and 4 h or for 24, 48 and 72 h, respectively. The apoptotic index (AI) was then evaluated in parallel by the following flow cytometric methods: (1) double staining of unfixed cells with fluoresceinated annexin V and propidium iodide (PI), this after detachment by trypsinization in the case of MCF‐7 cultures; (2) prefixation in 70% ethanol, extraction of degraded, low molecular weight DNA with 0.2 M phosphatecitrate buffer and analysis of the DNA content stained with PI; (3) TUNEL, i.e. labelling of DNA strand breaks with biotin‐dUTP, followed by standing with streptavidin‐fluorescein and counterstaining with PI. In HL‐60 cells, the three methods gave similar results for the AI (3‐4% in the controls and at 2 h of CPT treatment, and 35‐43% at 3 and 4 h after CPT). This indicates that CPT‐induced membrane alteration and DNA fragmentation occurred concomitantly in those cells. For MCF‐7 cells, CPT‐induced apoptosis developed more slowly, the AI, whether based on annexin V or on DNA content, remained unchanged at 24 h, then was increasing to 8% at 48 h and to 25% at 72 h of treatment. In these cells, the TUNEL index did not increase prior to 72 h and the increase was minor (up to 9% vs. 2‐3% in the controls) at 72 h of the treatment. This indicates that in MCF‐7 cells DNA strand breaks cannot be effectively labelled, which may be due to inaccessibility of 3′‐OH ends in the breaks to exogenous terminal deoxynucleotidyl transferase. The mechanism of endonucleolytic DNA fragmentation thus may be different, depending on the cell type.
Lipid‐induced changes in vascular smooth muscle cell membrane fluidity are associated with DNA synthesis
Authors: Potten Christopher , Darzynkiewicz Zbigniew , Sasaki Kohsuke , Sachinidis A. , Carniel M. , Seewald S. , Seul C. , Gouni‐Berthold I. , Ko Y. , Vetter H.
Published: March 2003

Abstract. In the present study, we examined whether changes in the membrane fluidity of vascular smooth muscle cells (VSMCs) alter their DNA synthesis. For this purpose, the membrane fluidity of the cells was modulated after treatment of VSMCs with 1,2‐dioleoyl phosphatidylcholine (PC). Treatment of VSMCs with 1,2‐dioleoyl PC‐rich medium containing 10% heat‐inactivated human serum and 3 mg/ml 1,2‐dioleoyl PC for 24 h resulted in an increase in VSMC membrane fluidity at all temperatures from 15° to 40°C as well as a 51% inhibition of DNA synthesis, compared with untreated cells. Remarkably, enrichment of VSMCs with 1,2‐dioleoyl PC/cholesterol‐rich medium containing 10% human serum, 3 mg/ml 1,2‐dioleoyl PC and 2 mg/ml cholesterol restored both membrane fluidity and DNA synthesis to the levels of untreated cells. The present findings show an inverse association between increased membrane fluidity and cellular DNA synthesis.
Proliferation of glial cells in vivo induced in the neural lobe of the rat pituitary by lithium
Authors: Levine S. , Saltzman A. , Klein A.W.
Published: March 2003

Lithium salts are widely used for treatment of psychiatric illness. Lithium also affects cell proliferation. During investigation of the effect of lithium chloride on the central nervous system (CNS) of nephrectomized rats, we noted numerous mitotic figures in the neural lobe of the pituitary. Morphologic criteria established that the mitotic cells were astrocytes, the supporting glial cells of the CNS, also known as pituicytes. Equimolar doses of chlorides of chemically related cations (sodium, potassium, rubidium) had no such effect.
Proliferation in murine epidermis after minor mechanical stimulation Part 2. Alterations in keratinocyte cell cycle fluxes
Authors: Barthel D. , Matthé B. , Potten C.S. , Owen G. , Loeffler M.
Published: March 2003

We have recently shown that a mild mechanical irritation (tape strip) of the epidermis on the back skin of adult mice induces a strong and long lasting increase in proliferative activity and cell production. This was revealed by following the fate of 3HTdR‐pulse labelled cells within the basal and suprabasal layers.

To obtain further insight into the dynamics of cell kinetic changes we also performed double labelling experiments with 3HTdR and BrdUrd at various times after tape stripping. The technique for analysing the data had to account for a non stationary cell flux. A novel biometrical technique was developed which provides parameter estimates on the S‐phase duration, the cell cycle duration and a parameter characterizing the degree of nonstationarity.

When applied to the mechanically irritated epidermis we observed that the cell flux through the S‐phase in the basal layer was accelerated by a factor of 10 between 18 and 36 h post tape strip. This activation declined slightly in the subsequent days and remained 4–6 fold higher than in the normal steady state for over 7 days post tape strip. The duration of the S‐phase was 3–5 h and showed little variation.

We conclude that mild mechanical irritation only affecting the stratum corneum has major stimulatory effects on the cell kinetics of proliferative keratinocytes in the basal layer of the epidermis indicating the existence of a powerful regulatory mechanism.
SERCA activity is required for timely progression through G1/S
Authors: Simon V. R. , Moran M. F.
Published: March 2003

Changes in intracellular Ca2+ correlate with specific events in the cell cycle. Here we investigated the role of Ca2+ in the G1 phase. HEK 293 cells were arrested in mitosis and subjected to short‐term treatments that alter Ca2+ homeostasis prior to their release into G1. Treatment with thapsigargin (TG), an irreversible inhibitor of the sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) lengthened the G1 phase. Moreover, TG treatment also resulted in a dramatic alteration in cellular morphology and attachment and in the reduction of MAPK activity and lower levels of cyclin D1 and cyclin E proteins. Treatments with reagents that transiently increase or decrease cytosolic Ca2+ or that temporarily inactivate SERCA did not alter any of the above parameters. Cells expressing a TG‐resistant form of SERCA progressed normally through the G1/S transition after TG treatment. These results suggest that long‐term SERCA inactivation affects cell cycle‐dependent events and compromises progression through G1/S.
Sensitivity of human glioma U‐373MG cells to radiation and the protein kinase C inhibitor, calphostin C
Authors: Acevedo‐Duncan M. , Pearlman J. , Zachariah B.
Published: March 2003

We assessed the radiosensitivity of the grade III human glioma cell line U‐373MG by investigating the effects of radiation and the specific protein kinase C inhibitor, calphostin C on the cell cycle and cell proliferation. Irradiated glioma U‐373MG cells progressed through G1‐S and underwent an arrest in G2‐M phase. The radiosensitivity of U‐373MG cells to graded doses of either photons or electrons was determine by microculture tetrazolium assay. The data was fitted to the linear‐quadratic model. The proliferation curves demonstrated that U‐373MG cells appear to be highly radiation resistant since 8 Gy was required to achieve 50% cell mortality. Compared to radiation alone, exposure to calphostin C (250 n

m) 1 h prior to radiation decreased the proliferation of U‐373MG by 76% and calphostin C provoked a weakly synergistic effect in concert with radiation. Depending on the time of application following radiation, calphostin C produced an additive or less than additive effect on cell proliferation. We postulate that the enhanced radiosensitivity observed when cells are exposed to calphostin C prior to radiation may be due to direct or indirect inhibition of protein kinase C isozymes required for cell cycle progression.
Cell growth and cholesterol metabolism in human glucose‐ 6‐phosphate dehydrogenase deficient lymphomononuclear cells
Authors: B. Batetta , R. R. Bonatesta , F. Sanna , M. Putzolu , M. F. Mulas , M. Collu , S. Dessì
Published: March 2003

Abstract. Atherosclerosis is an inflammatory‐fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth‐muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose‐6‐phosphate dehydrogenase (G6PD), the key enzyme of the hexose‐monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD‐normal (n = 5) and ‐deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]‐thymidine incorporation) cholesterol synthesis and esterification ([14C]‐acetate and [14C]‐oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT‐PCR) all increased following lectin stimulation in both normal and G6PD‐deficient cells. However, these parameters were significantly lower in G6PD‐deficient cells (P < 0.05). It is of interest that G6PD‐deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD‐deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.
Translocation of cytoplasmic HSP70 onto the surface of EL‐4 cells during apoptosis
Authors: Sapozhnikov Alexander M. , Gusarova Galina A. , Ponomarev Eugene D. , Telford William G.
Published: March 2003

Abstract. Heat shock proteins (HSPs) are involved in a variety of intracellular processes and can have both pro‐ and anti‐apoptotic action. However, little is known about the role of HSPs in the progression of apoptosis. Translocation of HSPs to the surface of apoptotic cells is a previously observed phenomenon demonstrating participation of these proteins in execution of the terminal stages of apoptosis. In a previous study we showed that development of EL‐4 lymphoma cell apoptosis in vitro is accompanied by elevation of surface HSP expression. In this study we used this model to analyse the relationship of HSP70 expression and its translocation to the cell surface during apoptosis with some key intracellular events. Our data demonstrate a synchronization of surface and intracellular HSP70 expression with bcl‐2 expression, intracellular reactive oxygen species (ROS) concentration and caspase‐3 activity. A maximum level of surface and intracellular HSP70 expression was observed at an irreversible phase of EL‐4 cell apoptosis after mitochondrial potential depolarization. In addition, an enhancement of the relative level of cytoplasmic HSP70 translocation to the cell surface was concomitant with EL‐4 cell apoptosis. However, the size of surface and intracellular pools of HSP70, increasing for initial and intermediate stages of cell death, decreased at the terminal phase of apoptosis. Western blot analysis of HSP70 in conditioned supernatant obtained from EL‐4 cell tissue showed that the observed decrease of HSP70 cell content might be due to surface HSP70 shedding into the intercellular space.
Cell kinetic studies in the murine ventral tongue epithelium: the effects of repeated exposure to keratinocyte growth factor
Authors: Potten C. S. , Booth D. , Cragg N. J. , O'Shea J. A. , Tudor G. L. , Booth C.
Published: March 2003

Abstract. Keratinocyte growth factor (KGF) stimulates proliferation and differentiation in various epithelial systems. Three daily subcutaneous injections of 125 µg of this protein into mice induce dramatic changes in the histology and histometric measurements of the ventral tongue epithelium. The thickness of the epithelium is increased two‐fold and the number of cells beneath a 1‐mm length of the surface is increased 1.6‐fold. KGF also induces a four‐fold increase in the number of S phase cells labelled with tritiated thymidine in the basal layer on the third day after KGF administration. The increase in thickness and cellularity persist for at least 4 days after the end of the KGF injections. However, there is a dramatic fall in the number of S phase cells detected by 3HTdR pulse labelling 2 days after the end of the KGF treatment. There are indications that by 7 days after the 3‐day regimen of KGF treatment, both thickness and cellularity have fallen back to near control levels. Continued exposure to KGF over a period of 7 days does not result in any further increases in thickness, cellularity or proliferation. In fact, the proliferation decreases on the fifth, sixth and seventh days of KGF injection to control values on day 7. These changes in the epithelium following KGF treatment suggest that the thicker and more cellular epithelium may be more able to cope with an exposure to a cytotoxic agent and hence be protected in comparison with normal or vehicle‐treated epithelium.
Services for disabled children: integrating the perspective of social workers
Authors: Middleton
Published: March 2003

The paper addresses questions about the appropriate focus and direction of social work with disabled children, by triangulating parental views with those of social workers. Previous studies concerning services for disabled children have concentrated either on the views of parents or, less often, on those of service providers. This study adds to the picture by linking the two together and allowing service providers to comment on the views of service users. Parents of nine disabled children were inter‐viewed following the introduction of a specialist disability team in an inner city borough, following the implementation of the Children Act 1989. The interviews took place over a 9‐month period in 1995, and the comments of parents were then shared with social workers both from the borough concerned and from elsewhere. The parents' views reflect confusion about service provision, ignorance of their children's legal (as opposed to moral) rights, a preference for proactive service provision and the need for emotional as well as material support, the last framed variously as counselling, advice and someone to listen. There was little evidence that the Children Act, which could have facilitated improvements in all these areas, had made any discernible difference. Social workers' comments on these findings, with which they identified strongly, revealed a lack of confidence in their own abilities, a lack of clarity in their role and increasing disillusion with the services of their organizations. It is argued that in order to meet parents' expressed needs, service providers require a confident and fundamental shift in emphasis back to the role of social worker as provider as well as enabler.
Holes in the safety net: the strengths and weaknesses of child protection procedures
Authors: Farmer
Published: March 2003

This paper uses findings from empirical research to demonstrate the strengths and weaknesses of the child protection procedures in the UK. Discontinuities in which child protection plans were not implemented arose because of limitations in the plans made, obstacles to implementation and weaknesses in the conduct of review meetings which rarely questioned the management of cases even when it was clearly deficient. The construction of risk made during the investigation carried over into the initial conference, fed into decisions about registration and had an enduring influence on the way in which later risks to children were interpreted. However, this meant that new information which challenged this view of risk was often ignored. Continuities were also evident between adequate plans for children’s safety made at initial conferences and their subsequent protection. However, when children remained at home with an abusing parent, this remained true only when a new key worker had been allocated at the time of the conference. These initial plans also had an impact on the interventions provided, especially those for treatment. These findings emphasize the importance of adequate planning for children and families at initial child protection conferences and the need for an overhaul of the conduct of reviews if they are to be used more effectively.
Reflections on risk in child protection: is it time for a shift in paradigms?
Authors: Houston  , Griffiths
Published: March 2003

Approaches to risk assessment and management in child protection have been developed largely within an objectivist paradigm and this has led to an emphasis on prediction, control and culpability. This paper argues that the objectivist paradigm has failed to provide valid and reliable measures of risk and has replaced a focus on the subject (the individual) with a one‐sided focus on objectified risk factors. Because of these limitations, it is argued that risk should be explored from an alternative, subjectivist paradigm. The paper outlines the implications of this shift for social work practice with children and their families, by advocating the re‐instatement of the subject and a return to ‘relationship’ as the guiding rationale for social work intervention.
Psycho‐social outcome of parents and young children after renal transplantation
Authors: Douglas  , Hulson  , Trompeter
Published: March 2003

This cross‐sectional study aims to assess whether renal transplantation in children under the age of 6 years has an effect on the child's later behaviour and eating and whether this outcome is related to differences in the levels of stress and coping skills shown by the parents. In this small sample of 14 children aged under 8 years, renal transplantation in the pre‐school age range did not have any marked adverse effect on the children's emotional or behavioural state. The children's severe eating problems dramatically improved after transplant. Long‐term, early tube‐feeding does not impair the development of normal feeding patterns in these children. Parental stress levels were not elevated in the post‐transplant period and parents tended to use passive coping strategies to manage the chronic illness in their child.
Assessment of parents and young children (Children Act 1989) — a child psychotherapy point of view
Authors: Baradon T. , Sinason V. , Yabsley S.
Published: March 2003

The criteria used by professionals in assessing child care cases are not always made explicit, partly because of the ambiguity of the terms ‘vulnerability’ and ‘at risk’. This paper presents a child psychotherapy view of what professionals may look at in terms of the interactions between parent and young child and how these may be understood. ‘Reasonable expectations’ of child development and parental care are considered. In terms of the child, overall attachment and communication needs and the specific developmental phase in terms child's maturing cognitive and socio‐emotional functions are emphasized. In terms of the parent, the capacity to see the baby as separate from their own internal conflicts and to reflect upon the infant's mental state are seen to be pivotal to the infant's psychological well‐being. The authors discuss the unconscious re‐enactment of malignant patterns from the past through the relationship with the baby, and why parents are sometimes unable to avoid this. Finally, the authors suggest that assessment of the capacity for change in vulnerable parent–infant constellations must take into account the baby's developmental timetable.Keywords: Children Act 1989, assessment of risk, unconscious representations, parent–infant interactions, child developmental time‐table
A prospective study on quality of life and traumatic events in early life — a 30‐year follow‐up
Authors: Ventegodt S.
Published: March 2003

Aim To investigate the connection between early life trauma and the quality of life some 30 years later in Denmark.

Design Prospective, longitudinal study with questionnaire‐based follow‐up survey.

Methods In ‘The Quality of Life Research Study of 10 000 Danes’, a newly designed questionnaire was mailed in February 1993 to 7222 persons from the Prospective Paediatric Cohort of persons born at the State University Hospital in Copenhagen (Rigshospitalet) between 1959 and 1961. Response rate was 64% (4626 people between the ages 31–33).

Variables Mother’s attitude towards her pregnancy, child being placed in a children’s home, mother using antipsychotic drugs indicating acute, mental illness, child adopted in the first year of life and quality of life of the child 31–33 years later.

Results Of the early life traumas studied, only relatively weak connections to the quality of life in later life were found.

Conclusions These relatively weak findings suggest that the children that survive to adulthood are resilient to many adverse events in early life.
Turn‐taking in early vocal interaction: a comparison of premature and term infants’ vocal interaction with their mothers
Authors: Reissland N. , Stephenson T.
Published: March 2003

Aims The present study was designed to test the hypothesis that mothers of premature infants compared with mothers of term infants differ in the structure which they impose on the vocal exchanges with their infants. Methods Thirteen mothers and their premature and term babies, were observed at discharge and 2 months later in three situations: free play, changing nappy, and feeding. Maternal child‐directed speech was coded as well as the timing of their utterances in respect to the infants’ vocalizations. The mean relative frequency of infant vocalizations following maternal child‐directed speech was computed. Results It was found that mothers of premature babies in comparison with mothers of term babies, followed significantly more often their infants’ vocalizations with an utterance directed at the child. In contrast, term infants compared with preterm infants followed significantly more often their mother’s utterances with a vocalization. Conclusion Mothers of premature and of term babies differ in their timing of child‐directed speech. This might have implications for the language development of premature and term infants.
Programme quality in Australian early special education: an example of participatory action research
Authors: Beamish W. , Bryer F.
Published: March 2003

A study of programme quality of early intervention in a large governmental early special education service in Queensland, Australia employed a collaborative methodology of participatory action research. This approach has been encouraged strongly for disability‐focused research, but the approach is demanding and few examples have been reported. In this multistage 4‐year project, indicators of programme quality were generated from staff and parents in the service, validated throughout the service, and generalized across the nation. Examples of the implementation of this methodology across these stages are reported, and benefits and compromises are examined.
How do Child Development Teams work? Findings from a UK national survey
Authors: McConachie H. R. , Salt A. , Chadury Y. , McLachlan A. , Logan S.
Published: March 2003

The area of child disability is the ‘Cinderella’ of community child health services. It lacks a clear commissioning model, agreed quality standards or guidance on the level of resources required. In this climate of uncertainty, a national survey of Child Development Teams was undertaken in order to describe their basic structure and processes. The paper reports information from 242 multidisciplinary teams providing local services, with statutory funding, to children with neurodevelopmental disability and their families. The picture presented is encouraging in part. For example, 79% of teams operate from a Child Development Centre, which may be expected to enhance team communication. In terms of the initial assessment process for a developmentally delayed child, most teams (91%) report that they would hold a case discussion afterwards, although only 74% would always include parents, and only 70% always give their report(s) to parents. The impression of management practices is weak, with only 62% giving a clear answer about who manages the team, and less than half having a written policy or contract for the team's work. The survey findings provide a sampling framework from which further evaluative research can be generated.
Enuresis and encopresis in a South Indian Population of Children
Authors: Hackett R , Hackett L , Bhakta P , Gowers S
Published: March 2003

Introduction

Though bladder and bowel control are important developmental milestones in all cultures, the prevalence of enuresis and encopresis has rarely been studied in developing countries despite there being factors in these countries that could affect it. This study reports the prevalence and associations of enuresis and encopresis in children in Kerala, India.

Method

The parents of 1403 randomly selected 8–12‐year‐old children were interviewed. The prevalence of enuresis and encopresis was ascertained using Rutter’s A2 scale. Subsamples of children underwent psychiatric, physical and psychometric evaluations.

Results

Of the children, 18.6% had had an episode of enursis in the past year and 4.3% in the past week. Four per cent had had an episode of encopresis in the past year. Enuresis was associated with parents’ education, physical and psychiatric symptoms in the child, poor academic achievement and lax parental attitudes to toilet training. Encopresis was associated with male sex, physical and psychiatric symptoms, poor academic achievement, early separation and not having a toilet.

Discussion

The prevalence of enuresis compares with western countries, but encopresis is commoner. The associations of enuresis suggested a multifactorial model in which parental competence was prominent. This study de‐emphasized the importance of neurodevelopmental factors in enuresis and encopresis in this age group.
Attrition among adolescents and infants involved in a parenting intervention
Authors: Letourneau N
Published: March 2003

Attrition was assessed in a randomized trial of a parenting intervention programme for adolescent mothers and their infants. Infants who were admitted to the neonatal intensive care unit, mothers who had partner difficulties, and mothers and infants who were visited for less than 60 min a week on average (typically in the control group) were more likely to miss one of the two follow‐up visits.
Children’s play
Authors: McArdle Paul
Published: March 2003

This paper draws upon research from a number of disciplines to examine the significance of children’s play. It concludes that play may well be central to normal personality development. However, its place in contemporary Western society is not secure, perhaps risking the development and well‐being of urban and disadvantaged children in particular.
‘Not by bread alone’: impact of a structured 90‐minute play session on development of children in an orphanage
Authors: Taneja V. , Sriram S. , Beri R.S. , Sreenivas V. , Aggarwal R. , Kaur R.
Published: March 2003

Background and objectives
In developing countries, caring for the large number of babies in orphanages is very hard work. Whereas the physical needs of most of the children are met, play often gets neglected. Studies have repeatedly shown that babies in such institutionalized settings suffer from severe psychomotor retardation. The aim of this project was to develop an intervention programme of structured play. We hypothesized that such an intervention would result in acceleration of psychosocial development in otherwise healthy institutionalized children.

Design
Prospective longitudinal.

Setting
Mother Teresa’s Orphanage, run by Missionaries of Charity.

Subject

and methods
All 30 children in the orphanage aged 6 months–2.5 years, were assessed for their Motor, Mental and Social Quotients, using the Indian adaptation of Bailey’s Scale of Infant Development(DASII) and the Vineland’s Social Maturity Scale. A structured ‘Regime of Play’ was then built into the routine of the orphanage. A repeat developmental assessment was performed at the end of 3 months to assess the impact.

Results
Out of the original cohort of 30, 19 children were available for post‐intervention assessments. The remainder were adopted before their assessments. Their mean Motor Quotient rose from 63.7 to 81.7, mean Mental Quotient rose from 65.8 to 89.6 and the mean Social Quotient rose from 61.9 to 91.3, a gain of 18, 23 and 30 points respectively (p < 0.0001). There was also an overall change in the environment of the orphanage. Children became more active, playful, responsive and independent. Contrary to what caretakers assumed, their workload actually decreased. The responsiveness in the children awakened as a result of play, acted as a positive feedback for caretakers to continue the play sessions.

Conclusions
This study shows that short daily sessions of play can significantly improve the development of children in such institutions. It is vital to remember that children grow ‘Not by Bread Alone’.
What families with children with brittle bones want to tell
Authors: Claesson I. Bernehäll , Brodin J.
Published: March 2003

Osteogenesis imperfecta or brittle bone disease (BBD) is a most unusual disease and a limited number of people in the world are suffering from it. Most studies focus on the medical aspects of the disease and very little has been done with regard to the pedagogical and psycho‐social aspects of the disease. This article is based on a questionnaire answered by 30 families, and interviews with 10 families with children and adolescents with BBD, and the purpose is to survey the consequences of the disease in daily life. Although medical treatment is of utmost importance, it is necessary to regard also other aspects, as it is significant to have a holistic view of the child in his/her environment.