bluuebunny/crossref_metadata_2025 huggingface dataset:
A dental practice placement scheme: benefits for practitioners and undergraduates
Authors: Pau* A. K. H. , Croucher R.
Published: March 2003

Objectives: To report the feedback from general dental practitioners (GDPs) and dental undergraduates who participated in a general dental practice placement scheme.

Methods: Subjects All 61 students in a year made 2 to 3 full day visits, individually or in pairs, to 44 general dental practices allocated to them. Thirty four GDPs completed and returned the questionnaire, representing a response rate of 77%. Data collection Formal feedback from the students and GDPs were obtained through 6 structured seminar sessions and a postal questionnaire respectively. Analysis Sifting, indexing and charting the data according to key issues and themes.

Results: All 61 students attended the feedback sessions, 34 GDPs (response rate 77%) returned the questionnaire. The two most common themes that students reported having gained insight into were personal/professional development and practice management. The common positive aspects reported by the GDPs included exposure to the General Dental Service (GDS), motivation for undergraduate training and benefits for GDPs. These benefits included encouragement for the GDPs to reflect critically on their clinical practice, focus on their practice facilities and management, and stay in touch with developments in dental education. Through their visits and assignments, students gained skills in observation, interviewing, communication, relation‐building and report writing.

Conclusions: Placements of dental undergraduates in general dental practices enable students to gain insight into the GDS, develop key transferable skills and undergo professional socialisation. They are also beneficial and enjoyable for the GDPs who participated.
2.2 Continuous quality improvement
Authors: Rohlin Madeleine , Schaub Rob M.H. , Holbrook Peter , Leibur Edvitar , Lévy Gérard , Roubalikova Lenka , Nilner Maria , Roger‐Leroi Valerie , Danner Gunter , Iseri Haluk , Feldman Cecile
Published: March 2003

Continuous quality improvement (CQI) can be envisaged as a circular process of goal‐setting, followed by external and internal evaluations resulting in improvements that can serve as goals for a next cycle. The need for CQI is apparent, because of public accountability, maintaining European standards and the improvement of dental education. Many examples are known where recommendations from both external and internal evaluation are used for the improvement of dental education. Unfortunately, the implementation of the recommendations is inconsistent, rarely systematic and usually not transparent. This section agreed that it is essential to apply CQI in a structured, systematic and transparent way if we are to improve and maintain the quality of dental education. A model is proposed which includes three aspects: a) the process of CQI; b) the subjects to which CQI should be applied; and c) the management tools to govern CQI. It is stressed, that CQI is a process that can be applied in any dental school irrespective of curriculum or educational approach within the relevant context of the country or the region. The approach needs to recognize the complexity and the need to balance a quality improvement with accountability. A CQI system is also constrained in any organization by the attitudes and values of the staff. Inevitably there has to be a wide range in the application of CQI. Nevertheless, an agreed model on CQI might enhance convergence towards higher standards of dental education. The process of CQI can be supported by developments in information and communication technology (ICT): collection of data, identifying the steps in CQI, formats of reports, etc. The section was set, as one of its tasks, to advise on the development of a network based on a number of case studies on the application of CQI in dental education.
Can inconspicuous legumes facilitate alien grass invasions? Partridge peas and fountain grass in Hawai‘i
Authors: Carino Debbie A. , Daehler Curtis C.
Published: March 2003

We investigated the potential role of a nitrogen‐fixing legume in facilitating invasion by an alien grass,Pennisetum setaceum(fountain grass) into nativeHeteropogon contortusgrasslands in Hawai‘i. Both grasses are C4perennials. Many formerly extensiveHeteropogongrasslands have been reduced to remnants surrounded byPennisetum. An inconspicuous annual legume,Chamaecrista nictitans(partridge pea), was commonly associated withPennisetumstands but was found at higher densities inPennisetum‐Heteropogonmixtures. In the field, we also found higher exchangeable soil nitrogen beneathChamaecrista‐Pennisetum‐Heteropogonmixtures than beneath neighboring pureHeteropogonstands. We then used greenhouse experiments to test the hypothesis that increased nitrogen facilitatesPennisetum's invasion of establishedHeteropogon. Under low nitrogen conditions,Pennisetumseedlings planted beneath establishedHeteropogonplants grew very little (<0.3 g biomass after 16 weeks), and their growth was not affected by high or low water treatments. In contrast, under high nitrogen conditions, in both low and high water treatments,Pennisetumseedlings grew rapidly, averaging 60 fold the biomass of seedlings in the low nitrogen treatment and exceeding the biomass of the establishedHeteropogonplants under which they were planted. We also comparedPennisetum‐Heteropogonseedling competition in the presence and absence of liveChamaecrista. The growth ofPennisetumwas not directly facilitated by liveChamaecristain the greenhouse pots, but theChamaecristadid not increase available soil nitrogen until after it had died. Our results suggest that increases in soil nitrogen, like those associated with an inconspicuous alien legume, can facilitate an alien grass’ invasion of a native grassland.
Variation in mistletoe seed deposition: effects of intra‐ and interspecific host characteristics
Authors: Aukema Juliann Eve , Del Rio Carlos Martínez
Published: March 2003

We investigated differences in host infection by a desert mistletoe, Phoradendron californicum, and examined one of the processes that contributes to these differences: variation in seed deposition among host individuals and species. In the Sonoran Desert, P. californicum parasitizes the sympatric leguminous trees Olneya tesota, Cercidium microphyllum, Prosopis velutina, Acacia constricta, and Acacia greggii. We hypothesized that seed deposition depends on host height and crown architecture. At a site in Arizona, frequency of infection did not reflect host relative abundance. Olneya tesota was parasitized at a higher frequency than expected from its abundance and maintained the highest mistletoe loads per individual host. In contrast, P. velutina was infected less frequently than expected. Infection frequency increased with host tree height for all hosts. Mistletoe seed deposition by avian dispersers differed among host species and was disproportionately high in O. tesota and P. velutina. Seed deposition was higher in infected than in non‐infected host trees, and increased with tree height in O. tesota but not in C. microphyllum. We suspect that increased seed deposition with height in O. tesota may be due to the preference of seed‐dispersing birds for higher perches. Some host tree species, such as C. microphyllum and A. constricta, probably received fewer mistletoe seeds because birds avoid hosts with dense and spiny crowns. Mistletoe populations are plant metapopulations in which host trees are patches and the frequency of infection in each host species/patch type is the result of interspecific differences in the balance between mistletoe colonization and extinction. From this perspective, our study of host use and seed dispersal is a metapopulation study of patch occupancy and propagule distribution among available patch types. Our seed‐dispersal study demonstrates that the mechanisms that create pattern in patchy plant populations can be investigated in mistletoe systems.
Dispersal and life span spectra in plant communities: a key to safe site dynamics, species coexistence and conservation
Authors: Strykstra Roel J. , Bekker Renée M. , Van Andel Jelte
Published: March 2003

Dispersal and life span of individual plant species within five plant communities were assessed to obtain a characterization of these communities in this respect. Such a characterization is important in the context of restoration and maintenance. The most frequent species of five communities were ranked in eight classes according to their level of seed dispersal capability, their seed bank formation (dispersal in time and space) and their individual life span. In the communities, all eight classes were found, but communities differed in the distribution of the species over the classes.  A theoretical framework was constructed to use the level of specialization of plant species in terms of dispersal in space and time, and life span, to define the characteristics of safe site dynamics within communities. Following simple rules, the relative reliability of the occurrence of safe sites in space and time was defined. After that, the relative reliability of the habitat was linked to the best fitting combination of trait specialization level. Having defined this link, communities could be characterized in a comparative way by their level and pattern of reliability of the opportunities for recruitment in space and time.  The meaning of the coexistence of a range of trait combinations in one community was discussed. It was postulated that habitat reliability can explain this by assuming that the habitat of the community is part of a larger system, or consists of several “subsystems”. These insights need to be considered in nature conservation. Succession and also specializations beyond the scope of dispersal and life span may influence the occurrence of species in a seemingly unfit habitat (for instance the occurrence of semi parasitic annuals in a community of perennials, because they use the perennial root system of other species). Finally, the meaning of safe site reliability in space and time in the context of restoration of communities was discussed. The reliability in space and time may be different today from that of the past, which restricts the feasibility of restoration of communities.
Forest bird diversity in Mediterranean areas affected by wildfires: a multi‐scale approach
Authors: Herrando Sergi , Brotons Lluís
Published: March 2003

Fire is a key mechanism creating and maintaining habitat heterogeneity in Mediterranean landscapes by turning continuous woody landscapes into mosaics of forests and shrublands. Due to the long historical role of fires in the Mediterranean, we hypothesised a moderate negative effect of this type of perturbation on forest bird distribution at a landscape level. We conducted point bird censuses in Aleppo pine forest patches surrounded by burnt shrublands and studied the relationships between three ecological groups of bird species (forest canopy species, forest understorey species, and ubiquitous species) and the features of local habitat, whole patch and surrounding landscape. We used a multi‐scale approach to assess the effects of landscape variables at increasing spatial scales on point bird richness. Regarding local habitat components, canopy species were positively associated with tall pines while understorey species with the cover of shrubs and plants from holm‐oak forests. Forest birds were positively related to patch size and irregular forest shapes, that is, with high perimeter/size ratios. Thus, these species did not seem to perceive edges as low quality but rather favourable microhabitats. We did not detect any negative effect of isolation or cover of woodlands in the landscape on the presence of forest species after local habitat factors had been accounted for. Finally, only local habitat factors entered the model for ubiquitous species. We suggest that mosaic‐like landscapes shaped by fires in the Mediterranean basin are not strongly associated with negative effects fragmentation on forest birds other than those related with habitat loss.
The impact of American mink Mustela vison and European mink Mustela lutreola on water voles Arvicola terrestris in Belarus
Authors: Macdonald D. W. , Sidorovich V. E. , Anisomova E. I. , Sidorovich N. V. , Johnson P. J.
Published: March 2003

In the U.K. the impact of introduced American mink Mustela vison, on water voles Arvicola terrestris, may be exacerbated by habitat loss and fragmentation. Pristine wetlands in Belarus, which American mink invaded in the early 1990s, provide a three‐pronged opportunity to test this hypothesis. First, we examine the evidence that, even in the unmanaged wetlands of our Belarussian study site, American mink have reduced water vole populations. Second, we ask whether habitat size, type and isolation mitigate the impact of American mink predation. Thirdly, we explore whether water voles are at greater risk of predation from American than European mink because of their patterns of habitat use. Following the invasion of American mink, water voles were most abundant in small, still‐water sites, far from river banks, while American mink were most active in large, running‐water sites. Small mammal remains were found in a higher percentage of American than European mink scats, and of these, more were water vole in American mink scats. The occurrence of water voles in scats of both mink species declined after the American mink invaded and established. Our results provide at least circumstantial evidence that American mink limit water vole populations even in unmanaged wetland eco‐systems, and that they have a greater impact than their European congener at least partly because they make greater use of isolated marshes. Although by no means providing complete protection, the configuration and dispersion of available habitat mitigated the impact of American mink on water voles. This raises the possibility that habitat restoration, especially through the establishment of isolated enclaves, could help reduce the effect of American mink in the U.K. These observations are of broader interest in the context of assessing the effect of multiple pressures on vulnerable species.
Diffuse coevolution: constraints on a generalist parasite favor use of a dead‐end host
Authors: Forbes Mark R. , Muma Katherine E. , Smith Bruce P.
Published: March 2003

Many evolutionary models and empirical studies of parasite‐host interactions consider single species of parasites exploiting single host species. However, many parasites are generalists in that they parasitize more than one host species (often many more) and establish associations with other hosts that cannot be described as true parasitism. We identify such an association, explain how constraints may maintain it, and indicate why such diffuse interactions are deserving of attention. We describe the use of two closely related Sympetrum dragonfly species by larvae of the water mite Arrenurus planus Marshall. Adults of one dragonfly species are resistant whereas adults of the other species are almost wholly susceptible to A. planus. However, A. planus attaches as often to the resistant host as it does to the susceptible host species when relative abundance and seasonal timing of adult emergence of both species is considered. We present evidence that mites track the susceptible host and are most active early in the season, when early‐emerging unsuitable hosts are also present. Thus, use of resistant hosts appears an unavoidable outcome of constraints promoting discovery and use of susceptible hosts. Such findings have implications for studies of local adaptation and host switching.
Patterns of commonness and rarity in central European birds: reliability of the core‐satellite hypothesis within a large scale
Authors: Storch David , Šizling Arnošt L.
Published: March 2003

The frequency distribution of species’ area of occupancy is often bimodal, most species being either very rare or very common in terms of number of occupied sites. This pattern has been attributed to the nonlinearity associated with metapopulation dynamics of the species, but there are also other explanations comprising sampling artifact and frequency distribution of suitable habitats. We tested whether the bimodal frequency distribution of occupied squares in central European birds could be derived solely from the frequency distribution of species population sizes (i.e. the sampling artifact hypothesis) or from the spatial distribution of their preferred habitats. Both models predict high proportion of very common species, i.e. the right side of frequency distribution. Bimodality itself is well predicted by models based on random placement of individuals according to their abundances but neither model predicts the observed prevalence of rare species. Even the combined models that assume random placement of individuals within the squares with suitable habitat do not predict such a high proportion of rare species. The observed distribution is more aggregated, rare species occupying a smaller portion of suitable habitat than predicted on the basis of their abundance. The pattern is consistent with metapopulation processes involving local population extinctions. The involvement of these processes is supported by two further observations. First, species rarity is associated with significant population trend and/or location on the edge of their ranges within central Europe, both situations presumably associated with metapopulation processes. Second, suitable habitats seem to be either saturated or almost unoccupied, which is consistent with the predictions of the metapopulation model based on nonlinear dynamics of extinction and colonization. Although the habitat suitability is an important determinant of species distribution, the rarity of many species of birds within this scale of observation seems to be affected by other factors, including local population extinctions associated with fragmentation of species’ habitats.
Inverse correlation between Ink4‐locus deletions and ICM‐DNA hyperdiploidyin childhood acute lymphoblasticleukaemia, relation to clinicalcharacteristics and outcome
Authors: Calero T. , Widell S. , Czader M. , Grandér D. , Söderhäll S. , Gustafsson G. , Einhorn S. , Porwit A. , Heyman M.
Published: March 2003

Abstract: Malignant cells from 72 children with ALL were analysed to investigate the relationship between DNA‐ploidy and deletion of the Ink4 locus containing the cell‐cycle regulating genes p16ink4a, p15ink4b and p14ARF. Image‐DNA cytometry (ICM) was used to assess DNA index (DI), and Southern hybridisation was carried out to detect deletions of the Ink4‐locus in the leukaemic cells. A DNA content equal to or exceeding 1.16, indicating hyperdiploidy, was detected in 21/72 patients (29%), 1/72 (1.3%) showed DNA‐hypodiploidy, and the remaining 50 patients (69%) had a DI within normal limits. Bi‐allelic deletion of at least two of the coding sequences from the Ink4 locus was observed in 23/70 (33%) patients. Mono‐allelic deletions within the locus were observed in 10/70 patients (14%), and 37/70 patients (53%) had normal signals for both sequences. Out of the 70 patients that could be analysed by both techniques only two had the combination of DNA hyperdiploidy and Ink4‐locus bi‐allelic deletion (p=0.004). DNA hyperdiploidy was not associated with any specific clinical characteristics, but there was a trend for a better prognosis for patients with DNA hyperdiploidy (p=0.09). Ink4‐locus deletion was associated with T‐cell phenotype and higher white blood cell counts at diagnosis and poor prognosis (p=0.0015). Multivariate analysis confirmed that Ink4‐locus deletion is an independent prognostic marker and a stronger determinant of outcome than DNA ploidy. When DNA ploidy and Ink4‐locus deletions were combined, novel subgroups with significantly different outcome could be observed. A group with DNA index 1.16 and no Ink4‐locus bi‐allelic deletions had an excellent prognosis (p‐EFS 0.93 at 60 months), patients with Ink4‐locus bi‐allelic deletion and a DNA index <1.16 fared worst (p‐EFS 0.57) and patients with no Ink4 deletions and without hyperdiploidy had an intermediate outcome (p‐EFS 0.79). The reason for the inverse correlation between DNA ploidy and Ink4 deletion and their combined impact on prognosis remains unclear, and possible reasons are discussed.
Detection of reticulated platelets: estimating the degree of fluorescence of platelets stained with thiazole orange
Authors: Joutsi‐Korhonen Lotta , Sainio Susanna , Riikonen Seija , Javela Kaija , Teramo Kari , Kekomäki Riitta
Published: March 2003

Abstract: The primary problem in the measurement of reticulated platelets (RP) stained with thiazole orange (TO) by flow cytometry is the definition of a threshold limit for fluorescence positivity. We evaluated settings for the threshold gate for TO positivity based on two principles: a fluorescence histogram (median FL1, Relative FL1) or a plot of forward light scatter (FSC; reflecting the distribution of the platelet size) versus fluorescence intensity (% RP). These methods were applied prospectively in examination of 54 healthy blood donors (16 females) and a total of 50 blinded patient samples: pregnant women with thrombocytopenia (Group 1A, n=11), thrombocytopenic women after delivery (Group 1B, n=9) and healthy women with a thrombocytopenic newborn (Group 2, n=30). Group 1A displayed higher median FL1 (mean 306, CI 279–332) as compared to that of Group 2 (mean 266, CI 255–277; p=0.0038) or to that of the female controls (mean 249, CI 231–268; p<0.001). Relative FL1 was also higher in the patients of Group 1A than those of Group 2 (p=0.037). When analysing the % RP, the difference between these groups was not significant. In the patients (n=50), the median FSC (mean 407, SD 40, CI 395–418) was also higher than that of the controls (n=54; mean 383, SD 25, CI 376–390; Mann–Whitney U‐test, p=0.0015). In Group 1A, a significant correlation was observed between the Patient median FL1 and Patient median FSC (r=0.62, p=0.043). When developing methods for the measurement of RP, it seems to be useful to analyse the data with more than one principle to define the threshold limit for TO positivity.
The plasminogen activator inhibitor (PAI)‐1 promoter 4G/4G genotype is not associated with ischemic stroke in a population of German children
Authors: Nowak‐Göttl Ulrike , Sträter Ronald , Kosch Andrea , Von Eckardstein Arnold , Schobess Rosemarie , Luigs Petra , Nabel Petra , Vielhaber Heinrich , Kurnik Karin , Junker Ralf ,   the Childhood Stroke Study Group
Published: March 2003

Abstract: Objectives: To investigate the relationship between an insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor (PAI)‐1 gene and childhood patients with a past history of ischemic stroke. Methods: The PAI‐1 4G/4G genotype and the coinheritance with lipoprotein (Lp) (a) levels, the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, and the methylenetetrahydrofolate reductase (MTHFR) T677T genotype were studied in 198 Caucasian children with stroke and 951 controls (same age, sex and ethnical distribution). In a randomly selected subgroup of patients/controls (n=60) PAI‐1 activities have been investigated. Results: The distribution of the 4G/5G genotypes was no different in childhood stroke patients and controls, with a 4G allele frequency of 55.8% in patients compared with 53.8% in control subjects (P=0.49). The 4G/4G genotype compared with the remaining genotypes was present in 43 cases and 167 (17.6% vs. 21.7%; OR/CI: 1.30/0.89–1.98; P=0.3). PAI‐1 activity was significantly elevated (P<0.001) in the patient group. Conclusions: Data presented here suggest that the 4G/4G genotype is not a major risk factor in the aetiology of childhood ischemic stroke.
Decreased amount of mpl and reduced expression of glycoprotein IIb/IIIa and glycoprotein Ib on platelets from patients with refractory anemia: analysis by a non‐isotopic quantitative ligand binding assay and immunofluorescence
Authors: Izumi Masakazu , Takeshita Akihiro , Shinjo Kaori , Naito Kensuke , Matsui Hirotaka , Shibata Kiyoshi , Ohnishi Kazunori , Kanno Takashi , Ohno Ryuzo
Published: March 2003

Abstract: Using a non‐isotopic ligand binding assay and immunofluorescence, we examined the amount of mpl, glycoprotein IIb/IIIa (gpIIb/IIIa) and glycoprotein Ib (gpIb) on platelets from healthy volunteers and patients with refractory anemia (RA). For the analysis of mpl expression, we applied both a non‐isotopic ligand binding assay and immunofluorescence using anti‐mpl monoclonal antibody, and compared the results from both methods. The non‐isotopic ligand binding assay has been developed in our laboratory and is suitable for the quantitative analysis of a small amount of cytokine receptors such as mpl on platelets. In platelets from patients with RA, the amount of mpl expressed by the D value was 0.05±0.03 (mean±standard deviation), and was significantly lower than that in healthy volunteers (0.15±0.05, p<0.0001). The mean fluorescence intensities (MFI) of gpIIb/IIIa and gpIb on platelets from RA patients were 28.8±8.8 and 20.8±7.7, respectively, and were significantly lower than those on normal subjects (93.2±22.6 and 67.4±9.1, p<0.0001 and p<0.0001, respectively). There was a good correlation between the amount of mpl and the MFI of gpIIb/IIIa (p=0.794, p<0.0001) or gpIb (p=0.774, p<0.0001), and between those of gpIIb/IIIa and gpIb (p=0.728, p<0.0001). We demonstrated a decreased amount of mpl as well as a reduced expression of gpIIb/IIIa and gpIb on platelets from RA patients.
Haemorheological adaptation during pregnancy in a Latin American population
Authors: Kametas Nikos , Krampl Elisabeth , McAuliffe Fionnuala , Rampling Michael W. , Nicolaides Kypros H.
Published: March 2003

Abstract: Objective: To investigate haemorheological changes during pregnancy in a Latin American population and compare to previously published data from Caucasian populations. Design: Cross‐sectional study. Population: 75 pregnant women at 10–36 wk of gestation and 17 non‐pregnant female controls in Lima, Peru. All the women and their ancestors for three generations were born and lived at sea level. Methods: Viscosity, haematocrit and plasma fibrinogen, albumin and total protein concentrations were determined in blood samples obtained after an overnight period of fasting. Results: At 10 wk of gestation, total protein concentration and plasma viscosity were above non‐pregnant levels by about 15% and subsequently decreased linearly with gestation. Fibrinogen concentration was increased in the first trimester; it then decreased to a nadir at about 20 wk and subsequently increased. Albumin concentration decreased linearly with gestation. Haematocrit decreased from pre‐pregnancy levels at 10 wk to a nadir at about 26 wk. Blood viscosity increased in the first trimester and then decreased with gestation to a nadir at about 26 wk. Conclusion: In the first trimester of pregnancy blood and plasma viscosity are increased and they subsequently fall with advancing gestation. Plasma viscosity reflects the changes in total protein concentration, and blood viscosity is dependent on the interplay of changes in plasma viscosity and haematocrit.
Increased serum levels of soluble Fas in progressive B‐CLL
Authors: Osorio Lyda M. , Aguilar‐Santelises Miguel , De Santiago Angelina , Hachiya Takahisa , Mellstedt Håkan , Jondal Mikael
Published: March 2003

Abstract: Clinical progression of B‐cell chronic lymphocytic leukemia (B‐CLL) depends on survival and accumulation of leukemic cells, regulated in part by physical cell contact and soluble molecules. Here we have studied the Fas/FasL system in relation to clinical progression in B‐CLL. Serum levels of soluble Fas (sFas) and FasL (sFasL) were determined by ELISA in 43 progressive and 40 non‐progressive B‐CLL patients and in 21 control individuals. Correlation between sFas serum levels and clinical progression, stage and survival were statistically analyzed. We found high levels of sFas in B‐CLL sera correlated with disease progression (p<0.01). In addition, higher sFas levels were found in patients in stages II, III and IV in comparison to patients in stage 0 (p<0.05, p<0.01, p<0.03, respectively). Survival was significantly shorter for patients with 6 ng/ml sFas serum levels, although a multivariate analysis did not show sFas to be a significant independent prognostic factor. Fresh B‐CLL cells showed only low levels of membrane expression, which were not correlated to sFas levels in serum. In vitro activation of B‐CLL cells increased Fas expression, as reported earlier, and induced cells to release sFas into the supernatant. In conclusion, our results indicate that sFas in serum may be a useful parameter for the prediction of clinical progression in B‐CLL.
Successful treatment of an acquired haemorrhagic diathesis due to factor X deficiency with chemotherapy
Authors: De Jager E. , Bieger R. , Castel A. , Kluin PH. M.
Published: March 2003

Abstract: A 70‐yr‐old woman presented with a severe haemorrhagic diathesis due to an acquired factor X deficiency. A plasma infusion study showed that exogenous factor X was eliminated very effectively from the patient's circulation. A bone marrow biopsy was consistent with plasma cell dyscrasia. Neither an abdominal fat biopsy nor the bone marrow biopsy confirmed an amyloidosis, although clinically no other diagnosis seemed possible. Treatment with intermittent chemotherapy, consisting of vincristine, cytoxan and prednisone, yielded definite clinical and laboratory improvement.
Effects of arsenic trioxide (As2O3) on leukemic cells from patients with non‐M3 acute myelogenous leukemia: studies of cytotoxicity, apoptosis and the pattern of resistance
Authors: Lehmann S. , Bengtzen S. , Paul A. , Christensson B. , Paul C.
Published: March 2003

Abstract: Arsenic oxide (As2O3) has recently been reported to induce remission in a high percentage of patients with acute promyelocytic leukemia (APL). The aim of this study was to investigate the effects of As2O3 at therapeutic concentrations on cell viability and apoptosis on leukemic cells from patients with non‐M3 acute myelogenous leukemia (AML) and to study the resistance profile compared to conventional AML drugs. Cells from 20 patients were exposed to therapeutic concentrations of As2O3 continuously for 96h. As2O3 reduced the viability in blast cells from all the 20 tested patients compared to unexposed controls (p‐value: 0.02 at 0.05 µM; <0.005 at 1.0 µM and higher concentrations). An increase in the apoptotic rate was also seen after incubation with As2O3. Parallel to the incubation with arsenic the in vitro sensitivity to a number of chemotherapeutic agents commonly used in AML was studied. Correlation coefficients for the in vitro sensitivity were highly significant between the conventional AML drugs except for Ara‐C. For As2O3, all the correlation coefficients were negative and ranged between −0.05 and −0.51. Furthermore, increased P‐gp expression in a multidrug resistant HL‐60 cell line did not decrease the sensitivity to As2O3 as compared to the parental cell line. Neither did a P‐gp‐transfected variant of the K562 cell line show decreased sensitivity to As2O3. We conclude that As2O3 at therapeutic concentrations induces apoptosis and cytotoxic effects in blast cells from patients with non‐M3 AML, and that As2O3 differs from conventional AML drugs with respect to the mechanisms that confer resistance to the drugs.
Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial
Authors: Semba R. D. , Kumwenda N. , Taha T. E. , Mtimavalye L. , Broadhead R. , Garrett E. , Miotti P. G. , Chiphangwi J. D.
Published: March 2003

Abstract: Introduction: Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans. Objective: To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia. Methods: A randomized, double‐blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 µg retinol equivalent), iron (30 mg), and folate (400 µg) versus iron (30 mg) and folate (400 µg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa. Results: Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (±SEM) change in haemoglobin from enrollment to 38 wk was 4.7±1.6 g/L (p=0.003) and 7.3±2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39±5.00 (p=0.63) and −2.87±3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow‐up within either group. Conclusions: Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi.
Haemoglobin concentrations appear to be lower in indigenous Greenlanders than in Danes: assessment of haemoglobin in 234 Greenlanders and in 2804 Danes
Authors: Milman Nils , Byg Keld‐Erik , Mulvad Gert , Pedersen Henning Sloth , Bjerregaard Peter
Published: March 2003

Abstract: Objective: To compare haemoglobin concentrations in Greenlanders and Danes.

Methods: Haemoglobin was measured in a population survey in 1993–1994 comprising 234 indigenous Greenlandic individuals (115 men) aged 19–82 yr and in Copenhagen County 1983–1984 comprising 2804 Caucasian Danes (1444 men) aged 30–60 yr. The Greenlandic participants were residents in the capital Nuuk (n=70), the town Ilulissat (n=74), and four settlements in the Uummannaq district (n=90). The significance of differences was assessed by Student's t‐test, and the ξ2‐test. Correlations were assessed by Spearman's correlation coefficient (rs).

Results: Greenlanders: Haemoglobin levels were not correlated with age or consumption of traditional foods, and were not significantly different in the three residential areas. Mean haemoglobin was higher in men, 146±9.6 (SD) g/L, than in women, 132±9.6 g/L (p<0.0001). Mean haemoglobin in iron‐replete men with serum ferritin >32 µg/L (n=104) was 146±9.3 g/L, and in iron‐replete women (n=68) 133±10.4 g/L (p<0.0001). The 5th percentile for haemoglobin in iron‐replete men was 133 g/L (8.3 mmol/L) and in women 118 g/L (7.3 mmol/L). The prevalence of iron deficiency anaemia (i.e. ferritin <13 µg/L and Hb <5th percentile for iron‐replete men and women) was 0% in men, 2.78% in women 50 yr of age and 0% in women >50 yr of age. Danes: Mean haemoglobin in men was 154±10.0 g/L and in women 138±10.4 g/L (p<0.0001). Haemoglobin in iron‐replete men (n=1379) (i.e. serum ferritin >32 µg/L) was 154±10.7 g/L, and in iron‐replete women (n=1003) 140±9.6 g/L (p<0.0001). Mean haemoglobin was lower in premenopausal than in postmenopausal women (p<0.0001). The 5th percentile for haemoglobin in iron‐replete men was 137 g/L (8.5 mmol/L) and in women 124 g/L (7.7 mmol/L). The prevalence of iron deficiency anaemia (i.e. ferritin <13 µg/L and Hb <5th percentile for iron replete men and women) was 0% in men, 1.92% in women 50 yr of age and 0% in women >50 yr of age.

Conclusion: Haemoglobin concentrations in Greenlanders were significantly lower than in Danes both in men (p<0.0001) and in women (p<0.0001). Δ(mean haemoglobin) in men was 8.0 g/L (0.5 mmol/L) and in women 6.2 g/L (0.4 mmol/L). Variations in haemoglobin levels may be due to genetic differences.
Steroid‐refractory chronic idiopathic thrombocytopenic purpura associated with hepatitis C virus infection
Authors: Sakuraya Masataka , Murakami Hirokazu , Uchiumi Hideki , Hatsumi Nahoko , Akiba Tohoru , Yokohama Akihiko , Matsushima Takafumi , Tsukamoto Norifumi , Morita Kimio , Karasawa Masamitsu , Ogawara Hatsue , Nojima Yoshihisa
Published: March 2003

Abstract: Objectives: Hepatitis C virus infection has often been suggested as a possible cause of various kinds of autoimmune diseases. The aim of this study was to determine the relationship between chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection and to characterize the clinical features of anti‐HCV antibody (HCVab) positive chronic ITP patients. Subjects and methods: We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age 42.3 yr, range 11–86 yr) using the third‐generation ELISA method. Results: HCVab was detected in 11 of the 79 patients (13.9%). Quantitative HCV‐RNA studies showed a high serum concentration of HCV‐RNA in these patients. The platelet counts in these 11 HCVab‐positive patients (Group 1) were lower than in the 68 HCVab‐negative patients (Group 2)[(2.6 ± 0.9) versus (4.9 ± 3.0) × 1010/L, respectively; p<0.02]. Significantly more patients in Group 1 required prednisolone therapy (10/11, 90.9%) than in Group 2 (31/68, 45.6%) (P < 0.005). The response rate to prednisolone treatment was significantly higher in Group 2 (19/31, 61.3%) than in Group 1(0/10, 0%) (P < 0.001). There was no difference in the response to splenectomy between Groups 1 (4/7, 57.1%) and 2 (3/5, 60%). Conclusion: Given these findings, we recommend that HCVab is measured upon diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab in the event that prednisolone treatment is ineffective.
Hyposialated 185 kDa CD45RA+ molecules attain a high concentration in B lymphoma cells and in activated human B cells
Authors: Yu Y. , Rabinowitz R. , Polliack A. , Ben‐Bassat H. , Schlesinger M.
Published: March 2003

Abstract: Alternate splicing of exons of the CD45 molecule generates multiple isoforms differing in their molecular weights (MWs). In B‐lymphocytes the CD45RA isoform was previously shown to be expressed on glycoproteins with MWs of 220 and 205 kDa, while the CD45RO isoform was expressed on glycoproteins with MW of 180 kDa. The present study demonstrated that B cell lymphomas and activated B‐cells contain CD45 molecules with a MW of 185 kDa that express the CD45RA and CD45RC specificities but neither the CD45RB nor the CD45RO specificities. 185 kDa CD45RA+ molecules were detected in B cell lymphoma B lines, in Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell lines, and in tonsillar B cells, but not in normal, unstimulated peripheral blood B cells. These molecules were not detected in neoplastic and normal T cells. CD45RA+ 185 kDa molecules were present in B cells from three non‐Hodgkin's patients in leukemic phase were not detected in B lymphocytes of seven of nine CLL patients tested. Trypsin treatment eliminated only 220 kDa CD45RA+ molecules but not 185 kDa CD45RA+ molecules, indicating that the 185 kDa CD45RA+ molecules are not expressed on the cell surface. Pulse‐chase experiments, and studies on the effects of tunicamycin, neuraminidase and O‐glycosidase, indicated that the 185 kDa molecules are partially glycosylated CD45RABC molecules that constitute precursors of the 220 kDa molecules. The high concentration of 185 kDa CD45RA+ molecules in B lymphoma cells and in activated B cells seems to reflect a high turnover of CD45RA+ molecules characteristic for these cells.
Multiple γc‐receptor expression in adult T‐cell leukemia
Authors: Baba Hirofumi , Yamada Yasuaki , Mori Naoki , Hayashibara Toshihisa , Harasawa Hitomi , Tsuruda Kazuto , Sugahara Kazuyuki , Soda Hiroshi , Takasaki Yumi , Tawara Masayuki , Hirakata Yoichi , Tomonaga Masao , Kamihira Shimeru
Published: March 2003

Abstract:  Constitutive expression of the IL‐2 receptor (IL‐2R) on adult T‐cell leukemia (ATL) cells and the presence of permanent IL‐2‐dependent ATL cell lines indicate that the signal transduction system via IL‐2R is a key element for the development of this disease. IL‐2R is a member of the common γ‐chain (γc)‐receptor family and shares γ with IL‐4R, IL‐7R, IL‐9R, and IL‐15R. In addition to IL‐2R, ATL cells express IL‐15R and respond to IL‐15. In the present study, we examined other members of this receptor family. ATL cells showed various levels of IL‐4Rα (CD124) and IL‐7Rα (CD127) expression, and responded to these cytokines. In contrast, ATL cells hardly responded to IL‐9. As primary samples were a mixed population and the results may have been modified by contaminating normal cells, we used ATL cell lines as pure ATL cell populations. Here, we report that IL‐2‐dependent ATL cell lines also express IL‐4Rα and respond to IL‐4, which was verified by the activation of cytoplasmic transcriptional activator Stat6 protein. Moreover, a novel ATL cell line that grows stably in an IL‐7‐dependent manner was established from one of the cell lines, and IL‐7 induced Stat5 activation in this cell line. These results indicated that ATL cells have the potential to express all γc‐receptors except IL‐9R. Overlapping and switching of cytokine receptors supported the idea that ATL cells can rapidly select the appropriate γc‐receptor according to conditions.
Haematological malignancies in a general population, based on information collected from a population study, hospital records, and the Cancer Registry of Norway
Authors: Skjelbakken T. , Løchen M.‐L. , Dahl I.M.S.
Published: March 2003

Abstract: Objectives
: To investigate the prevalence and incidence of haematological malignancies, and to compare the rates found with those reported from the Cancer Registry of Norway.
Methods
: Three sources of information were used: (1) automated blood cell counts from 27 145 persons older than 24 yr (72% of those invited), participating in a population study (the Tromsø Study 1994–95); (2) patient medical records at the University Hospital of Tromsø during 1991–96; (3) the Cancer Registry of Norway.
Results
: (1) In the population study, 13 new cases of haematological malignancies were diagnosed. For five of these the early detection was probably beneficial. (2) From the hospital records another 59 participants and 36 non‐participants to the population study were found to have haematological malignancies. (3) Additionally, six cases were identified from the Cancer Registry. Totally, we thus identified 114 period prevalent cases, of which 86% had been reported to the Cancer Registry. Age‐adjusted period prevalence of haematological malignancies was 4.7‰ in men and 2.9‰ in women. The prevalence increased with age. There were 84 cases with leukaemia, lymphoma, or multiple myeloma diagnosed at any time and still alive at 31 December 1996 (point prevalence 2.2‰). Our estimated incidence of haematological malignancies did not differ significantly from that reported from the Cancer Registry.
Conclusion : We found approximately the same rates of haematological malignancies as the Cancer Registry, although an underreporting of 14% to the Cancer Registry was detected. The point prevalence of leukaemia, lymphoma, and multiple myeloma was 2.2%.
Patients with idiopathic myelofibrosis show increased CD34+ cell concentrations in peripheral blood compared to patients with polycythaemia vera and essential thrombocythaemia
Authors: Andréasson Björn , Swolin Birgitta , Kutti Jack
Published: March 2003

Abstract: The aim of the present work was to compare the results for some haematological variables in 12 patients with idiopathic myelofibrosis (IMF) with those of 21 patients with polycythaemia vera (PV), 22 patients with essential thrombocythaemia (ET) and 10 healthy control subjects. In each patient and control subject peripheral blood was used for analysis of flow cytometric measurement of CD34‐positive (CD34+) cells, in vitro colony growth and plasma erythropoietin (EPO) concentration. The mean concentration of CD34+ cells in the IMF group was 568±686×103 mL, which significantly (P<0.001 for each group) exceeded the means in PV, ET and control groups ((10.2±32.0)×103 mL, 3.0±3.7×103 mL and 1.9±0.8×103 mL, respectively). The mean number of EPO‐independent erythroid colonies (EEC) was 110±215 colonies per105 cells for the IMF patients. In comparison with the means for PV and ET patients (40±140 and 12±27 colonies per 105 cells, respectively) the difference did not reach statistical significance. The mean EEC for IMF patients was, however, significantly higher compared with the mean for the control subjects (P<0.05). The means for total erythroid colony growth with EPO added to the growth medium as well as for granulocyte‐macrophage colony‐forming units were significantly higher in the IMF group compared with the means for PV, ET and control groups (P<0.001 for each group). The mean plasma EPO was 204±290 IU/L in the patients with IMF compared with 6.6±7.9 IU/L in PV patients, 19.1±23.2 IU/L in ET and 10.3±7.8 IU/L in the control subjects. Due to considerable differences in haemoglobin concentrations no relevant conclusions could be drawn from the results for plasma EPO concentrations. Indeed, the majority of patients with IMF, PV and ET were on myelosuppressive treatment; additionally most PV patients received phlebotomy therapy. The results of the present study suggest that the circulating pool of stem cells and progenitor cells in peripheral blood is significantly increased in IMF patients compared with PV and ET patients as well as healthy control subjects. The most likely source for the elevated CD34+ cell concentration in peripheral blood is progenitor cells of extra‐medullar origin.
Complex interactions of δβ hybrid haemoglobin (Hb Lepore‐Hollandia) Hb E (β26 G→A) and α+ thalassaemia in a Thai family
Authors: Viprakasit Vip , Pung‐Amritt Parichat , Suwanthon Lerlugh , Clark Kevin , Tanphaichitr Voravarn S.
Published: March 2003

Abstract: Haemoglobin Lepore‐Hollandia is an extremely rare condition in which a small deletion gives rise to a δβ hybrid, β‐like globin. There are two single reports of patients from South Pacific Islands and Bangladesh. We describe a family from central Thailand, in which this Hb Lepore‐Hollandia interacts with a common β globin variant (βE resulting from the codon 26, G→A mutation) and α+ thalassaemia (−α3.7). This intriguing interaction caused a troublesome diagnosis, as the two proband brothers were diagnosed as having Hb E/β thalassaemia. Molecular analysis of genomic DNA performed in this study allowed the definitive diagnosis of this complicated interaction. Such studies are required in the diagnosis of thalassaemia and haemoglobinopathies for particular regions like South‐east Asia, where many different genotypes may give rise to haemoglobin disorders.