bluuebunny/crossref_metadata_2025_split huggingface dataset:
High efficacy with five days schedule of oral fludarabine phosphate and cyclophosphamide in patients with previously untreated chronic lymphocytic leukaemia
Authors: Cazin Bruno , Divine Marine , Leprêtre Stéphane , Travade Philippe , Tournilhac Olivier , Delmer Alain , Jaubert Jérôme , Feugier Pierre , Dreyfus Brigitte , Mahé Béatrice , Grosbois Bernard , Maloisel Frédéric , Eghbali Houchingue , Dumontet Charles , Bénichou Jacques , Guibon Odile , Leleu Xavier , Leporrier Michel , Maloum Karim 
Published: August 2008

SummaryA multicentre single‐arm study testing the efficacy and toxicity of the oral combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with untreated B cell‐chronic lymphocytic leukaemia. Oral FC demonstrated high efficacy with overall (OR) and complete response (CR) rates of 80% and 53%, respectively. Out of the 30 CR patients studied for Minimal Residual Disease (MRD) using 4‐colour flow‐cytometry and the 22 using Clonospecific polymerase chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median survival and median treatment‐free interval had not been reached at 7 years of follow‐up. Median progression‐free survival (PFS) was 5 years. Toxicity was acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia and infections, respectively. Gastrointestinal toxicity was mild. Oral FC demonstrated a high efficacy and an acceptable safety profile and may be considered as the standard first line treatment in chronic lymphocytic leukaemia.
Does thrombophilia testing help in the clinical management of patients?
Authors: Middeldorp Saskia , Van Hylckama Vlieg Astrid 
Published: August 2008

SummaryThrombophilia can be identified in about half of all patients presenting with venous thrombosis. Testing has increased tremendously for various indications, but whether the results of such tests help in the clinical management of patients has not been settled. Here, we review the most commonly tested thrombophilic abnormalities, i.e. protein C, protein S, and antithrombin deficiencies, the F5 R506Q (factor V Leiden) and F2 G20210A (prothrombin G20210A) mutations, and elevated levels of coagulation factor VIII, and their association with venous and arterial thrombosis as well as pregnancy complications. We conclude that testing for hereditary thrombophilia generally does not alter the clinical management of patients with venous or arterial thrombosis or pregnancy complications. Because testing for thrombophilia only serves limited purpose this should not be performed on a routine basis.
Allogeneic transplantation for Hodgkin lymphoma
Authors: Peggs Karl S. , Anderlini Paolo , Sureda Anna 
Published: August 2008

SummaryThe majority of patients with Hodgkin lymphoma (HL) can now expect to be cured with conventional chemo‐ and/or radio‐therapy. However, a subgroup still exists that have poor outcomes, even following dose escalation and autologous stem cell transplantation. Furthermore, patients relapsing after autografting have limited therapeutic options available. Whilst the application of allogeneic transplantation strategies has historically been limited by prohibitive transplant‐related mortality, the exploration of reduced intensity approaches has demonstrated the feasibility of delivering allogeneic immunotherapies with more acceptable mortality rates. Although its role remains controversial, we are beginning to re‐evaluate the use of allogeneic transplantation in the management of patients with HL and to address a number of critical questions. These include whether a clinically relevant graft‐versus‐tumour response occurs in HL, and whether subgroups of patients who might benefit from allogeneic approaches can be identified in order to inform development of rational clinical studies. This review focuses on evaluating recent experience with reduced intensity allogeneic approaches in HL in order to inform opinion on its current role and to highlight areas for future investigation.
Expression of iodine metabolism genes in human thyroid tissues: evidence for age and BRAFV600E mutation dependency
Authors: Espadinha Carla , Santos Jorge Rosa , Sobrinho Luís G. , Bugalho Maria João 
Published: August 2008

SummaryContext  Children present a higher susceptibility to developing thyroid cancer after radioiodine exposure and also a higher frequency of functional metastases than adults.Objective  To assess the mRNA expression of the sodium/iodide (Na+/I−) symporter (NIS), the Pendred syndrome gene (PDS), thyroperoxidase (TPO), thyroglobulin (Tg) and TSH receptor (TSH‐R) in normal thyroid tissues (NTTs) and papillary thyroid carcinomas (PTCs) among different age groups.Methods  Analysis included 59 samples: 21 NTTs and 38 PTCs, of which 21 were the classic type (CPTC) and 17 the follicular variant (FVPTC). Patients were divided into three age groups: I (n = 16) 5–21 years, II (n = 13) 22–59 years, and III (n = 10) 60–91 years. The relative mRNA expression of the five target genes was determinate by quantitative reverse transcription polymerase chain reaction (QRT‐PCR).Results  Expression of all genes was significantly higher in NTTs than in PTCs, and it was not age dependent in the NTT group. Among PTCs, the mean expression of PDS, TPO and TSH‐R was significantly lower in group II than in group I. PDS, TPO and Tg expression was significantly lower in classic PTCs than in FVPTCs. The difference was related to a higher frequency of the BRAFV600E mutation in the former group.Conclusions  The finding of higher PDS, TPO and TSH‐R mRNA expression in paediatric vs. adult primary tumour tissues supports the hypothesis that this might contribute to the increased functional activity of metastases in the paediatric group. The finding that mRNA expression of the target genes in NTT was not age dependent does not provide an explanation for the higher susceptibility in the paediatric group.
Assessment of p27 (cyclin‐dependent kinase inhibitor 1B) and aryl hydrocarbon receptor‐interacting protein (AIP) genes in multiple endocrine neoplasia (MEN1) syndrome patients without any detectable MEN1 gene mutations
Authors: Igreja Susana , Chahal Harvinder S. , Akker Scott A. , Gueorguiev Maria , Popovic Vera , Damjanovic Svetozar , Burman Pia , Wass John A. , Quinton Richard , Grossman Ashley B. , Korbonits Márta 
Published: August 2008

Summary
Objective  Germline mutations in the MEN1 gene predispose to the multiple endocrine neoplasia (MEN1) syndrome; however, approximately 10–20% of patients with MEN1 do not have a detectable MEN1 mutation. A rat strain with multiple endocrine tumours, a phenotypic overlap of both MEN1 and MEN2, has been reported to have a homozygous germline p27 (CDKN1B) mutation. Recently, two MEN1 mutation‐negative MEN1 syndrome patients have been identified to harbour a germline CDKN1B mutation. The recently identified gene AIP can also cause familial isolated pituitary adenoma, but no other specific tumour is associated with this syndrome. The objective of this study was to evaluate the possible contribution of CDKN1B and AIP germline mutations in a cohort of MEN1 mutation‐negative MEN1 syndrome patients.
Patients  Eighteen sporadic and three familial cases of MEN1 mutation‐negative MEN1 syndrome were studied (18 pituitary adenomas, 12 hyperparathyroidism, 10 neuroendocrine tumours including 2 ACTH‐secreting lesions and one adrenal nodular hyperplasia). Clinical data and genomic DNA were analysed for mutations in the CDKN1B and AIP genes.
Results  There were no mutations in the coding region or exon/intron junction of the CDKN1B and AIP genes in any patient. Although we have a limited number of patients in our cohort, our data is consistent with others in the literature suggesting that CDKN1B and AIP mutations are extremely rare in MEN1 syndrome.
Conclusion  Our results suggest that mutations in the CDKN1B and AIP genes are relatively uncommon in MEN1 mutation‐negative MEN1 syndrome patients.
Diagnostic value of salivary cortisol in Cushing's syndrome (CS)
Authors: Cardoso Estela M. L. , Arregger Alejandro L. , Tumilasci Omar R. , Contreras Liliana N. 
Published: August 2008

SummaryObjective  The diagnosis of Cushing's syndrome (CS) remains a challenge in clinical endocrinology. The aim of this study was to determine the reproducibility and diagnostic value of late‐night salivary cortisol (SAF23) for CS and its utility along the follow‐up of treated patients. In addition, using the same radioimmunoassay reactives, the cut‐off values for saliva and serum cortisol, assessed synchronically after the overnight 1 mg dexamethasone suppression test (DST), were defined.Design  Twenty‐one patients with confirmed CS and 121 volunteers were studied. All the subjects collected 24‐h urine for cortisol (UFC). On the same day whole saliva was obtained from the subjects at 23 h for SAF23. The intraclass coefficient of correlation (ICC) of SAF23 was estimated in 47 subjects (21 CS and 26 C). At 8 h, after DST, simultaneous saliva and serum samples for cortisol (SAFdex and Fdex, respectively) were obtained in 51 subjects (17 CS and 34 C). After specific therapy, 18 patients with CS were followed with SAF23 measurements. SAF and F were expressed as nm.Results  The intraclass coefficient of correlation of SAF23 was 0·89 in CS and 0·83 in C. SAF23 > 3·8 nm showed a sensitivity and specificity of 100% and 97·5%, respectively, for diagnosing CS. SAF23 correlated positively with UFC (r = 0·685; P = 0·0001). After DST, SAFdex significantly correlated with Fdex (r = 0·61, P < 0·0001). A cut‐off value of SAFdex > 2·0 nm and Fdex > 50·0 nm detected CS with 100% sensitivity and specificity. After successful surgical therapy, 13 patients with CS had SAF23 levels < 3·8 nm (1·4 ± 0·8 nm).Conclusions  SAF23 and SAFdex seem to be good screening tools based on their noninvasive nature, remarkable reproducibility and diagnostic performances.
Characterization of the anaemia associated with Graves’ disease
Authors: Gianoukakis Andrew G. , Leigh Mary J. , Richards Patrick , Christenson Peter D. , Hakimian Aliza , Fu Paul , Niihara Yutaka , Smith Terry J. 
Published: August 2008

SummaryBackground  Graves’ disease (GD) is associated with hyperthyroidism. Thyrotoxicosis adversely affects multiple organ systems including haematopoiesis. Anaemia occurring specifically in GD has not been systematically studied previously.Objective  To define the prevalence and characteristics of the anaemia associated with GD.Design  Eighty‐seven newly diagnosed patients with GD were recruited. Haematological indices, thyroid function and inflammatory parameters were examined at presentation and following successful treatment of hyperthyroidism.Setting  Tertiary care academic referral centre.Results  Thirty‐three per cent of subjects presented with anaemia. The prevalence of anaemia not attributable to other causes (GD anaemia) was 22%. GD anaemia affected 41·6% (10/24) of men compared to 17·5% of women (11/63). Mean erythropoietin (EPO) levels (15·5 ± 5·3 mIU/ml) were within normal reference limits but significantly higher (P = 0·004) than those of the non‐anaemic controls. Hgb correlated inversely with EPO (P = 0·05) and CRP (P = 0·04) levels, a relationship that persisted after multivariate adjustment for TT3 or TT4. With antithyroid therapy for 16 ± 6·3 weeks, Hgb levels normalized in 8 out of 9 subjects with GD anaemia (10·7 ± 0·8 to 13·5 ± 1·3 g/dl, P = 0·0001). After normalization of Hgb, mean MCV and TIBC were significantly increased, and median ferritin and mean EPO were significantly decreased.Conclusions  GD anaemia is common, resembles the anaemia of chronic disease, and is associated with markers of inflammation. It corrects promptly with return to the euthyroid state following treatment.
Effects of genetic variation in the aldosterone synthase (CYP11B2) gene on enzyme function
Authors: Holloway C. D. , MacKenzie S. M. , Fraser R. , Miller S. , Barr M. , Wilkinson D. , Forbes G. H. , Friel E. , Connell J. M. C. , Davies E. 
Published: August 2008

SummaryObjective  Evidence suggests that high levels of aldosterone lead to hypertension and increased risk of cardiovascular disease. Around 15% of patients with essential hypertension have a raised aldosterone to renin ratio (ARR) suggesting that aldosterone production is inappropriately high in relation to its principal agonist angiotensin II. This may be due to increased activity of aldosterone synthase caused by genetic variation in the CYP11B2 gene. We screened the coding region of human CYP11B2 for genetic variants and tested their effects on function in vitro.Protocol  Normotensive subjects (n = 69) were screened for sequence variants in the coding region of CYP11B2 by single‐stranded conformation polymorphism (SSCP) analysis and sequencing. The effects of nonsynonymous variants on enzyme activity were assessed in JEG‐3 cells transiently transfected with wild‐type or variant expression plasmids. The conversion of the substrate 11‐deoxycorticosterone (DOC) to corticosterone (B) and aldosterone was measured.Results  Twenty variants were detected in CYP11B2 and eight analysed functionally (Arg87Gly, Asn281Thr, Gly288Ser, Lys296Asn, Asp335Asn, Gln404Arg, Ala414Pro and His439Tyr). Corticosterone synthesis was unaltered and aldosterone synthesis reduced in variant Arg87Gly; Asn281Thr increased corticosterone and decreased aldosterone production; Gly288Ser increased corticosterone production and abolished aldosterone production; Lys296Asn reduced both corticosterone and aldosterone production; Asp335Asn increased corticosterone synthesis but did not affect aldosterone production. Variants Gln404Arg, Ala414Pro and His439Tyr showed increases in both corticosterone and aldosterone synthesis compared to the wild‐type.Conclusion  The study confirms the genetic variability of the CYP11B2 gene and provides us with additional valuable structure–function information.
Use of the Leksell gamma knife in the treatment of prolactinoma patients
Authors: Ježková Jana , Hána Václav , Kršek Michal , Weiss Vladimír , Vladyka Vilibald , Liščák Roman , Vymazal Josef , Pecen Ladislav , Marek Josef 
Published: August 2008

SummaryObjective  Pharmacological treatment with dopaminergic agonists (DA) is the treatment of choice for prolactinomas. Surgical and radiation treatment is also indicated in certain situations. We describe our 12‐year experience in treating prolactinomas with the Leksell gamma knife (LGK).Design  We followed 35 prolactinoma patients (25·7% microprolactinomas, 74·3% macroprolactinomas) treated with LGK irradiation. The mean follow‐up period was 75·5 months. Prior to LGK irradiation, patients were treated with DA and 10 of them (28·6%) underwent neurosurgery. Indications for LGK irradiation were: DA intolerance (31·4%), DA resistance (45·7%) and efforts to reduce the DA dose or shorten the period of administration (22·9%). Pituitary function was monitored regularly at 6‐month intervals. The central radiation dose range was 40–80 Gy (median 70 Gy), and the minimal peripheral dose was 20–49 Gy (median 34 Gy).Results  Normoprolactinaemia was achieved in 37·1% of the patients who discontinued DA and in 42·9% of patients who continued DA treatment after LGK irradiation. The median time to prolactin normalization after discontinuation of DA was 96 months. No relapse was seen in any patient. After LGK irradiation, the prolactinoma stopped growing or decreased in size in all but one patient (97·1%).Conclusion  LGK treatment resulted in normoprolactinaemia in 80·0% of the patients, all of whom had failed pharmacological treatment due to DA resistance or intolerance. After achieving normoprolactinaemia, no relapse of hyperprolactinaemia was observed in any patient. The size of the adenoma decreased even in those patients in whom it was not changed by previous DA treatment.
Ghrelin concentrations in Prader–Willi syndrome (PWS) infants and children: changes during development
Authors: Haqq Andrea M. , Grambow Steven C. , Muehlbauer Michael , Newgard Christopher B. , Svetkey Laura P. , Carrel Aaron L. , Yanovski Jack A. , Purnell Jonathan Q. , Freemark Michael 
Published: August 2008

SummaryBackground  Prader–Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyperghrelinaemia and increased insulin sensitivity. The role of ghrelin excess in the pathogenesis of obesity is unclear.Objective  To determine if high ghrelin levels precede the onset of obesity in young PWS children.Design and methods  A cross‐sectional study of 33 infants with PWS and 28 healthy control subjects (C). Fasting ghrelin and other satiety hormones were measured.Results  Median total serum ghrelin in young children with PWS trended higher, but did not differ significantly from those in C of similar age, weight‐for‐age z‐score and sex. However, there was more variability in ghrelin concentrations of young PWS. Eleven of 33 PWS subjects had ghrelin levels greater than the 95th percentile for ghrelin values in the C subjects (> 2871 pg/ml). Six of the PWS subjects with high ghrelin levels had weight‐for‐age z‐scores < 0. Ghrelin concentrations in PWS and C infants exceeded those in older children. In youngsters with PWS, leptin was higher, suggesting a relative excess of fat to lean body mass and plasma adiponectin was increased.Conclusions  Young infants with PWS who have not yet developed hyperphagia or obesity have median fasting ghrelin levels similar to controls. However, a subset (33%) of young PWS is hyperghrelinaemic; approximately one‐half of those with hyperghrelinaemia have BMI z‐score < 0. The age‐related decline in ghrelin is blunted in PWS.
Long‐term plasma levels of leptin and adiponectin in Rett syndrome
Authors: Blardi P. , De Lalla A. , D’Ambrogio T. , Vonella G. , Ceccatelli L. , Auteri A. , Hayek J. 
Published: August 2008

SummaryObjective  Rett syndrome is a progressive neurological disorder affecting almost exclusively females after age 6 months and characterised by acquired microcephaly, psychomotor retardation, growth failure, purposeless hand movements, autistic‐like behaviour and wide‐based and stiff legged gait. Leptin and adiponectin, peptides secreted by adipose tissue, are involved in the regulation of body weight and energy expenditure.Design and patients  We investigated in patients with Rett syndrome the variations of plasma leptin and adiponectin and their relation over a 2‐year period. Sixteen female patients, mean age at the basal time 9·4 ± 4·3 years, with classical Rett syndrome were enrolled. Controls were 16 healthy female subjects, mean age at the basal time 9·9 ± 3·4 years.Measurements  Blood samples were withdrawn in the morning at the baseline, 12 months after and 24 months after; plasma leptin and adiponectin concentrations were detected by ELISA.Results  In patients, leptin concentrations significantly increased, while adiponectin concentrations significantly decreased. Both leptin and adiponectin values were significantly higher than those found in controls at each time. Leptin significantly correlated with adiponectin in patients, while there was not a significant correlation in controls.Conclusion  Since all patients were not obese, we might hypothesize that in Rett syndrome leptin and adiponectin might participate to clinical manifestations other than weight balance.
A comparative study of cannibalism and predation in seven species of flour beetle
Authors: ALABI TAOFIC , MICHAUD J. P. , ARNAUD LUDOVIC , HAUBRUGE ERIC 
Published: August 2008

Abstract1. The present study quantified egg and pupal cannibalism, and interspecific predation on eggs and pupae, by larvae and adults of seven species of flour beetle (Triboliumspp.) under laboratory conditions:T. anaphe,T. brevicornis,T. castaneum,T. confusum,T. destructor,T. freemani, andT. madens.2. Variation among species in cannibalism and predation propensities did not reflect taxonomic affinities within the genus, indicating that these behaviours were shaped by ecology at species level.3. Within species, larvae and adults displayed different propensities for cannibalism and predation, leading to the conclusion that these behaviours evolve independently in the two life stages.4. All species behaved as intraguild predators to some degree, especially in the adult stage.5. Three general patterns of cannibalism and predation were described by principal component mapping and cluster analysis.6. The first group comprised three cosmopolitan pest species that were more voracious as adults than as larvae:T. castaneum,T. confusum, andT. destructor. It is proposed that stored product environments select for high adult voracity because the costs associated with emigration from such rare, but resource‐rich, habitats intensifies interference competition among adults.7. The second group consisted of species that inhabit natural environments and that were more voracious as larvae:T. anaphe,T. freemani, andT. madens. Habitats for these species are probably numerous, but generally poor in quality, a situation that intensifies larval competition, while favouring earlier adult emigration.8. The largest species,T. brevicornis, demonstrated inconsistent voracity between life stages and was the only species with chemically defended pupae.9. It is proposed that consumption of eggs provides primarily nutritional benefits, whereas consumption of pupae has a more important role in interference competition.
Evolution of increased cold tolerance during range expansion of the elongate hemlock scale Fiorinia externa Ferris (Hemiptera: Diaspididae)
Authors: PREISSER EVAN L. , ELKINTON JOSEPH S. , ABELL KRISTOPHER 
Published: August 2008

Abstract 1. Alien species often face novel challenges to their spread and population growth. One critical hurdle often involves an organism’s ability to tolerate environmental extremes characteristic of their invaded range. Although abiotic factors often determine range limits, there is less evidence for local adaptation in invasive organisms whose initial arrival and rapid population growth is separated by a lengthy lag period.2. The invasive elongate hemlock scale Fiorinia externa feeds on Eastern hemlock, Tsuga canadensis, on the east coast of North America. Following its 1908 arrival, it remained localised until entering a period of rapid northward range expansion in the 1970s.3. The present study tested the survival of overwintering F. externa populations from four sites in the north and south of the invaded range (n = 8 sites total) when exposed to −15 °C for 0–36 h.4. This experiment was repeated on F. externa offspring that had been reared in a common‐garden environment in order to control for parental effects.5. Northern populations were more tolerant of exposure to cold temperatures than were southern populations. This held true in both the source‐population experiment and common‐garden experiment. The common‐garden experiment demonstrates that this difference has a genetic basis and may be the consequence of local adaptation to lower winter temperatures.6. The results provide evidence for local adaptation to extreme temperatures in F. externa. This provides one possible explanation for the lag period between the arrival of this species and its eventual northward range expansion.