bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upfront VIP‐reinforced‐ABVD (VIP‐rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS‐LTP95
Authors: Simon Audrey , Peoch Michel , Casassus Philippe , Deconinck Eric , Colombat Philippe , Desablens Bernard , Tournilhac Olivier , Eghbali Houchingue , Foussard Charles , Jaubert Jerome , Vilque Jean Pierre , Rossi Jean François , Lucas Virginie , Delwail Vincent , Thyss Antoine , Maloisel Frederic , Milpied Noel , Le Gouill Steven , Lamy Thierry , Gressin Rémy 
Published: August 2010

SummaryPeripheral T‐Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B‐cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front‐line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d’Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP‐reinforced‐ABVD; VIP‐rABVD) and compared it to CHOP/21 as front‐line treatment in non‐cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2‐year event‐free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty‐eight patients were identified between 1996 and 2002. Both arms were well balanced for patients’ characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2‐year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I–II were identified as two independent favourable prognostic factors influencing survival. VIP‐rABVD was not superior to CHOP/21 in terms of EFS as first‐line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.
The impact of bleeding history, von Willebrand factor and PFA–100® on the diagnosis of type 1 von Willebrand disease: results from the European study MCMDM‐1VWD
Authors: Castaman Giancarlo , Tosetto Alberto , Goodeve Anne , Federici Augusto B. , Lethagen Stefan , Budde Ulrich , Batlle Javier , Meyer Dominique , Mazurier Claudine , Goudemand Jenny , Eikenboom Jeroen , Schneppenheim Reinhard , Ingerslev Jorgen , Habart David , Hill Frank , Peake Ian , Rodeghiero Francesco 
Published: August 2010

SummaryThe relationships between the Platelet Function Analyzer (PFA)‐100 and von Willebrand factor (VWF) levels and bleeding score (BS) were evaluated within a multicentre project on Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand disease (MCMDM‐1VWD). PFA‐100 closure time, either with epinephrine (EPI) or adenosine diphosphate (ADP)‐cartridges, was measured in 107 index cases, 105 affected and 71 unaffected family members, and 79 healthy controls. By regression analysis VWF levels were strongly related to both closure times, with a non‐linear progression. In a multiple stepwise regression model, age‐ and sex‐adjusted PFA‐100 ADP and VWF ristocetin cofactor activity (VWF:RCo) were independently associated with BS. Most of the variation of BS was predicted by PFA‐100 ADP and VWF:RCo alone. In the subgroup of patients with subtle abnormalities of the multimeric pattern, VWF was invariably reduced and closure time prolonged in almost all of them. Neither PFA‐100 ADP nor EPI closure times appeared to significantly improve the diagnostic capability of VWF antigen (VWF:Ag) measurement. Thus, in an unselected population a normal PFA‐100 would be useful to exclude VWD, but whether it could replace the more specific VWF assay in patients with significant mucocutaneous bleeding symptoms remains to be investigated prospectively.
Common occurrence of monoclonal B‐cell lymphocytosis among members of high‐risk CLL families
Authors: Goldin Lynn R. , Lanasa Mark C. , Slager Susan L. , Cerhan James R. , Vachon Celine M. , Strom Sara S. , Camp Nicola J. , Spector Logan G. , Leis Jose F. , Morrison Vicki A. , Glenn Martha , Rabe Kari G. , Achenbach Sara J. , Algood Sallie D. , Abbasi Fatima , Fontaine Laura , Yau Michelle , Rassenti Laura Z. , Kay Neil E. , Call Timothy G. , Hanson Curtis A. , Weinberg J. Brice , Marti Gerald E. , Caporaso Neil E. 
Published: August 2010

SummaryMonoclonal B‐cell lymphocytosis (MBL) is an asymptomatic haematological condition characterized by low absolute levels of B‐cell clones with a surface immunophenotype similar to that of chronic lymphocytic leukaemia (CLL). In the general population, MBL increases with age with a prevalence of 5–9% in individuals over age 60 years. It has been reported to be higher among first‐degree relatives from CLL families. We report results of multi‐parameter flow cytometry among 505 first‐degree relatives with no personal history of lymphoproliferative disease from 140 families having at least two cases of CLL. Seventeen percent of relatives had MBL. Age was the most important determinant where the probability for developing MBL by age 90 years was 61%. MBL clustered in certain families but clustering was independent of the number of known CLL cases in a family. As is the case with CLL, males had a significantly higher risk for MBL than did females (P = 0·04). MBL patients had significantly higher mean absolute lymphocyte counts (2·4 × 109/l) and B‐cell counts (0·53 × 109/l) than those with a normal B‐cell immuno‐phenotype. Our findings show that MBL occurs at a very high rate in high risk CLL families. Both the age and gender distribution of MBL are parallel to CLL, implying a shared inherited risk.
The novel Hsp‐90 inhibitor SNX7081 is significantly more potent than 17‐AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway
Authors: Best O. Giles , Singh Nisha , Forsyth Cecily , Mulligan Stephen P. 
Published: August 2010

SummaryInhibitors of heat‐shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP‐70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL.
Genetic variability of TMPRSS6 and its association with iron deficiency anaemia
Authors: Delbini Paola , Vaja Valentina , Graziadei Giovanna , Duca Lorena , Nava Isabella , Refaldi Chiara , Cappellini Maria D. 
Published: August 2010

SummaryTransmembrane Protease, Serine 6 (TMPRSS6) has an important role in iron homeostasis and its mutations, performed in TMPRSS6‐deficient mice, have been recently associated with iron‐refractory iron deficiency anaemia (IRIDA). Several variants of TMPRSS6 have been already identified; however the role of polymorphisms and TMPRSS6 haplotypes, causing iron deficiency anaemia, have not yet been investigated. This study sequenced the TMPRSS6 gene in 16 subjects with IRIDA phenotype and identified 27 DNA polymorphisms. Eight single nucleotide polymorphisms and four haplotypes were significantly associated with iron‐refractory anaemia (P < 0·001). Our preliminary results suggest a possible association between specific haplotypes of TMPRSS6 and IRIDA.
What’s new in acne? An analysis of systematic reviews published in 2009–2010
Authors: Smith E. V. , Grindlay D. J. C. , Williams H. C. 
Published: August 2010

Summary
This review highlights clinically important findings about acne treatment identified in nine systematic reviews published or indexed in the period March 2009 to February 2010. A systematic review of dietary influences on acne suggested that a possible role of dietary factors in acne cannot be dismissed, as the studies to date have not been sufficiently large or robust. Another review looked at benzoyl peroxide, which may be enjoying a comeback because of increasing bacterial resistance to antibiotics, and suggested that there was a lack of evidence that stronger preparations were more effective than weaker ones. The same team also carried out a systematic review addressing the question of whether topical retinoids cause an initial worsening of acne. They found no evidence to suggest initial worsening of acne severity, although there was evidence of skin irritation that typically settled by 8–12 weeks. A review of oral isotretinoin and psychiatric side-effects reinforced a possible link between the two, although it pointed out that the better-quality primary studies were still inconclusive. An updated Cochrane Review confirmed the efficacy of combined oral contraceptives (COCs) in reducing acne lesion counts. It also found that the evidence to support COCs containing cyproterone acetate over others was very limited. Another Cochrane Review failed to show any benefit of spironolactone for acne, based on limited studies. Three reviews examined laser and light therapies, and found some evidence of superiority only for blue or blue/red light treatment over placebo light, but a general absence of comparisons against other acne treatments. Photodynamic therapy had consistent benefits over placebo but was associated with significant side-effects and was not shown to be better than topical adapalene.
Cutaneous adverse drug reactions in a hospital-based Chinese population
Authors: Huang H.-Y. , Luo X.-Q. , Chan L.-S. , Cao Z.-H. , Sun X.-F. , Xu J.-H. 
Published: August 2010

Summary
Background. Cutaneous adverse drug reactions (CADRs) are common skin adverse reactions associated with drugs.
Aim. To assess recent trends in CADRs and the drugs associated with them, using data from the past 5 years in the largest single database available on a hospital-based population in China.
Methods. All clinical records of inpatients admitted with a diagnosis of CADR to the Dermatology Ward, Huashan Hospital from January 2004 to December 2008 were retrospectively studied.
Results. In the 734 patients, the three most common types of CADRs were nonsevere reactions, erythema multiforme (EM)-like eruptions (n = 255), urticaria (n = 192) and exanthematous reactions (n = 159), followed by three severe reactions: Stevens–Johnson syndrome (n = 58), toxic epidermal necrolysis (n = 29) and exfoliative dermatitis (n = 22). The most common single drug associated with the development of all drug eruptions was allopurinol, followed by amoxicillin, cephalosporins, antiepileptic agents and antipyretic/analgesic agents. However, the most common single drugs associated with severe reactions were antiepileptic agents, followed by allopurinol, antipyretic/analgesic agents and cephalosporins. In contrast to patients with nonsevere reactions, patients with severe reactions were more likely to be male (P &lt; 0.001) and to have a greater mean age of onset (P &lt; 0.001), a longer latency period (P &lt; 0.001) and a longer duration of hospitalization (P &lt; 0.001).
Conclusion. In contrast to previous studies, we found allopurinol to be the most common single drug associated with CADRs followed by antibiotics (amoxicillin and cephalosporins), and antiepileptic, especially carbamazepine. A higher incidence of EM-like eruptions and urticaria was also seen.
Dermatology referrals in an East Asian tertiary hospital: a need for inpatient medical dermatology
Authors: Tay L. K. , Lee H. Y. , Thirumoorthy T. , Pang S. M. 
Published: August 2010

SummaryBackground. Within hospitals, there is a need for dermatological expertise, as hospitalized patients have a wider spectrum of severe and serious dermatological conditions, associated with significant morbidity.Aim. To characterize the patient profile and referral pattern of inpatient dermatology consultations, and to evaluate the diagnostic accuracy of non-dermatologists.Methods. This was a retrospective study reviewing all inpatient referrals for dermatology consultations during a 1-year period from July 2005 to June 2006 (inclusive), at the largest multi-disciplinary tertiary hospital in Singapore.Results. Of the 731 referrals made for dermatology consultations, 26.9% of patients had ≥ 3 important underlying comorbidities. Eczema/dermatitis (33.1%; n = 242) and cutaneous infections (23.4%; n = 171) accounted for over half of the dermatological consultations, followed by cutaneous adverse drug reactions (12.3%; n = 90). The provisional diagnoses of the referring doctors agreed with the final diagnoses confirmed by dermatologists in only 30.2% of all referrals; incorrect diagnoses were made in 35.2% of cases, and no provisional diagnoses were made in the remaining 34.6% of cases. Most misdiagnosed skin diseases were in fact common dermatoses (such as eczemas, cutaneous infections, drug rash) that required only standard treatment.Conclusion. Our study reiterates the importance of inpatient medical dermatology in terms of both service and education. There should be continual efforts to ensure that dermatologists have the highest level of training and experience in medical dermatology, to provide collaborative optimum care for hospitalized patients with dermatological diseases.
Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
Authors: Docena G , Rovedatti L , Kruidenier L , Fanning Á , Leakey N A B , Knowles C H , Lee K , Shanahan F , Nally K , McLean P G , Di Sabatino A , MacDonald T T 
Published: September 2010

SummaryCrohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) characterized by chronic relapsing mucosal inflammation. Tumour necrosis factor (TNF)-α, a known agonist of the mitogen-activated protein kinase (MAPK) pathway, is a key cytokine in this process. We aimed first to determine whether p38 MAPK is activated in IBD inflamed mucosa, and then studied the effect of four different p38α inhibitory compounds on MAPK phosphorylation and secretion of proinflammatory cytokines by IBD lamina propria mononuclear cells (LPMCs) and organ culture biopsies. In vivo phospho-p38α and p38α expression was evaluated by immunoblotting on intestinal biopsies from inflamed areas of patients affected by Crohn's disease and ulcerative colitis, and from normal mucosa of sex- and age-matched control subjects. Both mucosal biopsies and isolated LPMCs were incubated with four different p38α selective inhibitory drugs. TNF-α, interleukin (IL)-1β and IL-6 were measured in the organ and cell culture supernatants by enzyme-linked immunosorbent assay. We found higher levels of phospho-p38α in the inflamed mucosa of IBD patients in comparison to controls. All the p38α inhibitory drugs inhibited p38α phosphorylation and secretion of TNF-α, IL-1β and IL-6 from IBD LPMCs and biopsies. Activated p38α MAPK is up-regulated in the inflamed mucosa of patients with IBD. Additionally, all the p38α selective inhibitory drugs significantly down-regulated the activation of the MAPK pathway and the secretion of proinflammatory cytokines.
Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects
Authors: Huda M. S. B. , Mani H. , Dovey T. , Halford J. C. G. , Boyland E. , Daousi C. , Wilding J. P. H. , Pinkney J. 
Published: August 2010

SummaryObjective  Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects.Design  Randomized, double‐blinded, placebo‐controlled crossover.Subjects  Seven lean [mean body mass index (BMI) 23·6 ± 0·9 kg/m2], seven morbidly obese (mean BMI 50·9 ± 4·4 kg/m2) and seven post‐gastrectomy subjects (mean BMI 22·0 ± 1·1 kg/m2).Measurements  Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 min. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Total power (TP) represents overall autonomic function, low‐frequency (LF) power represents sympathetic and parasympathetic activity, and high‐frequency (HF) power represents parasympathetic activity. Very low (VLO) frequency represents the frequency band associated with thermogenesis.Results  Preliminary anova analysis, looking at all three subject groups together, showed that ghrelin had an overall highly significant inhibitory effect on TP (P = 0·001), HF power (P = 0·04), VLO power (P = 0·03) and no effect on LF (P = 0·07). Further subset analysis revealed that ghrelin had a significant effect on TP (P = 0·03), borderline effect on LF power (P = 0·06) and no effect on HF power (P = 0·1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (P = 0·3), LF (P = 0·5) and HF (P = 0·06) and also no effect in the vagotomized subjects on TP (P = 0·7), LF (P = 0·7) and HF (P = 0·9). Ghrelin had no effect on the LF/HF ratio.Conclusions  Ghrelin inhibits SNS activity in healthy controls with a moderate effect on parasympathetic nervous system activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin, suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS.
What is the best approach to an apparently nonmetastatic adrenocortical carcinoma?
Authors: Fassnacht Martin , Allolio Bruno 
Published: August 2010

SummaryIn suspected nonmetastatic adrenocortical carcinoma (ACC) a careful preoperative diagnostic work up is needed including comprehensive endocrine analysis as recommended by the European Network for the Study of Adrenal Tumors (http://www.ENSAT.org/ACC.htm). Staging prior surgery, in particular chest CT, is indispensable to exclude distant metastases. Open surgery is still the recommended approach in ACC. However, in localized non‐invasive ACC with a diameter <10 cm laparoscopic adrenalectomy by an expert surgeon is probably similarly effective and safe. As many patients will suffer from tumor recurrence after seemingly complete removal of ACC, adjuvant treatment based on the individual risk status is recommended. Key factors for risk assessment are tumor stage, resection status and the proliferation marker Ki67. All patients considered at high risk for recurrence should receive adjuvant mitotane for a minimum of 2 years aiming at a drug level of 14–20 mg/l. In selected patients (e.g. R1 resection) we recommend additional radiotherapy of the tumor bed. Patients with a low/intermediate risk for recurrence should be included in the Adiuvo trial comparing adjuvant mitotane with observation only (http://www.adiuvo‐trial.org). In low/intermediate risk patients who cannot be included in this trial observation only can be justified in cases with a tumor diameter of <8 cm and no microscopic evidence for invasion of blood vessels or tumor capsule. In all patients a structured follow‐up for 10 years is strongly recommended.
Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover
Authors: Crofton Patricia M. , Evans Nancy , Bath Louise E. , Warner Pamela , Whitehead Tessa J. , Critchley Hilary O. D. , Kelnar Christopher J. H. , Wallace W. Hamish B. 
Published: August 2010

AbstractBackground  The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF).Patients and Methods  In an open‐label randomized controlled crossover trial, 34 women with POF were randomized to 4‐week cycles of pSSR (transdermal oestradiol, 100 μg daily for week 1, 150 μg for weeks 2–4; vaginal progesterone, 200 mg twice daily for weeks 3–4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 μg and 1·5 mg norethisterone daily for weeks 1–3, week 4 ‘pill‐free’) for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12‐month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N‐terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre‐/postwashout and after 3, 6 and 12 months of each treatment.Results  Eighteen women, mean 27 (range 19–39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z‐score was −0·89 (95% CI −1·27 to −0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI −0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z‐score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = −0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anovaP < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001).Conclusion  We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.
Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas
Authors: Schmid S. , Tinguely M. , Cione P. , Moch H. , Bode B. 
Published: August 2010

S. Schmid, M. Tinguely, P. Cione, H. Moch and B. Bode  Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomasObjective:  Diagnosis of low grade non‐Hodgkin B‐cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service.Methods:  Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow‐up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains.Results:  Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B‐cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series.Conclusions:  FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B‐cell non‐Hodgkin lymphomas.