bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naturally occurring genetic variation in the age‐specific immune response of Drosophila melanogaster
Authors: Lesser Karen J. , Paiusi Ioana C. , Leips Jeff 
Published: June 2006

SummaryImmunosenescence, the age‐related decline in immune response, is a well‐known consequence of aging. To date, most studies of age‐related changes in immune response focused on the cellular and physiological bases of this decline; we have virtually no understanding of the genetic basis of age‐related changes in the immune system or if indeed such control exists. We used 25 chromosome substitution lines of Drosophila melanogaster derived from a natural population to address three questions: (i) How is the function of the innate immune system influenced by age? (ii) Is there a genetic basis for phenotypic variation in immune response at different ages? (iii) Is there a genetic basis for differences in the way that age influences the immune function? Virgin females from each line were assayed for immune response using clearance of infection with Escherichia coli at 1 and 4 weeks of age. We found significant genetic variation among lines in immune response at each age. Unexpectedly, when averaged across all lines, the immune response actually improved with age. However, there was significant variation in the effect of age on immune response with 11 lines showing improvement, nine lines showing no change and five exhibiting a decline with age. There was no genetic correlation of immune response across ages suggesting that different loci contribute to variation in immune response at each age. The genetic component of the variation in immune response increased with age, a pattern predicted by the mutation accumulation model of senescence. However, this increase in variation resulted in part from the improvement of the immune response in some lines with age. Thus the observed changes in genetic variation in immune function with age are not entirely explained by the mutation accumulation model.
Treatment and prognostic factors in patients with hepatocellular carcinoma
Authors: Martins A. , Cortez‐Pinto H. , Marques‐Vidal P. , Mendes N. , Silva S. , Fatela N. , Glória H. , Marinho R. , Távora I. , Ramalho F. , Carneiro de Moura M. 
Published: June 2006

Abstract: Introduction: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model.Aims: To evaluate the influence on survival of pretreatment parameters (clinico‐laboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities.Methods: We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery – six patients; radiofrequency ablation – 21; percutaneous ethanol injection – 29; transarterial chemoembolization – 49; tamoxifen – 49; supportive care alone – 53. Factors determining survival were assessed by Kaplan–Meier method and Cox regression models.Results: Median survival was 24 months. In univariate analysis, Child–Pugh classification and Model for end‐stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (P<0.001). α‐Fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (P<0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P=NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (P<0.001).Conclusion: This study reinforces the importance of baseline liver function (Child–Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.
Non‐invasive models for predicting histology in patients with chronic hepatitis B
Authors: Wai Chun‐Tao , Cheng Chee Leong , Wee Aileen , Dan Yock‐Young , Chan Edwin , Chua Winnie , Mak Belinda , Oo Aung Myat , Lim Seng Gee 
Published: June 2006

Abstract: Background and aim: In contrast to chronic hepatitis C (CHC), few studies had been performed in assessing non‐invasive models for predicting significant fibrosis or cirrhosis in chronic hepatitis B (CHB) patients. We aimed to evaluate non‐invasive markers for diagnosing significant fibrosis/cirrhosis in patients with CHB, and to evaluate accuracy of models from CHC in CHB patients.Patients and methods: Liver biopsies from consecutive treatment‐naïve CHB patients were evaluated histologically by a pathologist blindly, using the Ishak score. Patients were divided randomly into a training (65%) and a validation sets (35%). Markers of fibrosis were evaluated by univariate followed by multivariate analysis in the training set. Area under receiver operating characteristics curve (AUROC) was assessed and validated in the training set. AUROC of aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio, and AST‐platelets ratio index (APRI) (derived from studies from CHC) in diagnosing significant fibrosis/cirrhosis were also assessed.Results: Two‐hundred and eighteen CHB patients were evaluated: 83% male, 86% Chinese, 47% having significant fibrosis, 19% having cirrhosis. Platelets were the only factor significantly associated with significant fibrosis and cirrhosis at multivariate analysis but the AUROC was only modest at 0.63 and 0.73, respectively. Models derived from studies from CHC were even less accurate.Conclusion: Models with non‐invasive markers in predicting histology from CHC patients were unsuitable for CHB patients. No variables consisting of simple and readily available markers were able to predict cirrhosis accurately in patients with CHB.
Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience
Authors: Chiu Alexander , Chan Lina Mun Yee , Fan Sheung Tat 
Published: June 2006

Abstract: Background: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin‐bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong.Methods: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n=2), acute on chronic liver failure (n=12), posthepatectomy liver failure (n=4), and posttransplantation allograft failure (n=4).Results: MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P<0.001 for all three parameters). Five patients (22.7%) were able to bridge to transplantation and one patient (4.5%) made a spontaneous recovery. The 30‐day mortality rate was 72.7%.Conclusions: Our results indicated that MARS can effectively improve serum biochemistry and is suitable for temporarily supporting patients with liver failure where transplantation is not immediately available. There is, however, no clear evidence showing that MARS can increase survival, improve the chance of transplantation or assist liver regeneration. Future studies in the form of randomized‐controlled trials are crucial to characterize the true potential of this treatment.
Characterization of blood components prepared from whole‐blood donations after a 24‐hour hold with the platelet‐rich plasma method
Authors: Thibault Louis , Beauséjour Annie , De Grandmont Marie Joëlle , Lemieux Réal , Leblanc Jean‐François 
Published: June 2006

BACKGROUND: The preparation of platelet (PLT) concentrates (PCs) from PLT‐rich plasma (PRP) requires that whole blood (WB) be processed within 8 hours of collection. Increasing WB storage time to 24 hours would be logistically attractive. This study compares the in vitro quality of blood components prepared from WB stored for 8 and 24 hours at room temperature before processing with the PRP method.STUDY DESIGN AND METHODS: WB units were collected from ABO‐matched blood donors. To reduce individual variations, paired donations were drawn in parallel, pooled, and split back in the collection bag. One unit was held for 6 to 8 hours and the other for 22 to 24 hours at 20 to 24°C. Prestorage leukoreduced components were prepared with the PRP as intermediate product and analyzed during storage.RESULTS: RBC units prepared after an 8‐ or 24‐hour hold were comparable in terms of hemolysis, sodium, pH, and ATP levels. RBC 2,3‐ diphosphoglycerate (2,3‐DPG) was significantly lower in RBCs prepared from 24‐hour hold donations immediately after processing but not after 20 days of storage. Residual white blood cells were approximately fivefold higher (p  < 0.05) in 24‐hour RBC units. For PCs, measurements for glucose, ATP, lactate, pH, extent of shape change, hypotonic shock response, and CD62p activation were similar. No differences were observed in the von Willebrand factor, factor (F)V, FVIII, and fibrinogen content of fresh‐frozen plasma.CONCLUSIONS: The decrease in FVIII and RBC 2,3‐DPG can be acceptable as a compromise to improve blood component logistics, but leukoreduction efficiency must be improved before considering the adoption of an overnight storage of WB before PRP processing.
In vitro and in vivo evaluation of LEUKOSEP HRC‐600‐C leukoreduction filtration system for red cells
Authors: AuBuchon James P. , Cancelas Jose A. , Herschel Louise , Roger Jill , Rugg Neeta , Pratt Patricia G. , Joines Amy , Gormas Jennifer F. , Zia Majid , Spearman Michael R. 
Published: June 2006

BACKGROUND: Documentation of the benefits of leukoreduction has led to the increased use of this technique and the need for development of efficient and effective techniques for its accomplishment. This study investigated the in vitro properties and in vivo autologous radiolabeled recovery of leukoreduced red cells (RBCs) produced through a leukoreduction filtration system for RBCs (LEUKOSEP HRC‐600‐C, Hemerus Medical).STUDY DESIGN AND METHODS: Normal subjects donated 36 units of RBCs that were leukoreduced on Days 0, 3, or 5 through a “hands‐off” technique. Biochemical studies were performed before and after filtration and at the end of 42 days of storage. Units leukoreduced on Days 0 or 5 were held until Day 42 and used for autologous radiolabeled return to determine recovery with 51Cr single‐label radiolabeling techniques.RESULTS: Leukoreduction filtration was accomplished in 16.3 ± 2 minutes on Day 0 at room temperature or 27 to 30 minutes on Days 3 or 5 after refrigeration. Leukoreduction efficiency was 4.6 ± 0.6 log with a median residual white blood cell (WBC) content of fewer than 3.3 × 104 WBCs per unit. RBC recovery was 90 ± 2 percent. Hemolysis was 0.34 ± 0.16 percent at the end of 42 days of storage. The in vivo recovery of radiolabeled RBCs 24 hours after autologous return was 80.6 ± 4.5 percent for RBC units leukoreduced on Days 0 and 5 combined.CONCLUSION: The LEUKOSEP HRC‐600‐C WBC reduction filtration system produced leukoreduced RBCs efficiently and effectively with acceptable poststorage biochemical measures and posttransfusion recovery after 42 days of storage.
Outliers in RhD membrane integration are explained by variantRHhaplotypes
Authors: Yu Xinjian , Wagner Franz F. , Witter Bernd , Flegel Willy A. 
Published: June 2006

BACKGROUND:Variations in a multipass transmembrane protein may affect its membrane integration. To study this effect, the systematic molecular characterization of variant D antigen density is a suitable model. Unlike most other membrane proteins, the expression of the D antigen is often determined by a single allele, because it occurs frequently in hemizygous form.STUDY DESIGN AND METHODS:The D antigen density distribution of 530 CcDee, 475 ccDEe, and 514 ccDee random samples was established by flow cytometry. The molecular bases of samples with D antigen densities outside a bell‐shaped peak was investigated.RESULTS:The antigen densities of 499 CcDee, 437 ccDEe, and 480 ccDee samples formed bell‐shaped peaks. Three, 10, and 12 samples, respectively, had decreased antigen densities and carried variantRHDalleles. Weak D type 19,RHD(I204T); weak D type 20,RHD(F417S); and the partial D DYU (also known as DQC),RHD(R234W) were newRHDalleles. Twenty‐eight CcDee, 28 ccDEe, and 22 ccDee samples had increased antigen densities; 53 of them lacked a hybridRhesus boxand were thus predicted to beRHDhomozygous. Eight ccDee samples were predicted to be heterozygous despite a large relative dose ofRHDtoRHCEalleles in quantitative polymerase chain reaction. One of these samples was further investigated and carried anRHD‐CEhybrid transcript characteristic for a‐D‐haplotype.CONCLUSIONS:Unusual little and large RhD protein integration into the membrane could be traced to a host of distinct protein variants. Weak expression of D antigen was invariably associated with variantRHDalleles. Larger than normal D antigen density may often be caused by the presence of two D encoding alleles, which may be located in cis, and confounding zygosity testing that is solely based on gene copy number.
The natural history of childhood‐acquired hepatitis C infection in patients with inherited bleeding disorders
Authors: Posthouwer Dirk , Fischer Kathelijn , Van Erpecum Karel J. , Mauser‐Bunschoten Eveline P. 
Published: June 2006

BACKGROUND: Although many patients with inherited bleeding disorders have been infected with hepatitis C in early childhood, the natural history of infection in this patient group remains poorly defined.STUDY DESIGN AND METHODS: A total of 212 patients with inherited bleeding disorders born between 1976 and 1992 were evaluated for hepatitis C virus (HCV) infection, spontaneous clearance, and (by noninvasive tests) progressive liver disease.RESULTS: A total of 120 of 212 patients had been exposed to non‐HCV–inactivated clotting products, and 68 of these 120 patients (57%) were anti‐HCV–positive. Of these patients, 44 (65%) had chronic hepatitis C (HCV RNA–positive) and 24 (35%) showed spontaneous clearance (HCV RNA–negative). Five patients with hepatitis C were coinfected with hepatitis B virus and/or human immunodeficiency virus (HIV). Multivariate analysis indicated that hepatitis C infection was independently associated with longer treatment period (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3‐1.9) and exposure to a larger number of donors (OR, 2.1; 95% CI, 1.1‐3.9). Spontaneous HCV clearance was associated with a younger age at first exposure to clotting product (p = 0.02). After a mean infection period of 21 years, evidence of cirrhosis was present in 2 patients (5%), both of whom were coinfected with HIV.CONCLUSION: Spontaneous HCV clearance is associated with young age at infection. Despite frequent childhood‐acquired hepatitis C infection among patients with inherited bleeding disorders, progression to cirrhosis after 21 years of infection is rare. The diagnosis of cirrhosis without biopsy, however, remains challenging in this population, and new, noninvasive means must be developed to accurately identify cirrhotic patients.
Does blood donor history accurately reflect the use of prescription medications? A comparison of donor history and serum toxicologic analysis
Authors: Melanson Stacy E.F. , Stowell Christopher P. , Flood James G. , Lewandrowski Elizabeth Lee , Zak Rychard J. , Lewandrowski Kent B. 
Published: June 2006

BACKGROUND: Blood donor screening is performed to accomplish several goals, including donor safety during collection and recipient safety during transfusion. Donors taking certain medications such as teratogens or platelet‐inhibiting drugs are deferred from donation. Studies investigating the accuracy of the donor history are limited and only provide data on select groups of drugs. This study compares the results of an extended serum toxicology analysis to the medication use reported on the donor questionnaire.STUDY DESIGN AND METHODS: Whole‐blood samples were collected from 108 volunteer blood donors. A serum toxicology analysis was performed with high‐performance liquid chromatography with photodiode array detection. The results were compared to those reported on the donor history questionnaire.RESULTS: The medication history was consistent with the reported medications in 96 (89%) donors. Serum toxicology testing detected medications that were not reported on the donor history form in 12 (11%) donors. Most of the donors who did not accurately report their medication use (8 or 67%) were taking psychotropic medications.CONCLUSION: Eleven percent of the donors did not fully disclose their recent medication history. Although none of the omitted medications would have been grounds for deferral, the finding of underreporting questions the reliability of donor screening. Despite a negative medication history, blood donor centers cannot assume that donors are medication‐free. This study reveals a bias to omit psychotropic medications such as antidepressants and anxiolytics.
Progenitor cell recruitment during individualized high‐flow, very‐large‐volume apheresis for autologous transplantation improves collection efficiency
Authors: Fontana Stefano , Groebli Rachel , Leibundgut Kurt , Pabst Thomas , Zwicky Caroline , Taleghani Behrouz Mansouri 
Published: June 2006

BACKGROUND: Individual adaptation of processed patient’s blood volume (PBV) should reduce number and/or duration of autologous peripheral blood progenitor cell (PBPC) collections.STUDY DESIGN AND METHODS: The durations of leukapheresis procedures were adapted by means of an interim analysis of harvested CD34+ cells to obtain the intended yield of CD34+ within as few and/or short as possible leukapheresis procedures. Absolute efficiency (AE; CD34+/kg body weight) and relative efficiency (RE; total CD34+ yield of single apheresis/total number of preapheresis CD34+) were calculated, assuming an intraapheresis recruitment if RE was greater than 1, and a yield prediction models for adults was generated.RESULTS: A total of 196 adults required a total of 266 PBPC collections. The median AE was 7.99 × 106, and the median RE was 1.76. The prediction model for AE showed a satisfactory predictive value for preapheresis CD34+ only. The prediction model for RE also showed a low predictive value (R2 = 0.36). Twenty‐eight children underwent 44 PBPC collections. The median AE was 12.13 × 106, and the median RE was 1.62. Major complications comprised bleeding episodes related to central venous catheters (n = 4) and severe thrombocytopenia of less than 10 × 109 per L (n = 16).CONCLUSION: A CD34+ interim analysis is a suitable tool for individual adaptation of the duration of leukapheresis. During leukapheresis, a substantial recruitment of CD34+ was observed, resulting in a RE of greater than 1 in more than 75 percent of patients. The upper limit of processed PBV showing an intraapheresis CD34+ recruitment is higher than in a standard large‐volume leukapheresis. Therefore, a reduction of individually needed PBPC collections by means of a further escalation of the processed PBV seems possible.
Rapid succession of peripheral blood progenitor cell mobilization cycles in patients with chronic heart failure: effects on the hematopoietic system
Authors: Hüttmann Andreas , Gutersohn Achim , Noppeney Richard , Neumann Till , Erbel Raimund , Dührsen Ulrich 
Published: June 2006

BACKGROUND: Circulating hematopoietic peripheral blood progenitor cells (PBPCs) may contribute to the regeneration of nonhematopoietic organs. An increase in circulating PBPC numbers may enhance this process. Therefore, an exploratory trial of repeated PBPC mobilization in patients with chronic heart failure was conducted. The safety and cardiovascular efficacy data have been described elsewhere. In the hematopoietic system, the trial offered an opportunity to study several new aspects of granulocyte–colony‐stimulating factor (G‐CSF) action.STUDY DESIGN AND METHODS: Fourteen male patients with chronic heart failure were treated successively with G‐CSF (four 10‐day treatment periods interrupted by treatment‐free intervals of equal length; daily dose adjustment to maintain a white blood cell [WBC] count of 45 × 109‐50 × 109/L).RESULTS: G‐CSF induced a rapid increase in cells of all WBC lineages with return to levels equal to (neutrophilic, eosinophilic, and basophilic granulocytes) or lower than those before treatment (monocytes, lymphocytes) during the treatment‐free intervals. Red cell counts remained unchanged, but platelet counts decreased followed by rebound thrombocytosis. The extent of CD34+ cell mobilization was highly variable. For each patient, the changes induced were identical through all cycles, but the G‐CSF dose required in the first cycle was significantly higher than in subsequent cycles. In the cohort of patients, an inverse correlation was observed between the WBC level reached and the dose of G‐CSF administered.CONCLUSIONS: Rapid alternation between PBPC mobilization and recovery periods is feasible, with identical alterations in all treatment cycles. G‐CSF responsiveness varies among patients and is increased by pretreatment with G‐CSF.
Phrenic Nerve Injury After Catheter Ablation: Should We Worry About This Complication?
Authors: BAI RONG , PATEL DIMPI , BIASE LUIGI DI , FAHMY TAMER S. , KOZELUHOVA MARKETA , PRASAD SUBRAMANYA , SCHWEIKERT ROBERT , CUMMINGS JENNIFER , SALIBA WALID , ANDREWS‐WILLIAMS MICHELLE , THEMISTOCLAKIS SAKIS , BONSO ALDO , ROSSILLO ANTONIO , RAVIELE ANTONIO , SCHMITT CLAUS , KARCH MARTIN , URIARTE JORGE A. SALERNO , TCHOU PATRICK , ARRUDA MAURICIO , NATALE ANDREA 
Published: June 2006

Introduction: Phrenic nerve injury (PNI) is a complication that can occur with catheter ablation. Methods: Data from 17 patients with PNI following different catheter ablation techniques were reviewed. PNI was defined as decreased motility (transient) or paralysis (persistent) of the hemi‐diaphragm on fluoroscopy or chest X‐ray. Patient's recovery was monitored. Normalization of chest images and sniff test would be considered as complete clinical recovery. Results: Out of the 17 PNI patients (16 right, 1 left), 13 (11 persistent, 2 transient) occurred after pulmonary veins isolation with or without superior vena cava ablation. Three patients had persistent PNI after sinus node modification and one other patient experienced PNI after epicardial ventricular tachycardia ablation. Ablation was performed with different energy source including radiofrequency (n = 13), cryothermal (n = 1), ultrasound (n = 2) and laser (n = 1). Patient's symptoms varied broadly from asymptomatic to dyspnea, and even to respiratory insufficiency that required temporary mechanical ventilation support. Two patients with transient PNI resolved immediately after the procedure and the other 15 persistent PNI patients resolved within a mean time of 8.3 ± 6.6 months. Conclusions: PNI caused by catheter ablation appears to functionally recover over time regardless of the energy sources used for the procedure.