bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep Pattern in Patients with β-Thalassemia Minor.
Authors: Cetin Turker , Yetkin Sinan , Ozgen Fuat 
Published: October 2019

Abstract
Introduction: Although sleep disturbances, anxiety, and sadness are some of the most common symptoms in patients with chronic anemia, there is little knowledge about sleep structures in patients with chronic anemia such as thalassemia. The aim of this study is to investigate sleep structure in patients with beta-thalassemia minor.
Methods: Seventeen drug free subjects with beta-thalassemia minor and age-matched healthy subjects were enrolled in the study. The patients were diagnosed by complete blood count including reticulocyte count and hemoglobin electrophoresis. In addition, blood smear, erythrocyte sedimentation rate, serum level of urea, creatinine, indirect bilirubin, lactate dehydrogenase, ferritin, folate, vitamin B12, and thyroid hormones were determined. The other causes of anemia were ruled out. Subjects also were screened for excessive daytime sleepiness with the Epworth sleepiness scale, and for insomnia using insomnia severity index. All subjects slept in laboratory for two consecutive nights. First night served as adjustment nights. The second night results were used for analysis. Their sleep patterns were compared with healthy normal controls. Sleep was recorded and scored according to the criteria of Rechtschafffen and Kales.
Results: Four female and thirteen male patients (mean age, 26.1 ± 5.9 years) completed both nights of sleep recordings. In patients groups, one patient complained snoring and daytime sleepiness. Nine of them complained daytime weakness. Ten patients were anemic (Hb < 13,2 g/dL for men, <11,7 g/dL for women). In polysomnographic investigation, the patients with β-thalassemia minor showed increased total sleep time, sleep period time, PLM index and the increased percentage of REM sleep. The percentage of stage 4, and REM latency are decreased. Sleep fragmentation and periodic leg movement syndrome (PLMS) have been reported.
Conclusion: The disturbances of sleep continuity was prominent finding in this polysomnographic study. They also showed decreased REM latency and the increased percentage of REM sleep, although they didn’t have major depressive disorders.
Polysomnographic variables in patients with beta-thalassemia minor Polysomnographic variables Thalassemia (n: 17) Normal Controls (n: 17) Results (P value) NS: not sinificant, REM: rapid eye movement, PLM: periodic leg movement Sleep effiency 90.8±4.6 93.7±2.1 NS Total time in bed (min) 467.6±60.1 415.1±51.1 .008 Total sleep time (min) 425.8.4±65.1 388.5±49.2 .031 Sleep period time (min) 453.2.4±62.0 404.4±52.2 .012 Sleep latency (min) 9.9±9.0 8.2±5.2 NS Percentage of stage 1 (SPT) 2.5±1.0 1.8±1.1 NS Percentage of stage 2 (SPT) 61.9±6.9 64.1±7.3 NS Percentage of stage 3 (SPT) 4.8±1.9 6.5±2.4 NS Percentage of stage 4 (SPT) 8.0±6.4 12.2±6.1 .022 Percentage of stage REM (SPT) 16.3±3.8 12.5±3.4 .006 REM latency 67.9±25.0 96.8±32.5 .016 PLM index 7.4 ± 5.7 0.0 .000
Lack of Heart Iron Overload in Patients with Thalassemia Intermedia.
Authors: Galanello Renzo , Tanner Mark , Matta Gildo , Barella Susanna , Bina Patrizio , Origa Raffaella 
Published: October 2019

Abstract
Iron loading in patients with thalassemia intermedia occurs slowly and is mainly due to increased gastrointestinal iron absorption secondary to chronic anemia, while in patients with thalassemia major iron overload is faster and secondary to the chronic transfusion therapy. Moreover, iron accumulation in thalassemia intermedia is prevalent in parenchymal cells, while in thalassemia major iron derived from red cell breakdown firstly accumulates in the reticulo-endothelial cells and subsequently in the parenchymal cells. Although heart disease represents the main determinant of survival in beta thalassemias, the cardiac complications are different in the two clinical forms, that are thalassemia major and thalassemia intermedia. In this study we evaluated liver and iron overload in patients with thalassemia intermedia.
We have studied 8 patients with thalassemia intermedia with a mean age of 36 ± 12 years. All these patients were homozygotes for the beta zero 39 non-sense mutation (C→T) and were never transfused or had received only sporadic transfusions (less than 10 blood units throughout their life). Myocardial iron (heart T2*, Anderson et al 2001), echocardiographic left ventricular ejection fraction, serum ferritin (mean of the last 5 years) and hemoglobin (mean of the last 2 years) have been evaluated in each patient. Hepatic iron content was determined in 5 patients with atomic absorption after liver biopsy. Six patients were on chelation therapy with subcutaneous desferrioxamine (mean 2 ± 1 grams/week).
Mean ferritin was 637 ± 497 ng/ml and mean hemoglobin 8.0 ± 1.0 g/dl. Heart T2* was normal in all patients (mean 46 ± 11 msec, range 36 – 62 msec). The mean left ventricle ejection fraction was 61 ± 6 % (range 51 – 70 %). Echocardiogram showed in all the patients a mild enlargement of both ventricles. Three patients had pulmonary hypertension and two had an extrasystolic arrhythmia. To our knowledge this is the first study reporting the results of heart T2* in thalassemia intermedia. As a consequence of the mechanism and rate of accumulation patients with thalassemia intermedia do not have heart iron overload, while liver iron concentration is quite relevant. Cardiac complications in thalassemia intermedia are mainly due to the hyperdynamic circulation associated with chronic anemia and to pulmonary hypertension.
Free Versus Neutrophil-Bound Antibodies in 100 Consecutive Italian Children with Chronic Neutropenia.
Authors: Porretti Laura , Lopa Raffaella , Cattaneo Alessandra , Portararo Paola , Ghilardi Roberta , Farruggia Piero , Martire Baldassarre , Corti Alessandra , Rebulla Paolo 
Published: October 2019

Abstract
Chronic neutropenia (CN) is defined as a blood absolute neutrophil count (NC) below 1500/ml, lasting for at least 6 months. We report the results of serological screening for anti-neutrophil antibodies, performed in our laboratory during 2002–2005, in 100 consecutive children affected from CN and followed in 4 Italian pediatric centers.
The patients, 65 males (m) and 35 females (f), had a median age of 18 months (range: 1–180). Both IgG bound to patient neutrophils (CD16+ cells) and the patient serum reactivity against healthy donor granulocytes (Direct and Indirect Granulocyte-Immunofluorescence Test, D-GIFT and I-GIFT) were assessed by flow-cytometry. The results are shown in the table, grouped according to the pattern of reactivity observed with D- and I-GIFT:
A NC above 1500/ μl on the day of serological screening was found in 5.5%, 22.4%, 0% and 35% of patients in groups 1, 2, 3 and 4, respectively. Secondary CN, usually in association with other autoimmune disorders or malignant diseases, was reported in 5.5%, 10.3%, 0% and 50% of patients in groups 1, 2, 3 and 4, respectively. Infections were present in 72%, 79%, 25% and 8% of patients in groups 1, 2, 3 and 4, respectively. In group 2, 50 of the 58 patients (86%), who didn’t show anti-neutrophil antibodies in their sera, presented neutropenia with concomitant infections. In these patients only D-GIFT was able to detect neutrophil antibodies.
Patients testing positive for I-GIFT had more severe neutropenia. Patients negative by both techniques were mostly found to have non-immunomediated neutropenia at clinical follow up. Although many laboratories perform only an indirect test to detect antineutrophil antibodies, our results suggest that direct test is more sensitive in identifying immunomediated chronic neutropenia.
table group GIFT no. of patients m/f NC (cells/μl)* WBC (x102/μl)* * Mean ± SD 1 D+ I+ 18 15/3 757 ± 520 7.58 ± 3.1 2 D+ I− 58 36/22 968 ± 818 7.29 ± 5.3 3 D– I+ 4 3/1 525 ± 369 6.71 ± 2.3 4 D- I− 20 11/9 1693 ± 1510 8.28 ± 3.2
Zoledronic Acid Inhibits the Function of Toll-Like Receptor 4 Ligand Activated Dendritic Cells.
Authors: Bringmann Anita , Schmidt Susanne M. , Brauer Katharina M. , von Schwarzenberg Karin , Werth Daniela , Kanz Lothar , Brossart Peter 
Published: October 2019

Abstract
Zoledronic acid (ZA; Zometa®) is a cyclic nitrogen-containing bisphosphonate with anti-tumor activity used to treat patients with malignant diseases. As a side effect, ZA induces inflammatory responses which are accompanied by expansion of gd T cells that probably mediate its anti-tumor activity. In our study we analyzed the effects of ZA on the function and differentiation of monocyte-derived dendritic cells (DC). We investigated the differentiation of immature and LPS-stimulated DCs incubated with different ZA concentrations which are usually achieved in treated patients. Expression of DC-specific marker molecules was assessed by FACS. Furthermore, the activation state and involvement of different signal transduction pathways were evaluated by Western blot. To monitor DC function we used a migration assay and analyzed the cytokine secretion. We found that DC activation with TLR4 ligand LPS is modulated by ZA. We show that the expression of the surface maturation markers CD80, CD86, CD40, CD54, CD83 and DC-SIGN is diminished with increasing ZA levels upon LPS activation. The migratory capacity of LPS stimulated DCs towards the chemokine CCL19/MIP-3beta and the secretion of the activatory cytokine IL-12 are reduced at higher ZA levels. Increasing ZA concentrations lead to the down-regulation MyD88 and diminish the nuclear localization of NF-kB family members RelB and c-Rel as well as interferon-regulatory factors IRF-3 and IRF-8 in LPS activated DCs. Hence, ZA concentrations used to treat patients have inhibitory effects on DC differentiation and activation. This might lead to immuno-suppression and negatively affect tumor rejection or result in infectious complications.
Genetic Screening of Familial Mediterranean Fever in Japan.
Authors: Miyahara Yasuko , Yamashita Kouhei , Miyoshi Takashi , Takaori Akifumi , Sasada Masataka , Uchiyama Takashi 
Published: October 2019

Abstract
There have been few reports of the patients with Familial Mediterranean Fever (FMF) in Japan, probably because FMF patients are preoccupied to be rare in Japan. We experienced 10 cases likely to be clinically diagnosed as FMF with periodic fever of unknown origin. FMF is an autosomal recessive disease resulting from the genetic mutations in the FMF gene (MEFV), which codes for a protein named Pyrin. Pyrin is expressed in mainly polymorphonuclear cells and monocytes and it is proposed that it regulates inflammation. The MEFV gene is located on chromosome 16p13.3 and comprises 10 exons. Several mutations in the MEFV gene have been identified, however the mutations are mostly located in exon 2 and 10. Therefore, we performed genetic screening of exon 2 and 10 in the 10 patient samples. The median age of the patients was 34 (17–49) years old. They are four males and six females. DNA was isolated from polymorphonuclear cells of the patients and PCR was performed with selective primers of exon 2 and 10 of MEFV gene, respectively. Thereafter, direct sequence of exon 2 and 10 of the PCR products was performed. As a result, the mutations of E148Q in exon 2 and M694I in exon 10, which are commonly observed in previous reports, were identified in seven and six out of 10 patients, respectively. All patients had either E148Q or M694I mutation. Three patients have both E148Q and M694I mutations. One 50-year-old female patient, who had a homozygous M694I mutation, suffered from severe renal AA amyloidosis. The mutation at M694 has been mostly reported as M694V, particularly in Mediterranean countries, however interestingly, all of the mutations of M694 were M694I, not M694V in our 10 Japanese patients. It is reported that healthy carrier frequency of the E148Q mutation was about 16% in Japan, so it is suggested that E148Q mutation may be profoundly involved in cause of disease, because E148Q mutation is observed among 70% of our patients. We herein report the unique genetic features of FMF patients in Japan. A further large scale of investigation would be necessary for confirming the significance of E148Q and M694I mutations in FMF patients in Japan.
Variation of Serum Lipid Profile during Enzyme Replacement Therapy, in Patients with Type 1 Gauchers Disease.
Authors: Symeonidis Argiris , Hughes Derralynn , Richfield Linda , Mehta Atul 
Published: October 2019

Abstract
Enzyme Replacement Therapy (ERT) has dramatically changed the clinical course and prognosis of patients with Gaucher disease. We have assessed the extent to which the recently defined Goals of Therapy (Pastores et al, Semin Hematol 41(suppl 5):4–14) in 9 major fields (anemia, thrombocytopenia, hepatomegaly, splenomegaly, skeletal pathology,biomarkers, pulmonary manifestations, growth and functional health and well being) were achieved in our cohort of patients with type I Gaucher disease. Fifty-seven patients (27 females, 30 males, median age at diagnosis 30 years (range 2–77 years) and at start of ERT 39 years (range 5–79 years) were assessed. The median period of ERT was 94 months (range 24–155 months). Patients on ERT for less than 2 years were excluded. Twenty five specific goals are defined within the 9 fields. The median overall success rate was 20 of 25 goals or 80% per patient (range 12–25 goals or 60–100%). The success rate for 9 goals was 100% ( normalization of hemoglobin 1 year post-splenectomy, no major bleeding 1 year after ERT start, doubling of baseline platelet count in severely thrombocytopenic patients 2 years after ERT start, maintenance of platelet count in non-thrombocytopenic patients, prevention of bone crises, reversion of hepatopulmonary syndrome and dependence on oxygen, amelioration of pulmonary hypertension and prevention of rapid deterioration of pulmonary disease and sudden death). Higher success rates were achieved for the goals related to thrombocytopenia (97.9%) and pulmonary manifestations (97%) although in the latter case the applicability was low. Lower success rates were achieved for the goals related to bone manifestations (78.7%). There was no significant difference in the success rate between males and females, splenectomised and non-splenectomised patients, and between patients treated less or more than 6 years. However patients started on ERT before the 40th year of age exhibited significantly higher success rate as compared to patients started after the 40th year (p=0.047) and there was a significant inverse correlation between overall success rate and patient’s age at treatment start (r = − 0.437). Finally, the success rate was higher among double heterozygotes, carrying the N370S mutation, as compared to patients homozygous for the N370S mutation (89.2±9.6% vs. 80.2±12.9%, p=0.016).
Identification of Specific Chemokines and Apoptosis Molecules in Pediatric Idiopathic Neutropenia.
Authors: Callejas Angel , Nadeau Kari , Bakshi Kokil , Wong Wendy , Carroll Tanya , Lau Ken , Yang Ya-Wun , Schilling Jim , Clayberger Carol , Krensky Alan , Jeng Michael 
Published: October 2019

Abstract
In order to explore possible mechanisms for idiopathic neutropenia, molecular and functional analyses on neutrophils and plasma of pediatric neutropenic patients were performed. 22 subjects, 8 acute and 14 chronic neutropenia, aged 5 months to 12 years, were recruited through Lucile Salter Packard Children’s Hospital hematology clinics with an IRB-approved consent. Patients with known neutrophil elastase mutations were excluded. We first examined whether the neutrophils of neutropenia patients had increased expression of molecules associated with cell death. QT-PCR was performed and transcript levels in neutrophils of neutropenia subjects were compared against those of normal subjects. In addition, to assess if a factor(s) in the plasma of neutropenia patients induced neutrophil cell death, neutrophil survival assays were done by incubating neutrophils isolated from normal healthy controls with 200 ul of undiluted plasma from chronic neutropenic subjects. Neutrophil death was then analyzed via Annexin V-PI staining. Finally, to identify specific plasma proteins, which may have a potential role in neutrophil-mediated cell death, 2D gels were run on neutropenic and control plasma.
Results: Due to limited sample size, assays were not run on all subjects. Acute and chronic neutropenic patients (n=10) experienced an increase in FAS, an apoptotic marker and protein known to be associated with neutrophil cell death. There were no significant differences in fold expression between acute and chronic patients. Neutrophil survival assays (n=9) revealed a median of 6.5 and mean 6.8 fold (range 2–24 fold) higher level of plasma-mediated cell death with neutropenic plasma. Preliminary studies of 2D gels on plasma revealed differential expression of inflammatory proteins in neutropenia patients compared to normal healthy controls. Further investigation on these proteins is ongoing. In summary, rapid cell death can be induced in normal neutrophils through neutropenia plasma incubation. Further identification of these apoptosis-associated plasma proteins is in process. In addition, the increase in certain apoptosis-associated chemokines and cytokines could lead to further target identification for diagnostic and/or treatment purposes of neutropenia.
Table 1 Patient Number Trascripts Expressed in Neutrophils (Fold Over Trancripts from Neutrophil of Normal, Healthy Control *= acute neutropenic patient TNF-α R1 FAS 1 2 13 2* 1.5 12.5 3 2 10 4 1 14 5* 2 12 6 2 13.5 7* 1 11 8* 2 10.5 9 2 7 10 1.5 10
Proliferative Function of Bone Marrow Hematopoietic Stem Cells of Patients with Systemic Lupus Erythematosus.
Authors: Fu Rong , Deng Jizi , Yuan Shang , Gong Lu , Sun Jun , Shao Zonghong 
Published: October 2019

Abstract
Objective:To investigate the bone marrow function of stem cells in patients with systemic lupus erythematosus (SLE), and to explore the pathogenesis of cytopenia in patients with SLE.
Methods:Sixteen patients with SLE and 10 healthy controls were studied for in vitro cultures of CFU-E, BFU-E and CFU-GM from bone marrow mononuclear cells.
Results:49.43±34.65 of CFU-E colonies per 105 BMMCs, 49.2±39.61 of CFU-GM colonies per 105 BMMNCs and 3.01±4.54 of BFU-E colonies per 105 BMMCs were seen in the group of SLE patients with normal blood count. 143.33±152.8 of CFU-E colonies per 105 BMMCs, 122.2±169.87 of CFU-GM colonies per 105 BMMCs, and 2.76±3.28 of BFU-E colonies per 105 BMMCs were seen in the group of SLE with hemocytopenia. 66.3±12.95 of CFU-E colonies per 105 BMMCs, 36.7±11.95 of CFU-GM colonies per 105 BMMCs, and 36±11.66 of BFU-E colonies per 105 BMMCs were seen in the group of normal controls.The quantity of BFU-E colonies per 105 BMMCs in SLE patients were significant lower than that in normal controls. There were no significant differences of the quantities of CFU-GM and CFU-E colonies between the SLE patients and normal controls.
Conclusions: 1. There were no significant differences of CFU-GM and CFU-E colonies between the SLE patients and normal controls, that suggested that SLE patients have normal proliferate function of bone marrow hematopoietic stem cells.2 There were significant lower BFU-E colonies per 105 BMMCs in SLE patients than that in normal controls.
The Frequency of Occurrence of Koxakie-Viruses at the Patients with Hematological Malignancies and Pulmonary Infections.
Authors: Domnikova Natalia P. , Bryakotnina Elena V. , Evstropov Alexandr N. 
Published: October 2019

Abstract
Aim: To determine frequency of occurrence of Koxakie-viruses at the patients with hematological malignancies and pulmonary infections.
Methods: A total 53 patients with hematological malignancies and pulmonary infections, admitted of the Novosibirsk Regional Clinical Hospital were examined. The analysis of serum in first three days was carried out at occurrence of attributes of pulmonary infection (1-st serum) and in dynamics - in 3 weeks from a beginning of an infection (2-nd serum). Definition of antibodies to a virus Koxakie-B3 (strain “Nancy”) was made in reaction of neutralization in 3-daily cultures Hep-2. Results took into account after approach of cytopathogenic effect in cultures Hep-2, containing 100 dozes of a virus in control titration. Limiting cultivation of serum, neutralizing of 100 cytopathogenic dozes of a virus, was considered as its titer.
Results: At 43 of 53 examined patients on admission or in a debut of an infection (at the patients with the developed infectious complication) the neutralized antibodies to a virus Koxakie-B3 were found out in serum. Thus the titer of antibodies from 1:4 up to 1:8 was revealed at 28 patients, at 14 it has made 1:16 – 1:32 and only at one patient on admission the titer of antibodies to a virus Koxakie B3 was 1:64. The total titer of virusneutrolized antibodies on admission or in a debut of an infection was accordingly 2,03 log2 and 2,84 log2. At research of serum taken after three weeks of stay in hospital of the patients, at which the infection was not developed (after a beginning of an infection at the patients with the developed infectious complication), in both groups the increase of a titer of antibodies in 1,97 and 1,5 times was marked, accordingly, and the total titer of antibodies in log2 has made 4,0 and 4,3. It is necessary to take into account, however, that at an estimation of serologic status at virus infections the absolute parameters of antibodies titers, how many their growth in pair serums matter not so much. Thus, authentic confirmation of the current virus infection is the increase of a titer of antibodies in dynamics in 4 times and more. The essential distinctions between two chosen groups were here again revealed. And, in group with hematological malignancies without infectious complications the four-multiple increase of a antibodies titer was marked only at 4 of 26 patients, and in group with infectious complications the authentic growth of a level of antibodies to a virus Koxakie-B3 was marked more than at half of surveyed patients (15 of 27), OR=6,88; 95%CI=1,61–31,87.
Conclusions: On the basis of the received results it is possible to conclude, that Koxakie B3 - virus infection is the factor enough frequently accompanying clinical current of pulmonary infections in patients with hematological malignancies.