bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Incidence of Ancestral HLA Haplotype 8.1 and Incomplete DH-JH Immunoglobulin Rearrangement in Persistent Polyclonal B-Cell Lymphocytosis.
Authors: Wolowiec Dariusz , Majewski Miroslaw , Nowak Jacek , Stella-Holowiecka Beata , Krawcewicz Angelika , Mika-Witkowska Renata , Makuch-Lasica Hanna , Solarska Iwona , Haus Olga , Duszenko Ewa , Kuliczkowski Kazimierz , Warzocha Krzysztof 
Published: October 2019

Abstract
Four women aged from 48 to 51 years with persistent polyclonal B-cell lymphocytosis (PPBCL) were studied for the clonality of B-cell population and HLA haplotype. All patients were smokers, one presented an immune deficiency syndrome due to decreased IgG and IgA levels, the others were asymptomatic. All patients presented serum increase of polyclonal IgM (5.55 – 8.12 g/L), absolute peripheral lymphocytosis ranging from 6100 to 10500/μL with elevated proportion of B cells, the percentage of CD5/CD19 lymphocytes < 5%, and binucleated/bilobulated lymphocytes accounting for 5–9% of nucleated cells on the blood smear. In one patient, cytogenetic study revealed trisomy 3 in 4 out of 40 metaphases, +18 in 2 cells, and i(18q), +15, t(13,14) in single cells. In the remaining patients no clonal chromosomal abnormalities were found. All patients were HLA typed by PCR based sequence specific primer amplification. HLA allele and haplotype incidence in patients’ group were compared to healthy population of 286 ethnically matched (Caucasian, Polish) controls. DRB1*07 allele was found in 2/4 patients, seems than to be elevated than in general Polish population but a small number of patients does not allow to perform relevant statistical tests. Moreover we found significantly more frequent B*08-DRB1*03 fragment of ancestral HLA 8.1 haplotype (8.1 AH) in PPBCL patients (3/4) than in control group (47/286) (OR=15.3; 95% CI 1.55–150; p=0.02). Peripheral blood mononuclear cells from all PPBCL patients were also studied for monoclonality in immunoglobulin (IGH VH-JH, incomplete DH-JH, IGK, IGL) and crosslineage TCR (TCRB, TCRG, TCRD) genes rearrangements according to BIOMED-2 protocol. The multiplex PCR reactions were followed with heteroduplex analysis of PCR products. We found polyclonality of lymphocytes population in all tests except incomplete DH7-JH IGH rearrangements in 2 patients. The described gene rearrangement was not related to other upstream DH or downstream JH gene segments. The HLA incidence we found is distinct from previously described elevated incidence HLA DRB1*07 allele and may suggest another genetic background of PPBCL pathogenesis. Moreover, our finding of high prevalence of 8.1 AH, known to be more frequent in autoimmune diseases, and to worsen the prognosis in some infectious diseases and non-Hodgkin lymphomas, as well as of the incomplete DJ monoclonality in 2/4 patients, warrant further studies aiming to determine the relationship between PPBCL, immune disorders and true lymphoproliferative diseases.
Vascular Endothelium Is Severely Perturbed and Undergoes Apoptosis in Experimental Heatstroke in Primates.
Authors: Roberts George T. , Chishti Muhammad A. , Al-Mohanna Fallah H. , El-Sayed Raafat M. , Bouchama Abderezak 
Published: October 2019

Abstract
Introduction: Ultrastructural evidence of endothelial cell (EC) injury has been associated with diffuse microvascular thrombosis in human heatstroke (HS). In vitro studies have also shown that heat stress accelerates apoptotic cell death. Using a recently described baboon model of heatstroke, we sought to examine pathological changes in the vascular endothelium and whether apoptosis is a mechanism of endothelial cell death.
Hypothesis: Major structural vascular endothelium alterations occur in HS and apoptosis is a mechanism of endothelial cell death in HS.
Methods: Anesthetized baboons (Papio hamadyras) were heat-stressed in a neonatal incubator maintained at 44 1.5 °C, until rectal temperature attained 42.5°C (moderate heatstroke; n =4) or systolic blood pressure fell to < 90 mm Hg (severe heatstroke n =4). Animals were resuscitated with normal saline and allowed to cool at room temperature. Four sham-heated animals served as control group. Spleen, liver, heart, kidney, gut, lung and adrenal tissue were obtained either by immediate autopsy in non-survivors or after euthanasia at 72-h for survivors. Vascular endothelium ultrastructure was evaluated by transmission electron microscopy (TEM) of ultra-thin tissue sections. Biological activity of EC was determined by light microscopy (LM) using a polyclonal antibody targeting von Willebrand Factor (vWF). Apoptosis was assessed, also in tissue sections, by deoxyuridine triphosphate nick end-labeling (TUNEL) procedure.
Results: In heatstroke animals, there were marked EC changes in lungs, spleen, jejunum, kidneys and liver, demonstrated by TEM, as increased cytoplasmic membrane convolutions that included formation of villi projecting into the vessel lumina, and increase in the width of the gaps between ECs. Migration of neutrophils, platelets and erythrocytes through these widened gaps was noted. Weibel-Palade bodies were increased both in size and number in EC of jejunum, lungs and kidneys. This increase correlated with increased endothelial expression of immunologically detectable vWF. TEM also showed that there was increased apoptosis manifested by nuclear chromatin condensation and karyorrhexis and formation of cytoplasmic myelin whorls. Increased EC apoptosis was also observed by TUNEL in the jejunum, lungs, liver and spleen. All these changes were greater in animals with severe HS than in animals with moderate HS, whereas sham heated control animals showed no significant changes.
Conclusion: Widespread EC injury with apoptotic cell death is consistent with the hypothesis that the endothelium may play a pathogenic role in heatstroke.
The Prognostic Value of Thrombocytosis Associated with Non Small Cell Lung Carcinoma.
Authors: Quispe Dolly , Hanbali Amr , Wollner Ira 
Published: October 2019

Abstract
Non small cell lung carcinoma (NSCLC) is the most common cause of cancer related death in US. During its clinical course patients may develop paraneoplastic syndromes such as thrombocytosis, which has been found in 17–21% patients with lung cancer. Thrombocytosis is associated with extensive disease and a poor prognosis. The objective of this study was to characterize the prognostic value of thrombocytosis in patients with NSCLC.
A retrospective study of inpatient and outpatient medical records at a large, midwestern, urban medical center was performed. Medical records from patients containing a new diagnosis of non small cell lung carcinoma based on ICD-9 codes from 1994 to 2000 were reviewed. Patients with a prior history of malignancy, less than 6 months of follow-up, or without an assessment of their platelet count were excluded. All records were reviewed for the following: TNM stage, histologic type by WHO criteria, and survival. Laboratory data was obtained prior to invasive diagnostic procedures, and thrombocytosis was defined as a platelet count &gt; 400 K/uL. Survival was calculated by Kaplan Meier curves and the difference in survival curves was tested by log rank test.
Thrombocytosis was observed in 113/858 patients (13.2 %). The group with thrombocytosis in comparison with the group without thrombocytosis had a significantly lower mean age at diagnosis (63 y vs 67 y, p&lt;0.001), hemoglobin (11.6 mg/dl vs 13.0 mg/dl, p&lt;0.001) and advanced stages were more frequent, TNM III and IV (79.8% vs 66.2%, p=0.007). No difference was observed between histologic types. 5 year survival was lower in patients with thrombocytosis (4% vs 18%, p &lt;0.001).
Thrombocytosis in patient with non small cell lung carcinoma is associated with advanced stages of the disease and poor survival.
5 Year survival non smell cell lung cancer 5 Year survival non smell cell lung cancer
Hyperhomocysteinemia and Heat Shock Proteins. Epidemiological Study in a General Population.
Authors: Dulin Elena , Guisasola Maria Concepcion , Desco Mª Mar , Suarez Antonio , Garcia-Barreno Pedro 
Published: October 2019

Abstract
Records and objectives: This study is planned with the objective of identifying new efficacious risk vascular markers. For this work the hyperhomocysteinemia as independent thrombotic vascular risk factor, atherosclerosis as inflammatory illness and Heat Shock Proteins (HSP70i) as molecules likely involved in the vascular damage are considered.
Subjects and methods: Workers of the HGGM have volunteered and given their consent. 53 male (M) and 54 female (F) were studied randomly. Anamnesis and epidemiological questionnaire were performed. Arterial pressure was measured and blood samples were taken for neutrophils leukocytes isolation by gradient, biochemical study and DNA extraction. We performed quantification of homocysteine (tHcy)
by HPLC; Reactive-C-Protein (RCP), serum and intraleukocitary HSP70i, and HSP70i antibodies by ELISA; molecular study of the polymorphism of C677T of the enzyme metilentetrahidropholatereductase (MTHFR) by PCR-RFLP. Task force of coronary risk was applied for the population classification.
Results: The studied population present [tHcy] ≥ 11 umol/L in the 12% of the cases. The mutation C677T appears in heterozygote subjects (CT) in the 45% of the cases and in homozygote subjects in the 17%.
Subjects were classified into 3 groups: G-0, without vascular risk factors, n=77 (32M and 45F); G-1, with a moderated risk factor (>10%) but without illness n=26 (18M and 8F) and G-2, with an evident atherosclerotic illness n=4 (3M and 1F)
Conclusions: The following correlations have been proved:
Inverse (p<0.05) between [tHcy] and [HSP70i] in neutrophils in females G-0 and males G1 wild type (CC) Inverse (p<0.05) between [tHcy] and serum [HSP70i] in males G-1 homozygotes (TT) Direct (p<0.05) between [tHcy] and [RCP] in females G-0 heterozygotes (CT) Direct (p<0.05) between [tHcy] and cholesterol in females G-0 homozygotes (TT) Direct (p<0.01) between [tHcy] and HTA in males G-0 heterozygotes (CT)
This study has been partially financed by FIS 03/1308
Acquired Risk Factors Play a Major Role in Venous Thrombosis in Chinese Population.
Authors: Feng Ying , Zhou X. , Xiong X. , Xiong Y. , Wang Y. , Jiang S. , Hu H. , Lu D. , Wang Z. 
Published: October 2019

Abstract
Acquired and genetic risk factors are associated with the occurrence of venous thrombotic embolism (VTE). In the Western population, 30 to 50% of the patients suffering from VTE are due to a genetic tendency to thrombosis. However, some common thrombotic risk factors in thrombophilia such as the factor V Leiden and the G20210A mutation of prothrombin are very rare in China and other Asiatic countries. Recently, we prospectively investigated the incidence of VTE among 768 hospitalized patients who had at least one of acquired risk factors such as prolonged immobilization, surgery, fracture, pregnancy, post-partum, cancer, diabetes mellitus, and some autoimmune diseases. The clinical VTE diagnosis was confirmed with Doppler ultrasonography, CT or/and venography. 17 patients (2.2%) developed VTE with one being complicated with pulmonary thromboembolism during their hospitalization. 90% of these cases had proximal deep vein thrombosis. It is notable that a high incidence of VTE (13.04%) has been found in patients in the intensive care unit, associated with many medical conditions including severe diseases, long lying in bed, multi-organ failure, infection and hypercoagulability. All these 17 VTE patients were extensively studied to identify and characterize the genetic anomalies predisposing possibly to thrombosis. Two were found to be of inherited antithrombin deficiency, and one of inherited protein C deficiency. Each of the three patients had the characteristics of recurrent VTE and/or familial history of VTE with episodes recognized at least in 2 family members. Our results suggest there might be a great variation according to the geographic origin of the population. The acquired risk factors play a much more important role than genetic risk factors in occurrence of VTE in Chinese population in comparison with Caucasians.
Drotrecogin Alfa (Xigris) Induced Coagulopathy as Measured by Routine Lab Tests in a Community Hospital Setting.
Authors: Maini Archana , Madangopal Chudaratna , Sheth Kishor 
Published: October 2019

Abstract
Drotrecogin alfa - Recombinant Human Activated Protein C (Xigris) is FDA approved for the reduction of mortality in adult patients with severe sepsis who have a high risk of death as determined by APACHE II. Patients with sepsis have decreased circulating levels of protein C and that is associated with increased mortality. Drotrecogin alfa presumably has three main mechanisms of action: anticoagulant, anti-inflammatory and pro-fibrinolytic. In the protein C pathway, protein C circulates as a zymogen which is converted to activated protein C (APC) when thrombin complexes with thrombomodulin, further augmented by Endothelial Protein C Receptor (EPCR). This APC, alongwith protein S, inactivates Factors Va and VIIIa, thereby limiting thrombin generation. Endogenous protein C activation is blunted in severe sepsis due to down-regulation of thrombomodulin and EPCR. PROWESS study was the first phase III landmark study to demonstrate an absolute 6.1% reduction in 28 day all cause mortality. The only significant toxicity was a 3.5% bleeding risk, especially with laboratory parameters of aPTT>120 secs, INR>3 and platelet count < 30,000/microliter as well as gastrointestinal ulceration and traumatic injury. Since then several other studies have been conducted with slightly varying results and as many as 19 different systemic biomarkers of thrombosis, coagulation, fibrinolysis and inflammation have been used. But practically, in the ICU setting, the anticoagulant activity of Drotrecogin alfa may be demonstrated by the prolongation of aPTT and PT during the drug infusion. No significant difference has been found in platelet counts in the major studies. The hematocrit is insignificantly changed in the absence of a bleeding complication. We report here a retrospective review of 10 adult patients with sepsis from our ICU who met the criteria to get drotrecogin alfa based on APACHE II. Their PT, INR, aPTT, Hb, Hct and platelet counts were recorded prior to drug infusion not exceeding 24 hours pre infusion. These counts were again looked at post infusion. The highest post infusion coagulation profile was selected and concordant Hb and Hct were recorded. We found the following mean changes in the selected parameters: Increase in aPTT of 58% (20.32 sec); increase in PT of 15% (2.61 sec); decrease in platelet count of 16% (26,000/microliter); decrease in Hb of 13% (1.44 gm/dl); decrease in Hct of 13% (4.09 %). Despite the seeming worsening of coagulopathy and some drop in Hb, Hct and platelets, patients did not have any major bleeding episodes attributable to Drotrecogin alfa. Out of our 10 patients, 7 have expired and 3 have survived for a mean of 130 days (range 118 days to 141 days) till today. Thus in our small retrospective sample, Drotrecogin alfa was found to be a safe and effective drug, based on routine blood tests and clinical observation alone in the ICU of a community hospital.
Clopidogrel Use in Children.
Authors: Finkelstein Yaron , Nurmohamed Laila , Avner Marina , Benson Lee N. , Koren Gideon 
Published: October 2019

Abstract
Background: Children with congenital heart problems have an increased incidence (up to 4%) of thrombotic vascular complications, particularly after interventional catheterization procedures that include device implantation. Clopidogrel, a thienopyridine derivative, is a specific platelet aggregation inhibitor. The preferred anti-thrombotic therapy after percutaneous coronary intervention (PCI) with stent placement in adults has evolved from aspirin and systemic anticoagulation with warfarin to dual antiplatelet therapy with aspirin and clopidogrel. Presently, no published data exists on clopidogrel use in children.
Objective: The aim of the present study was to report the first experience with clopidogrel therapy for primary and secondary prevention of thrombotic phenomena in children with complex heart disease after interventional cardiac catheterization, and to suggest a dose regimen for a paediatric population.
Methods: A retrospective chart review of all infants and children with complex heart disease treated with clopidogrel in the Hospital for Sick Children, Toronto between January 2001 and April 2004. Clopidogrel dosages, duration of therapy, complications and adverse effects in a paediatric population were explored.
Results: Fifteen infants and children with congenital and acquired heart disease were treated with clopidogrel (median age 3.5 years; range 6 weeks- 16 years). In 10 of them endovascular stents were inserted. Dosages ranged from 1 to 6 mg/kg/day, for periods ranging between 1 to 6 months. No thrombotic events were reported in these patients during clopidogrel therapy. One child had a bleeding complication (gastrointestinal) while on triple antithrombotic therapy. Other complications reported in adults, such as rash, were not noted in this paediatric series.
Conclusion: Clopidogrel was well tolerated, and there were no thrombotic events during treatment. We suggest a dose of 1mg/kg/day for children to be started.
The Effect of IL-3 in Ex Vivo Expansion of UCB CD34+ Cells.
Authors: Paek Jin-Young , Kim Do-Yeon 
Published: October 2019

Abstract
Background: Human umbilical cord blood (UCB) has been recognized as a source of hematopoietic stem cells for transplantation and the CD34+ cell dose is important factor predicting the hematologic recovery. However, the cell dose and CD34 (+) cells in one unit UCB are limited. This study compared the ex vivo culture conditions for expansion of total nucleated cells (TNC) and CD 34+ cells using isolated from UCB CD34 (+) and CD 133 (+) subset cells.
Material and method: The isolation of CD34 (+) and CD133 (+) cells from UCB was done by AutoMACS and the purity was more than 95%. We set three different cell culture conditions in stroma-free, serum-free medium. The culture conditions were 1) TPO, stem cell factor (SCF), Flt3-1 2) TPO/SCF/FLT3-1 and IL 3 10ng/dl, 3) TPO/SCF/FLT3-1 and IL 6 10ng/dl. After 7 days and 14days culture, we have been evaluated TNC and CD 34 (+) cell number for expansion potential.
Results: The TNC after 7 days and 14 days culture, in the CD 34(+) subset, the TPO/SCF/Flt3-1 condition was 15.6 fold and 8.0 fold and the TPO/SCF/Flt3-1 + IL-3 condition was 31.6 fold and 20.1 fold and the TPO/SCF/Flt3-1 + IL-6 condition was 25.5 fold and 12.0 fold, respectively. In the CD133 (+) subset, the TPO/SCF/Flt3-1 condition was 7.1 fold and 8.4 fold and in the TPO/SCF/Flt3-1 + IL-3 condition was 17.9 fold and 24.8 fold and in TPO/SCF/Flt3-1 + IL-6 condition was 15.9 fold and 19.8 fold, respectively. In terms of CD34 (+) cell population in the expanded cells, in the CD34 (+) subset, the TPO/SCF/Flt3-1 condition was 40%, the TPO/SCF/Flt3-1 + IL-3 condition was 64% and in the TPO/SCF/Flt3-1 + IL-6 condition was 40%, respectively. In the CD 133 (+) subset, the TPO/SCF/Flt3-1 condition was 83% and in TPO/SCF/Flt3-1 + IL-3 condition was 48% and in TPO/SCF/Flt3-1 + IL-6 condition was 62%, respectively.
Conclusions: To obtain more CD 34(+) cell population among ex vivo expanded cells, 7 days culture was more effective than 14 days culture and CD 133(+) subset was better than CD 34(+) subset. In terms of cell expansion ratio TPO/SCF/Flt3-1 + IL-3 was better than TPO/SCF/Flt3-1 and TPO/SCF/Flt3-1+ IL-6, which would be support the relevance of 7 days culture and CD133 (+) subset and IL-3 for expansion of hematopoietic stem cell ex vivo expansion.
Fig 1: The expansion ratio of both CD (34+)(a) and CD133 (+)(b) subset after 7 days and 14 days cultures in the 3 different cell culture conditions Fig 1:. The expansion ratio of both CD (34+)(a) and CD133 (+)(b) subset after 7 days and 14 days cultures in the 3 different cell culture conditions
Fig 2: The CD34(+) cell percentages in the different culture conditions both CD34(+) and CD133(+) subsets. Fig 2:. The CD34(+) cell percentages in the different culture conditions both CD34(+) and CD133(+) subsets.
Autologous Bone Marrow Stem Cells (ABMC) for Cardiormyoplasty in 15 Patients with Acute and Chronic Myocardial Disease (ACMD) in Colombia.
Authors: Cuéllar-Ambrosi Francisco , Senior-Sánchez Juan Manuel , Velásquez-Uribe Oscar , Navas-Rios Claudia , Londoño-Blair Juan Luis , Velásquez-Lopera Margarita 
Published: October 2019

Abstract
Introduction: ACMD disease accounts for 50% of all cardiovascular deaths and is the leading cause of congestive heart failure as well as premature permanent disability in workers. Unfortunately no medication or procedure has shown efficacy in replacing myocardial tissue or neovascularization. Some clinical human trials indicate that ABMC transplantation improves cardiac function and is feasible, safe and beneficial. We report the first experience in Colombia with this type of therapy
Methodology: This is the six months follow-up of 15 patients 23 - 60 years-old, 10M/5F with: A. an extensive, viability absence, acute myocardial infarction of anterior myocardial wall, 10 patients, with ejection fraction ≤ 40% that received standard postinfarction medical treatment, successful coronary percutaneous intervention and after intracoronary transfer of G-CSF mobilized ABMC, CD34 range 15–20 in millions. B. Five patients with chronic coronary heart disease and/or severe ischemic heart failure without option for standard revascularization therapies recibed epicardic implantation of G-SCF mobilized ABMC, CD34 range 14.5–19 in millions.
Results: It was demonstrated in both groups:
improvement in the mean ejection fraction from 29.44±3.36% before to 45±14,97% (p<0.001) after six months the exercise capacity increased in meaningful form evidenced by mean increase in the six minutes test from 295.07±66.04ms before to 648.4±93.15 ms after six months (p<0.001), the treadmill exercise time and the functional capacity in Mets from a mean of 4,8±1.02 before to 12.8±2.59 (p<0.001). there were significant changes in the myocardial perfusion at six months follow-up by nuclear images at diagnosis
Figure Figure
and 6 months later
Figure Figure
There were no presented complications related to the Cellular Transplant or the utilization of the G-CSF.
Conclusions: This is the first experience in Colombia with stem cells for intracoronary and epicardic cardiomyoplasty in acute and chronic coronary heart disease. It was observed functional recovery of the left ventricle, improvement in the exercise capacity without adverse effects or complications related to this therapy. In patients with ACMD, treatment with G-CSF to mobilize ABMC is feasible and safe and seems to be effective under clinical conditions. The therapeutic effect might be attributed to ABMC-associated promotion of myocardial regeneration and neovascularization.