Elevated Complement (C) and IgG Bound Microparticles (MP) in Immune Thrombocytopenic Purpura (ITP) and Hemolytic Anemia (HA).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1313-1313
Author(s):  
Wenche Jy ◽  
Lawrence L Horstman ◽  
Andrew Lin ◽  
Carlos Bidot ◽  
Yeon-Soong Ahn
Keyword(s):  
Flow Cytometry ◽  
Cell Activation ◽  
Conflicts Of Interest ◽  
Linear Regression Analysis ◽  
Red Cell ◽  
Major Mechanism ◽  
Cell Destruction ◽  
The Mean ◽  
Underlying Mechanisms ◽  
Normal Controls

Abstract Abstract 1313 Poster Board I-337 Background Cell derived microparticles (MP) are shed during cell activation and apotosis and MP profiles reflect the status of cell disturbances in various forms of pancytopenias. It was demonstrated that when antibodies fix complement (C) on the membrane, red cells evade C mediated lysis by shedding MP with bound C. We analyzed C and IgG bound to MP to gain insight on the underlying mechanisms of cell destruction. We measured C1q fragment and IgG on cell-derived (MP) in plasmas of patients with ITP, hemolytic anemias (HA) and thrombosis (TBS). Methods (1) Patient population. Consenting patients consisted of 18 TBS, 14 ITP and 6 HA (5 AIHA and 1 TTP), as well as 20 normal controls (NC). (2) Flow cytometry. MP were centrifuged from 1 mL fresh (not frozen) platelet-poor plasma (PPP), washed twice with saline, resuspended in 100 μL, then incubated with fluorescent mAb to C1q and IgG, then analyzed by flow cytometry. In addition, MP in the PPP were analyzed for MP from RBC (RMP) using marker glycophorin A, and MP from platelets (PMP) by CD42b. Values were considered elevated if >2SD above the mean of NC. Control values were (mean ±SD per μL): C1q+ MP = 536 ±151; IgG+ MP = 5,542 ±2,081; RMP = 823 ±246; PMP = 7,520 ±2,084. Results We observed significant elevation of C1q+ and IgG+ MP in patients with ITP (2-3 fold) and hemolytic anemias (6-10 fold) but not in those with thrombosis. These findings indicate that complement mediated cell destruction or disturbance in these disorders is frequent. (1). The ITP group consisted of 2 subgroups, one of which had elevated C1q+ and IgG+ MP, the other not, and these subgroups also differed in RMP. Specifically, six ITP with high C1q+ MP also had high RMP (1,899 ±682 /μL) and PMP (16,602 ±4,216 /μL) while those with normal C1q+ MP had normal RMP (504 ±186 /μL) and PMP (3,472 ±1196 /μL). This suggests that platelet destruction in ITP can proceed via C in some but not all cases, probably depending on the autoantibodies. We have previously reported high RMP in ITP. These findings suggest subclinical C mediated hemolysis in a subset of ITP. (2) In HA patients, all 6 had elevated C1q+ MP (3,934 ±1,419 /μL, p<0.001) as compared to normal controls (536 ±151 /μL). The mean in HA was nearly 6-fold greater than NC. The HA group also had higher IgG+ MP, with mean counts about 10-fold higher than NC (61,531 ±20,733 vs. 5,542 ±2,081 /μL, p<0.001). Furthermore, the HA patients also had elevated RMP (2,191 ±635 /μL, p<0.01). This suggests that C-mediated destruction of RBC is a major mechanism in HA. (3) Linear regression analysis showed that C1q+ MP is well correlated with IgG+ MP (R = 0.84, p<0.0001) and RMP (R = 0.79, p<0.001). (4) The TBS group did not show higher levels of any of the measures assayed. It is widely believed that phagocytosis is the mechanism of cell destruction in ITP and AIHA. Our findings support the concept that complement (C) -mediated platelet or red cell destruction play an important role and is common in these disorders. Assay of C and IgG on MP can provide new insight to underlying mechanisms of immune mediated platelet and red cell destruction. Disclosures No relevant conflicts of interest to declare.

scholarly journals OCT-Angiography Findings in Patients with Amblyopia: Comparison between Healthy Controls, Treatment-Responsive, and Treatment-Unresponsive Amblyopic Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1751
Author(s):  
Annabella Salerni ◽  
Gloria Gambini ◽  
Chiara Fedeli ◽  
Ludovica Paris ◽  
Emanuele Crincoli ◽  
...  
Keyword(s):  
Linear Regression Analysis ◽  
Vascular Density ◽  
Ocular Motility ◽  
Ophthalmological Examination ◽  
Light Stimulation ◽  
Cross Sectional ◽  
Vascular Plexus ◽  
The Mean ◽  
Normal Controls ◽  
Expert Physician

There is no consensus on whether amblyopia affects the retinal vascular plexus and morphology. Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy, OCTA was used. All patients underwent a comprehensive ophthalmological examination, including visual acuity, refraction, ocular motility tests, and anterior and posterior segment examination. OCTA was performed by an expert physician using the Zeiss Cirrus 5000-HD-OCT Angioplex (Carl Zeiss, Meditec, Inc., Dublin, OH, USA). OCTA scans were performed using a 3 × 3 mm2 and 6 × 6 mm2 fovea-centered image setting. The mean outer macular vessel density in the previously amblyopic group was 19.15 ± 0.51%. This was statistically significantly higher than in both the amblyopic group (18.70 ± 1.14%) and the normal controls (18.18 ± 1.40%) (p = 0.014). The previously amblyopic group also significantly differed from both normal controls and amblyopic eyes with regards to the inner (p = 0.011), outer (p = 0.006), and full (p = 0.003) macular perfusion. Finally, linear regression analysis revealed that BCVA was linearly correlated to outer perfusion in amblyopic (p = 0.003) and ex amblyopic eyes (p < 0.001). Considering the cross-sectional nature of our study, from our results, we can only hypothesize a possible correlation between light stimulation and retinal vasculature development. However, further longitudinal studies are needed to support this hypothesis.

Carfilzomib and Bortezomib Containing Regimens Yield High Rates Of MRD Negative Autologous Hematopoietic Progenitor Cell (HPC) Grafts In Multiple Myeloma (MM) and High Risk Smoldering Myeloma (SMM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2030-2030
Author(s):  
Nishant Tageja ◽  
Neha Korde ◽  
Constance Yuan ◽  
Kristen Cole ◽  
Jennifer Hsu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
High Risk ◽  
Tumor Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Hematopoietic Progenitor Cell ◽  
Myeloma Cells ◽  
Cd34 Cells ◽  
The Mean

Abstract Background Regimens incorporating modern anti-myeloma drugs, such as carfilzomib (CFZ) and bortezomib (BOR), produce rapid, deep and durable responses in newly diagnosed myeloma patients but their effect on collection of autologous HPC is not well known, including minimal residual disease (MRD) testing of stem cell grafts. Employing older induction regimens (such as VAD), less sensitive flow cytometry techniques detected circulating myeloma cells in 38-46% of autologous HPC grafts (Stewart, et al. JCO. 2001 and Bourhis, et al. Haematologica. 2007). We hypothesized that the use of modern CRd combination therapy including Carfilzomib (CFZ)-Lenalidomide (LEN)-Dexamethasone (DEX) would significantly lower the rates of HPC product contamination. Methods Thirty-six patients, including 29 with MM and 7 with high-risk SMM, underwent HPC mobilization and collection following induction with CRd (n=30), LEN-BOR-DEX (RVd, n=4), Cyclophosphamide-BOR-DEX (CyBorD, n=1) and Cyclophosphamide-BOR-Prednisone (CyBorP, n=1). For HPC mobilization, all patients received 5 days of filgrastim at 10-16 mcg/kg/dose. A combination of the patient’s weight and a peripheral blood CD34 count after 4 doses was used to determine the likelihood of collecting > 4 x106 CD34+ cells/ kg in a single apheresis procedure after a fifth filgrastim dose, according to a previously published algorithm from our institution. Only subjects predicted to require > 1 apheresis by the algorithm received Plerixafor (PLX) at 240 mcg/kg/dose on the fifth day along with the fifth filgrastim dose. HPC collection occurred on day 6, 8 hours after the last mobilizing agent(s) administration. Product contamination with myeloma cells (i.e. MRD status) was evaluated using multi-parameter flow cytometry with a minimum of 3 x 106 events obtained (sensitivity detection rate 1 x 10-5) to examine expression of 9 antigens by the plasma cells. Results The median age at mobilization was 56.2 years (range 40-73) and 19 (53%) were male. At the time of HPC collection, 20 (55%) patients were in sCR/CR/nCR, 11 (30%) had VGPR with 4 PR (11%) and 1 SD (3%). The mean CD34+ cells in the peripheral blood were 33/uL on day 5 and 55/uL on day 6 for the whole cohort. Thirteen (36%) patients did not need PLX. Interestingly, the mean CD34+ count dropped by a mean of 2% from D5 to D6 in patients not receiving PLX while, as expected, it increased by 304% in those who did. The median number of CD34+ cells collected was 6.86 million/kg (range 2.6-12.5) for the whole cohort, (6.6 million/kg without PLX and 7.52 million with PLX p=0.46). Thirty-three of 36 patients (92%) achieved a collection of > 4 million cells /kg in a single apheresis procedure. The 30 patients treated with CRd had a median of 5 (range = 3-7) prior cycles containing LEN with a median of 12 days (range 1-34) between mobilization and last LEN dose. Only 2 of 36 (5%) products were found to have evidence of tumor cell contamination (i.e. MRD positive) using sensitive multiparameter flow cytometry, one patient in PR after 6 cycles of CRd and a second patient in CR after 5 cycles of RVd. Conclusions Modern anti-myeloma therapies, such as CRd and RVd, allow adequate HPC collection in a single apheresis procedure in most cases and improve the quality of the HPC product with greatly reduced tumor cell contamination compared to historical controls. Indeed, 34/36 (94%) patients treated with modern anti-myeloma therapy collected an MRD negative HPC product. Future prospective studies are needed to assess whether autologous stem cell transplants (ASCT) using tumor-free HPC products collected in the era of modern induction therapies have better outcomes. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Correlations of Red Cell-Derived Micropareticles (RMP) with Other MP Species in Hematological and Thrombotic Disorders

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4723-4723
Author(s):  
Lawrence L Horstman ◽  
Wenche Jy ◽  
Mohamed EL Dinali ◽  
Gabriel Tinoco ◽  
Carlos Bidot ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Annexin V ◽  
Red Cell ◽  
Leukocyte Activation ◽  
Data Set ◽  
Hematological Disorders ◽  
Inflammatory Processes ◽  
Species Markers ◽  
Normal Controls

Abstract Background: We have recently observed that increased levels of circulating RMP are associated with several hematological disorders and thrombophilic states, and that levels were significantly higher when thrombosis was present. However, other species of MP, such as from platelets (PMP), endothelia (EMP), leukocytes (LMP) and annixin V-binding (AnV) have also been shown to be associated with thrombophilic states. The purpose of this study was to determine if correlations exist between RMP and other MP. Methods: This is a retrospective analysis of 702 laboratory samples over an 8 year period, limited to elevated values: >2SD above normal controls (>2,000/uL).. About 87% were individuals, the remaining 13% were tested 2-3 times and all tests >3 per patient were excluded. The disorders were hemolytic anemia (HA, n=38), hypercoagulable state (HCS, n=64), immune thrombocytopenia (ITP, n=86), thrombocytopenia of all causes (TP, n=69), myeloprolifereative disorder (MPD, n=29), thrombotic thrombocytopenic purpura (TTP, n=29), antiphospholipid syndrome (APS, n=34), pulmonary embolism (PE, n=21), and all-cause thrombosis (TBS, n=251). Some were classified in more than one way. MP species assayed were RMP by glycophorinA, PMP by CD41 (PMP41), PMP by CD42 (PMP42), EMP by CD31+/42- (EMP31), EMP by CD62E (EMP62E), LMP by CD45, annexin V binding (AnV), and counts by lectin, FITC-Ulex, which efficiently detects total MP including very small. Results: In HCS, the RMP >2,000/uL correlated well with PMP41 (R=0.407, p <0.001) and with PMP42 (R=0.285, p =0.02). In ITP, the RMP correlated solely with PMP42,31 (R=0.331, p =0.003). In HA, the RMP correlated with LMP (R=0.408, p =0.009) and with PMP42 (R=0.340, p =0.03). In all-cause TBS, RMP correlated with PMP41 (R=0.164, p =0.0120 and with LMP (R=0.231, p <0.001). In MPD, the RMP correlated solely with ulex (R=0.343, p <0.01). There was no significant correlation between RMP >2,000/uL and any of the MP markers in APS, TP, or TTP. The MP species markers, EMP31, EMP62E, and AnV, failed to show correlation with RMP in any of the disorders analyzed. In addition, we tested for correlations between elevated RMP and other MP for the entire data set (all disorders combined) and found that only LMP was significant (p <0.05). However, when the data was sorted by increasing LMP, it was found that the highest quintile showed improved correlation with RMP (p <0.01) while the lowest quintile of LMP values yielded no correlation at al (p > 0.05). Discussion: These correlation analyses shows that RMP correlated most frequently with PMP, as seen in HA, ITP, HCS, and TBS, followed by LMP, as seen in HA and TBS. These observations suggest that platelet or/and leukocyte activation may be involved in RMP generation. Of added interest is the finding that the overall data correlated well with LMP only at the higher LMP levels, not at all in the lower quintile of LMP. This suggests that RMP elevations are associated with immunolgic, inflammatory processes. In summary, correlation analysis reveals likely interaction between red cells and platelets or leukocytes during immunologic, inflammatory or in thrombophilic states, resulting in elevated RMP. Disclosures No relevant conflicts of interest to declare.

Renal Disease in Sickle Cell: Clinically Varied and Associated with Increased Mortality

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 90-90
Author(s):  
Sabarish Ayyappan ◽  
Paul Drawz ◽  
Mehdi Nouraie ◽  
Mariana E Hildesheim ◽  
Yingze Zhang ◽  
...  
Keyword(s):  
Renal Function ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multivariate Analyses ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Red Cell ◽  
Cell Disease ◽  
Cell Destruction ◽  
Increased Risk

Abstract Abstract 90 The Walk-Phasst Study of sickle cell disease (SCD) affords a unique opportunity to examine renal function in a large number of adults with SCD. Extensive clinical and laboratory data were obtained on 463 adults with HbSS and 127 adults with HbSC. Where possible, correlates for estimated glomerular filtration rate (eGFR, calculated by the 4-value MDRD equation) and albuminuria/proteinuria were also evaluated in historical data, from SS adults in the CSCCD cohort and the Multicenter Study of Hydroxyurea (MSH) in sickle cell disease. Adjusted decline in eGFR was more rapid in SS compared with SC, at −2.6 and −0.92 ml/min/1.73 m2/year, respectively (p<0.001). In SS, similar declines in cross-sectional eGFR with age were seen in adults in the CSCCD (n=705) and MSH (n=298) cohorts, at −2.9 and −1.9 ml/min/year (BSA corrected), respectively. Multivariate analysis of the SS cohort in of Walk-Phasst revealed that depressed eGFR values were associated with an elevated estimated pulmonary arterial systolic pressure (as reflected in a higher tricuspid regurgitant jet velocity, measured by echocardiogram, p=0.007) and with evidence for inflammation (an elevated white blood cell count, p=0.018). In SC adults, in contrast, lower eGFRs were primarily associated with a diminished erythroid reserve (depressed absolute reticulocyte counts, P=0.005). Albuminuria (≥30 mg albumin/gm creatinine) was detectable in 66 and 41 % of adults with HbSS and HbSC in Walk-Phasst (185/287 evaluable SS and 25/61 evaluable SC, p=0.001). In Walk-Phasst, albuminuria in SS was associated with evidence of increased red cell destruction (lower total hemoglobin (P=0.07), higher LDH (P<0.001), and higher reticulocyte count (P=0.017)). In SC, albuminuria was associated with a higher LDH (P=0.01). 159/657 (24%) of adult SS subjects in the CSCCD cohort had trace to 4+ proteinuria, using a method (urine dipstick analysis) that is less sensitive and less quantitative than the albumin-to-creatinine ratio used in Walk-Phasst. Multivariate analyses again suggested a strong association between a depressed Hgb and proteinuria (P<0.001) in CSCCD, and LDH was also associated with proteinuria, in univariate analyses (P<0.001). In Walk-Phasst the absence of albuminuria in all subjects with SCD was associated with lesser mortality in multivariate analyses (Hazard ratio 0.62 (0.4–0.9, P=0.02). No similar association was seen between eGFR and mortality. Subjects with SS in Walk-Phasst had depressed serum bicarbonate levels, of 23.8±3.4 compared with 24.7±3.2mEq/dL in SC (p<0.005) and 24.8±3.3 mEq/dL in the non-CKD general population (Shah et al, 2009). In multivariate analyses, acidemia was associated with both increased destruction and decreased production of red cells, e.g. higher EPO (P=0.003) and total bilirubin levels (P<0.001), but lower reticulocyte counts (P=0.06). Impaired physiologic functioning in acidemic subjects with HbSS, manifest as a depressed 6MWD (P<0.001) and a lower eGFR (P<0.001), was seen. No effect of bicarbonate level on mortality in SCD patients was evident in Walk-Phasst. In conclusion, renal function is perturbed in sickle cell syndromes in several ways, including more rapid decrement in eGFR, highly prevalent albuminuria, and, in SS, marked abnormalities in acid-base balance. Albuminuria is associated with anemia in two large cohorts of sickle cell disease patients and, in Walk-Phasst, with evidence for enhanced red cell destruction. Importantly, albuminuria correlated with an increased risk for mortality in sickle cell disease. (We acknowledge the many contributions made by the Walk-PHASST Investigators: Badesch DB, Barst RJ, Castro OL, Girgis RE, Gibbs JS, Goldsmith JC, Hannoush H, Hassell KL, Kato GJ, Krishnamurti L, Lanzkron S, Machado RF, Morris CR, Novelli EM, Rosenzweig EB, Sachdev V, Schraufnagel DE, Taylor JG 6th.) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mechanism of Erythrocyte Destruction in the Burned Rat

1955 ◽  
Vol 184 (1) ◽  
pp. 151-154 ◽  
Author(s):  
A. K. Davis ◽  
E. L. Alpen
Keyword(s):  
Survival Time ◽  
Red Cell ◽  
Body Area ◽  
Short Survival ◽  
Mean Survival Time ◽  
Short Survival Time ◽  
Cell Destruction ◽  
Normal Rat ◽  
The Mean ◽  
And Control

The rate of disappearance of Fe59-tagged erythrocytes made by burned and control rats has been measured in both normal and in rats with a 25% body area burn. The erythrocytes made by a burned rat have a mean survival time of 9 days when injected into burned rats. The same cells injected into normal rats have a mean survival time of 42 days. When erythrocytes made by a normal rat were injected into a burned rat the mean survival time was 18 days compared with 40 days when the same cells were injected into unburned controls. These data indicate an increased rate of red cell destruction in the burned rat. As the erythrocytes made by a burned rat do not display an abnormally short survival time in the normal rat and since an increased rate of destruction of erythrocytes is observed when cells from either normal or burned rats are injected into burned rats, it appears that the process of red cell destruction is an abnormality initiated by the burn.

Expression of Differentiation Antigens on Bone Marrow Myeloid Cells of the Patients with Myelodysplastic Syndromes and it's Clinical Significances

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4967-4967
Author(s):  
Zonghong Shao ◽  
Lijuan Li ◽  
Rong Fu ◽  
Huaquan Wang ◽  
Lanzhu Yue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
High Risk ◽  
Myeloid Cells ◽  
Antigen Expression ◽  
Low Risk ◽  
Glycophorin A ◽  
Hla Dr ◽  
The Mean ◽  
Normal Controls

Abstract Abstract 4967 Objective To study the abnormal differentiation of bone marrow myeloid cells in myelodysplastic syndromes (MDS) and its correlation with the prognosis of MDS patients. Methods Quantitative assessment of CD11b, CD13, CD16 and HLA-DR expression on the membrane of bone marrow granulocytes, and CD71 and glycophorin A on erythroblasts of 12 MDS patients in low-risk, 22 in high-risk and 31 normal controls was conducted with flow cytometry. The correlation between the abnormality of these antigen expression and the prognosis of MDS cases were analyzed. Results The granulocytic differentiation was analyzed with the combinations of CD13/CD11b, CD13/CD16 and CD11b/CD16. The “right hook”, “sickle” and “retroflex 7” shape expressions were found in normal controls while there were various changes in MDS groups. The ratios of CD11b-/CD11b+(0.39±0.34)and CD16-/CD16+(1.33 ±0.77)of high-risk MDS group were significantly higher than those of control group (0.07±0.05 and 0.39 ±0.31 respectively) (P<0.05). The MFI (mean fluorescence index) of SSC (side scatter) in the granulocyte gate of MDS groups was lower while their MFI of CD13 was higher. The mean percentages of CD11b-HLA-DR+ (3.88%±3.07%), CD11b- HLA-DR- (16.23%±15.59%), CD16-HLA-DR- (41.12%±24.53%), CD11b+CD16- (33.53%±17.26%) and CD13+CD16- (44.51%±21.99%) granulocytes of high-risk MDS group were significantly higher than those of low-risk and control groups (P<0.05). The erythroid cell lineage differentiation was analyzed with CD71/glycophorin A combination. Double antigen positive expression was found in all controls, but asynchronous expression of CD71/glycophorin A was found in some MDS cases. The mean percentage of double antigen positive cells in CD45- and glycophorin A+ cell population was significantly lower in low-risk and high-risk MDS groups. The abnormal numbers and patterns of the antigen expression of MDS cases correlated directly with their IPSS (international prognostic scoring system) (r=0.690, P=0.000) and WPSS (WHO adapted prognostic scoring system) (r=0.651, P=0.000) scores. Conclusion There were abnormal expressions of differentiation antigens on bone marrow myeloid cells of MDS patients. And the severity of these abnormal expressions was correlated with their prognosis. The abnormal differentiation of myeloid cells is probably involved in the pathogenesis of MDS. So the examination of these antigenic expressions with flow cytometry might be helpful for diagnosis and prognosis of MDS. Disclosures: No relevant conflicts of interest to declare.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

The Clinical Usefulness of the Platelet Aggregation Test for the Diagnosis of Heparin-Induced Thrombocytopenia

1993 ◽  
Vol 69 (04) ◽  
pp. 344-350 ◽  
Author(s):  
B H Chong ◽  
J Burgess ◽  
F Ismail
Keyword(s):  
Platelet Aggregation ◽  
Heparin Therapy ◽  
Serotonin Release ◽  
Point System ◽  
Control Groups ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Concentration ◽  
Release Test ◽  
The Mean ◽  
Normal Controls

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.

scholarly journals Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts

2021 ◽  
Vol 9 (1) ◽  
pp. e001615
Author(s):  
Rachel A Woolaver ◽  
Xiaoguang Wang ◽  
Alexandra L Krinsky ◽  
Brittany C Waschke ◽  
Samantha M Y Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Immune Responses ◽  
Single Cell ◽  
T Cell Activation ◽  
Antitumor Immunity ◽  
Cell Activation ◽  
Tcr Repertoire ◽  
Underlying Mechanisms ◽  
Personalized Cancer

BackgroundAntitumor immunity is highly heterogeneous between individuals; however, underlying mechanisms remain elusive, despite their potential to improve personalized cancer immunotherapy. Head and neck squamous cell carcinomas (HNSCCs) vary significantly in immune infiltration and therapeutic responses between patients, demanding a mouse model with appropriate heterogeneity to investigate mechanistic differences.MethodsWe developed a unique HNSCC mouse model to investigate underlying mechanisms of heterogeneous antitumor immunity. This model system may provide a better control for tumor-intrinsic and host-genetic variables, thereby uncovering the contribution of the adaptive immunity to tumor eradication. We employed single-cell T-cell receptor (TCR) sequencing coupled with single-cell RNA sequencing to identify the difference in TCR repertoire of CD8 tumor-infiltrating lymphocytes (TILs) and the unique activation states linked with different TCR clonotypes.ResultsWe discovered that genetically identical wild-type recipient mice responded heterogeneously to the same squamous cell carcinoma tumors orthotopically transplanted into the buccal mucosa. While tumors initially grew in 100% of recipients and most developed aggressive tumors, ~25% of recipients reproducibly eradicated tumors without intervention. Heterogeneous antitumor responses were dependent on CD8 T cells. Consistently, CD8 TILs in regressing tumors were significantly increased and more activated. Single-cell TCR-sequencing revealed that CD8 TILs from both growing and regressing tumors displayed evidence of clonal expansion compared with splenic controls. However, top TCR clonotypes and TCR specificity groups appear to be mutually exclusive between regressing and growing TILs. Furthermore, many TCRα/TCRβ sequences only occur in one recipient. By coupling single-cell transcriptomic analysis with unique TCR clonotypes, we found that top TCR clonotypes clustered in distinct activation states in regressing versus growing TILs. Intriguingly, the few TCR clonotypes shared between regressors and progressors differed greatly in their activation states, suggesting a more dominant influence from tumor microenvironment than TCR itself on T cell activation status.ConclusionsWe reveal that intrinsic differences in the TCR repertoire of TILs and their different transcriptional trajectories may underlie the heterogeneous antitumor immune responses in different hosts. We suggest that antitumor immune responses are highly individualized and different hosts employ different TCR specificities against the same tumors, which may have important implications for developing personalized cancer immunotherapy.

scholarly journals Happiness, quality of working life, and job satisfaction among nurses working in emergency departments in Iran

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Somayeh Javanmardnejad ◽  
Razieh Bandari ◽  
Majideh Heravi-Karimooi ◽  
Nahid Rejeh ◽  
Hamid Sharif Nia ◽  
...  
Keyword(s):  
Job Satisfaction ◽  
Emergency Departments ◽  
Economic Status ◽  
Linear Regression Analysis ◽  
Working Life ◽  
Least Square ◽  
Life Questionnaire ◽  
Quality Of Working Life ◽  
The Mean

Abstract Background Nurses have a vital role in the healthcare system. One of the basic steps to increase their happiness is to recognize factors such as job satisfaction and quality of working life. Therefore, the goal of the present study was to examine the relationship between happiness and quality of working life and job satisfaction among nursing personnel. Methods This descriptive study was carried out on 270 hospital nurses who worked in emergency departments in Iran. Nurses were recruited through the census method. Data collection instruments included the Oxford Happiness Inventory (OHI), the Quality of Work Life Questionnaire (QWL), and the Job Satisfaction Questionnaire (JSQ). Data were explored using descriptive statistics, and stepwise multiple linear regression analysis. Results The mean age of participants was 30.1 ± 6.26 years. The mean happiness score was 38.5 ± 16.22, the mean Quality of Working Life (QWL) score was 84.3 ± 17.62, and the mean job satisfaction score was found to be 45.5 ± 13.57); corresponding to moderate levels of attributes. The results obtained from the ordinary least-square (OLS) regression indicated that happiness significantly was associated with economic status and satisfaction with closure (R2: 0.38). Conclusion Overall the current study found that nurses who work in emergency departments did not feel happy. Additionally, the findings suggest that their happiness were associated with their economic status, and closure over their duties.

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