Therapeutic Management of Acute Myeloid Leukemia Patients after Stratification on Age, Prognosis and Allogeneic Hematopoietic Stem Cell Transplantation Eligibility

Abstract We evaluated in this study the therapeutic management of all newly diagnosed acute myeloid leukemia (AML) patients followed in our center between July 2007 and September 2013, after stratification on age, prognostic factors, whether they were candidate to allogeneic hematopoietic stem cell transplantation (allo-HSCT), transplanted or not with the evaluation of each therapeutic strategy and its impact on overall survival. A total of 572 consecutive newly diagnosed AML patients were included; there were 311 (54%) males and 261 females with a median age of 63 years (range: 20-92), 406 (71%) were de novo AML and 166 (29%) secondary AML. Complete cytogenetic and molecular biology data were collected for all patients and prognosis was differentiated according to the European LeukemiaNet classification (Dohner et al. Blood 2010). Accordingly, 335 (59%) patients were unfavorable, 83 (15%) favorable, 48 (8%) intermediate I and 106 (18%) were in intermediate II category. Following the Acute Leukemia French Association (ALFA) guidelines for allo-HSCT in AML, patients with intermediate II and unfavorable prognosis ≤ 65 years should receive intensive chemotherapy followed by allo-HSCT in the presence of related or unrelated HSCT donors. We divided the population into two sub-populations, the first was considered as young with age ≤ 65 years (N=318, 56%) and the second considered as old with age > 65 years (N=254, 44%). In the young population, there was 4 groups, group 1: patients with good prognosis (favorable/intermediate1) who received intensive chemotherapy within or according to ALFA protocols (N=105, median age= 47 years); group 2: patients with poor prognosis (intermediate2 /unfavorable) who received intensive chemotherapy within or according to ALFA protocols followed by allo-HSCT (N=126, median age= 50 years), group 3: patients with poor prognosis who received only intensive chemotherapy without allo-HSCT (N=69, median age= 57 years), and group 4: patients with poor prognosis who could not be treated due to early death (N=18). In the old population we distinguished, group 1: patients with good prognosis who received moderate intensity chemotherapy within or according to ALFA protocols (N=25, median age=73 years); group 2: patients with poor prognosis who received azacitidine (N=25, median age=76 years), group 3: patients with poor prognosis who received moderate intensity chemotherapy (N=89, median age=76 years), group 4: patients with poor prognosis who received low dose Ara-C (N=28, median age=76 years), group 5: patients with poor prognosis who received other treatment (N=38, median age=77 years) and finally group 6: patients with poor prognosis considered as palliative or who did not receive any treatment (N=49, median age=77 years). After a median follow-up of 34 months (range: 4-77) for surviving patients, the 2-years probability of overall survival (OS) in the young population for groups 1,2,3 and 4 was 84%, 56%, 31% and 0% respectively; and in the old group it was 71%, 37%, 31%, 5%, 21% and 0% for groups 1,2,3,4,5 and 6 respectively (figure). We showed that newly diagnosed AML patients with good prognosis all ages included could achieve very good survival rates after intensive chemotherapy; allo-HSCT after induction chemotherapy remains the best therapeutic option for fit patients with poor prognosis while the same fit patients with no donor have significantly lower survival (p<0.001) and for whom allo-HSCT could be proposed by using haploidentical donors in case of cord blood or unrelated donors absence. Interestingly, in the old population, we showed that poor prognosis patients receiving azacytidine had a significantly better survival compared to those receiving low dose Ara-C (p=0.015), with a comparable outcome to those receiving induction chemotherapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Management of Acute Myeloid Leukemia (AML) in First Relapse: Retrospective Analysis about 101 Adults Cases Receiving Homogeneous First-Line Therapy. Impact of Prognostic Factors and Treatment.

Blood ◽

10.1182/blood.v104.11.882.882 ◽

2004 ◽

Vol 104 (11) ◽

pp. 882-882

Author(s):

Cecile Fohrer ◽

Brigitte Witz ◽

Jean Luc Harousseau ◽

Francis Witz ◽

Shanti Ame ◽

...

Keyword(s):

Prognostic Factors ◽

Median Survival ◽

Complete Response ◽

Intensive Chemotherapy ◽

Group 4 ◽

Line Therapy ◽

First Relapse ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract We retrospectively analyzed impact of prognostic factors and salvage therapy in 101 patients (pts) with AML in 1st relapse. All pts were treated as 1st line according protocols GOELAMs 1 (87–94) or 2 (95–99). They all achieved complete remission after one (85%) or two (16%) induction with a combination of anthracycline and cytarabine. Consolidation therapy included one course of high-dose cytarabine (HiDAC) and a second consolidation (amsacrine-VP16) or, for a subset of pts, intensification with allogeneic or autologous stem cell transplantation (SCT). Data were collected in 3 of the centers participating to these trials. Main characteristics of pts at initial diagnosis were: median age : 39 y (range 17–64); sex : 55 male, 46 female; WBC count > 30 000/μl in 42 (42%) pts; 16/85 (18%) pts had unfavorable karyotype. Median duration of 1st complete remission (CR1) was 10 months (range: 1–101). Duration of CR1 was shorter than 6 months in 22 (22%) pts, between 6 and 12 months in 41 (40%) pts and longer than 12 months in 38 (38%) pts. At time of 1st relapse, median age was 40 y (range 18–66) and 10/38 (26%) unfavorable karyotype. There were no specific recommendations in the GOELAMs protocols for the second line therapy: modalities of treatment were therefore left to investigator’s decision. First step of relapse treatment was based on intensive chemotherapy in 79 (79%) pts including 55 pts who received a regimen containing HiDAC (Group 1) and 24 pts who received a chemotherapy without HiDAC (Group 2). Eight pts received an autologous SCT (4 pts) or an allogeneic SCT (4 pts) without any previous salvage chemotherapy (Group 3). One pt received gemtuzumab ozogamicin and thirteen pts received only oral chemotherapy and/or supportive care (Group 4). Fifty-seven pts (56%) achieved a second CR. Response rate and median survival according to initial therapy of relapse are shown in the following table. Differences are not significant. Complete response (%) Median survival (months) Group 1 (n = 55) 39 (71%) 11.5 Group 2 (n = 24 10 (42%) 8 Group 3 (n = 8) 6 (75%) 7.5 Group 4 (n = 14) 2 (14%) 3.5 Twenty seven pts out of the 49 pts who achieved a CR2 after intensive chemotherapy (Group 1 and 2) received subsequent intensification with either an allogeneic SCT (7 pts) or an autologous SCT (20 pts). Median survival of these pts subsequently transplanted was 18 months compared to only 10 months in the 22 pts of group 1 and 2 who did not receive a subsequent transplantation. Difference is not significant (log rank test, p = 0.65). Nine (33%) of the 27 transplanted pts are alive more than 36 months after relapse (range 41–120). Univariate analysis demonstrated that adverse prognosis factors on survival at 1st relapse were duration of RC1 shorter than 12 months (p= 0.005)and complex cytogenetic abnormalities (p= 0.0086). Conclusion: Intensive chemotherapy including HiDAC at 1st relapse in AML in adults provided a high rate of complete response. Intensification with SCT after CR2 was obtained can provide a very long survival in a limited number of pts. At 1st relapse, adverse prognostic factors on survival were short CR1 and unfavorable karyotype. Risk-adapted of AML in first relapse may therefore be warranted. Figure Figure

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Impact of Peripheral Blood Stem Cell Recruitment on Outcome of Single or Double Autologous Hematopoietic stem Cell Transplantation for Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.5221.5221 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5221-5221

Author(s):

Mauricette Michallet ◽

Quoc-Hung Le ◽

Anne-Sophie Michallet ◽

Anne Thiebaut ◽

Emmanuelle Tavernier ◽

...

Keyword(s):

Multiple Myeloma ◽

Multivariate Analysis ◽

Stem Cell ◽

Light Chains ◽

Hematopoietic Stem ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Multiple myeloma remains one of the best indication for intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (autoT). Intensive therapy followed by autologous transplantation is superior to conventional chemotherapy and it was demonstrated that two autoT were superior to one except for patients in very good partial response or in complete response after the first autotransplant. Peripheral blood stem cells (PBSC) can be used as well as bone marrow as HSC source with the same efficacy but very few data have been reported regarding PBSC recruitment. The main goal of our work was to study the impact on overall and event-free survival (OS and EFS) of PBSC recruitment using either growth factors (GF) alone (steady state) or chemotherapy followed by GF. Secondly, we performed a multivariate analysis studying influence on OS and EFS of sex, age, lines of therapy, pretransplant status, TBI, PBSC recruitment and number of autoT. We have analyzed 193 PBSC autoT (1 autoT=160, 2 autoT=33) performed for 160 MM patients [81 males and 71 females, mean age: 55 years (39–71)]. At diagnosis, 88 patients presented a MM Ig G (70k and 18l), 28 Ig A (16k and 12l), 3 Ig D (1k and 2l), 21 light chains k and 13 light chains l, 3 non secreting and 4 with plasmocyte leukemias. According to Durie and Salmon classification 75% of patients were in stage III, 15% in stage II and 10% in progressive I. Before transplantation, patients have received 1 line of poly-chemotherapy (n=141), 2 lines (n=15) or 3 lines (n=4) and 154 were evaluated for the response with 11 complete remission, 113 partial remission and 30 stable or evolutive disease just before transplant. As HSC (n=189), patients received PBSC which were recruited by GF alone (n=105) or cyclophosphamide+GF (n= 84). Conditioning (n=189),consisted in melphalan and TBI (n=51), melphalan alone (n=132), melphalan associated to cyclophosphamide or busulfan (n=6). We divided the population into 4 groups : group 1 who received one autoT of PBSC recruited by GF (n=76), group 2 one autoT of PBSC recruited by chemotherapy+GF (n=50), group 3 two autoT of PBSC recruited by GF (n=16) and group 4 two autoT of PBSC recruited by chemotherapy+GF (n=17). The median follow-up (FU) of the 4 groups were different with shorter FU (group 3: 9.9 months, group 4: 13 months) for patients who received tandem autoT because of the recent character of this strategy as compared to a long term follow-up for patients who received only one transplant (group 1: 35months, group 2: 55.3 months). Probabilities of OS and EFS at 2 years were 76% (95%CI 67–87) and 60% (95%CI 49.5–73) for group 1, 77% (95%CI 65–90.5) and 70% (95%CI 57.5–85) for group 2, 87.5% (95%CI 73–100) and 72.9% (95%CI 49–100) for group 3, 100% and 66.7% (95%CI 36–100) for group 4. The difference was not significant because of follow-up differences between the 4 groups and small number of patients in groups 3 and 4. In addition, multivariate analysis did not show any significant influence of the different studied parameters on OS and EFS. Nevertheless, because of these interesting preliminary results, a longer follow-up is warranted for definitive conclusions.

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Leukemic and Hematopoietic Stem Cells Compete for the Same Functional Marrow Niche in a MLL-AF9 Murine Leukemia Model

Blood ◽

10.1182/blood.v120.21.4897.4897 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4897-4897

Author(s):

Ronan G. Desmond ◽

Taha Bat ◽

Olena Kamenyeva ◽

Benjamin Mizukawa ◽

James C. Mulloy ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Murine Model ◽

Leukemic Cells ◽

Hematopoietic Stem ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Abstract 4897 Much is known regarding the location, cellular composition, signaling pathways, and functional role of the normal hematopoietic stem cell (HSC) niche in the bone marrow microenvironment. Microenvironmental cells including osteoblasts, other specialized mesenchymal cells, and vascular endothelial cells exert control over HSC self-renewal, differentiation, and engraftment. Niche occupancy appears to be competitive and limiting in terms of controlling the number of HSCs per organism. Leukemia stem cells (LSCs), through their inherent properties of quiescence and resistance to chemotherapeutic agents, are thought to be one of the principal mechanisms underlying disease relapse in patients. Much less is known regarding the interaction of LSCs and the marrow microenvironment. It is not clear whether LSCs localize to the same niches as HSCs, compete with HSCs for niche occupancy, or share dependence on niche signals, and whether those signals affect tumor responses to chemotherapy. Using a human pre-B ALL xenograft mouse model, Colmone et al (Science 2008) recently showed that leukemic cells may alter the normal microenvironment, resulting in initial homing of transplanted normal HSPCs in distinct atypical niches. Shiozawa et al (JCI 2011) showed that metastatic prostate cancer cells, a tumor type known to target bone, impeded HSC engraftment in a murine model, suggesting competition for the same niche. To investigate the relationship between HSC and LSC niche localization and functional occupancy, we used murine progenitor cells transduced with an MLL-AF9 vector expressing GFP in a murine syngeneic competitive transplantation model. MLL-AF9 cells are highly enriched for LSCs, particularly the c-kit+ compartment (Somervaille Cancer Cell 2006). We found that between approximately 21% and 24% of cells were c-kit+ by FACS in 2 separate experiments. In our model, mice transplanted with unsorted MLL-AF9 cells (1×107) died of AML with a latency of 11–14 days. We cotransplanted a fixed number of MLL-AF9-GFP cells (1×106) with increasing numbers of normal mouse whole bone marrow (WBM) cells, derived from dsRed transgenic mice to facilitate distinction from the GFP+ MLL-AF9 cells, into mice irradiated with 1000 rads: 1×105 [group 1], 1×106 [group 2], 1×107 [group 3], 5×107 [group 4]. Control groups received 1×105 and 1×106 normal WBM cells only. Survival was monitored daily. The control group receiving 1×105 cells only all died with median time to death of 16.5 days from lack of count recovery, those receiving 1×106 cells are still alive 35 days after transplant, indicating that 1×106 cells is adequate to rescue from irradiation. Mice were bled weekly until death and samples were analyzed by flow cytometry. Complete blood counts, blood smears, and splenic sections were obtained from these mice. As expected, there were no circulating blasts detected 7 days post transplant and all mice were healthy. However, 14 days after transplant the percentages of GFP+ leukemic cells detected in the blood were inversely proportional to the number of normal dsRed WBM cells transplanted (group 1 vs. group 2 vs. group 3 vs. group 4 mean percentage of GFP+ cells, 83.97 v 66.53 v 18.73 v 9.275 p< 0.0001). At day 15, mice from group 1, but not from groups 2 to 4, became moribund and were sacrificed. Spleens in this group were heavier than in those mice transplanted with 1×105 normal WBM cells alone and 2 out of 3 showed leucocytosis compared to leucopenia in all mice in the group transplanted with normal cells alone. When mice in the other groups had blood samples taken for analysis while moribund, GFP+ cells were greater than 80% suggesting that mice in group 1 died from complications relating to leukemic infiltration. Confocal microscopy confirmed the colocalization of normal HSPCs and MLL-AF9-GFP LSCs in the niche. Most interestingly, survival was proportional to the numbers of normal WBM cells transplanted, with a continuous delay in leukemic death proportional to the number of normal WBM cells cotransplanted with the same dose of MLL-AF9 cells (Figure 1). Hence, this murine model of leukemia suggests that normal and leukemic cells compete for the same functional niche, that manipulation of the niche could impact on response to anti-leukemic therapies, and that cell dose in the context of stem cell transplantation for leukemia may have an impact on outcome via niche competition. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

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The Risk of Bladder Cancer in Type 2 Diabetes Mellitus with Combination Therapy of SGLT-2 Inhibitors and Pioglitazone

Journal of Personalized Medicine ◽

10.3390/jpm11090828 ◽

2021 ◽

Vol 11 (9) ◽

pp. 828

Author(s):

Yan-Rong Li ◽

Chi-Hung Liu ◽

Wei-Chiao Sun ◽

Pei-Yi Fan ◽

Feng-Hsuan Liu ◽

...

Keyword(s):

Bladder Cancer ◽

Combination Therapy ◽

Reference Group ◽

Newly Diagnosed ◽

Group 4 ◽

All Cause Mortality ◽

Group 3 ◽

Group 2 ◽

Group 1

Background: Either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or pioglitazone (Pio) has doubtful issues of bladder cancer, especially for the combination therapy with these two drugs. Our study aimed to investigate the risk of bladder cancer under combination therapy of SGLT-2 inhibitors and Pio. Materials and Methods: We included 97,024 patients with type 2 diabetes mellitus (T2DM) in the Chang Gung Research Database in Taiwan from 1 January 2016 to 31 December 2019. The primary outcome was newly diagnosed bladder cancer after combination therapy with SGLT-2 inhibitors and Pio. Group 1 received both study drugs, group 2 received SGLT-2 inhibitors, group 3 received Pio, and group 4 received non-study drugs (the reference group). The secondary outcome in each group was all-cause mortality. Results: In group 1, no newly diagnosed bladder cancer was detected after a mean 2.8-year follow-up and all-cause mortality decreased significantly (adjusted hazard ratio (AHR), 0.70; 95% confidence interval (CI), 0.54–0.92) in comparison to the reference group (group 4). In group 2 and group 3, no trend of increased bladder cancer was observed (group 2: AHR 0.49, 95% CI 0.05–4.94; group 3: AHR 0.48, 95% CI 0.15–1.58) and it still reduced all-cause mortality (group 2: AHR 0.83, 95% CI 0.70–0.99; group 3: AHR 0.90, 95% CI 0.83–0.99). Conclusions: In T2DM patients without previous or active bladder cancer, the combination therapy of SGLT-2 inhibitors and Pio was not associated with newly diagnosed bladder cancer and had lower all-cause mortality.

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The Modulating Effect of Azacitidine (Aza C) on the Cytogenetically Tracked MDS Clone Impact Survival.

Blood ◽

10.1182/blood.v104.11.1429.1429 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1429-1429 ◽

Cited By ~ 5

Author(s):

Vesna Najfeld ◽

Angela Scalise ◽

Rosalie Odchimer-Reissig ◽

Lewis R. Silverman

Keyword(s):

Therapy Group ◽

Bone Marrow Failure ◽

Prognostic Significance ◽

Survival Group ◽

Hematopoietic Stem ◽

Group 4 ◽

Clinical Consequences ◽

Group 3 ◽

Group 5 ◽

Group 2

Abstract MDS is a clonal hematopoietic stem cell disorder characterized by progressive bone marrow failure leading to death from infections and bleeding in the majority of patients. Transformation to acute leukemia occurs in 35-40%. Most treatments, other than allogeneic SCT, have been ineffective. Treatment with Aza C has been shown to be clinically effective and alters the natural history of disease (Silverman et al JCO 2002). We have previously demonstrated Aza C modulation of the MDS clone and established five different cytogenetic categories based on its modulating effect (Najfeld et al, ASH 2002). The goal of this extended study was to determine biological and clinical consequences of Aza C modulation on the five cytogenetic categories. Among 224 patients treated with AzaC, multiple sequential studies were performed in187 pts, while 41 pts without follow up studies, were excluded from this report. The initial karyotype prior to therapy with Aza C was normal in 99 pts (53%) and abnormal in 88 pts (47%). These latter patients were not further subdivided into good, intermediate or poor risk according to IPSS. The table below shows the Kaplan Meier median survival of the 5 subcategories based on the modulating effects of Aza C on the cytogenetically identified MDS clone. Cyto Category No of Frequency of Hematological Survival Group Pts Emerging Response In No Chromosome Abnormalities Months 1 Normal->Normal 67 None CR:3, PR:10, IMP:31 29.3 2 Normal->Abnormal 32 +8:25%l+1q:25% CR:1, PR:6, IMP:18 28.1 +21:9% 3 Abnormal-> Abnormal 50 −7/del(7q):24%; CR:1, PR:4, IMP:30 11.7 −5/del(5q):20%,+1q:14% 4 Abnormal->Clonal 20 −7/del(7q):25%;+21:20% IMP:8 9.1 5 Abnormal->Normal 18 del(7q):33%,+8,28% CR:1, PR:1,IMP:8 22.7 When survival was compared between cytogenetic subgroups there was a statistical difference between some groups. Survival of patients with normal cytogenetics (group 1) was superior when compared to either group 3 (p=.0001) or group 4 (p=.00015). Even for pts who developed an abnormal clone while on AzaC (group 2) survival was significantly longer when compared to either group 3 (p=0004) or group 4 (p=00001). Moreover, prognostic significance was observed for pts who initially had an abnormal karyotype that was diminished or eradicated on AZA C therapy (group 5) when compared to groups 3 (p=0.009) and 4 (p-0.0006). The emergence of a cytogenetically abnormal clone while on treatment with Aza C is not associated with shortened survival compared to those who remain cytogenetically normal. Response to Aza C can occur even with the persistence of the MDS clone or with the emergence of a new clone. This suggest that AZA C can modulate the responsivness of MDS hematopoietic progenitors. Our findings demonstrate that AZA C modulation of the cytogenetically marked MDS clone is associated with distinct subgroups with differing survival characteristics.

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MBRS-38. MOLECULAR CLASSIFICATION AND CLINICAL CHARACTERISTICS OF 236 MEDULLOBLASTOMAS IN JAPAN

Neuro-Oncology ◽

10.1093/neuonc/noaa222.549 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii404-iii405

Author(s):

Yonehiro Kanemura ◽

Tomoko Shofuda ◽

Ema Yoshioka ◽

Daisuke Kanematsu ◽

Koichi Ichimura ◽

...

Keyword(s):

Poor Prognosis ◽

Pediatric Neurosurgery ◽

Molecular Classification ◽

Pediatric Brain Tumors ◽

Good Prognosis ◽

Histopathological Diagnosis ◽

Chromosome 11 ◽

Methylation Array ◽

Group 4 ◽

Group 3

Abstract Recent intensive genomic and molecular biological analyses have made a consensus that medulloblastomas (MBs) are at least classified into four core subgroups, and the new 2016 WHO brain tumor classification has introduced the classification of MBs genetically defined in addition to classical histopathological diagnosis. To establish a nationwide network of a molecular diagnosis system for pediatric brain tumors, the JPMNG co-organized by the Japan Society for Neuro-Oncology and the Japanese Society for Pediatric Neurosurgery have started the clinical researches in 2012, and we have summarized results of molecular analysis of Japanese MBs. Total 236 primary MBs have been subclassified by gene expression profile using the NanoString nCounter system or DNA methylation array, and their single nucleotide mutations and copy number aberrations have been also examined. Mean follow up time was 68.9 months. Proportion of four core subgroups were WNT (16.9%), SHH (25.4%), Group 3 (17.4%) and Group 4 (40.3%), respectively. In cases of less than 3 years old, no WNT have been found and 63.2% cases were SHH. In cases between 3 to 17 years old, Group 4 is the most (47%), and these trends is almost consistent with published references. TP53 mutations were identified in 23.3% of SHH, and they were significantly poor prognosis. Metastatic or MYC gain Group 3 MBs were poor prognosis, while Group 4 MBs with loss of chromosome 11 or whole chromosomal aberration were good prognosis. These findings reveal molecular properties of Japanese MBs and will contribute to develop new therapeutic strategies.

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Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079851 ◽

1977 ◽

Vol 35 ◽

pp. 484-485

Author(s):

P. Bagavandoss ◽

JoAnne S. Richards ◽

A. Rees Midgley

Keyword(s):

Cell Surface ◽

Granulosa Cell ◽

Morphological Changes ◽

Follicular Development ◽

Female Rats ◽

Functional Changes ◽

Group 4 ◽

Group 3 ◽

Group 5 ◽

Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

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Correlation of γ-radioactivity and Scanning Electron Microscopy in measurement of retention of 111Indium-labeled canine endothelial cells on synthetic vascular grafts

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100156419 ◽

1989 ◽

Vol 47 ◽

pp. 886-887

Author(s):

E.J. Prendiville ◽

S. Laliberté Verdon ◽

K. E. Gould ◽

K. Ramberg ◽

R. J. Connolly ◽

...

Keyword(s):

Blood Flow ◽

Ex Vivo ◽

Vascular Grafts ◽

Retention Data ◽

Vascular Prostheses ◽

Group 4 ◽

Human Fibronectin ◽

Insufficient Time ◽

Group 3 ◽

Group 2

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.

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In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽

10.1024/0301-1526/a000867 ◽

2020 ◽

Vol 49 (4) ◽

pp. 281-284

Author(s):

Atıf Yolgosteren ◽

Gencehan Kumtepe ◽

Melda Payaslioglu ◽

Cuneyt Ozakin

Keyword(s):

Vascular Graft ◽

Graft Infection ◽

Vascular Graft Infection ◽

Group 4 ◽

Significant Difference ◽

Group 3 ◽

Group 2 ◽

Prosthetic Vascular Graft Infection ◽

Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

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Defensive activity of Hesperidin against Ciprofloxacin induced hepatic injury in rabbits.

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.10.3.29 ◽

2019 ◽

Vol 10 (03) ◽

Author(s):

Hawraa M. Murad ◽

Tamadhur Hani Hussein ◽

Audai Sulaiman Khudhair ◽

Manal Muhi Murad ◽

Jawad Kadhim Faris

Keyword(s):

Body Weight ◽

Bacterial Infections ◽

Hepatoprotective Activity ◽

The Body ◽

Local Breed ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Defensive Activity ◽

Antioxidant Effects

This study was conducted to find out hepatoprotective activity of hesperidin (HES) 100mg/kg body weight (b.w.) against ciprofloxacin (CPX) 100 mg/kg induced hepatotoxicity in local breed rabbits .CPX is a broad spectrum antibiotic used for treatment of many bacterial infections. Twenty four male rabbits were divided into four groups ,group1: control, (1 ml/kg Saline orally) group 2: CPX (100 mg/kg orally) for (14) consecutive days , group 3: HES (100 mg//kg) orally for (14) consecutive days group 4: CPX (100 mg/kg orally) plus HES (100 mg//kg orally ) for (14) consecutive days. All the rabbits were killed on the (15) day of the experiment, and then the blood, and livers samples were taken. CPX induced hepatotoxicity was proved by a significant (p less than 0.01) reduction in the body weight ,and a significant (p less than 0.01) increased serum aspartate transaminase (AST), alanine transaminase (ALT) , Malonaldehyde enzyme (MAD) and histopathological changes. Protective hepatic toxicity effect and oxidative damage caused by CPX significantly (p less than 0.01) increasing in body weight and significantly (p less than 0.01) decreasing AST , ALT, MAD and improving tissue morphology in HES (100 mg//kg) . These results assure that HES (100 mg//kg) antioxidant effects can protect CPX-induced hepatotoxicity in rabbits.

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