scholarly journals The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1

2018 ◽  
Vol 19 (4) ◽  
pp. 1132 ◽  
Author(s):  
Evelin Csepanyi ◽  
Attila Czompa ◽  
Peter Szabados-Furjesi ◽  
Istvan Lekli ◽  
Jozsef Balla ◽  
...  
Keyword(s):  
Beta Carotene ◽  
High Dose ◽  
Zucker Diabetic Fatty Rats

scholarly journals Laporan Kasus: Manifestasi Oral Penderita Hipertensi berupa Ginggival Enlargement

2020 ◽  
Vol 17 (2) ◽  
pp. 54
Author(s):  
Anindita L. ◽  
Aris Aji K. ◽  
Arcadia Sulistijo J.
Keyword(s):  
Case Reports ◽  
Gingival Tissue ◽  
High Dose ◽  
Gingival Inflammation ◽  
Gingival Enlargement ◽  
History Of ◽  
Root Planning ◽  
Pro Inflammatory Cytokines

Hypertension presents an increase in blood pressure following the oral manifestations, such as gingival enlargement. A 42-year-old woman came to the General Sudirman University Dental and Oral Hospital complaining of enlarged front gums seven years ago. The patient had a history of hypertension and regularly consumed drugs, amlodipine 5 mg. Extraoral examination revealed no lymphadenopathy and no swelling of the head and neck area. Intraoral examination revealed a gingival enlargement involving the papilla to the gingival margin present on the entire upper and lower labial gingival surface. The patient's diagnosis was gingival enlargement caused by gingival enlargement due to the use of amlodipine. Gingival enlargement has been noted with long-term or high-dose amlodipine use. The mechanism of amlodipine in causing gingival enlargement is through the role of fibroblasts with abnormal susceptibility to the drug, resulting in increased levels of protein synthesis, especially collagen. The role of pro-inflammatory cytokines occurs through an increase in interleukin-1β (IL-1β) and IL-6 in the inflamed gingival tissue due to the gingival fibrogenic response to drugs. Therapies were DHE and scaling and root planning as phase I in periodontal treatment. Plaque elimination is vital to reduce gingival inflammation that may occur. Substitution of the drug amlodipine may be needed if there is no improvement. Based on case reports, hypertension patients who took amlodipine could have gingival enlargement. The therapy given was plaque elimination in the form of DHE and Scaling and regular check-ups with the dentist.

Ironclad: A randomized phase III study of ibrutinib (Ibr) or no consolidation following autologous hematopoietic stem cell transplantation (AutoHCT) for relapsed/refractory activated-B-cell (ABC) subtype diffuse large B-cell lymphoma (DLBCL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS7566-TPS7566
Author(s):  
Charalambos Andreadis ◽  
Timothy S Fenske ◽  
Brian Thomas Hill ◽  
Patrick J. Stiff ◽  
David L. Grinblatt ◽  
...  
Keyword(s):  
B Cell ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
High Dose ◽  
Eligibility Criteria ◽  
Hematopoietic Stem ◽  
Phase Iii Study

TPS7566 Background: Relapsed DLBCL in the rituximab era portends a poor prognosis with only about 25% of patients achieving long-term disease control following 2ndline therapy and AutoHCT. Patients with the ABC subtype have an inferior prognosis at diagnosis than those with GC and are overrepresented at relapse. In order to improve outcomes in ABC-DLBCL, we designed a study targeting disease pathobiology at the time of AutoHCT. Ibr has a safety profile allowing combination with cytotoxic chemotherapy and has single-agent activity with a 37% response rate in patients with relapsed/refractory ABC-DLBCL. Methods: This is an intergroup, randomized, placebo-controlled phase III study combining Ibr or placebo with high-dose chemotherapy during conditioning with AutoHCT and for 12 months following AutoHCT. Pts with relapsed or refractory DLBCL have tissue submitted centrally for real-time review and subtype assignment by GEP (Frederick Laboratory). Key eligibility criteria include no more than 3 prior regimens, no active CNS involvement, no need for long-term anticoagulation, and no progression on prior Ibr. Pts with chemosensitive ABC-DLBCL are randomized to Ibr 560 mg or placebo with BEAM or CBV chemotherapy until day 0. After engraftment, pts receive Ibr 560 mg daily or placebo for 12 additional cycles. Pts with progressive disease on placebo can cross over to Ibr monotherapy. An initial safety cohort of 6 pts is being enrolled to evaluate the tolerability of Ibr with concurrent BEAM and CBV therapy. The primary endpoint is superior 2-year PFS (Ha/H0: 67% vs 50%). Secondary endpoints include time to count recovery, post-transplant response rates, OS, PFS, and incidence of 2arymalignancies. In correlative studies, we will assess the prognostic and predictive role of pre-transplant FDG-PET in the setting of Ibr or placebo therapy, the role of emergent BCR pathway mutations, double hit genetics, and pharmacogenetic determinants on treatment outcome and toxicities. We expect to accrue 296 patients over 4 years. An Alliance/BMT-CTN study: NCT02443077 Clinical trial information: NCT02443077.

Impact of Chromosome 13 Deletion and Plasma Cell Load on Long-Term Survival of Patients with Multiple Myeloma Undergoing Autologous Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5148-5148
Author(s):  
Esbjörn Paul ◽  
Tolga Sutlu ◽  
Evren Alici ◽  
Goesta Gahrton ◽  
Hareth Nahi
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Autologous Transplantation ◽  
High Dose ◽  
Prognostic Impact ◽  
Term Survival ◽  
Chromosome 13 ◽  
First Line Therapy

Abstract High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common treatment for patients under 60–65 years of age with multiple myeloma (MM). In this study, we present a retrospective analysis of the prognostic impact of different factors in patients who have received this treatment as first line therapy in our centre. Abnormalities in chromosome 13 were identified by fluorescence in situ hybridization at the time of diagnosis. The median OS and PFS from transplantation time in the whole group of 193 patients were 90 and 48 months respectively. The median follow-up was 65 months (range: 6–186 months). The complete remission (CR) rate in patients with and without del(13) was 31% and 40% respectively whereas the median OS in patients with del(13) was 58 months but not reached in patients without del(13) (p=0.006). The PFS was 26 months in patients with del(13) and 84 months in those without del(13) (p=0.001). The transplantation related mortality was 2.5% both in the absence and presence of del(13). Patients who achieved CR following ASCT had longer OS and PFS when compared to those who only achieved partial remission. Thus, this study confirms the role of del(13) as a marker of poor prognosis. Multivariate analysis showed that the existence of del(13) was the only single independent factor effecting survival (p=0.001). In patients without del(13), the prognostic impact was even stronger when combined with the plasma cell load in the bone marrow (p=0.020), whereas the plasma cell load had no effect on survival of patients with del(13). Overall, the absence of del(13) in combination with low plasma cell infiltration at diagnosis predicts the best survival.

scholarly journals Anthophyllite Asbestos: The Role of Fiber Width in Mesothelioma Induction Part 1: Epidemiological Studies of Finnish Anthophyllite Asbestos

2017 ◽  
Vol 7 (1) ◽  
pp. 9
Author(s):  
Edward B. Ilgren ◽  
John A. Hoskins
Keyword(s):  
Fiber Diameter ◽  
Important Determinant ◽  
Epidemiological Studies ◽  
High Dose ◽  
Fibre Width ◽  
Mineral Fibre ◽  
Amphibole Asbestos ◽  
The One

Anthophyllite asbestos only occurs in a few parts of the world in sufficient quantities to be mined. The largest deposits of anthophyllite asbestos occur in Finland where it was mined for more than 75 years and very extensively used and distributed, anciently, for more than six millennia. Anthophyllite is one of the five minerals known collectively as amphibole asbestos. Studies of the effect of these five mineral fibre types when inhaled have shown that fibre width is an important determinant of mesothelioma induction. Only the “thinner” fibres or those with fiber diameter dimensional profiles predominantly less than 0.25 – 0.30 µm, are clearly mesotheliogenic. The “thicker” ones or those whose predominant widths are greater than these diameters do not appear to show an observable attendant risk of mesothelioma. Observations based on studies of at least, two “thick” forms of amphibole asbestos support these hypotheses. The one is Bolivian crocidolite; the other Finnish anthophyllite. The Finnish anthophyllite industry presents an important opportunity to study the robustness of the theory that fibre width is key to mesothelioma genesis as vast numbers of people in all sectors of the Finnish industry and their families have historically incurred massive fiber exposures sufficient to cause a gross excess of asbestosis. Nonetheless, in spite of these long term, high dose exposures clear evidence for a mesothelioma risk due to anthophyllite asbestos is still lacking.

scholarly journals A critical reflection on our first patient presenting with Anti-Nmethyl- D-aspartate receptor encephalitis

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Susanne Buechner ◽  
Igor Florio ◽  
Gabriele J. Sixt ◽  
Francesco Teatini
Keyword(s):  
Treatment Guidelines ◽  
Autoimmune Encephalitis ◽  
Complete Recovery ◽  
Intravenous Immunoglobulins ◽  
High Dose ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis ◽  
One Year

One of the best characterized autoimmune encephalitis is the Anti-Nmethyl-D-aspartate receptor (NMDAR) encephalitis, which may occur in the presence of cancer. First- and second-line immunotherapy and oncological investigations are suggested. We present here a case of an 18-year-old female who was our first patient suffering from Anti-NMDAR encephalitis more than 9 years ago. She was satisfactorily treated with intravenous immunoglobulins and high dose steroid therapy. After more than one year the patient had a relapse. First-line immunotherapy was repeated; however, a complete recovery was achieved only after plasmapheresis. Afterwards, she continued maintenance immunotherapy with steroids for two years and with Azathioprine for about five years associated to regular oncological assessment. In the last years our therapeutical approach of Anti-NMDARencephalitis has significantly changed. Nevertheless, established treatment guidelines are still missing and the role of long-term maintenance immunotherapy is largely unexplored. In addition, oncological revaluation might be indicated in selected patients.

Hypercholesterolemia and Its Association with Enhanced Stem Cell Mobilization and Harvest After High-Dose Cyclophosphamide + G-CSF

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2247-2247
Author(s):  
Martina Crysandt ◽  
Ralf-Dieter Hilgers ◽  
Sabine von Hobe ◽  
Albrecht Eisert ◽  
Edgar Jost ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Prior Therapy ◽  
Cholesterol Levels ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2247 Hematopoietic stem cells (HSC) reside in specific niches in the bone marrow and various signals regulate survival, self-renewal, proliferation, differentiation and trafficking. Egress of HSCs into the peripheral blood (PB) is enhanced by multiple agonists, although the exact mechanisms that regulate this critical process are largely unknown. After treatment with cyclophosphamide and G-CSF, long-term HSC in the bone marrow enter the cell cycle. Additionally, G-CSF induces a reduction of the chemokine stromal cell derived factor 1 (SDF-1) and an increase of its receptor CXCR4 in the bone marrow leading to mobilization of HSC to the PB. Very recently, hypercholesterolemia was identified to promote stem cell mobilization in mice by also disrupting the SDF-1/CXCR4 axis. We retrospectively examined the role of cholesterol and a number of possible confounding factors on mobilization results and stem cell harvests in a patient cohort undergoing a standard mobilization procedure. We retrospectively identified 104 patients receiving high-dose cyclophosphamide (CY) for stem cell mobilization between 1997 and 2009 using a clinical database. We examined the role of cholesterol and a number of additional possible confounding factors (e.g. gender, weight, age, number of prior therapy lines, laboratory results like creatinine, uric acid, bilirubin, potein, LDH and long-term medication with common drug classes) on stem cell mobilization and harvest using univariate and multivariate analyses. Out of the 104 patients, 21 did not have cholesterol levels available. Among the remaining 83 patients included, 33 (39.8%) were identified as having hypercholesterolemia (defined as >6.2 mmol/L). The mean number of prior lines of anti-neoplastic therapy was 1.52 (median 1, range 1–6). A lower number of prior therapy lines (p=0.010), higher lactate dehydrogenase levels (LDH, p=0.006), higher cholesterol (p=0.012) and triglycerides (TG, p=0.041) as well as long-term medication with beta-blockers (p=0.024) were significantly correlated with better CD34+-mobilization. Since, as expected, cholesterol and TG were highly correlated (p<0.001), TG were excluded from further multivariate analysis as a single factor. A multivariate ANCOVA model then allowed the adjusted assessment of the influencing factors on the peak CD34+-counts and revealed a positive linear dependence on LDH (slope: 0.41, p=0.047) and on cholesterol (slope: 0.60, p=0.012) only. Patients with hypercholesterolemia had a higher CD34+-peak compared to patients with normal cholesterol levels (135.5 vs. 73.4/μL, p=0.015). The mean CD34+-cell counts in the PB showed significantly higher levels on day 12 (109.1 vs. 53.8/μL, p=0.033) and on day 13 (123.7/μL vs. 45.7/μL, p=0.002). This clinical data is in high accordance with data in the mouse model that could show a major effect of a high-cholesterol diet on the number of circulating progenitor cells. Accordingly, the overall number of harvested CD34+-cells was higher in patients with hypercholesterolemia (1027.5 vs. 644.4×106, p=0.039, adjusted to body weight: 14.7 vs. 8.5×106/kg, p=0.060) and a sufficient number for at least one stem cell transplantation (more than 2.0 CD34+ cells × 106/kg) was achieved in a remarkably higher proportion (84.9%vs. 52.9%, p=0.004). In summary, our retrospective multivariate analysis including multiple possible factors extends this significant and potentially clinically relevant observation to the human system, since patients with hypercholesterolemia showed better mobilization, higher stem cell yields and a sufficient harvest for at least one autologous transplantation in a remarkably higher proportion. Whether in patients with successfully treated hypercholesterolemia, cholesterol-lowering therapy should be stopped during mobilization therapy in order to increase stem cell harvest will need to be assessed in the context of a clinical trial following prospective validation of the results reported here. Furthermore, it remains to be seen whether this effect is still preserved under stem cell mobilization with other regimens such as plerixafor. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document