scholarly journals Critical Organ Volume

2020 ◽  
Author(s):  
Keyword(s):  
Organ Volume ◽  
Critical Organ

Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

1995 ◽  
Vol 53 ◽  
pp. 1042-1043
Author(s):  
H. Nishimura ◽  
R Nishimura ◽  
D.L. Adelson ◽  
A.E. Michaelska ◽  
K.H.A. Choo ◽  
...  
Keyword(s):  
Metal Binding ◽  
Immunohistochemical Staining ◽  
Squamous Epithelium ◽  
Rabbit Antiserum ◽  
Slight Modification ◽  
Positive Control ◽  
Heavy Metal Binding ◽  
Critical Organ ◽  
Metal Binding Protein ◽  
Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

scholarly journals Radiation Risks in Cis-Lunar Space for a Solar Particle Event Similar to the February 1956 Event

Aerospace ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 107
Author(s):  
Fahad A. Zaman ◽  
Lawrence W. Townsend
Keyword(s):  
Effective Dose ◽  
Energy Transport ◽  
Radiation Transport ◽  
Organ Doses ◽  
Solar Particle Events ◽  
Solar Particle ◽  
Transport Code ◽  
On Line ◽  
Critical Organ ◽  
In Cis

Solar particle events (SPEs) can pose serious threats for future crewed missions to the Moon. Historically, there have been several extreme SPEs that could have been dangerous for astronauts, and thus analyzing their potential risk on humans is an important step towards space exploration. In this work, we study the effects of a well-known SPE that occurred on 23 February 1956 on a mission in cis-Lunar space. Estimates of the proton fluence spectra of the February 1956 event were obtained from three different parameterized models published within the past 12 years. The studied geometry consists of a female phantom in the center of spherical spacecraft shielded by aluminum area densities ranging from 0.4 to 40 g cm−2. The effective dose, along with lens, skin, blood forming organs, heart, and central nervous system doses, were tallied using the On Line Tool for the Assessment of Radiation In Space (OLTARIS), which utilizes the High Z and Energy TRansport code (HZETRN), a deterministic radiation transport code. Based on the parameterized models, the results herein show that thicknesses comparable to a spacesuit might not protect against severe health consequences from a February 1956 category event. They also show that a minimum aluminum shielding of around 20 g cm−2 is sufficient to keep the effective dose and critical organ doses below NASA’s permissible limits for such event. In addition, except for very thin shielding, the input models produced results that were within good agreement, where the doses obtained from the three proton fluence spectra tended to converge with slight differences as the shielding thickness increases.

REGIONAL ARTERIOVENOUS DIFFERENCES IN Pco2 AND pH CAN REFLECT CRITICAL ORGAN OXYGEN DELIVERY DURING ENDOTOXEMIA

Shock ◽  
1996 ◽  
Vol 5 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Haibo Zhang ◽  
Peter Rogiers ◽  
Daniel De Backer ◽  
Herbert Spapen ◽  
Panayotis Manikis ◽  
...  
Keyword(s):  
Oxygen Delivery ◽  
Critical Organ

scholarly journals Radiation Absorbed Dose to the Basal Ganglia from Dopamine Transporter Radioligand18F-FPCIT

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
William Robeson ◽  
Vijay Dhawan ◽  
Yilong Ma ◽  
David Bjelke ◽  
Claude Margouleff ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Dopamine Transporter ◽  
Absorbed Dose ◽  
Normal Subjects ◽  
Residence Times ◽  
Time Activity ◽  
High Affinity ◽  
Critical Organ ◽  
Left And Right ◽  
Critical Structure

Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers,18F-FDOPA and18F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using18F-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations.S-factors were computed using the MIRDOSE3 nodule model for each caudate and putamen. For18F-FPCIT, BG dose ranged from 0.029 to 0.069 mGy/MBq. In half of all subjects, BG dose exceeded 85% of the published critical organ (bladder) dose, and in three of those, the BG dose exceeded that for the bladder. The BG can become the dose-limiting organ in studies using dopamine transporter ligands. For some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure.

Association of combined phase I/II study of a novel bicyclic peptide and MMAE conjugate BT8009 in patients with advanced malignancies with Nectin-4 expression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS2668-TPS2668
Author(s):  
Meredith McKean ◽  
Gerald Steven Falchook ◽  
Johanna C. Bendell ◽  
Babar Bashir ◽  
Neil Palmisiano ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Single Agent ◽  
Pancreatic Head ◽  
Uncontrolled Hypertension ◽  
Clinical Activity ◽  
Highly Active ◽  
History Of ◽  
Cyp3a4 Inhibitors ◽  
Critical Organ ◽  
Peptide Targeting

TPS2668 Background: BT8009 is a Bicycle Toxin Conjugate (BTC), a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting Nectin-4 tumor antigen, linked to cytotoxin (monomethyl auristatin E [MMAE]) via a valine-citrulline (val-cit) cleavable linker. Nectins (Nectin-1, -2, -3, and -4) and nectin-like molecules (Necl) are Ca2+ independent immunoglobulin-like cell adhesion molecules. Recent studies have shown the importance of Nectin-4 in several human cancers, including lung, ovarian, breast and bladder cancer; however, the precise roles and clinical relevance of Nectin-4 in tumors remain largely unknown. The Nectin-4 targeted enfortumab vedotin, linked to MMAE via a val-cit linker, is highly active in late-stage bladder cancer and demonstrates notable additional clinical activity as a single agent and in combination with pembrolizumab1. Skin toxicities, bone marrow suppression, peripheral neuropathy and diabetes have been associated with enfortumab, with some of these toxicities already noted with MMAE-bearing antibody therapies. We anticipate a similar toxicity profile for BT8009 in clinical studies. BT8009 exhibited a favorable preclinical profile and was effective in a range of cell-derived xenograph tumor models. Methods: Study BT8009-100 (NCT04561362) will evaluate safety and tolerability of weekly and every other week BT8009 administration, alone and in combination with q4w nivolumab. Determination of both a realistic phase 2 dose and a sequence will also be key to further exploration of safety and efficacy signals, along with an early examination of the role of baseline immunohistochemistry-ascertained levels of tumor Nectin-4. Patients will be recruited with advanced solid tumors associated with Nectin-4 expression after exhausting SOC options (i.e., bladder, breast, pancreatic, head and neck, gastric, esophageal and ovarian). Patients must have available tumor tissue, acceptable hematologic and other critical organ function and be willing to participate. Appropriate ethical and regulatory approvals and advice will be in place and adhered to. Exclusion criteria include uncontrolled brain metastases, uncontrolled hypertension, concomitant CYP3A4 inhibitors and significant history of autoimmune disease for the nivolumab cohorts. PK serial collections will be taken on D1 through D15. Radiologic tumor assessments for response per RECIST will be taken every two months. 1. Enfortumab Vedotin. FDA_data. 761137Orig1s000MultiDiscliplineR.pdf (fda.gov). Clinical trial information: NCT04561362.

Venous thromboembolism prevention with fondaparinux 1.5 mg in renally impaired patients undergoing major orthopaedic surgery

2012 ◽  
Vol 107 (06) ◽  
pp. 1151-1160 ◽  
Author(s):  
Patrick Mismetti ◽  
Charles-Marc Samama ◽  
Nadia Rosencher ◽  
Claude Vielpeau ◽  
Philippe Nguyen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Real World ◽  
Orthopaedic Surgery ◽  
Clinical Trial Data ◽  
Hip Fracture Surgery ◽  
Vein Thrombosis ◽  
Fatal Bleeding ◽  
Venous Thromboembolism Prevention ◽  
Critical Organ ◽  
Major Orthopaedic Surgery

SummaryDespite the need for effective and safe thromboprophylactic drugs for patients with renal impairment, clinical trial data on anticoagulant agents are limited in this population. The study aim was to assess in the real-world setting the use of the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this context. In this prospective cohort study, patients with a creatinine clearance (CrCl) of 20–50 ml/ minute, undergoing total hip (THR) or knee (TKR) replacement or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main clinical outcomes were bleeding (major/clinically relevant nonmajor), symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353 women; median age: 82 years; 39.4% in ASA class ≥3; mean ± SD CrCl: 39.0 ± 8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean ± SD duration of 16.0 ± 12.5 days. At postoperative day 10, the rates (95% confidence interval) of major bleeding, clinically relevant bleeding and symptomatic VTE were 4.5% (2.8–6.9), 0.5% (0.1–1.6) and 0.5% (0.05–1.62), respectively; no fatal bleeding, bleeding into a critical organ, pulmonary embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9–3.6). This large clinical prospective study provides for the first time, under conditions reflecting “real-world” routine clinical practice, data on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic surgery in renally impaired patients. It shows that these patients constitute a very elderly and fragile population.ClinicalTrials.gov number, NCT00555438

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