Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal

Perfusion ◽  
2001 ◽  
Vol 16 (6) ◽  
pp. 460-468 ◽  
Author(s):  
J A Murphy ◽  
C M Savage ◽  
S K Alpard ◽  
D J Deyo ◽  
J B Jayroe ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Low Dose ◽  
Burn Injury ◽  
Degradation Products ◽  
Randomized Study ◽  
Carbon Dioxide Removal ◽  
Smoke Inhalation ◽  
High Dose ◽  
Post Injury ◽  
Fibrin Degradation Products

The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep ( n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300 s, n = 6) and LD heparin (ACT > 200 s, n = 7) and placed on AVCO2R for approximately 72 h using an oxygenator with the Trillium Bio-Passive Surface™. Mean ACTs were significantly different, as expected (HD: 446 ± 26 s, LD: 213 ± 12 s, p < 0.05). AVCO2R shunt flow averaged approximately 13% of cardiac output with mean CO2 removal similar in HD and LD, p = NS. The hematocrit, platelet count, and fibrin degradation products for the two groups were not different. No differences in thrombosis or bleeding were noted. In conclusion, LD systemic heparin (ACT < 200 s) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep.

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

1996 ◽  
Vol 14 (2) ◽  
pp. 351-356 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
F Carnino ◽  
A Gadducci ◽  
R Algeri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Total Dose ◽  
Low Dose ◽  
Residual Disease ◽  
Randomized Study ◽  
Pathologic Complete Response ◽  
Dose Intensity ◽  
Clinical Response Rate ◽  
High Dose ◽  
Survival Times

PURPOSE The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

A Double-Blind, Randomized Study of Extended-Release Molindone for Impulsive Aggression in ADHD

2020 ◽  
pp. 108705472090908 ◽  
Author(s):  
Gianpiera Ceresoli-Borroni ◽  
Azmi Nasser ◽  
Toyin Adewole ◽  
Tesfaye Liranso ◽  
Jiahong Xu ◽  
...  
Keyword(s):  
Extended Release ◽  
Low Dose ◽  
Behavioral Therapy ◽  
Randomized Study ◽  
High Dose ◽  
Double Blind ◽  
Impulsive Aggression ◽  
Pediatric Populations ◽  
Dose Ranging ◽  
Medium Dose

Objective: To evaluate efficacy and safety of SPN-810 (extended-release molindone) in a Phase-2b, randomized, double-blind, placebo-controlled, dose-ranging study of children (6–12 years) with ADHD and persistent impulsive aggression (IA). Method: After lead-in, children were randomized to (a) placebo ( N = 31); (b) low-dose ( N = 29, 12/18 mg/day); (c) medium-dose ( N = 30, 24/36 mg/day); and (4) high-dose ( N = 31, 36/54 mg/day) groups. Treatment included ~2.5-week titration, 3-week maintenance, and 1-week tapering/conversion, alongside existing monotherapy (stimulants/nonstimulants) and behavioral therapy. The primary endpoint was change in Retrospective-Modified Overt Aggression Scale (R-MOAS) score at end of study, with safety monitored. Results: A total of 95 (78.5%) children completed the study. Aggression (R-MOAS) improved with low and medium doses (low dose: p = .031; medium dose: p = .024; high dose: p = .740). The most common adverse events were headache (10.0%), sedation (8.9%), and increased appetite (7.8%). Conclusion: These results suggest SPN-810 may be effective in reducing residual IA behaviors in children with ADHD. Research is still needed to support the benefit–risk profile of SPN-810 in pediatric populations.

Direct Delivery of Low-Dose 7-Nitroindazole Into the Bronchial Artery Attenuates Pulmonary Pathophysiology After Smoke Inhalation and Burn Injury in an Ovine Model

Shock ◽  
2011 ◽  
Vol 36 (6) ◽  
pp. 575-579 ◽  
Author(s):  
Atsumori Hamahata ◽  
Perenlei Enkhbaatar ◽  
Matthias Lange ◽  
Robert A. Cox ◽  
Hal K. Hawkins ◽  
...  
Keyword(s):  
Low Dose ◽  
Burn Injury ◽  
Bronchial Artery ◽  
Smoke Inhalation ◽  
Ovine Model ◽  
Direct Delivery

scholarly journals Randomized Study of High-Dose and Low-Dose Interleukin-2 in Patients With Metastatic Renal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3127-3132 ◽  
Author(s):  
James C. Yang ◽  
Richard M. Sherry ◽  
Seth M. Steinberg ◽  
Suzanne L. Topalian ◽  
Douglas J. Schwartzentruber ◽  
...  
Keyword(s):  
Overall Survival ◽  
Low Dose ◽  
Performance Status ◽  
Randomized Study ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Complete Response ◽  
High Dose ◽  
Metastatic Renal Cancer ◽  
Survival Difference

Purpose: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P = .048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P = .033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P = .04). Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.

A Randomized Study of High-Dose versus Low-Dose cis-Platinum Combined with Cyclophosphamide in the Treatment of Advanced Ovarian Cancer

Chemotherapy ◽  
1989 ◽  
Vol 35 (3) ◽  
pp. 221-227 ◽  
Author(s):  
H.Y.S. Ngan ◽  
Y.C. Choo ◽  
M. Cheung ◽  
L.C. Wong ◽  
H.K. Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Low Dose ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
High Dose

scholarly journals Advantages of immediate excision of burn eschar

2020 ◽  
Vol 48 (2) ◽  
pp. 89-92
Author(s):  
John E Greenwood
Keyword(s):  
Gold Standard ◽  
Burn Injury ◽  
Smoke Inhalation ◽  
Survival Outcomes ◽  
Post Injury ◽  
Burn Care ◽  
Major Burn ◽  
The Hours

Early excision of deep burn eschar and the expeditious closure of the resultant wounds have become established as gold standard burn care. However, early burn excision has been accepted as up to four days post injury based on a series of misconceptions, not least that the patient is too unwell to undergo surgery and tolerate anaesthesia too soon after injury. There are several reasons why immediate burn excision yields superior survival outcomes, and these are expounded in this article. The systemic pathophysiology following major burn injury, especially when complicated by the respiratory pathophysiology accompanying smoke inhalation, evolves. The hours immediately after burn injury offer several windows of surgical opportunity, windows closed by the pathophysiological events that peak 24 hours later and make surgery and anaesthesia at that time both dangerous and ill-advised.

Synthetic smoke with acrolein but not HCl produces pulmonary edema

1988 ◽  
Vol 64 (3) ◽  
pp. 1121-1133 ◽  
Author(s):  
C. A. Hales ◽  
P. W. Barkin ◽  
W. Jung ◽  
E. Trautman ◽  
D. Lamborghini ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Low Dose ◽  
Smoke Inhalation ◽  
High Dose ◽  
Lung Water ◽  
Thermodilution Technique ◽  
Carbon Particles ◽  
Delayed Onset ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in concentrations of 0.1-6 N when added to heated carbon (120 degrees C) and cooled to 39 degrees C produced airway damage but no pulmonary edema. Acrolein, in contrast, produced airway damage but also pulmonary edema, whereas capillary wedge pressures remained stable. Low-dose acrolein smoke (less than 200 ppm) produced edema in two of five animals with a 2- to 4-h delay. Intermediate-dose acrolein smoke (200-300 ppm) always produced edema at an average of 147 ± 57 min after smoke, whereas high-dose acrolein (greater than 300 ppm) produced edema at 65 ± 16 min after smoke. Thus acrolein but not HCl, when presented as a synthetic smoke, produced a delayed-onset, noncardiogenic, and peribronchiolar edema in a roughly dose-dependent fashion.

Randomized study of high-dose versus low-dose methotrexate in the treatment of extensive small cell lung cancer

1982 ◽  
Vol 73 (3) ◽  
pp. 413-419 ◽  
Author(s):  
Kenneth R. Hande ◽  
Robert K. Oldham ◽  
Mehmet F. Fer ◽  
Ronald L. Richardson ◽  
F. Anthony Greco
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Low Dose ◽  
Randomized Study ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Dose Methotrexate

P101. Direct delivery of low dose of 7-nitroindazole into bronchial artery ameliorates pulmonary dysfunction after smoke inhalation and burn injury in sheep

Nitric Oxide ◽  
2008 ◽  
Vol 19 ◽  
pp. 66-67
Author(s):  
Atsumori Hamahata ◽  
Perenlei Enkhbaatar ◽  
Robert Cox ◽  
Matthias Lange ◽  
Collette Jonkam ◽  
...  
Keyword(s):  
Low Dose ◽  
Burn Injury ◽  
Bronchial Artery ◽  
Smoke Inhalation ◽  
Pulmonary Dysfunction ◽  
Direct Delivery

Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 52-57 ◽  
Author(s):  
Hagop Kantarjian ◽  
Yasuhiro Oki ◽  
Guillermo Garcia-Manero ◽  
Xuelin Huang ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Low Dose ◽  
Adaptive Design ◽  
Randomized Study ◽  
Objective Response ◽  
Dose Intensity ◽  
Chronic Myelomonocytic Leukemia ◽  
Epigenetic Therapy ◽  
High Dose ◽  
Myelomonocytic Leukemia

Abstract Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2 subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P &lt; .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS.

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