scholarly journals Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques

2004 ◽  
Vol 48 (5) ◽  
pp. 1469-1487 ◽  
Author(s):  
Koen K. A. Van Rompay ◽  
Laurie L. Brignolo ◽  
Dennis J. Meyer ◽  
Christopher Jerome ◽  
Ross Tarara ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Dose ◽  
Biological Effects ◽  
Daily Administration ◽  
Time Range ◽  
High Dose ◽  
Short Term ◽  
Therapeutic Benefits ◽  
Short Period ◽  
Renal Tubular Disorder

ABSTRACT The reverse transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) was previously found to offer strong prophylactic and therapeutic benefits in an infant macaque model of pediatric human immunodeficiency virus (HIV) infection. We now summarize the toxicity and safety of PMPA in these studies. When a range of PMPA doses (4 to 30 mg/kg of body weight administered subcutaneously once daily) was administered to 39 infant macaques for a short period of time (range, 1 day to 12 weeks), no adverse effects on their health or growth were observed; this included a subset of 12 animals which were monitored for more than 2 years. In contrast, daily administration of a high dose of PMPA (30 mg/kg subcutaneously) for prolonged periods of time (>8 to 21 months) to 13 animals resulted in a Fanconi-like syndrome (proximal renal tubular disorder) with glucosuria, aminoaciduria, hypophosphatemia, growth restriction, bone pathology (osteomalacia), and reduced clearance of PMPA. The adverse effects were reversible or were alleviated following either complete withdrawal of PMPA treatment or reduction of the daily regimen from 30 mg/kg to 2.5 to 10 mg/kg subcutaneously. Finally, to evaluate the safety of a prolonged low-dose treatment regimen, two newborn macaques were started on a 10-mg/kg/day subcutaneous regimen; these animals are healthy and have normal bone density and growth after 5 years of daily treatment. In conclusion, our findings suggest that chronic daily administration of a high dose of PMPA results in adverse effects on kidney and bone, while short-term administration of relatively high doses and prolonged low-dose administration are safe.

scholarly journals High and low doses of clarithromycin treatment are associated with different clinical efficacies and immunomodulatory properties in chronic rhinosinusitis

2014 ◽  
Vol 128 (3) ◽  
pp. 236-241 ◽  
Author(s):  
Y Fan ◽  
R Xu ◽  
H Hong ◽  
Q Luo ◽  
W Xia ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Clinical Efficacy ◽  
Low Dose ◽  
Symptom Assessment ◽  
Nasal Symptom ◽  
High Dose ◽  
Life Questionnaire ◽  
Short Term ◽  
Interleukin 5 ◽  
Cytokine Levels

AbstractBackground:Low-dose clarithromycin has been recommended for the treatment of chronic rhinosinusitis without nasal polyps. However, it is uncertain whether a high dose of clarithromycin is more effective than a low dose.Methods:Forty-three chronic rhinosinusitis patients were randomised to low-dose or high-dose clarithromycin groups, and clinical efficacy was evaluated. Pre- and post-treatment measures included: nasal symptom assessment, endoscopic inspection (Lund–Kennedy system), a quality of life questionnaire (the Sino-Nasal Outcome Test 20) and examination of cytokine levels (interleukin-5 and -8) in nasal secretions.Results:The high dose of clarithromycin was significantly better in terms of clinical efficacy than the low dose for the treatment of chronic rhinosinusitis (p < 0.025). Significant differences in nasal cytokine levels (interleukin-5 and -8) were also observed between the low-dose and high-dose groups after short-term clarithromycin treatment (p < 0.025).Conclusion:Short-term, high-dose clarithromycin appears to be more effective for the treatment of chronic rhinosinusitis than low-dose clarithromycin.

scholarly journals Short-Term Effect of Low-Dose Atropine and Hyperopic Defocus on Choroidal Thickness and Axial Length in Young Myopic Adults

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Beata P. Sander ◽  
Michael J. Collins ◽  
Scott A. Read
Keyword(s):  
Axial Length ◽  
Choroidal Thickness ◽  
Low Dose ◽  
Term Effect ◽  
Short Term ◽  
Short Term Effect ◽  
Ocular Biometry ◽  
Short Period ◽  
Fixed Order ◽  
Optical Blur

Purpose. To examine the interaction between a short period of hyperopic defocus and low-dose atropine upon the choroidal thickness and ocular biometrics of healthy myopic subjects. Methods. Twenty young adult myopic subjects had subfoveal choroidal thickness (ChT) and ocular biometry measurements taken before and 30 and 60 min following the introduction of optical blur (0.00 D and −3.00 D) combined with administration of 0.01% atropine or placebo. Each combination of optical blur and drug was tested on different days in a fixed order. Results. The choroid exhibited significant thinning after imposing hyperopic defocus combined with placebo (mean change of −11 ± 2 μm, p<0.001). The combination of hyperopic blur and 0.01% atropine led to a significantly smaller magnitude of subfoveal choroidal thinning (−4 ± 8 μm), compared to placebo and hyperopic defocus (p<0.01). Eyes treated with 0.01% atropine with no defocus exhibited a significant increase in ChT (+6 ± 2 μm, p<0.01). Axial length also underwent small but significant changes after treatment with hyperopic blur and placebo and 0.01% atropine alone (both p<0.01), but of opposite direction to the changes in choroidal thickness. However, the 0.01% atropine/hyperopic blur condition did not lead to a significant change in axial length compared to baseline (p>0.05). Conclusion. Low-dose atropine does inhibit the short-term effect of hyperopic blur on choroidal thickness and, when used alone, does cause a slight thickening of the choroid in young healthy myopic adults.

Methylphenidate in Hyperkinetic Children: Differences in Dose Effects on Impulsive Behavior

PEDIATRICS ◽  
1979 ◽  
Vol 64 (4) ◽  
pp. 408-411
Author(s):  
Ronald T. Brown ◽  
Esther K. Sleator
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Memory Task ◽  
High Dose ◽  
Impulsive Behavior ◽  
Short Term ◽  
Dose Effects ◽  
Hyperactive Children ◽  
Matching Familiar Figures Test ◽  
Primary Index

This research tested the hypothesis that in hyperactive children a low dose of methylphenidate (0.3 mg/kg) would produce scores superior to those with a high dose (1.0 mg/kg) or placebo on the matching familiar figures test (MFF), a primary index of impulsivity. The hypothesis was based on an earlier finding that the highest percentage of correct responses on a short-term memory task were found in hyperactive subjects who were receiving 0.3 mg/kg of methylphenidate whereas at 1.0 mg/kg the percentage correct returned to the placebo level. The hypothesis was verified in that the low dose reduced the number of errors on the MFF significantly more than did placebo or the high dose. This work demonstrates that, for both learning and impulsivity in hyperactive children, the lower dose of the two doses of methylphenidate studied produced the preferable effect.

Abstract 12540: High-Dose Statins Reduce the Risk of Contrast-Induced Nephropathy in Patients Undergoing Angiography: Meta-Analysis of 27 Randomized Controlled Trials

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Firas Rabbat ◽  
Shadi Al Halabi ◽  
Mehdi H Shishehbor
Keyword(s):  
Randomized Controlled Trials ◽  
Low Dose ◽  
Random Effect Model ◽  
Controlled Trials ◽  
High Dose ◽  
Short Term ◽  
Contrast Induced Nephropathy ◽  
Coronary Syndrome ◽  
Randomized Controlled ◽  
Significant Difference

Introduction: Contrast-induced nephropathy (CIN) is a common complication of contrast administration during angiography. Short-term high-dose statins have been suggested for the prevention of CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). Hypothesis: Multiple randomized controlled trials (RCT) have examined the role of statin in preventing CIN with conflicting results. We expanded on previous meta-analyses by including additional RCTs to provide a better outlook on the efficacy of statins in the prevention of CIN. Methods: We searched Pubmed, Medline, Embase, Cochrane, and conference abstracts for prospective RCTs that compared short-term high-dose statins to low-dose statins or placebo in patients undergoing CAG, PCI, computed tomography angiography, or peripheral angiography. High-dose statin was defined as Atorvastatin 40-80 mg, Simvastatin 40 mg, and Rosuvastatin 10-40 mg. Study quality was assessed using the Jadad score. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mantel Haenszel relative risk was calculated using the random effect model. Results: Twenty seven trials (N=9559) were included in the analysis. Eight of the included trials enrolled patients with acute coronary syndrome (ACS) exclusively. High-dose statin was associated with statistically significant reduction in the incidence of CIN (RR=0.56; 95% CI 0.46, 0.69; P<001) compared to low-dose statin or placebo. This protective effect remained significant upon looking on trials that enrolled patients with ACS only (RR=0.40; 95% CI 0.29, 0.56; P<001). Subgroup analysis based on the type of statin showed no significant difference between simvastatin, atorvastatin, or rosuvastatin. No heterogeneity was detected among the studied outcomes (I2=0%). Conclusions: Peri-procedural Short-term high-dose statin administration significantly reduces the incidence of CIN in patients undergoing angiography.

scholarly journals Similar short-term clinical response to high-dose versus low-dose methotrexate in monotherapy and combination therapy in patients with rheumatoid arthritis

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Sytske Anne Bergstra ◽  
Cornelia F. Allaart ◽  
Rosaline van den Berg ◽  
Arvind Chopra ◽  
Nimmisha Govind ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Clinical Response ◽  
Low Dose ◽  
High Dose ◽  
Short Term ◽  
Dose Methotrexate

scholarly journals Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pradeesh Sivapalan ◽  
Niklas R. Jørgensen ◽  
Alexander G. Mathioudakis ◽  
Josefin Eklöf ◽  
Therese Lapperre ◽  
...  
Keyword(s):  
Corticosteroid Therapy ◽  
Dose Group ◽  
Low Dose ◽  
Corticosteroid Treatment ◽  
High Dose ◽  
Short Term ◽  
Copd Patients ◽  
Dose Corticosteroid

Abstract Background Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy. Methods The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits. Results CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group. Conclusion Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients. Trial registration ClinicalTrials.gov Identifier: NCT02857842. Submitted August 2nd, 2016.

Sign in / Sign up

Export Citation Format

Share Document