Effects of Dexamethasone and Oxymetazoline on “Postintubation Croup”: A ferret model

1987 ◽  
Vol 96 (6) ◽  
pp. 554-558 ◽  
Author(s):  
Charles I. Woods ◽  
Duncan S. Postma ◽  
Jiri Prazma ◽  
James Sidman

Several studies recommend the use of steroids and racemic epinephrine for treatment of postintubation croup. Few controlled clinical or laboratory studies, however, support their effectiveness, and many questions remain about their use. The present study was undertaken to develop a reproducible animal model for postintubation croup and to perform initial controlled studies of the effects of dexamethasone (4 mg/kg) and the long-acting vasoconstrictor oxymetazoline (0.01 solution). An animal model for intubation trauma was developed with ten 10-week-old ferrets. Two models were created to reflect the spectrum of trauma—from simple mucosal contusion to mucosal ulceration. The first was to surgically strip mucosa in a circumferential manner at the level of the cricoid ring; the second was intubation trauma to the glottic and subglottic regions by use of a circular brush. Neither dexamethasone nor oxymetazoline had any statistically significant effect on subglottic edema in the mucosal stripping model. In the brush intubation model, oxymetazoline decreased subglottic edema at 2, 4, and 8 hours ( P < 0.05), while dexamethasone and combination therapy decreased edema at 2,4, 8, and 24 hours ( P < 0.05). At 24 hours, combination therapy was demonstrated to be the most effective in reducing subglottic edema. Oxymetazoline was as effective as dexamethasone and combination therapy at 2, 4, and 8 hours ( P < 0.05). In this preliminary study, we have established the potential usefulness of the brush intubation model for the study of this disorder. This model was shown to have a reproducible and reversible lesion. The mucosal stripping model was not shown to have reversible lesion and—while further study needs to be performed—may only be useful as a model for very severe cases of this disorder. These initial studies also demonstrated high-dose dexamethasone and oxymetazoline to be effective in treatment of subglottic edema secondary to mucosal trauma. They also indicate that combination therapy is a more effective treatment than either agent alone.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4629-4629
Author(s):  
Michael Doubek ◽  
Martin Simkovic ◽  
Anna Panovska ◽  
Monika Hrudkova ◽  
David Belada ◽  
...  

Abstract Abstract 4629 Background: Patients with refractory CLL have poor outcome despite currently used salvage treatment. Regimens based on high-dose corticosteroids seem to offer a promising treatment option in this scenario. High-dose methylprenisolone combined with rituximab (R-HDMP) demonstrated significant activity in relapsed/refractory CLL but serious infectious complications occurred in a substantial proportion of patients. Pilot data have shown that combination of dexamethasone and rituximab (R-Dex) may provide comparable results with less toxicity. Aims and Methods: We performed a retrospective analysis of the efficacy and safety of R-Dex in patients (pts) with CLL treated at two tertiary centers between April 2006 and February 2010. Patients received two versions of R-Dex regimen: the dose of rituximab was either 500 mg/m2 on day 1, 8, 15, 22 (375 mg/m2 in 1st cycle), repeated every 4 weeks (n=25) or 500 mg/m2 on day 1 (375 mg/m2 in 1st cycle) repeated every 3 weeks (n=16). The dose of dexamethasone was identical in both regimens: 320 mg per cycle (40 mg on day 1–4 and 10–13 or 15–18). Results: R-Dex was administered to 41 patients (19 males) with median age of 68 years (range, 44–81) indicated for treatment according to NCI-WG criteria. Autoimmune hemolytic anemia or thrombocytopenia was the only indication for the treatment in 7 patients. Rai stage III/IV was present in 37/41 pts. IgVH genes were unmutated in 24/29 pts with available results. Cytogenetic aberrations detected by FISH (n=33) revealed del 17p in 7 patients; del 11q in 11 patients; del 13q in 15 patients and trisomy 12 in 5 patients. Median number of previous therapies was 2 (0-8); 29/41 pts were previously treated with fludarabine-based regimens. The effect of R-Dex in evaluable patients without hemolysis (n=32) was: overall response rate (ORR), n= 21 (62%), complete remission (CR), n=6 (18%), partial remission (PR), n=15 (44%), stable disease (SD), n=4 (12%) and progressive disease (PD), n=5 (15%). All patients treated with R-Dex for autoimmune cytopenia achieved complete resolution of hemolysis. Grade III or IV toxicity included infections in 13 patients (32%), steroid diabetes in 6 patients (15%) and rituximab infusion-related side effects in 3 patients (7%). At the time of analysis (February 2010), median progression free survival (PFS) was 9 months; median overall survival has not been reached. There was no difference in ORR, PFS or OS between the two versions of R-Dex regimen. Conclusions: This pilot study shows that R-Dex is a feasible and effective treatment for relapsed/refractory CLL. In particular, R-Dex appears to be highly effective in CLL with autoimmune cytopenias. However, infectious toxicity remains a serious issue. In addition, long-term disease control can be expected in minority of patients only. Interestingly, higher dose of rituximab per cycle did not result in improved efficacy. Supported by research project MZO 00179906 from Ministry of Health, Czech Republic, by research grant MSM 0021620808 and by the Czech Leukemia Study Group for Life. Disclosures: Smolej: Roche: Honoraria; Bayer-Schering: Honoraria; Genzyme: Honoraria.


2021 ◽  
Vol 12 (1) ◽  
pp. 1-7
Author(s):  
Marvin Wei Jie Chua

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists are important drugs in our armamentarium of treatment for Type 2 diabetes mellitus (DM). In addition to their glucose-lowering effects, they have effects on weight, other metabolic diseases and perhaps most importantly, a cardioprotective and reno-protective effect. Liraglutide is a long-acting GLP-1 agonist which was originally used at 1.8 mg daily for the treatment of DM. However, high-dose liraglutide—liraglutide 3 mg daily, has been demonstrated to be a safe and effective treatment for obesity, with or without DM. In this manuscript, I present two patients who had unusual responses to combination therapy with high-dose liraglutide and SGLT2 inhibitor—marked and/or rapid improvement in glycemic control and weight loss. Drawing from the observations in both cases, I discuss the complementary mechanisms of actions of both drugs, review the clinical effects of combination therapy and distil them into clinical pearls of practical utility for the physician. Given the “clash of the two pandemics” of obesity and COVID-19 and the burgeoning rates of obesity which loom in the near horizon, this is most timely.


2010 ◽  
Vol 104 (8) ◽  
pp. 1110-1120 ◽  
Author(s):  
Helen K. Reddel ◽  
Peter G. Gibson ◽  
Matthew J. Peters ◽  
Peter A.B. Wark ◽  
Ingrid B. Sand ◽  
...  

2016 ◽  
Vol 174 (5) ◽  
pp. 663-667 ◽  
Author(s):  
A Muhammad ◽  
A J van der Lely ◽  
R D O’Connor ◽  
P J Delhanty ◽  
J Dal ◽  
...  

Abstract Context Although combination therapy of acromegaly with long-acting somatostatin analogs (LA-SSAs) and pegvisomant (PEGV) normalizes insulin-like growth factor-1 (IGF1) levels in the majority of patients, it requires long-term adherence. Switching from combination therapy to monotherapy with weekly PEGV could improve patients’ comfort, but the efficacy is unknown. Objective To assess the efficacy of switching to PEGV monotherapy in patients well controlled on combination therapy of LA-SSAs and PEGV. Design Single-center, open-label observational pilot study. LA-SSA therapy was discontinued at baseline and all patients were switched to PEGV monotherapy for 12 months. If IGF1 levels exceeded 1.0 times upper limit of normal (ULN), PEGV dose was increased by 20 mg weekly. Subjects and methods The study included 15 subjects (eight males), with a median age of 58 years (range 35 – 80) on combination therapy of high-dose LA-SSAs and weekly PEGV for >6 months, and IGF1 levels within the normal range. Treatment efficacy was assessed by measuring serum IGF1 levels. Results After 12 months of weekly PEGV monotherapy, serum IGF1 levels of 73% of the subjects remained controlled. In one patient, LA-SSA had to be restarted due to recurrence of headache. IGF1 levels increased from a baseline level of 0.62 × ULN (range 0.30 – 0.84) to 0.83 × ULN (0.30 – 1.75) after 12 months, while the median weekly PEGV dose increased from 60 (30 – 80) mg to 80 (50 – 120) mg. Conclusion Our results suggest that switching from combination therapy of LA-SSAs and PEGV to PEGV monotherapy can be a viable treatment option for acromegaly patients without compromising efficacy.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 996-P
Author(s):  
JAEHYUK CHOI ◽  
HYOSANG JO ◽  
JUNG KUK KIM ◽  
SANG DON LEE ◽  
SANG HYUN LEE ◽  
...  

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