scholarly journals Sustained hemodynamic and antianginal effect of high dose oral isosorbide dinitrate.

Circulation ◽  
1977 ◽  
Vol 55 (2) ◽  
pp. 381-387 ◽  
Author(s):  
D T Danahy ◽  
D T Burwell ◽  
W S Aronow ◽  
R Prakash
Author(s):  
Fiona V Cresswell ◽  
David B Meya ◽  
Enock Kagimu ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
...  

Abstract Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in HIV co-infection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomised to standard-of-care control (PO-10, rifampicin 10mg/kg/day), intravenous rifampicin (IV-20, 20mg/kg/day), or high-dose oral rifampicin (PO-35, 35mg/kg/day). We performed PK sampling on day 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration and grade 3-5 adverse events. Results We enrolled 61 adults, 92% were HIV-positive, median CD4 count was 50cells/µL (IQR 46–56). On day 2, geometric mean plasma AUC0-24hr was 42.9h.mg/L with standard-of-care 10mg/kg dosing, 249h.mg/L for IV-20 and 327h.mg/L for PO-35 (P<0.001). In CSF, standard-of-care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0-24hr 0.27mg/L, compared with 1.74mg/L (95%CI 1.2–2.5) for IV-20 and 2.17mg/L (1.6–2.9) for PO-35 regimens (p<0.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (p=0.34) Conclusion Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe, and respectively resulted in exposures ~6- and ~8-fold higher than standard-of-care, and CSF levels above the MIC


1987 ◽  
Vol 10 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Stephen B. Edge ◽  
William K. Funkhouser ◽  
Arlene Berman ◽  
Claudia Seipp ◽  
Anne Tanner ◽  
...  

Open Medicine ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. 631-633
Author(s):  
Yoshiro Horai ◽  
Tomoya Miyamura ◽  
Karin Shimada ◽  
Soichiro Takahama ◽  
Rumi Minami ◽  
...  

AbstractWe report a 71-year-old male with microscopic polyangiitis (MPA) who developed sudden-onset, progressive, bilateral visual loss associated with a relapse of MPA symptoms. The patient was referred to our hospital, and treated with intravenous pulse steroid therapy and high-dose oral prednisolone. Although the right eye remained vision deficient, visual acuity in the left eye recovered. Ocular manifestations of MPA are quite uncommon. This case emphasizes the necessity of early detection and initiation of prompt therapy where ocular manifestations of MPA occur.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1036.1-1036
Author(s):  
A. Vornicu ◽  
B. Obrisca ◽  
R. Jurubita ◽  
B. Sorohan ◽  
A. Andronesi ◽  
...  

Background:Infection remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) treated with systemic immunosuppression (IS).Objectives:We sought to describe the infection profile in patients with LN treated with aggressive immunosuppression (induction and maintenance therapy) and to identify the associated risk factors.Methods:Patients with LN followed in the Nephrology Department of Fundeni Clinical Institute, were retrospectively reviewed for any infection that occurred from initiation of induction therapy. Infections were graded (1-5) according to the Common Terminology Criteria for Adverse Events. Infection site and type of microorganism were also recorded. Univariate and multivariate Cox proportional hazard regression analysis were performed in order to identify independent risk factors for infection.Results:The study cohort comprised 101 patients (86.1% females) with a mean age of 34 ± 14 years. Forty-eight patients (47.5%) had at least one infection with a total 92 episodes of infection occurring during a median follow-up of 17 months (IQR:8.5-52.5 months). The majority of patients (31 of 48) had infections during the first 12 months since IS treatment initiation. The most common site was lung infection (in 24.8% of patients), followed by urinary tract (20.8% of patients) and cutaneous/mucosal infections (11% of patients). Thirty-eight percent of patients had bacterial infections. Nineteen percent of patients had severe infections (grade 3 or higher) with 3.3% of infection-related deaths (3 patients). The most common induction regimen was cyclophosphamide in addition to corticosteroids (48.5%), with 44.6% of patients receiving pulse methylprednisolone and 45.5% of patients receiving more than 30 mg/d of prednisone as the maximum oral dose. In univariate Cox regression analysis, female gender (HR 3.34; 95% CI, 1.03-10.8, p=0.04), pulse methylprednisolone (HR 2.9; 95% CI, 1.6-5.24, p=0.001), high-dose (≥30 mg/day) oral corticosteroids (HR 4.22; 95% CI, 2.21-8.02,p=0.001) and SLEDAI score (HR 1.047; 95% CI, 1.012-1.084, p=0.008) were risk factors for infection. In multivariate Cox regression analysis, female gender (HR 6.35; 95%CI, 1.86-21.64,p=0.003), high-dose oral corticosteroids (HR 4.7; 95% CI, 2.25-9.87, p=0.003) and SLEDAI score (HR 1.046; 95% CI, 1.003-1.09, p=0.034) remained independent predictors of infection risk. Of the risk factors associated with severe infections (grade 3 or higher), in univariate analysis we identified younger age (HR 0.96, 95%CI, 0.92-0.99, p=0.035), neurological involvement (HR 2.59; 95%, 0.86-7.83, p=0.09), pulse methylprednisolone (HR 5.42; 95% CI, 1.79-16.35, p=0.003) and high-dose oral corticosteroids (HR 8.32; 95% CI, 2.4-28.77, p=0.001) as risk factors for infection. After multivariate adjustment, neurological involvement (HR 4.33; 95%, 1.29-14.51, p=0.01) and high-dose oral corticosteroids (HR 7.6; 95% CI, 1.6-35.39, p=0.01) were identified as independent predictors of infection risk.Conclusion:A high-dose oral corticosteroid regimen increased the risk for any infection and for severe infections by 4.7-fold and 7.6-fold, respectively. In addition, female gender and a higher SLEDAI score were identified as risk factors for any infection, while neurological involvement was associated with an increased risk for severe infections.References:[1]Jung JY, Yoon D, Choi Y, Kim HA, Suh CH. Associated clinical factors for serious infections in patients with systemic lupus erythematosus. Sci Rep. 2019;9(1):9704.Disclosure of Interests: :None declared


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