Clinical and Pharmacokinetic Evaluation of Long-Term Therapy With Didanosine in Children with HIV Infection

PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 724-731 ◽  
Author(s):  
Brigitta U. Mueller ◽  
Karina M. Butler ◽  
Vicki L. Stocker ◽  
Frank M. Balis ◽  
Philip A. Pizzo ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Area Under The Curve ◽  
Chronic Administration ◽  
Cd4 Count ◽  
Term Therapy ◽  
Short Term ◽  
Apparent Relationship ◽  
Term Administration ◽  
Long Term Therapy

Background. Didanosine has demonstrated promising antiviral activity and a tolerable toxicity profile in short term studies. We describe a cohort of HIV-infected children who were treated for a prolonged period of time with didanosine. Methods. Children (6 months to 18 years of age) with symptomatic HIV infection or an absolute CD4 count < 0.5 x 109 cells/L, received oral didanosine at doses between 20 mg/m2 to 180 mg/m2 every 8 hours. Clinical, immunological, and virological parameters were assessed at least every 2 months. The pharmacokinetics of didanosine were evaluated in 85 patients. Results. Previously untreated children (n = 51) and children who had received prior antiretroviral therapy (n = 52) were enrolled in the study (median time on study 22.6 months; range 2 to 48). The long-term administration of didanosine was well tolerated and no new toxicities were observed. The absolute CD4 count increased by ≥ .05 x 109 cells/L in 28 of 87 (32%) of patients after 6 months of therapy. Responses were also sustained in 41% of these children after 3 years of therapy. Children entering the study with a CD4 count >0.1 x 109 cells/L (n = 51) had a marked survival advantage (P = .00002) with an estimated survival probability after 3 years of 80% compared to 39% for children with lower CD4 counts. Although the area under the curve of didanosine increased proportionally with the dose, there was considerable interpatient variability at each dose level. There was no apparent relationship between surrogate markers of clinical outcome and plasma drug concentration. Conclusions. Didanosine was well tolerated with chronic administration, and toxicities were uncommon and usually reversible. In 41% of patients, the CD4 count increased and was maintained at the higher level even after years of treatment.

scholarly journals The effect of short-term and long-term application of fisetin on experimentally induced airway hyperreactivity

2017 ◽  
Vol 64 (1) ◽  
pp. 7-9
Author(s):  
I. Kazimierová ◽  
L. Pappová ◽  
M. Šútovská ◽  
S. Fraňová
Keyword(s):  
Airway Inflammation ◽  
Airway Resistance ◽  
Chronic Administration ◽  
Airway Hyperreactivity ◽  
Whole Body ◽  
Short Term ◽  
Specific Airway Resistance ◽  
Term Administration

AbstractBackground:Fisetin, a derivate from the flavonol group may possess a variety of pharmacological effects. The aim of the presented study was to evaluate the bronchodilatory effect of fisetin after the acute or the chronic administration to guinea pigs with allergic airway inflammation.Methods:Experimental animals were sensitized and challenged by ovalbumin. Fisetin was administered in dose 5mg/kg/p.o., either once after the end of 21-days sensitization or daily during the 21-days sensitization. By using the whole-body plethysmograph, we monitored the specific airway resistance, a parameter of airway hyperreactivityin vivo. The changes of the specific airway resistance were evaluated after the short-term inhalation of the bronchoconstriction mediator-histamine (10−6mol.1−1).Results:Our results showed that the short-term as well as the long-term administration of fisetin caused decrease of the specific airway resistance values. The bronchodilatory effect of fisetin was comparable to the long-acting beta2sympathomimetic – salmeterol after the long-term administration. The measurements of the bronchodilatory activity after single administration have revealed more prolonged effect of fisetin comparing to the short-acting beta2sympathomimetic – salbutamol, as this remained even after the 5 hours, when salbutamol was already ineffective.Conclusion:In conclusion, flavonol – fisetin has shown bronchodilatory potential. In the light of this fact, fisetin may represent potential substance that can be effective in both prevention as well as control of airway inflammation symptoms.

scholarly journals Ambulatory Intravenous Antibiotic Therapy in Quebec: The Hôpital Charles LeMoyne Experience in 1996

2000 ◽  
Vol 11 (suppl a) ◽  
pp. 6A-10A
Author(s):  
Laurent Delorme ◽  
Charles Frenette ◽  
Isabelle Le Corre ◽  
Julie Duchesne ◽  
Carole Delorme ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Term Therapy ◽  
Outpatient Therapy ◽  
Short Term ◽  
Intravenous Antibiotic ◽  
Therapy Program ◽  
Intravenous Antibiotic Therapy ◽  
Short Term Therapy ◽  
Long Term Therapy

From January 1, 1996 to December 31, 1996, 343 patients received outpatient intravenous antibiotic therapy at Charles LeMoyne Hospital, a 436-bed, acute care hospital in Greenfield Park, south of Montréal, Québec. The infectious diseases department saved 2660 bed-days using outpatient therapy. The mean duration of outpatient therapy was 7.76 days; 81.6% of patients were admitted to the program directly from the emergency room, or outpatient hospital clinics or private offices in the community. Hospitalized patients constituted only 18.4% of admissions to the outpatient intravenous antibiotic therapy program. Forty per cent of the surgical/medical staff participated in the program and they were able to generate a significant impact by diverting patients to outpatient therapy. Two types of patients can benefit from an outpatient intravenous antibiotic therapy program. One group of patients needs empirical short term therapy and can be switched to oral sequential therapy after two to five days of outpatient intravenous antibiotic therapy. A second group of patients needs specific long term therapy for the full duration of the antibiotic therapy. Empirical short term therapy can be managed by emergency department or hospital-based primary physicians, or medical/surgical specialists. Specific long term therapy can be managed by microbiology/infectious disease specialists or medical/surgical specialists. Hospitals that want to relieve pressure on emergency rooms and hospital bed demands should create facilities for both types of patients. Cefazolin and gentamicine/tobramycine were the most commonly used antibiotics in empirical short term therapy and in terms of number of patients treated. Ceftriaxone and vancomycin were most commonly used for long term therapy. The Drug acquisition antibiotic cost was $73,117 but constituted only 20% of the total outpatient intravenous antibiotic therapy cost. The per diem ambulatory cost was $140/patient/day.

scholarly journals Experience of long-term use of denosumab in women with osteoporosis and various concomitant diseases

2021 ◽  
Vol 24 (2) ◽  
pp. 48-55
Author(s):  
I. A. Skripnikova ◽  
O. V. Kosmatova ◽  
V. E. Novikov ◽  
M. A. Myagkova ◽  
V. N. Shishkova
Keyword(s):  
Drug Withdrawal ◽  
Term Therapy ◽  
First Year ◽  
Outpatient Basis ◽  
Term Administration ◽  
Discontinue Therapy ◽  
Long Term Therapy ◽  
Reliable Increase ◽  
Subsequent Administration

Background: Possible differences in the results of planned RCTs and real clinical practice were the reason for the analysis of long-term therapy with denosumab in patients with osteoporosis (OP) of various origins on an outpatient basis.Aim: To assess the effectiveness of long-term administration of denosumab in terms of the effect on BMD and markers of bone metabolism, tolerance and consequences of drug withdrawal in patients with OP of various etiologies.Materials And Methods: A retrospective analysis of the outpatient records of women with OP of various etiology, who were observed at the FSBI «NMRC TPM» from 1 to 10 years and regularly received denosumab 60 mg once every 6 months subcutaneously (at least 2 injections), was carried out. All completed examination and anthropometric research; DXA of the lumbar spine and proximal femur (PF); laboratory tests: marker of bone resorption CTx (β-crosslaps) in blood serum; survey on the presence of adverse events.Results: The study included 148 patients who were divided into 2 groups: 1 (N=98) - did not take anti-osteoporotic therapy (AT), 2 (N=50) - who took AT before the appointment of denosumab. Long-term therapy with denosumab was associated with a steady and reliable increase in BMD in the spine and PF, as well as a decrease in the concentration of CTx of both those who didn’t take and who previously took AT. In 54% of patients BMD in the spine reached values of osteopenia, in 43.4% of women target BMD values in the femoral neck were determined. During the first year of therapy, there was a decrease in the concentration of CTx by 67% in those who didn’t take AT and by 58% in those who had previously taken AT. Discontinuation of denosumab therapy without subsequent administration of AT was associated with a significant decrease in BMD in the spine (by 4.4-8.2%) during the first year after discontinuation of the drug.Conclusion: Denosumab therapy effectively increases BMD in the spine and PF and decreases CTx levels both in untreated patients and in those who previously received AT. It is necessary to discontinue therapy, further management of the patient should be discussed to prevent «withdrawal syndrome».

scholarly journals Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Huan Du ◽  
Shuke Nie ◽  
Guiqin Chen ◽  
Kai Ma ◽  
Yan Xu ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
Chronic Administration ◽  
Term Therapy ◽  
Dependent Manner ◽  
Abnormal Involuntary Movements ◽  
Extracellular Signal ◽  
6 Hydroxydopamine ◽  
Long Term Therapy ◽  
Dose Dependent

L-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson’s disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators of LID in rats with 6-hydroxydopamine (6-OHDA) lesions. Following chronic administration of L-DOPA (12 mg/kg, twice daily for 14 days), rats developed abnormal involuntary movements (AIMs), but co-administration of levetiracetam (15, 30, and 60 mg/kg) with equivalent L-DOPA dosing significantly reduced AIMs scores in a dose dependent manner. The effects of levetiracetam were associated with changes in striatal expression ofΔFosB, phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and phosphorylated cAMP-regulated phosphoprotein of 32 kDa (p-DARPP-32). These data support that levetiracetam acts at multiple sites in the pathogenetic cascade of LID, and that further understanding of these actions of antiepileptics may contribute to developing new LID therapies.

Selective Streptokinase Fibrinolysis in Femoro-Iliac Arterial Obstruction

1986 ◽  
Vol 27 (3) ◽  
pp. 279-283 ◽  
Author(s):  
K. Sørensen ◽  
V. Hegedüs
Keyword(s):  
Low Dose ◽  
Transluminal Angioplasty ◽  
Term Therapy ◽  
High Dose ◽  
Short Term ◽  
Short Term Therapy ◽  
One Year ◽  
High Level ◽  
Long Term Therapy

Percutaneous transluminal angioplasty of iliac and femoral arteries was in 17 patients combined with selective intra-arterial streptokinase treatment. The patients were divided into two groups, one given low dose long-term therapy and the other high dose short-term therapy. The experiences obtained during an observation period of over one year revealed greater benefit from high dose short-term therapy. It seems that the major cause of complications must be attributed to the development of a high level of streptokinase antibodies during low dose long-term therapy. References

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