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PubMed2006

Role of adenosine as adjunctive therapy in acute myocardial infarction.

Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy.

Adenosine↗

PubMed2002

Low dose and slow titration of topiramate as adjunctive therapy in refractory partial epilepsies: a multicentre open clinical trial.

PURPOSE: A multicentre open clinical trial was conducted to evaluate the clinical usefulness of a slower titration of topiramate (TPM) to 300 mg /day as adjunctive therapy for medically intractable partial epilepsies. METHODS: Nineteen centres participated in the trial. Study patients had to have had two or more seizures per 4 weeks whilst taking maximum tolerated doses of one but not more than two anti-epileptic drugs. The starting dose of TPM was 25 mg /day and the dose was increased weekly by 25 mg /day until 100 mg /day was reached. Thereafter TPM was increased by 50 mg /day weekly up to the target dose of 300 mg /day, which was followed by an 8 week maintenance phase. Seizure outcomes were measured by intention-to-treat analysis (ITTA). RESULTS: Two hundred and thirteen patients entered the study. Median seizure frequency reduction rate was 44.8%, responder rate was 47.6%, and seizure free rate was 9.0%. These results were comparable to that of TPM 600 mg /day in our previous controlled trial. In subgroup analysis, seizure free rate was higher in those patients with a lower baseline seizure frequency rate. Seventeen patients (8.0%) were prematurely withdrawn from the study due to adverse events (AE) or lack of effect. One or more AEs were reported in 22% of patients, with dizziness being the most frequent AE. Other AEs occurred in less than 5% of patients. CONCLUSION: TPM 300 mg /day was effective and in conjunction with a slower dose-titration, markedly reduced the incidence of AEs, compared with previous study.

Adolescent↗

PubMed1993

Hyperbaric oxygen therapy adjunctive to mild hypertensive hypervolemia for symptomatic vasospasm.

The efficacy of hyperbaric oxygen (HBO) therapy was evaluated retrospectively in 43 patients who developed symptomatic vasospasm following acute aneurysm surgery. HBO therapy was given as an adjunct to mild hypertensive hypervolemia in 24 patients. Before HBO therapy, 17 patients had no infarct (Group 1), and seven had infarcts (Group 2) caused by vasospasm. A further 19 patients received mild hypertensive hypervolemia alone (Group 3). Cerebral infarcts developed in four Group 1 and 12 Group 3 patients. A good outcome 1 month after surgery was achieved by 13 Group 1 (76%), one Group 2, and seven Group 3 patients (37%). Fifteen of the 24 patients who received HBO therapy responded to HBO exposure, and 12 responding patients (80%) had a good outcome. During HBO exposure, electroencephalographic improvements were all accompanied by neurological improvements. There were no complications related to HBO therapy. HBO therapy adjunctive to mild hypertensive hypervolemia is helpful in preventing cerebral infarction associated with symptomatic vasospasm.

Adult↗

PubMed2004

Recombinant interferon- gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis.

We conducted a phase 2, double-blind, placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)- gamma 1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis. Patients received 100 or 200 microg of rIFN- gamma 1b or placebo, thrice weekly for 10 weeks, plus standard therapy with intravenous amphotericin B, with or without flucytosine, followed by therapy with fluconazole. End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks, resolution of symptoms, and survival. Among 75 patients, 2-week culture conversion occurred in 13% of placebo recipients, 36% of rIFN- gamma 1b (100 microg) recipients, and 32% of rIFN- gamma 1b (200 microg) recipients. There was a trend toward improved combined mycologic and clinical success in rIFN- gamma 1b recipients (26% vs. 8%; P=.078). Therapy with rIFN- gamma 1b was well tolerated, and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements. Adjunctive therapy with rIFN- gamma 1b holds promise for patients with acute cryptococcal meningitis and warrants further study.

AIDS-Related Opportunistic Infections↗

PubMed1994

Beta 2-adrenergic agonist as adjunct therapy to levodopa in Parkinson's disease.

We studied the effect of the beta 2-adrenergic agonist albuterol on Parkinson's disease (PD) patients receiving chronic levodopa treatment. The albuterol-treated patients demonstrated reduced parkinsonian symptoms and an increased ability to tap their index finger between two points 20 cm apart, and were able to perform a "walk test" in 70% of their control time. Three patients currently on chronic albuterol therapy still show amelioration of their parkinsonian symptoms, and two have reduced their daily levodopa dose. This study suggests that beta 2-adrenergic agonists as adjunct therapy to levodopa may be beneficial in PD.

Aged↗

PubMed1999

Risperidone as an adjunct therapy for post-traumatic stress disorder.

Risperidone, an atypical antipsychotic medication, has gained wide acceptance as a first-line drug for several indications. Recently, interest has arisen in the use of risperidone as an adjunct therapy in post-traumatic stress disorder (PTSD). PTSD is a possible sequela of exposure to traumatic events. The military population, because of occupational exposure, is at a higher risk than the general population to develop PTSD, and the treatment of PTSD may be a significant issue for military practitioners. PTSD may be complicated by social issues and comorbid psychiatric conditions, and it is often difficult to treat. We present two case reports on the use of risperidone in the treatment of the intrusive thoughts and subsequent emotional reactivity experienced by some PTSD patients, along with a discussion of some possible mechanisms of action for the efficacy of risperidone in the treatment of these symptoms.

Adult↗

PubMed1995

Neuroanesthesia adjunct therapy (mannitol and hyperventilation) is as effective as cerebrospinal fluid drainage for prevention of paraplegia after descending thoracic aortic cross-clamping in the dog.

We compared cerebrospinal fluid (CSF) drainage (Group D; n = 8) to neuroanesthesia adjunct therapy (hyperventilation and mannitol administration; Group N; n = 8) for the prevention of paraplegia using a canine model of descending thoracic aortic cross-clamping (AXC; 2.5 mm distal to the left subclavian artery for 30 min). We expected no difference in neurologic outcome between groups. After surgical preparation and a 30-min stabilization period, dogs in Group D had CSF drained prior to application of the AXC. During the period of AXC, CSF was allowed to drain freely in an attempt to have cerebrospinal fluid pressure (CSFP) no greater than central venous pressure (CVP). Dogs in Group N were hyperventilated (PaCO2 28-32 mm Hg) and received 2 g/kg of mannitol prior to AXC and then 1 g.kg-1.hr-1 during clamping. Systemic hemodynamics, CSFP, and arterial blood gases were measured at 1) baseline, 2) 2 min after AXC, 3) 20 min after AXC, 4) 5 min after AXC release, and 5) 30 min after resuscitation. With release of the AXC, PaCO2 was not controlled in Group D; in Group N the minute ventilation was further increased to maintain PaCO2 constant. At precisely 24 h after AXC, the animals were assessed for incidence and severity of paraplegia, using the Tarlov score, by an observer unaware of the experimental protocol. The animals were then killed, and the entire spinal cord was removed for histologic assessment. Multiple sections of the lumbar spinal cord were processed and stained with hematoxylin and eosin, then examined by light microscopy for nonviable neurons in the anterior spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1998

The efficacy and safety of dorzolamide as adjunctive therapy to timolol maleate gellan solution in patients with elevated intraocular pressure. Additivity Study Group.

PURPOSE: Two parallel, randomized, double-masked, placebo-controlled studies were conducted to assess the efficacy and safety of 2% dorzolamide hydrochloride as adjunctive therapy to 0.5% timolol maleate ophthalmic gellan (gel-forming) solution in patients with elevated intraocular pressure (IOP) that was inadequately controlled with 0.5% timolol maleate gellan solution alone. METHODS: Both studies began with an open-label 2-week run-in period on 0.5% timolol maleate gellan solution once a day. The only variation in method between the two studies was the dosage of 2% dorzolamide. In one study, 202 patients received 0.5% timolol maleate gellan solution once daily plus either 2% dorzolamide or placebo three times daily. In the other study, 181 patients received 0.5% timolol maleate gellan solution once daily plus either 2% dorzolamide or placebo twice daily. RESULTS: After 85 days, additional mean percent reductions in IOP from baseline at morning trough for the groups receiving 2% dorzolamide three times daily and placebo three times daily were 12.5% and 8.4%, respectively. Mean percent reductions for the groups receiving 2% dorzolamide twice daily and placebo twice daily were 13.1% and 6.5%, respectively. Burning and/or stinging on instillation were the only adverse experiences that affected significantly more of the patients receiving 2% dorzolamide twice or three times daily than those receiving placebo. CONCLUSION: When administered concomitantly with 0.5% timolol maleate gellan solution, 2% dorzolamide three times daily or twice daily produced a statistically significant reduction in IOP at morning trough and peak and was generally well tolerated.

Adrenergic beta-Antagonists↗

PubMed2003

Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.

BACKGROUND: Pregabalin is an alpha(2)-delta ligand that has anxiolytic, analgesic, and anticonvulsant properties. OBJECTIVE: To establish the efficacy, safety, and tolerability of pregabalin administered twice-daily (BID) without dose titration as adjunctive treatment in patients with partial seizures and to confirm the dose-response relationship. METHODS: This 76-center, double-blind, randomized, placebo-controlled, parallel-group study consisted of an 8-week baseline and a 12-week double-blind phase. Patients with refractory partial seizures on one to three antiepileptic drugs were randomly assigned to one of five treatment groups (placebo or 50, 150, 300, and 600 mg/d pregabalin, all administered BID). Efficacy was assessed using seizure frequency reduction and responder rate (> or =50% seizure reduction from baseline). Pharmacokinetic parameters were estimated. RESULTS: A total of 453 patients were included in the intent-to-treat analysis. The median baseline seizure rate was 10 per month. Seizure frequency reductions from baseline were 7% (placebo; n = 100), 12% (50 mg/d; n = 88), 34% (150 mg/d; n = 86), 44% (300 mg/d; n = 90), and 54% (600 mg/d; n = 89). Responder rates (> or =50% seizure reduction) were 14% (placebo), 15% (50 mg/d), 31% (150 mg/d), 40% (300 mg/d), and 51% (600 mg/d). Discontinuation rates due to adverse events were 5% (placebo), 7% (50 mg/d), 1% (150 mg/d), 14% (300 mg/d), and 24% (600 mg/d). The 150-, 300-, and 600-mg/d pregabalin groups were associated with greater reductions in seizures (p < or = 0.0001) and greater responder rates compared with the placebo group (p < or = 0.006). There was a favorable dose-response trend for both seizure reductions (p < or = 0.0001) and responder rate (p < or = 0.001). CONCLUSION: Adjunctive therapy with pregabalin 150, 300, and 600 mg/d, given in twice-daily doses without titration, is significantly effective and well tolerated in the treatment of patients with partial seizures as demonstrated in patients with refractory partial seizures.

Adolescent↗

PubMed1986

Systemic tetracycline hydrochloride as adjunctive therapy in the treatment of persistent epithelial defects.

Recent evidence shows tetracyclines have anticollagenolytic activity that may be clinically effective in disease treatment. This led us to use systemic tetracycline (oral tetracycline hydrochloride 1 g daily divided into 4 doses) as adjunctive therapy in treating 18 patients with persistent corneal epithelial defects. Fourteen of 18 patients healed their defects; within 48 hours (9 patients) and within two weeks (the other 5 responding patients). Two patients showed no effect and two showed disease progression.

Adolescent↗

PubMed1995

Adjunctive therapy for septic shock: a review of experimental approaches.

Septic shock remains a major cause of morbidity and mortality, especially in the intensive care setting. A vast array of treatment strategies is under investigation; despite success in animal models, no effective adjunctive therapy has yet been approved for clinical use. This paper reviews the development of experimental therapies for sepsis and discusses those treatments that show promise for application in humans. Approaches to treatment fall into three broad categories: strategies directed against bacterial components, those directed against host-derived inflammatory mediators, and those designed to limit tissue damage. Because septic shock is a dynamic and evolving condition, different strategies may be needed at different stages in the pathogenesis of sepsis. Through carefully performed trials and thoughtful selection of combination therapy aimed at different points in the pathological process, it may be possible in the future to modify the course of this serious condition.

Acute-Phase Proteins↗

PubMed1992

Prevention of peripheral side-effects of transdermal hyoscine by adjunctive therapy with low dosage of pyridostigmine.

1. The value of low dosage of pyridostigmine (30 mg three times daily) in preventing peripheral anti-muscarinic side effects of a transdermal controlled-release formulation of hyoscine, was tested in a double-blind placebo-controlled study, involving 47 healthy subjects. 2. Salivary excretion was repeatedly measured during 48 h of combined therapy of two transdermal hyoscine patches with pyridostigmine and 14 h after its cessation. Blood acetylcholinesterase activity was also measured, serving as an index of pyridostigmine bioavailability. 3. The adjunctive therapy with pyridostigmine was highly effective in preventing the substantial impairment in salivary flow caused by the transdermal formulation. An associated 23% inhibition of blood acetylcholinesterase activity was observed. 4. Small doses of pyridostigmine may therefore have a role in increasing the tolerability of transdermal hyoscine therapy. In some patients this drug combination might also allow some increment of the hyoscine dose.

Acetylcholinesterase↗

PubMed2002

Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children.

In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3-15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.

Adjuvants, Immunologic↗

PubMedDate not supplied

Thrombolysis and adjunctive therapies in acute myocardial infarction.

Thrombolysis and percutaneous transluminal angioplasty represent the cornerstone of the pharmacologic treatment of and the interventional approach to patients with myocardial infarction (MI). They are very effective. However, they are hampered by some critical limitations. Therefore, alternatives to standard thrombolytic therapy have been developed. Platelet glycoprotein (GP) IIb/IIIa blockade is under investigation and seems very attractive. This review will focus on the use of GP IIb/IIIa antagonists and thrombin inhibitors as adjunctive therapies to the thrombolytic treatment of patients with acute MI.

Acute Disease↗

PubMed2005

Neoaortic reconstruction for aortic graft infection: need for endovascular adjunctive therapies?

Neoaortic reconstruction using an autogenous conduit is an increasingly accepted option for the management of aortic graft infections. However, this approach is not without technical challenges and potential graft-related problems, some of which can be solved with endovascular techniques. All patients who underwent neoaortic reconstruction with femoral-popliteal vein for aortic graft infection over a 6-year period were identified from the operative registry. Those patients requiring endovascular adjunctive therapies form the basis of this report. Of 17 cases of neoaortic reconstruction for aortic graft infection, five (29%) required endovascular adjunctive procedures. These included stent placement for graft stenosis (n = 3), stent graft placement for proximal anastomotic stenosis (n = 1), and stent graft placement for anastomotic disruption (n = 1). While two of these procedures occurred within 30 days of the original neoaortic reconstruction, three were required during late follow-up. Although there were no direct complications related to the endovascular procedures, the patient with anastomotic disruption died within 30 days of causes unrelated to the endovascular procedure. Primary patency of neoaortic reconstruction was 87% at 30 days and 61% at 3 years, with assisted primary patency increasing to 100% at 3 years after endovascular adjunctive intervention. While neoaortic reconstruction using an autogenous conduit for aortic graft infection has proven durability, it is not without potential early and late graft complications. When graft problems occur, endovascular options are an attractive alternative to reoperative open aortic procedures, especially in the setting of a vastly altered surgical field.

Aged↗

PubMed1986

The role of beta blocking agents as adjunct therapy to membrane stabilizing drugs in malignant ventricular arrhythmia.

Antiarrhythmic drugs are often either partially or totally ineffective for the suppression of ventricular arrhythmias in a given patient. Drug combinations afford an additional therapeutic option. We report the role of beta-blocking agents as adjunct therapy to membrane stabilizing drugs in the management of patients with malignant ventricular arrhythmias. The study group included 54 patients who were evaluated by 24-hour ambulatory monitoring and symptom-limited exercise testing. Patients underwent control studies without antiarrhythmic drugs, were evaluated on membrane stabilizing drugs and beta blocking agents separately, and were then tested on combination therapy. The combination of a beta-blocking agent and a membrane stabilizing drug abolished ventricular tachycardia and couplets in 83% and 86% of exercise tests in patients with this arrhythmia present during therapy with membrane drugs alone (p less than 0.01). The addition of a beta blocker to a membrane drug, as evaluated by ambulatory monitoring, resulted in an abolition of ventricular tachycardia and couplets in 43% and 20% of studies (p less than 0.05). Ventricular premature beat frequency was reduced by more than 50% in 65% of exercise tests and in 52% of monitoring studies (p less than 0.05). In this population, beta-blocking agents failed to reduce ventricular arrhythmias when used alone. Thus the addition of a beta blocker to a membrane stabilizing drug significantly enhances the suppression of ventricular arrhythmia, especially when assessed by exercise testing. This results from synergistic drug effects of the combination rather than from the effect of the individual drugs.

Adrenergic beta-Antagonists↗

PubMed2006

Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer.

The mainstay of dyspnea palliation remains altering its central perception. Morphine is the main drug and anxiolytics have a less established role. This trial assessed the role of midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in terminally ill cancer patients. One hundred and one patients with severe dyspnea were randomized to receive around-the-clock morphine (2.5 mg every 4 hours for opioid-naïve patients or a 25% increment over the daily dose for those receiving baseline opioids) with midazolam rescue doses (5 mg) in case of breakthrough dyspnea (BD) (Group Mo); around-the-clock midazolam (5 mg every 4 hours) with morphine rescues (2.5 mg) in case of BD (Group Mi); or around-the-clock morphine (2.5 mg every 4 hours for opioid-naïve patients or a 25% increment over the daily dose for those receiving baseline opioids) plus midazolam (5 mg every 4 hours) with morphine rescue doses (2.5 mg) in case of BD (Group MM). All drugs were given subcutaneously in a single-blinded way. Thirty-five patients were entered in Group Mo, 33 entered in Mi, and 33 entered in MM. At 24 hours, patients who experienced dyspnea relief were 69%, 46%, and 92% in the Mo, Mi, and MM groups, respectively (P = 0.0004 and P = 0.03 for MM vs. Mi and MM vs. Mo, respectively). At 48 hours, those with no dyspnea relief (no controlled dyspnea) were 12.5%, 26%, and 4% for the Mo, Mi, and MM groups, respectively (P = 0.04 for MM vs. Mi). During the first day, patients with BD for the groups Mo, Mi, and MM were 34.3%, 36.4%, and 21.2%, respectively (P = NS or not significant), whereas during the second day, these percentages were 38%, 38.5%, and 24%, respectively (P = NS). The data demonstrate that the beneficial effects of morphine in controlling baseline levels of dyspnea could be improved with the addition of midazolam to the treatment.

Adult↗

PubMed2000

Use of adjunctive therapy to heal a diabetic amputation site.

Diabetes can result in a range of complications, and is responsible for many lower limb amputations. This case report discusses a diabetic patient with a complex, non-healing wound following amputation of the foot. A number of adjunctive therapies were used to promote healing, and led to the complete healing of the wound.

Aged↗