B1tta/Drug-ACE huggingface dataset:
[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.
[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.
[Drug-Disease]: Ketamine - stroking hyperalgesia
[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.
[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.
[Drug-Disease]: Ketamine - pain
[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.
[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.
[Drug-Disease]: Alfentanil - stroking hyperalgesia
[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.
[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.
[Drug-Disease]: Alfentanil - pain
[Title]: Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma.
[Abstract]: BACKGROUND: The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin, TLC D-99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first-line treatment of metastatic breast carcinoma (MBC). METHODS: Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 (75 mg/m(2)) or doxorubicin (75 mg/m(2)) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF). RESULTS: Median age was 54 years in both treatment groups. All relevant prognostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group. Protocol-defined cardiotoxicity was observed in 13% of TLC D-99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m(2) for TLC D-99 versus 570 mg/m(2) for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D-99, although the difference was not statistically significant. There was only one report of palmar-plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin. CONCLUSIONS: Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity.
[Drug-Disease]: doxorubicin - MBC
[Title]: Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects.
[Abstract]: BACKGROUND: Use of sulphasalazine in ulcerative colitis patients is hampered by a variety of side-effects, including male infertility. 5-aminosalicylic acid is better tolerated and has been increasingly used to treat patients intolerant/allergic to sulphasalazine but it may also be associated with side-effects. AIM: To evaluate tolerance of long-term treatment with sulphasalazine and 5-aminosalicylic acid in ulcerative colitis. METHODS: Side-effects to sulphasalazine (2-3 g/day) and 5-aminosalicylic acid (1.2-2.4 g/day) were recorded in 685 patients: 410 patients received only sulphasalazine, 130 only 5-aminosalicylic acid, and 145 both drugs. In patients with side-effects to sulphasalazine, a desensitisation protocol (rechallenge) was attempted to improve tolerance, and patients still presenting side-effects after desensitisation were switched to 5-aminosalicylic acid. Male fertility was also assessed in 42 males on sulphasalazine and on 5-aminosalicylic acid. RESULTS: Side-effects were observed in 110/555 patients (20%) on sulphasalazine and in 18/275 patients (6.5%) on 5-aminosalicylic acid during a median period of follow-up of 7 and 5 years, respectively. Desensitisation was achieved in 40% of patients intolerant to sulphasalazine. 5-aminosalicylic acid intake induced side-effects in 2/130 patients (1.5%) who had not taken sulphasalazine before versus 4/91 patients (4%) tolerating sulphasalazine and 12/54 patients (22%) intolerant/allergic to sulphasalazine, the difference in incidence of side-effects in the two latter groups being statistically significant (4.4% vs 20.8%, p=0. 001). Fertility was found to be affected in all patients on sulphasalazine but improved when put onto 5-aminosalicylic acid. CONCLUSIONS: 5-aminosalicylic acid should be considered the drug of choice in the treatment of ulcerative colitis bearing in mind that intolerance or allergy may occur in a few patients also on this drug.
[Drug-Disease]: 5-aminosalicylic acid - ulcerative colitis
[Title]: Amisulpride: efficacy in the management of chronic patients with predominant negative symptoms of schizophrenia.
[Abstract]: Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses substantial efficacy in chronic schizophrenic patients with enduring predominant negative symptoms. This unique property has been demonstrated in a series of short (6 weeks) and medium-/long-term (6-12 months) double-blind placebo-controlled studies. The patients in these studies were carefully selected and assessed to avoid confounding results with non-specific changes in other symptom domains. The results not only show effects on negative symptoms at the optimal dose of 100 mg/day, but also significant improvement in global functioning. The effect observed in short-term studies was maintained over longer treatment periods (6-12 months). Amisulpride was well tolerated with a safety profile similar to placebo. These results open a new therapeutic approach for negative symptoms, one of the most disabling aspects of schizophrenia.
[Drug-Disease]: Amisulpride - schizophrenia
[Title]: Divalproex as a calmative adjunct for aggressive schizophrenic patients.
[Abstract]: BACKGROUND: Selection of appropriate pharmacotherapy for psychotic patients who exhibit dangerousness is an important issue. Divalproex is a fast-acting agent which appears to be safe and effective in such circumstances. The objective of the following inpatient study was to investigate divalproex as a pharmaceutical adjunct in treating agitated and/or violent, psychotic schizophrenic subjects. METHODS: For the purpose of comparison, 147 hospitalized patients were separated into violent (n = 60) and non-violent (n = 87) groups. In addition to antipsychotic drugs given to all subjects, divalproex was preferentially prescribed for the more dangerous patients (n = 40). The clinical status of demographics and parameters related to dangerousness in all participants was assessed to document differences during these admissions and for rehospitalization over one year. RESULTS: Divalproex was well tolerated; however, one individual developed a transient granulocytopenia. Its use in agitated and/or violent psychotic persons appears to have included a calmer, less dangerous hospital course, like that observed among their less disruptive counterparts. CONCLUSIONS: Divalproex seemed to have been helpful in this study at facilitating a more routine hospital course for agitated psychotic patients, similar to that of less overtly disturbed individuals. No significant adverse events were observed. The validity of this study is limited by its retrospective, uncontrolled nature.
[Drug-Disease]: Divalproex - violent psychotic
[Title]: [Usefulness of olanzapine in the levodopa-induced psychosis in patients with Parkinson's disease].
[Abstract]: BACKGROUND: To evaluate the antipsychotic efficacy of olanzapine (OLZ) in patients with Parkinson's disease (PD) and drug-induced psychosis (DIP) and its repercussion on the motor function. METHODS: Ten patients (5 women and 5 men) diagnosed of PD and DIP, aged 67 years (range: 50-81), with PD duration of 11.1 years (range: 6-23), treated chronically with levodopa per day, received a dose of 2.5 or 5.0 mg OLZ daily. Data concerning improvement of psychosis and worsening of motor function was based on Positive And Negative Symptoms Scale (PANSS) and Unified Parkinsons Disease Rating Scale (UPDRS) motor. RESULTS: Psychotic symptoms were improved in all patients. In most of them the improvement was almost total. Seven patients increased levodopa dose on OLZ, but significant worsening of motor function was reported just in one patient. None of the patients had agranulocytosis in the blood monitoring. Two patients presented weight gain. Seven patients improved their cognitive status. CONCLUSIONS: We conclude that OLZ at the doses studied may have efficacy for DIP which appears in PD and does not induce worsening of motor function in most of the patients.
[Drug-Disease]: OLZ - Psychotic symptoms
[Title]: Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies--CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study.
[Abstract]: BACKGROUND: Despite the available evidence from randomized clinical trials, beta-blockers are often not used optimally in patients with congestive heart failure (CHF). This meta-analysis aims at providing a precise and quantitative estimate of the benefit and risks of long-term bisoprolol on major clinical events in patients with CHF, both overall and in selected subgroups. This may help clinicians in their decisions as to whether to prescribe bisoprolol for their individual patients. METHODS: Meta-analysis was performed of results from the 2 randomized, controlled clinical studies in which bisoprolol was compared with placebo (Cardiac Insufficiency Bisoprolol Study [CIBIS and CIBIS II]), which included 3288 patients with proven CHF. The main outcomes were total death, cardiovascular death, sudden death, hospitalization for heart failure, and myocardial infarction. RESULTS: A highly significant 29.3% relative reduction of death (17%, 40%; P =.00003) was observed, as well as significant risk reduction in cardiovascular death and sudden death in favor of bisoprolol. Also, a highly significant relative reduction of 18.4% (25%, 11%; P =.00001) in hospital admission or death was observed. A similar relative reduction of death was consistently observed in selected subgroups of patients. CONCLUSIONS: Bisoprolol prevents major cardiovascular events in patients with CHF with a high benefit-to-risk ratio and can be recommended for these patients.
[Drug-Disease]: Bisoprolol - CHF
[Title]: Levodopa-induced dyskinesias and continuous subcutaneous infusions of apomorphine: results of a two-year, prospective follow-up.
[Abstract]: Twelve patients with levodopa-induced dyskinesias were treated with continuous subcutaneous apomorphine. A markedly significant reduction in peak dose dyskinesias occurred over a two-year follow-up.
[Drug-Disease]: apomorphine - dyskinesias
[Title]: From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis.
[Abstract]: The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.
[Drug-Disease]: Ramipril - myocardial infarction
[Title]: From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis.
[Abstract]: The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.
[Drug-Disease]: Ramipril - atherosclerosis
[Title]: Tolerability of statin-fibrate and statin-niacin combination therapy in dyslipidemic patients at high risk for cardiovascular events.
[Abstract]: Achieving recommended cholesterol and triglyceride targets for the prevention of cardiovascular events is difficult and frequently requires the use of &gt;1 lipid-lowering medication. This study evaluated the tolerability and effectiveness of combination regimens in high-risk dyslipidemic patients resistant to monotherapy. A retrospective chart review of all patients referred to a cardiovascular risk reduction clinic over a 7.5-year period identified 136 patients who received combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30) regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued combination therapy: 11 (8.1%) experienced myalgia with or without elevated creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine kinase elevation. No patient had combination therapy discontinued due to elevated liver enzymes. Medications were stopped in 8 patients for reasons other than reported adverse effects or biochemical abnormalities, and 5 patients were switched to alternate monotherapy. Mean percent change from baseline to treatment with combination therapy for total cholesterol (-35%), low-density lipoprotein cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (-62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%) were all statistically significant (p &lt;0.01). These results demonstrate that combination statin-fibrate and statin-niacin regimens are safe and effective in managing dyslipidemias in most patients at risk for cardiovascular events who are inadequately treated with one of these agents alone.
[Drug-Disease]: niacin - dyslipidemias