B1tta/Drug-ACE huggingface dataset:
[Title]: Combination of trastuzumab and vinorelbine in metastatic breast cancer.
[Abstract]: BACKGROUND: Since the clinical introduction of trastuzumab (Herceptin) for metastatic breast cancers that overexpress human epidermal growth factor receptor 2 (HER2), this anticancer agent has played an important role in breast cancer treatment. We examined the effects of trastuzumab and vinorelbine (Navelbine) as a second- or third-line therapy in 24 patients whose HER2-positive tumors did not respond to or relapsed after administration of trastuzumab alone or in combination with taxane. METHODS: Trastuzumab was administered at 2 mg/kg (loading dose 4 mg/kg) once weekly and vinorelbine at 25 mg/m(2) once weekly. The median treatment duration was 118.5 days (range, 22-351 days). RESULTS: The response rate was 42% (95% confidence interval (CI): 22%-63%). The adverse events of NCI-CTC grade 3 or above consisted of neutropenia in three patients; other adverse events, including vasculitis, generalized fatigue, anemia and thrombocytopenia, were grade 1 or 2. All adverse events were reversible after treatment withdrawal and were easily manageable. CONCLUSION: A combination of trastuzumab and vinorelbine can be safely administered on an outpatient basis, and is useful in the treatment of patients with HER2-overexpressing metastatic breast cancer.
[Drug-Disease]: vinorelbine - breast cancer
[Title]: XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.
[Abstract]: OBJECTIVE: It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND METHODS: In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS: Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].
[Drug-Disease]: orlistat - obese
[Title]: [Propofol-LCT versus propofol-MCT/LCT with or without lidocaine - a comparison on pain on injection].
[Abstract]: OBJECTIVE: A disadvantage of Propofol (commercial preparation containing long-chain triglycerides; Propofol-LCT) is pain on injection, which is reported by 54 - 100 % of the patients. Many different approaches have been used in an attempt to decrease the pain on injection of propofol. The currently most efficacious treatment is lidocaine given intravenously with a tourniquet prior to Propofol injection. In previous studies, larger concentrations of free propofol in the aqueous phase of an emulsion were associated with more pain on injection. A new formulation of propofol (a mixture of long-chain and medium-chain triglycerides in the carrier emulsion; Propofol-MCT/LCT) reduces the incidence of pain on bolus injection. This study was designed to investigate, whether the use of Propofol-MCT/LCT alleviates pain on injection to a similar degree as pretreatment with lidocaine. METHODS: Eighty patients (ASA I - III) were randomly assigned to four groups according to a double-blinded protocol, to receive either lidocaine 2 % or normal saline given iv. with a 60 seconds tourniquet time before the injection of Propofol-LCT or Propofol-MCT/LCT. (group 1: 2 ml NaCl 0,9 %, Propofol-LCT; group 2: 2 ml NaCl 0,9 %, Propofol-MCT/LCT; group 3: 2 ml lidocaine 2 %, Propofol-LCT; group 4: 2 ml lidocaine 2 %, Propofol-MCT/LCT). Assessment of pain on injection was performed after 30 % of the induction dose was given. RESULTS: Pain on injection caused by Propofol-LCT with pre-treatment of lidocaine and Propofol-MCT/LCT alone is shown to be equivalent. Comparison of Propofol-MCT/LCT with pre-treatment of lidocaine and Propofol-LCT alone shows a statistical noticeable p-value of 0.035. Propofol-MCT/LCT with pre-treatment of lidocaine suggests a tendency of causing less pain compared to Propofol-MCT/LCT. Analysis of the postoperative questionnaire supplies no significant difference. CONCLUSION: The results suggest that pain on injection is reduced equivalent using either Propofol-MCT/LCT alone or Propofol-LCT with pre-treatment of lidocaine. Pre-treatment with lidocaine before Propofol-MCT/LCT seems to have an additional effect.
[Drug-Disease]: lidocaine - pain
[Title]: Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.
[Abstract]: OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP &gt; or =95 mmHg and &lt; or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P&lt;0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P&lt;0.05 vs baseline and P&lt;0.01 vs enalapril) and the word list recall score (+18.7%; P&lt;0.05 vs baseline and P&lt;0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.
[Drug-Disease]: valsartan - hypertensive
[Title]: Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.
[Abstract]: OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP &gt; or =95 mmHg and &lt; or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P&lt;0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P&lt;0.05 vs baseline and P&lt;0.01 vs enalapril) and the word list recall score (+18.7%; P&lt;0.05 vs baseline and P&lt;0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.
[Drug-Disease]: valsartan - episodic memory
[Title]: Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.
[Abstract]: OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP &gt; or =95 mmHg and &lt; or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P&lt;0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P&lt;0.05 vs baseline and P&lt;0.01 vs enalapril) and the word list recall score (+18.7%; P&lt;0.05 vs baseline and P&lt;0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.
[Drug-Disease]: enalapril - hypertensive
[Title]: Monitoring methotrexate-induced hepatic fibrosis in patients with psoriasis: are serial liver biopsies justified?
[Abstract]: BACKGROUND: Reports that up to 26% of subjects with psoriasis develop cirrhosis have led to a recommendation of serial liver biopsies after each cumulative dose of 1500 mg of methotrexate. AIM: To evaluate the progression of liver injury in patients with psoriasis and the impact of monitoring by liver biopsy on their management. METHODS: One hundred and twenty-one liver biopsies from 66 subjects (aged 11-79 years) with psoriasis, receiving a median cumulative dose of 3206 mg of methotrexate over a period of 280.5 weeks, were evaluated. RESULTS: The assessment of advanced fibrosis according to the Ishak system (&gt;or= 4) correlated perfectly with that of the Scheuer system (&gt;or= 3) and poorly with that of the Roenigk scale (&gt;or= 3b) (r2 = 1.0 and 0.31, respectively). Two of 24 pre-treatment biopsies showed advanced fibrosis and both subjects were heavy drinkers. The cumulative probabilities of advanced fibrosis (Ishak &gt;or= 4) were 0%, 2.6%, 2.6%, 8.2% and 8.2% at cumulative doses of 1500, 3000, 4500, 5000 and 6000 mg, respectively. None of the subjects developed cirrhosis during follow-up or discontinued therapy on the basis of liver biopsy findings. CONCLUSIONS: Advanced hepatic fibrosis with low-dose methotrexate therapy is much less frequent than previously reported. Pre-treatment or monitoring liver biopsies in accordance with the current guidelines have little impact on patient management.
[Drug-Disease]: methotrexate - psoriasis
[Title]: Treatment of cochlear tinnitus with transtympanic infusion of 4% lidocaine into the tympanic cavity.
[Abstract]: Tinnitus is an otological symptom that is encountered often, yet its treatment is difficult. If tinnitus is of cochlear origin, a reasonable assumption is that a total depression of the cochlear function will abolish cochlear tinnitus. To achieve this depression, transtympanic infusion of a local anesthetic (4% lidocaine) to anesthetize the inner ear was conducted in a patient suffering from tinnitus. Transtympanic infusion of 4% lidocaine was performed as a treatment for cochlear tinnitus, and its efficacy was investigated. The overall efficacy rate for the 292 patients with 369 affected ears was 81%. In the investigation of the treatment results in cases of different underlying ear diseases, the efficacy rate was high for tinnitus accompanying sudden deafness and labyrinthine vertigo. However, vestibular symptoms, such as vertigo and nausea, developed after lidocaine infusion. No permanent side effects were noted. Lidocaine infusion is thought to be a useful treatment option for tinnitus and should be considered before surgical treatment. Inner ear anesthesia into the tympanic cavity has been carried out in patients who had cochlear tinnitus and in whom conservative methods of therapy, such as oral medication, had proved unsuccessful. This treatment method is useful as a local therapy for cochlear tinnitus.
[Drug-Disease]: Lidocaine - tinnitus
[Title]: Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity.
[Abstract]: AIMS: Prophylactic administration of N-acetylcysteine (NAC) (600mg orally twice daily), along with hydration, prevents contrast agent-associated nephrotoxicity (CAN) induced by a low dose of non-ionic, low-osmolality contrast dye. We tested whether a double dose of NAC is more effective to prevent CAN. METHODS AND RESULTS: Two-hundred-twenty-four consecutive patients with chronic renal insufficiency (creatinine level &gt; or =1.5mg/dl and/or creatinine clearance &lt;60ml/min), referred to our institution for coronary and/or peripheral procedures, were randomly assigned to receive 0.45% saline intravenously and NAC at the standard dose (600mg orally twice daily; SD Group; n=110) or at a double dose (1200mg orally twice daily; DD Group; n=114) before and after a non-ionic, low-osmolality contrast dye administration. Increase of at least 0.5mg/dl of the creatinine concentration 48h after the procedure occurred in 12/109 patients (11%) in the SD Group and 4/114 patients (3.5%) in the DD Group (P=0.038; OR=0.29; 95% CI=0.09-0.94). In the subgroup with low (&lt;140ml, or contrast ratio &lt;=1) contrast dose, no significant difference in renal function deterioration occurred between the 2 groups. In the subgroup with high (&gt; or =140ml, or contrast ratio &gt;1) contrast dose, the event was significantly more frequent in the SD Group. Conclusions Double dose of NAC seems to be more effective than the standard dose in preventing CAN, especially with high volumes of non-ionic, low-osmolality contrast agent.
[Drug-Disease]: NAC - nephrotoxicity
[Title]: Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.
[Abstract]: PURPOSE: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. EXPERIMENTAL DESIGN: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. RESULTS: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P &lt; 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016). CONCLUSIONS: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.
[Drug-Disease]: gemcitabine - NSCLC
[Title]: Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.
[Abstract]: PURPOSE: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. EXPERIMENTAL DESIGN: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. RESULTS: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P &lt; 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016). CONCLUSIONS: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.
[Drug-Disease]: cisplatin - NSCLC
[Title]: Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.
[Abstract]: BACKGROUND: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. METHODS: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. RESULTS: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p&lt;0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p&lt;0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. CONCLUSIONS: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.
[Drug-Disease]: ribavirin - SARS