B1tta/Drug-ACE huggingface dataset:
[Title]: Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer.
[Abstract]: A phase I study of S-1 and biweekly docetaxel (DOC) combination therapy was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic parameters. Fourteen patients with advanced or recurrent gastric cancer were analyzed. The treatment consisted of S-1 [body surface area (BSA) &lt;1.25 m2:80 mg/day, 1.25&lt;or= BSA &lt;1.50 m2: 100 mg/day, 1.50 m2&lt;or= BSA; 120 mg/day, orally, day 1-14) and DOC (30-40 mg/m2/day, intravenously, day 1 and 15], which were repeated as often as possible every four weeks. Pharmacokinetic analysis was done at DOC 40 mg/m2/day. Initially, patients were administered S-1 and 40 mg/m2/day of DOC, and DOC 40 mg/m2/day was considered as MTD. In detail, one patient developed neutropenia (grade 4, G4), and two other patients had no day 15 DOC administration because of neutropenia (grade 3, G3). When S-1 and 35 mg/m2/day of DOC were administered to three patients, no adverse reactions were noted. In six patients treated with S-1 and 30 mg/m2/day of DOC, one patient developed neutropenia (G4), and another patient developed diarrhea (G3) and anorexia (G3). The rest of this cohort showed no adverse reactions. Although 5-fluorouracil and gimeracil concentrations remained high under impaired renal function, no pharmacokinetic interactions appeared between S-1 and DOC under normal renal function. The dose limiting toxicity of a combination of S-1 and biweekly DOC was leukopenia and neutropenia. The recommended dose for this combination in phase II study is DOC 35 mg/m2/day.
[Drug-Disease]: DOC - neutropenia
[Title]: Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer.
[Abstract]: A phase I study of S-1 and biweekly docetaxel (DOC) combination therapy was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic parameters. Fourteen patients with advanced or recurrent gastric cancer were analyzed. The treatment consisted of S-1 [body surface area (BSA) &lt;1.25 m2:80 mg/day, 1.25&lt;or= BSA &lt;1.50 m2: 100 mg/day, 1.50 m2&lt;or= BSA; 120 mg/day, orally, day 1-14) and DOC (30-40 mg/m2/day, intravenously, day 1 and 15], which were repeated as often as possible every four weeks. Pharmacokinetic analysis was done at DOC 40 mg/m2/day. Initially, patients were administered S-1 and 40 mg/m2/day of DOC, and DOC 40 mg/m2/day was considered as MTD. In detail, one patient developed neutropenia (grade 4, G4), and two other patients had no day 15 DOC administration because of neutropenia (grade 3, G3). When S-1 and 35 mg/m2/day of DOC were administered to three patients, no adverse reactions were noted. In six patients treated with S-1 and 30 mg/m2/day of DOC, one patient developed neutropenia (G4), and another patient developed diarrhea (G3) and anorexia (G3). The rest of this cohort showed no adverse reactions. Although 5-fluorouracil and gimeracil concentrations remained high under impaired renal function, no pharmacokinetic interactions appeared between S-1 and DOC under normal renal function. The dose limiting toxicity of a combination of S-1 and biweekly DOC was leukopenia and neutropenia. The recommended dose for this combination in phase II study is DOC 35 mg/m2/day.
[Drug-Disease]: DOC - gastric cancer
[Title]: A novel mixture of propofol, alfentanil, and lidocaine for regional block with monitored anesthesia care in ophthalmic surgery.
[Abstract]: STUDY OBJECTIVE: The purpose of this study is to determine the efficacy and safety of sedation/analgesia using a mixture of propofol, alfentanil, and lidocaine. DESIGN: A retrospective case review was undertaken. SETTING: This study took place at a university medical center. PATIENTS: Eighty-nine American Society of Anesthesiologists physical status 1, 2, and 3 adult patients undergoing ophthalmic surgery with regional block and monitored anesthesia care were studied. INTERVENTION: Six milliliters of propofol, 2 mL of alfentanil, and 2 mL of 2% lidocaine (6-2-2 mixture) were freshly mixed. The bolus dose was determined based on the patients' age: 5 microg/kg of alfentanil (and 0.3 mg/kg of propofol) for patients older than 75 years; the dose increased 1 mug/kg per 10-year decrease in age; and up to 9 microg/kg of alfentanil (0.54 mg/kg of propofol) for patients younger than 45 years. Regional block was performed at 1 minute after bolus completion. Blood pressure (BP), Sa(O2), electrocardiogram, capnography, clinical signs of sedation, responses to block, need for airway support, nausea and vomiting (N/V), pain due to propofol infusion, recall, and patient and surgeon satisfaction were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy-eight percent of patients achieved analgesia and sedation without adverse response to the block. Twelve percent achieved good analgesia and sedation with only eyebrow movement upon needle insertion. Twenty-seven percent had respiratory depression but were able to follow commands and maintain adequate ventilation. Two percent had brief apnea alleviated by chin lift or jaw thrust. None had pain because of propofol infusion or N/V. Before sedation, average systolic BP was significantly increased (P &lt; 0.0001) compared with baseline. After sedation and block, systolic BP decreased 6% from baseline (P &lt; 0.005). CONCLUSION: Adjusted for age and weight, the dose of the 6-2-2 mixture met the sedation requirements for most patients. With a low incidence of need for airway support, no pain during infusion, and no N/V, this novel mixture of propofol, alfentanil, and lidocaine provided adequate analgesia and sedation as well as hemodynamic stability for ophthalmic surgery under regional block.
[Drug-Disease]: lidocaine - pain
[Title]: A novel mixture of propofol, alfentanil, and lidocaine for regional block with monitored anesthesia care in ophthalmic surgery.
[Abstract]: STUDY OBJECTIVE: The purpose of this study is to determine the efficacy and safety of sedation/analgesia using a mixture of propofol, alfentanil, and lidocaine. DESIGN: A retrospective case review was undertaken. SETTING: This study took place at a university medical center. PATIENTS: Eighty-nine American Society of Anesthesiologists physical status 1, 2, and 3 adult patients undergoing ophthalmic surgery with regional block and monitored anesthesia care were studied. INTERVENTION: Six milliliters of propofol, 2 mL of alfentanil, and 2 mL of 2% lidocaine (6-2-2 mixture) were freshly mixed. The bolus dose was determined based on the patients' age: 5 microg/kg of alfentanil (and 0.3 mg/kg of propofol) for patients older than 75 years; the dose increased 1 mug/kg per 10-year decrease in age; and up to 9 microg/kg of alfentanil (0.54 mg/kg of propofol) for patients younger than 45 years. Regional block was performed at 1 minute after bolus completion. Blood pressure (BP), Sa(O2), electrocardiogram, capnography, clinical signs of sedation, responses to block, need for airway support, nausea and vomiting (N/V), pain due to propofol infusion, recall, and patient and surgeon satisfaction were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy-eight percent of patients achieved analgesia and sedation without adverse response to the block. Twelve percent achieved good analgesia and sedation with only eyebrow movement upon needle insertion. Twenty-seven percent had respiratory depression but were able to follow commands and maintain adequate ventilation. Two percent had brief apnea alleviated by chin lift or jaw thrust. None had pain because of propofol infusion or N/V. Before sedation, average systolic BP was significantly increased (P &lt; 0.0001) compared with baseline. After sedation and block, systolic BP decreased 6% from baseline (P &lt; 0.005). CONCLUSION: Adjusted for age and weight, the dose of the 6-2-2 mixture met the sedation requirements for most patients. With a low incidence of need for airway support, no pain during infusion, and no N/V, this novel mixture of propofol, alfentanil, and lidocaine provided adequate analgesia and sedation as well as hemodynamic stability for ophthalmic surgery under regional block.
[Drug-Disease]: alfentanil - pain
[Title]: T-889C IL-1alpha promoter polymorphism influences the response to oral cyclophosphamide in scleroderma patients with alveolitis.
[Abstract]: Cyclophosphamide (CYC) is the cornerstone of the treatment of systemic sclerosis (SSc)-associated fibrosing alveolitis (FAS). Despite treatment with CYC, in a not negligible proportion of SSc-FAS patients, deterioration in lung function can be observed. Interleukin-1 (IL-1) cluster gene single nucleotide polymorphisms (SNPs) were implicated in the pathogenesis of some interstitial lung diseases and may favor the progression of restrictive lung disease in SSc. The present retrospective case-control study was conducted on 18 SSc patients previously treated with oral CYC (2 mg/kg) and medium-dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day) for the presence of FAS-defined as the presence of areas of ground-glass attenuation on high-resolution computed tomography (HRCT) and a recent deterioration in lung function. The T/C substitution at position -889 of the IL-1alpha promoter gene (T-889C) was determined by polymerase chain reaction and restriction length fragment analysis. Patients carrying the T allele showed a significant decrease in forced vital capacity (FVC) values after 12 months of therapy (2.46+/-1.09 vs 2.59+/-1.17 l), while wild-type patients showed an increase in FVC values (2.73+/-0.54 vs 2.54+/-0.5 l) (p=0.005 between the two groups, analysis of variance for repeated measures). Patients with the T-889C polymorphism presented higher baseline erythrocyte sedimentation rates (ESR) compared to wild-type patients (50.3+/-25.4 vs 23.3+/-17.7 mm/h). Baseline ESR inversely correlated with the variation of FVC (DeltaFVC) after 12 months of therapy (r=-0.50 and p&lt;0.05). The two groups were otherwise similar with respect to autoantibodies, age, disease duration, disease subset, radiological HRCT grade, and baseline lung physiology. The T-889C polymorphism represents a marker for worse functional responses to CYC in SSc-FAS. The mechanisms by which this SNP may negatively influence the response to CYC therapy are unknown, but might be linked to increased inflammatory responses in the lungs.
[Drug-Disease]: CYC - alveolitis
[Title]: T-889C IL-1alpha promoter polymorphism influences the response to oral cyclophosphamide in scleroderma patients with alveolitis.
[Abstract]: Cyclophosphamide (CYC) is the cornerstone of the treatment of systemic sclerosis (SSc)-associated fibrosing alveolitis (FAS). Despite treatment with CYC, in a not negligible proportion of SSc-FAS patients, deterioration in lung function can be observed. Interleukin-1 (IL-1) cluster gene single nucleotide polymorphisms (SNPs) were implicated in the pathogenesis of some interstitial lung diseases and may favor the progression of restrictive lung disease in SSc. The present retrospective case-control study was conducted on 18 SSc patients previously treated with oral CYC (2 mg/kg) and medium-dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day) for the presence of FAS-defined as the presence of areas of ground-glass attenuation on high-resolution computed tomography (HRCT) and a recent deterioration in lung function. The T/C substitution at position -889 of the IL-1alpha promoter gene (T-889C) was determined by polymerase chain reaction and restriction length fragment analysis. Patients carrying the T allele showed a significant decrease in forced vital capacity (FVC) values after 12 months of therapy (2.46+/-1.09 vs 2.59+/-1.17 l), while wild-type patients showed an increase in FVC values (2.73+/-0.54 vs 2.54+/-0.5 l) (p=0.005 between the two groups, analysis of variance for repeated measures). Patients with the T-889C polymorphism presented higher baseline erythrocyte sedimentation rates (ESR) compared to wild-type patients (50.3+/-25.4 vs 23.3+/-17.7 mm/h). Baseline ESR inversely correlated with the variation of FVC (DeltaFVC) after 12 months of therapy (r=-0.50 and p&lt;0.05). The two groups were otherwise similar with respect to autoantibodies, age, disease duration, disease subset, radiological HRCT grade, and baseline lung physiology. The T-889C polymorphism represents a marker for worse functional responses to CYC in SSc-FAS. The mechanisms by which this SNP may negatively influence the response to CYC therapy are unknown, but might be linked to increased inflammatory responses in the lungs.
[Drug-Disease]: CYC - systemic sclerosis
[Title]: Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.
[Abstract]: BACKGROUND: The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. METHODS: Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. RESULTS: Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p &lt; .0001). Prolactin levels were also significantly increased at 6 months (32.4 +/- 17.8 ng/ml; N = 43, p &lt; .0001) and at 22 months (N = 30, 25.3 +/- 15.6 ng/ml, p &lt; .0001). Prolactin levels were not associated with adverse effects and DRD2 alleles (Taq1A, -141C Ins/Del, C957T) did not significantly influence baseline levels or risperidone-induced increases in prolactin. CONCLUSIONS: Risperidone treatment was associated with two- to four-fold mean increases in serum prolactin in children with autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.
[Drug-Disease]: risperidone - autism
[Title]: Iron fortification reduces blood lead levels in children in Bangalore, India.
[Abstract]: OBJECTIVE: Chronic lead poisoning and iron deficiency are concentrated in urban children from lower socioeconomic strata, and both impair neurocognitive development. Our study objective was to determine if iron fortification reduces blood lead levels in urban, lead-exposed, iron-deficient children in Bangalore, India. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, controlled school-based feeding trial was done in 5- to 13-year-old iron-deficient children (n = 186). At baseline, a high prevalence of lead poisoning was found in the younger children. Subsequently, all 5- to 9-year-old children participating in the trial (n = 134) were followed to determine if iron fortification would affect their blood lead levels. INTERVENTION: Children were dewormed and fed 6 days/week for 16 weeks either an iron-fortified rice meal (approximately 15 mg of iron per day as ferric pyrophosphate) or an identical control meal without added iron. Feeding was directly supervised and compliance monitored. OUTCOME MEASURES: Hemoglobin, serum ferritin, C-reactive protein, transferrin receptor, zinc protoporphyrin, and blood lead concentrations were measured. RESULTS: The prevalence of iron deficiency was significantly reduced in the iron group (from 70% to 28%) compared with the control group (76% to 55%). There was a significant decrease in median blood lead concentration in the iron group compared with the control group. The prevalence of blood lead levels &gt; or =10 microg/dL was significantly reduced in the iron group (from 65% to 29%) compared with the control group (68% to 55%). CONCLUSIONS: Our findings suggest providing iron in a fortified food to lead-exposed children may reduce chronic lead intoxication. Iron fortification may be an effective and sustainable strategy to accompany environmental lead abatement.
[Drug-Disease]: ferric pyrophosphate - lead poisoning
[Title]: Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.
[Abstract]: BACKGROUND: The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established. METHODS: We randomly assigned 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to 60 mg of raloxifene daily or placebo and followed them for a median of 5.6 years. The two primary outcomes were coronary events (i.e., death from coronary causes, myocardial infarction, or hospitalization for an acute coronary syndrome) and invasive breast cancer. RESULTS: As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor-positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000). CONCLUSIONS: Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. (ClinicalTrials.gov number, NCT00190593 [ClinicalTrials.gov].).
[Drug-Disease]: raloxifene - invasive breast cancer
[Title]: An open prospective study of zonisamide in acute bipolar depression.
[Abstract]: OBJECTIVE: To examine the effectiveness and safety of zonisamide in the treatment of acute bipolar depression. METHODS: An open-label, prospective, nonrandomized, 8-week study conducted in bipolar outpatients (type I, type II, or not otherwise specified) with depressive symptoms. No patient was manic or mixed at study entry. Previous treatments were continued unchanged, but no new treatments were allowed. Montgomery Asberg Depression Rating Scale and the Mania Rating Scale from the Schedule of Affective Disorders and Schizophrenia-Change Version were used. RESULTS: Twenty patients (10 men, 10 women) with bipolar disorder (17 type I, 2 type II, 1 NOS), aged 38.1 +/- 8.81 years, received zonisamide at mean dose of 222.5 +/- 85.1 mg/d. Mean Montgomery Asberg Depression Rating Scale scores improved significantly from baseline to endpoint (mean difference = -8.4, 95% confidence interval [4.1, 12.6], P = 0.001). Ten patients (50%) terminated early due to adverse effects, mostly side effects including nausea/vomiting, cognitive impairment, and sedation. One patient experienced increased suicidal ideation, and one patient experienced hypomania. CONCLUSIONS: This study suggests improvement of depressive symptoms in this sample with 8 weeks of open-label zonisamide treatment.
[Drug-Disease]: zonisamide - hypomania
[Title]: An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism.
[Abstract]: Long-term effectiveness of controlled-release melatonin in 25 children, aged 2.6-9.6 years with autism without other coexistent pathologies was evaluated openly. Sleep patterns were studied using Children's Sleep Habits Questionnaire (CSHQ) and sleep diaries at baseline, after 1-3-6 months melatonin treatment and 1 month after discontinuation. Sleep diary and CSHQ showed a more problematic sleep in autistic children compared with controls. During treatment sleep patterns of all children improved. After discontinuation 16 children returned to pre-treatment score, readministration of melatonin was again effective. Treatment gains were maintained at 12 and 24-month follow-ups. No adverse side effects were reported. In conclusion, controlled-release melatonin may provide an effective and well-tolerated treatment for autistic children with chronic sleep disorders.
[Drug-Disease]: melatonin - sleep disorders
[Title]: The safety and tolerability of quinapril.
[Abstract]: Quinapril, a new angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action, has been extensively studied in patients with hypertension and congestive heart failure (CHF) during a worldwide clinical development program. A comprehensive safety data base was established to allow appropriate analyses of the extensive patient safety data. The safety of quinapril has been evaluated in 2,697 patients with hypertension and CHF, including 451 elderly patients (greater than or equal to 65 years), and has been compared with safety data from a total of 1,058 patients receiving a comparative therapy. A comparison of the double-blind studies demonstrated that quinapril has a lower incidence of adverse events and/or withdrawals than reported for captopril or enalapril. An analysis of the onset of adverse events did not show either an increase with time on quinapril therapy or a dose relationship. The proportion of patients who experienced orthostatic hypotension or hypotension was less than that of patients who were treated with captopril or enalapril. An analysis of all events (from both double-blind and long-term, open-label studies) showed no increase in the incidence of events reported in patients with CHF compared with hypertensive patients. When the data for all studies were combined, an age analysis showed no increase in the total reporting of adverse events in elderly patients compared with the younger patients studied. The incidence of adverse events was lower in those patients not receiving concomitant diuretic therapy. An overall analysis of clinical laboratory data indicated that quinapril did not have significant adverse effects on clinical laboratory parameters when compared with captopril, enalapril, or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
[Drug-Disease]: quinapril - CHF