Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Child ; Dasatinib ; Female ; Humans ; Male ; Molecular Targeted Therapy ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Protein Kinase Inhibitors ; administration & dosage ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; administration & dosage ; adverse effects ; Thiazoles ; administration & dosage ; adverse effects

The paper is aimed to establish a method of residue analysis for thiamethoxam and to study its degradation dynamic and final residue and its standard of safe application of thiamethoxam on Lonicera japonica. Samples extracted with methanol by ultrasonication were purified with dichloromethane by liquid-liquid extraction and SPE column and analysed by HPLC-UV. The results showed that average rate was 84.91%-94.44% and RSD 1.74%-4.96% with addition of thiamethoxam in respectively diverse concentration, which meets inspection requirement of pesticide residue. Two kinds of dosages of thiamethoxam were treated- varying from recommended dosage (90 g x hm(-2)) to high dosage (135 g x hm(-2)), Results of two years test showed that thiamethoxam was degraded more than 90% seven days after application and the half - life period of thiamethoxam was 1.54-1.66 d. The digestion rate of thiamethoxam was fast in the L. japonica. The recommended MRL of thiamethoxam in the L. japonica is 0.1 mg x kg(-1), the dosage of 25% thiamethoxam WDG from 90-135 g x hm(-2) is sprayed less than three times a year on L. japonica and 14 days is proposed for the safety interval of the last pesticide application's and harvest's date.
Agriculture ; methods ; standards ; Chromatography, High Pressure Liquid ; Flowers ; chemistry ; growth & development ; parasitology ; Half-Life ; Insect Control ; methods ; standards ; Insecticides ; adverse effects ; chemistry ; Lonicera ; chemistry ; growth & development ; parasitology ; Neonicotinoids ; Nitro Compounds ; adverse effects ; chemistry ; Oxazines ; adverse effects ; chemistry ; Pesticide Residues ; adverse effects ; chemistry ; Plant Diseases ; parasitology ; prevention & control ; Thiazoles ; adverse effects ; chemistry

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.

METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.

RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.

CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.

REGISTRATION NUMBERChiCTR-TRC-13003776.

Adult ; Blood Glucose ; drug effects ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Metformin ; administration & dosage ; adverse effects ; therapeutic use ; Middle Aged ; Thiazoles ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Adult ; Aged ; Alanine/administration & dosage/adverse effects/*analogs & derivatives ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Anti-Ulcer Agents/*administration & dosage/adverse effects ; Arthritis/drug therapy ; Butanones/adverse effects ; Diclofenac/adverse effects/analogs & derivatives ; Double-Blind Method ; Drug Administration Schedule ; Gastric Mucosa ; Humans ; Middle Aged ; Misoprostol/*administration & dosage/adverse effects ; Quinolones/*administration & dosage/adverse effects ; Stomach Ulcer/chemically induced/*prevention & control ; Thiazines/adverse effects ; Thiazoles/adverse effects ; Treatment Outcome

Dasatinib ; Humans ; Pyrimidines ; adverse effects ; Thiazoles ; adverse effects ; Tumor Lysis Syndrome ; etiology

OBJECTIVETo study the clinical features and prognosis of pulmonary arterial hypertension associated with dasatinib.

METHODSTo present a case of pulmonary arterial hypertension (PAH) associated with long-term exposure to dasatinib and review the related literatures.

RESULTSA 23-year-old female with chronic myelogenous leukemia was treated with dasatinib at a dosage of 140 mg/d after failure of imatinib treatment and achieved complete cytogenetic response. The patient was presented with exertional dyspnea after 35 months of administration with dasatinib. The electrocardiogram showed right ventricular hypertrophy and right axis deviation; transthoracic Doppler echocardiography documented a reduction in diameters of left heart chambers with normal systolic left ventricular function, right heart chambers and pulmonary trunk dilatation, an estimated pulmonary arterial pressure of 114 mmHg; Computed tomography showed thickened pulmonary artery. PAH related to dasatinib was diagnosed and dasatinib was permanently discontinued. The symptom of dyspnea disappeared quickly after withdrawal of dasatinib. The heart structure and pulmonary arterial pressure completely recovered after 7 months of dasatinib discontinuation.

CONCLUSIONPAH is a rare adverse effect of dasatinib treatment. Echocardiograhpy, as a non-invasive screening test for PAH, should be performed before starting dasatinib treatment and repeated during the administration with dasatinib. Dasatinib should be withdrawn permanently in patients with PAH.

Dasatinib ; Female ; Humans ; Hypertension, Pulmonary ; chemically induced ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Prognosis ; Pyrimidines ; adverse effects ; Thiazoles ; adverse effects ; Young Adult

OBJECTIVETo compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP).

METHODS37 CML-CP patients were randomized to receive dasatinib 100 mg orally daily or imatinib 400 mg orally daily. The efficacy and safety data were collected and compared.

RESULTSOf 37 CML-CP patients, 18 received dasatinib and 19 received imatinib. The both of median duration of drug therapy and follow-up were 38 months. (1) The rate of complete cytogenetic response (CCyR) at 12 months was higher in dasatinib group than in imatinib group (89% vs 68%), but there was no significantly statistic significance between two groups (P = 0.232). The cumulative CCyR rate by 36 months was 89% in both arms. The major molecular response (MMR) at 18 months was 76% in dasatinib arm, being significantly higher than that in imatinib arm (37%) (P = 0.017). The cumulative MMR rate by 36 months was 82% versus 68% in dasatinib or imatinib (P = 0.694). The median time to CCyR and MMR was significantly faster for dasatinib than for imatinib (3 months vs. 6 months, and 14 months vs. 34 months, respectively). (2) The drug-related adverse events were mostly grade 1/2 and were well-tolerated. Increase of serum glutamic pyruvic transaminase, pleural effusion and thrombocytopenia were more common in dasatinib arm, while hypophosphatemia, edema and neutropenia were more common in imatinib arm.

CONCLUSIONDasatinib is an effective and safe therapy option and can be used as first-line therapy for newly diagnosed CML-CP patients.

Adult ; Aged ; Benzamides ; adverse effects ; therapeutic use ; Dasatinib ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Male ; Middle Aged ; Piperazines ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Survival Rate ; Thiazoles ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Aged ; Aged, 80 and over ; Drug Therapy, Combination/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee/*drug therapy ; Pain Measurement ; Thiazines/administration & dosage/adverse effects/*therapeutic use ; Thiazoles/administration & dosage/adverse effects/*therapeutic use ; gamma-Aminobutyric Acid/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use

OBJECTIVE: To investigate the effect of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia. METHODS: A total of 260 schizophrenics were assigned randomly to receive ziprasidone or olanzapine for 6 weeks. The weight was measured at baseline, week 2, 4 and 6. Fasting blood glucose (FBS), fasting insulin, high-density lipoprotein (HDL), total-cholesterol (TC) and triglycerides (TG) were measured at baseline and the end of 6-week treatment. Low-density lipoprotein (LDL) was measured in some patients at baseline and the end of 6-week treatment. Body mass index (BMI) and insulin resistance index (IRI) were counted. RESULTS: A total of 245 patients completed the trial, including 121 ziprasidone patients and 124 olanzapine patients. The average dose was 137.5 mg/d for ziprasidone and 19.5 mg/d for olanzapine. Patients treated with olanzapine had higher weight gain than those treated with ziprasidone [(4.55±3.37) kg vs (-0.83±2.05) kg, P<0.001]. After the treatment, FBS, fasting insulin, HDL, TC, TG, LDL and IRI levels were significantly increased in the olanzapine group (all P values<0.001 ). However, in the ziprasidone group, FBS decreased significantly and HDL and TG levels increased significantly after the 6-week treatment (all P values<0.05). The mean changes of FBS, fasting insulin, TC, TG, LDL and IRI were significantly different in the two groups (all P values<0.001). CONCLUSION Ziprasidone has less glucose and lipid metabolic effect for first-episode schizophrenia patients in short-term treatment. However, olanzapine induces weight gain and dysfunction of glucose and lipid metabolism significantly, which is associated with increased risk of complications. When the doctors choose antipsychotics in the clinic, they should consider the side effects of the medication.
Adolescent ; Adult ; Benzodiazepines ; adverse effects ; therapeutic use ; Blood Glucose ; drug effects ; Female ; Humans ; Lipid Metabolism ; drug effects ; Male ; Middle Aged ; Olanzapine ; Piperazines ; adverse effects ; therapeutic use ; Schizophrenia ; drug therapy ; Thiazoles ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficiency and safety of dasatinib in Chinese patients (pts) with chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated-phase (AP) or blast-phase (BP) who are resistant or intolerant to imatinib (IM).

METHODS119 CML pts received dasatinib 100 mg once daily for pts in CP or 70 mg twice daily for pts in AP/BP. The hematologic/cytogenetic response, progression-free-survival (PFS), overall survival (OS) and adverse effects (AE) of the pts were assessed.

RESULTS59 pts in CP, 25 in AP and 35 in BP received dasatinib treatment. The median duration of dasatinib treatment were 19.32, 20.99 and 3.22 months respectively. Complete hematologic response (CHR), major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were achieved by 91.5%, 50.8% and 42.4% of pts in CP respectively. The median times to achieving MCyR was 12.1 weeks. None of the pts in CP achieved MCyR progressed or died till to last follow-up. CHR and major hematologic response (MaHR) were achieved by 52.0% and 84.0% of pts in AP, respectively. The median time to CHR and MaHR were 16.0 and 12.1 weeks, respectively. 10 pts in AP achieved MCyR and 9 of them were CCyR. The median duration of PFS was 25.7 months for pts in AP. For 35 pts in BP, the rates of CHR and MaHR were 17.1% and 31.4% respectively. Both of the median time to CHR and MaHR were 12.1 weeks and median time of duration of MaHR was 11.2 months. 8 pts in BP achieved MCyR and the median time of duration of MCyR was 13.2 months. The median duration of PFS and OS for the pts in BP were 4.3 and 16.7 months respectively. Grade 3-4 of hematologic AEs related to dasatinib were frequent but manageable by dose interruption/reduction or supportive care. 52.5% and 61.0% of pts in CP experienced grade 3-4 of neutropenia and thrombocytopenia. More than 80% pts in AP/BP occurred grade 3-4 cytopenia. The common non-hematologic AEs related to dasatinib were including grade 1-2 pleural effusion, headache, pneumonia and diarrhea. The frequency of non-hematologic AE was higher in pts with AP/BP than in pts with CP.

CONCLUSIONChinese pts with CML resistant or intolerant to IM treated by dasatinib can achieve relatively sustained hematologic and even cytogenetic remission and are well tolerated.

Adolescent ; Adult ; Aged ; Benzamides ; adverse effects ; pharmacology ; Dasatinib ; Drug Resistance, Neoplasm ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Middle Aged ; Piperazines ; adverse effects ; pharmacology ; Pyrimidines ; adverse effects ; pharmacology ; therapeutic use ; Thiazoles ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult