OBJECTIVETo study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation.

METHODSNinety patients undergoing aortic and mitral valve replacement were randomly divided into 3 equal groups to receive treatment with phentolamine (group A), urapidil (group B), or both (group C) during extracorporeal circulation. The mean arterial pressure (MAP) before and after drug administration, time interval of two administrations, spontaneous recovery of heart beat after aorta unclamping, ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, post-parallel cycle time, dopamine dose after cardiac resuscitation, and perioperative changes of plasma TNF-α and IL-6 levels were recorded.

RESULTSThere was no significant difference in MAP between the 3 groups before or after hypotensive drug administration (P>0.05). The time interval of two hypotensive drug administrations was longer in group C than in groups A and B (P<0.05). The incidence of spontaneous recovery of heart beat after aorta unclamping, incidence of ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, and post-parallel cycle time were all comparable between the 3 groups. The dose of dopamine administered after cardiac resuscitation was significantly larger in group B than in groups A or group C (P<0.05). The plasma levels of TNF-α and IL-6 were significantly increased after CPB and after the operation in all the groups, but were lowed in group C than in groups A and B at the end of CPB and at 2 h and 12 after the operation.

CONCLUSIONSUrapidil combined with phentolamine can control hypertension during extracorporeal circulation without causing hypotension.

Extracorporeal Circulation ; Heart Rate ; Humans ; Hypertension ; prevention & control ; Interleukin-6 ; blood ; Phentolamine ; therapeutic use ; Piperazines ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo analyze the clinical efficacy of imatinib mesylate (IM) for Ph-positive or BCR-ABL positive chronic myeloid leukemia (CML) to couple the trough plasma concentrations (C mins) of IM with clinical responses and adverse events (AEs).

METHODSOne hundred and one CML patients received IM therapy, and Cmins of IM were determined in 30 patients.

RESULTS(1) Cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and negative BCR/ABL fusion gene rates were 96.6%, 86.5%, 77.5% and 47.2%, respectively, in CML-CP patients. In accelerated and blastic phases (AP and BC) patients, CHR, MCyR, CCyR and negative BCR-ABL fusion gene rates were 58.3%, 25.0%, 25.0%, 8.3%, respectively. (2) Mean Cmins of IM was significantly higher in the CCyR at 1 year [(1472 +/- 482) microg/L] group than in the non-CCyR at 1 years group [(1067 +/- 373) microg/L] (P < 0.05), and higher in the MMR at 1 year group than in the non-MMR at 1 years group [(1624 +/- 468) microg/L vs (1137 +/- 404) microg/L, P < 0.05].

CONCLUSIONIM significantly improves cytogenetic and molecular response, event-free survival, and overall survival for patients with Ph-positive CML. The Cmins of IM exerts a significant impact on clinical response (CCyR and MMR at 1 year).

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; blood ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

Benzamides ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Piperazines ; pharmacokinetics ; therapeutic use ; Pyrimidines ; pharmacokinetics ; therapeutic use

OBJECTIVETo observe the efficacy of Gleevec combined with myeloablative allogeneic stem cells transplantation(Allo-SCT) for the treatment of chronic myeloid leukemia (CML).

METHODSNine patients with CML were treated with Gleevec before and after Allo-SCT, with 5 in the chronic phase (CP), 2 in the accelerated phase (AP) and 2 in the blast-crisis phase (BP). The donors were HLA matched identical siblings (n=7) and matched unrelated donors (n=2). The conditioning regimen is BuCy2. Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for the prevention of acute GVHD.

RESULTSAll patients achieved completed hemopoietic remission (HCR) treated with pre-transplant Gleevec. The median period to gain absolute neutrophil count>0.5x10(9)/L was 12 d (8 approximately 26 d) and that for platelet count>20x10(9)/L was 20 d (8 approximately 25 d). Three cases suffered from acute GVHD and 4 from chronic GVHD. All patients achieved completed engraftment and completed molecular remission. The rate of disease free survival was 88.9% after a median follow-up of 31 m (range 7 approximately 34 m).

CONCLUSIONThe treatment of CML consisting of myeloablative Allo-SCT combined with Gleevec before and after transplantation is an effective and safe method for CML.

Adult ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Combined Modality Therapy ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Transplantation Conditioning ; methods ; Treatment Outcome

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

This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib. 27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph(+) ALL) received 100 - 140 mg/d dasatinib orally. Their overall survival and tolerance were evaluated. The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27 imatinib-resistant BCR/ABL positive leukemia cases, with a median follow-up of 54 (3-75) months. After the dasatinib treatment, 88.8% of all the 27 cases achieved complete hematologic response (CHR), 29.6% of them achieved major cytogenetic response (mCyR), 37% of all achieved complete cytogenetic response (CCyR) and 18.5% cases achieved major molecular response (MMR). Patients who received dasatinib in progress of disease (CML-AP, CML-BC and bone marrow relapse Ph(+) ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph(+) ALL) (P = 0.0377), and 3 - 4 grade adverse events occurred more frequently in progress of disease than that in stable disease. Overall survival of the patients who achieved CCyR after dasatinib therapy was statistically longer than those who did not achieve CCyR (63 m vs 9 m, P = 0.0126). The most common grade 3 - 4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%), neutropenia (48.1%), anemia (33.3%), and non-hematologic events such as pleural effusion (18.5%), pulmonary infection (18.5%), pericardial effusion (11.1%). The 3-4 grade adverse events occurred within 12 months from dasatinib therapy, and were mainly observed in patients with progress of disease. It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients, the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.
Adult ; Aged ; Benzamides ; therapeutic use ; Dasatinib ; Drug Resistance, Neoplasm ; Female ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines ; therapeutic use ; Thiazoles ; therapeutic use ; Treatment Outcome ; Young Adult

Imatinib, the first-line treatment in patients with advanced gastrointestinal stromal tumors (GIST), is generally well tolerated, although some patients have difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage by plasma level monitoring may facilitate management of patients who experience intolerable toxicities due to overexposure to the drug. We present two cases of advanced GIST patients in whom we managed imatinib-related toxicities through dose modifications guided by imatinib plasma level monitoring. Imatinib blood level testing may be a promising approach for fine-tuning imatinib dosage for better tolerability and optimal clinical outcomes in patients with advanced GIST.
Aged ; Antineoplastic Agents/blood/*therapeutic use ; Benzamides/blood/*therapeutic use ; Drug Monitoring ; Exons ; Gastrointestinal Neoplasms/*drug therapy/pathology/radiography ; Gastrointestinal Stromal Tumors/*drug therapy/pathology/radiography ; Humans ; Liver Neoplasms/secondary ; Male ; Mutation ; Piperazines/blood/*therapeutic use ; Positron-Emission Tomography ; Proto-Oncogene Proteins c-kit/genetics ; Pyrimidines/blood/*therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo measure the levels of hormones in chronic myelogenous leukemia (CML) patients receiving imatinib mesylate (IM) and evaluate the effects of IM on endocrine system.

METHODS69 patients with CML while taking IM were enrolled and a total of 86 peripheral blood samples were detected. The levels of total triiodothyronine (TT3), total tetraiodothyronine (TT4), thyroid stimulating hormone (TSH), testosterone, progesterone, estradiol (E2), plasma total cortisol (PTC) at 8:00-10:00 am measured. Concentration of hormones in different groups were measured to evaluate the effects of IM on endocrine system and relationships with its administration duration, plasma concentration and clinical symptoms.

RESULTS(1) Of the 7 types of hormones, an elevation of TSH level was found in 14 patients (20.3%), a decrease of TT3 and testosterone in 8 patients (11.6%) and 8 males (18.6%), respectively. (2) A significant decline of TT3 and testosterone was observed in all patients divided by different administration duration. Negative correlation was seen between TT3 level and duration of administration (r=-0.273, P=0.010), which was also found for testosterone (r=-0.302, P=0.025). (3) There was no correlation between serum levels of the seven hormones and concentration of IM.

CONCLUSIONIM affect the levels of thyroid and sex hormones in some patients with clinical manifestations: a decrease of TT3, testosterone and testosterone, an increase of TSH, which have relationship with the duration of administration.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Benzamides ; administration & dosage ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; administration & dosage ; blood ; therapeutic use ; Pyrimidines ; administration & dosage ; blood ; therapeutic use ; Thyrotropin ; blood ; Triiodothyronine ; blood ; Young Adult

OBJECTIVETo investigate the protective effect of L-carnitine (LC) combined with sildenafil on the reproductive endocrine function of male rats with diabetes mellitus (DM).

METHODSA total of 40 male SD rats were randomly divided into five groups, group A taken as normal controls, and groups B, C, D and E made into DM models by injection of streptozotocin at 65 mg/kg. Then the rats in groups A and B were treated with normal saline, C with sildenafil at 5 mg per kg per d, D with LC at 300 mg per kg per d, and E with sildenafil at 5 mg per kg per d plus LC at 300 mg per kg per d, all via gastric gavage for 6 weeks, followed by determination of the levels of testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum of the rats.

RESULTSAfter 6 weeks of treatment, the T, FSH and LH levels were (25.25 +/- 2.67) nmol/L, (5.78 +/- 0.61) IU/L and (625.21 +/- 43.45) ng/L in group A, (9.63 +/- 1.71) nmol/L, (1.98 +/- 0.42) IU/L and (479.89 +/- 27.62) ng/L in group B, (18.98 +/- 3.07) nmol/L, (5.08 +/- 0.33) IU/L and (586.57 +/- 31.72) ng/L in group C, (16.18 +/- 2.65) nmol/L, (4.63 +/- 0.30) IU/L and (540.78 +/- 25.52) ng/L in group D, and (23.65 +/- 2.66) nmol/L, (5.59 +/- 0.48) IU/L and (621.53 +/- 36. 40) ng/L in group E. The three parameters were significantly lower in B than in the other four groups (P < 0.01), and so were they in C and D than in A and E (P < 0.05), but showed no significant differences either between C and D (P > 0. 05) or between A and E (P > 0.05).

CONCLUSIONSix-week medication of either sildenafil or LC alone could increase the levels of T, FSH and LH in the serum of DM rats, but the combination of the two had an even more obvious increasing effect, which indicates a still better protective effect on the reproductive endocrine function of diabetic male rats.

Animals ; Carnitine ; adverse effects ; therapeutic use ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Drug Therapy, Combination ; Follicle Stimulating Hormone ; blood ; Luteinizing Hormone ; blood ; Male ; Piperazines ; administration & dosage ; therapeutic use ; Purines ; administration & dosage ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfones ; administration & dosage ; therapeutic use ; Testosterone ; blood