OBJECTIVE: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. MATERIALS AND METHODS: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. RESULTS: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. CONCLUSION: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*adverse effects/therapeutic use ; Ascites/pathology/radiography ; Benzamides/*adverse effects/therapeutic use ; Echocardiography/methods ; Edema/pathology/radiography ; Female ; Gastrointestinal Stromal Tumors/drug therapy/pathology/*radiography ; Gastrointestinal Tract/pathology/*radiography ; Heart Failure/radiography ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/*adverse effects ; Pericardial Effusion/pathology/radiography ; Peritoneal Neoplasms/diagnosis/radiography/secondary ; Piperazines/*adverse effects/therapeutic use ; Pleural Effusion/pathology/radiography ; Pyrimidines/*adverse effects/therapeutic use ; Radiology ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo observe the clinical efficacy and safety of sildenafil in the treatment of high altitude heart disease associated with severe pulmonary arterial hypertension (PAH) in children.

METHODSFifty children (aged 2 months to 2 years) with high altitude heart disease associated with severe PAH, who were continuously transferred to the Intensive Care Unit between January 2011 and October 2013, were randomly assigned to observation and control groups. The control group was given conventional treatment, while the observation group received oral sildenafil [1 mg/(kg . d)] three times daily for 7-10 days in addition to the conventional treatment. Before and after treatment, hemodynamics, blood gas, routine blood parameters, and blood biochemical parameters were recorded.

RESULTSAfter treatment, the observation group had a significantly higher decrease in mean pulmonary artery pressure and significantly higher increases in arterial partial pressure of oxygen, cardiac output, cardiac index, and oxygenation index compared with the control group (P<0.05). In the observation group, there were no significant changes in mean arterial pressure, routine blood parameters and blood biochemical parameters (P>0.05), and no obvious adverse reactions were found.

CONCLUSIONSFor children with high altitude heart disease associated with severe PAH, sildenafil can effectively reduce pulmonary artery pressure and improve cardiac function and does not cause adverse reactions. This therapy has good safety according to the preliminary evaluation.

Altitude ; Familial Primary Pulmonary Hypertension ; Female ; Heart Diseases ; drug therapy ; Humans ; Hypertension, Pulmonary ; complications ; physiopathology ; Infant ; Male ; Piperazines ; adverse effects ; therapeutic use ; Purines ; adverse effects ; therapeutic use ; Sildenafil Citrate ; Sulfones ; adverse effects ; therapeutic use ; Vasodilator Agents ; adverse effects ; therapeutic use

OBJECTIVETo assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea.

METHODSSeventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group, 35 in each group. All patients received antipsychotic drug therapy. Patients in the treatment group additionally took WP, while those in the control group took aripiprazole (at the daily dose of 5 mg, once daily). The therapeutic course for all was 4 weeks. Prolactin levels and obesity indices[body weight, waist aircumstance, body mass index (BMI) and waist-hit ratio (WHR)] were determined before and after treatment. The efficacy was evaluated.

RESULTSThe treatment course was completed in 95.71% of patients. The total effective rate of the 33 patients of the treatment group was 93.94% (31/33), while it was 91.18% (31/34) in the 34 patients of the control group. There was no difference in the total effective rate between the two groups (P > 0.05). Prolactin levels in both group after treatment were significantly lower than those of the baseline (P < 0.01). There was no significant difference in prolactin levels between the two groups after treatment (P > 0.05). Compared with before treatment, body weight, BMI, waist circumstance, and waist-hip ratio obviously decreased after treatment, showing significant difference when compared with the control group (P < 0.05). There was no significant difference in body weight, BMI, waist circumstance, and waist-hip ratio in the control group between before and after treatment (P > 0.05).

CONCLUSIONSBoth WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea. They showed equivalent efficacy. But WP showed more obvious effect in reducing obesity indices.

Aged ; Amenorrhea ; drug therapy ; Antipsychotic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Aripiprazole ; Body Mass Index ; Body Weight ; Drug Therapy, Combination ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Galactorrhea ; drug therapy ; Humans ; Obesity ; Piperazines ; administration & dosage ; adverse effects ; therapeutic use ; Quinolones ; administration & dosage ; adverse effects ; therapeutic use ; Waist-Hip Ratio

Imatinib has been recognized as the frontline therapy drug in chronic myeloid leukemia (CML), however, only limited patients could achieve complete molecular remission (CMR). Recent clinical and basic proofs indicated an improved treatment outcome by the combination of interferon and Imatinib. This study was purposed to evaluated systematically the efficacy and safety of interferon plus Imatinib in patients with CML. Data from relative clinical trials were from clinical trial of gov and Cochrane Collaboration. A comprehensive literature search was performed from data bases such as pubMed and EM. The results indicated that 7 clinical trials and 12 research papers met the criteria enrolled in study, included 697 cases in total. The combination group had higher complete cytogenetic remission (CCgR) rate than imatinib alone at 6 months (58% vs 42%; P = 0.0001) and 12 months (74% vs 68%; P = 0.004). The major molecular remission (MMR) rate was also higher in the combination group at 6 months (58% vs 34%; P = 0.0001) and 12 months (66% vs 47%; P < 0.0001). Furthermore, compared with single drug, the combination group had superior CMR rate at 6 months (13% vs 2%; P = 0.0002) and 12 months (14% vs 5%; P = 0.0009). The major adverse effects of combination therapy were rash, asthenia, edema and musculoskeletal events, and combination therapy was more prone to inducing neutropenia, thrombocytopenia and mild anemia. It is concluded that compared with Imatinib alone, the combination of interferon and Imatinib has better clinical efficacy in treating CML with earlier cytogenetic and molecular remission. It is also a safe therapy in spite of slightly weaker tolerance than single drug therapy.
Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Benzamides ; administration & dosage ; adverse effects ; Humans ; Imatinib Mesylate ; Interferons ; administration & dosage ; adverse effects ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Piperazines ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Treatment Outcome

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

Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.
Anoxia ; Antihypertensive Agents/adverse effects/*therapeutic use ; Clinical Trials as Topic ; Databases, Factual ; Epoprostenol/adverse effects/analogs & derivatives/therapeutic use ; Humans ; Hypertension, Pulmonary/complications/*drug therapy ; Piperazines/adverse effects/therapeutic use ; Pulmonary Disease, Chronic Obstructive/*etiology ; Purines/adverse effects/therapeutic use ; Questionnaires ; Risk Factors ; Sulfonamides/adverse effects/therapeutic use ; Sulfones/adverse effects/therapeutic use

OBJECTIVETo study the effect and safety of aripiprazole in the treatment of childhood autism.

METHODSThirty-five children (aged from 4 to 16 years) with autism presenting as behavioral disorders were treated with aripiprazole for 8 weeks. They were evaluated according to the Clinical Global Impression (CGI) and the Autism Treatment Evaluation Checklist (ATEC) before treatment and at the end of the 2nd, 4th and 8th weeks of treatment. Adverse reactions were observed.

RESULTSThe CGI showed illness severity decreased from the second week of aripiprazole treatment (P<0.05) and more significantly decreased illness severity was observed at the end of the 8th week (P<0.01). The curative effect score significantly increased at the end of the 8th week (P<0.05). The ATEC total scores were significantly reduced at the end of the 8th week after aripiprazole treatment. Besides the social intercourse ability, great improvements were shown in verbal communication, apperception and behavioural symptoms after aripiprazole treatment (P<0.01). Self-harm, sleep disorders and psychiatric symptoms were greatly improved after treatment and attention deficit, excessive activities, impulse to attack behavior, stereotyped behaviors and irritability were also improved to some extent. No severe adverse effects were found.

CONCLUSIONSAripiprazole is safe and effective for the treatment of childhood autism.

Adolescent ; Antipsychotic Agents ; therapeutic use ; Aripiprazole ; Autistic Disorder ; drug therapy ; Child ; Child, Preschool ; Female ; Humans ; Male ; Piperazines ; adverse effects ; therapeutic use ; Quinolones ; adverse effects ; 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

OBJECTIVETo probe the cause for triggering HBV reactivation and possible management of the chronic hepatitis B individuals received imatinib.

METHODSThis study presented two cases of transient hepatitis B virus (HBV) reactivation and hepatic dysfunction during oral imatinib for chronic myeloid leukemia (CML) and made a literatures review about the pathogenesis, possible prophylactic and therapeutic management of such chronic hepatitis B individuals receiving imatinib.

RESULTSTwo CML patients, without prior liver dysfunction but with chronic HBV infection, suffered from transient HBV reactivation occurred during oral imatinib. Both of them finally obtained good outcome following the additional oral nucleotide antiviral therapy.

CONCLUSIONIt remained unclear whether imatinib induced the reactivation of HBV in patients with a latent HBV infection. From our study, all candidates receiving oral imatinib should be screened for HBsAg and anti-HBc antibodies prior to initiation of imatinib. Prophylactic antiviral therapy should be offered to HBV-infected individuals along with a close monitoring for signs of reactivation.

Adult ; Benzamides ; adverse effects ; therapeutic use ; Hepatitis B ; virology ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; virology ; Male ; Piperazines ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Virus Activation ; drug effects