Objective To establish a high performance liquid chromatography (HPLC) method for determining phenytoin concentration in epilepsy patients' plasma,and compare this method with chemiluminescence microparticle immunoassay (CMIA),and to evaluate the consistency of the two methods.Methods HPLC and CMIA methods were applied to determine the plasma concentration of phenytoin in 60 epileptic patients,respectively.The difference of results was analyzed by two-side paired t-test,and then the correlation and consistency of the two methods were investigated with Passing-Bablok regression and Bland-Altman method.Results There was no significant difference between the results of the two methods (P ＞0.05).The regression equation of the determination results by HPLC (Y) and CMIA (X) was Y=0.992 9X +0.143 7 (R2 =0.992 6,n =60),which indicated the correlation of the two methods was good.Bland-Altman analysis showed that the consistency of the two methods for determining was good.Conclusion HPLC and CMIA method in monitoring plasma concentration of phenytoin have good correlation and consistency.Both methods can be used for therapeutic drug monitoring of phenytoin.

Objective To detect changes of regional grey matter and white matter volume in patients of neuromyelitis optica (NMO) by voxel-based morphometry (VBM),and investigate its relationship with clinical variables.Methods Conventional magnetic resonance imaging (MRI) and structural threedimensional MRI were obtained from 20 NMO and 20 sex-and age-matched healthy volunteers.The comparison of grey matter and white matter volume between the two groups was analyzed by VBM tools of statistical parametric mapping (SPM) 5.Pearson correlational analysis was used to assess correlations between regional volume decrease and disease duration and expanded disability status scale (EDSS) scores in NMO patients.Results Compared with normal controls,NMO patients had grey matter atrophy in several cortical regions,such as right inferior frontal gyrus (cluster size 514),left superior temporal gyrus (282),right middle temporal gyvus (229) and right insula (211) (t =3.58-5.11,AlphaSim corrected,P ＜0.05).White matter atrophy was found in several subcortical regions in NMO patients,such as right precentral and postcentral gyrus (cluster size 457,110),left middle frontal gyrus (285),and right inferior parietal lobule (231) (t =2.90-4.25,AlphaSim corrected,P ＜ 0.05).Grey matter and white matter volume loss were not significantly correlated with clinical duration or EDSS score in NMO.Conclusion By means of VBM,regional atrophy of grey matter and white matter is found in NMO patients,which may provide evidence for brain structural abnormality in NMO.

Altitude ; Heart Rate ; Humans ; Oxygen ; Oxygen Consumption

Animals ; Brain-Derived Neurotrophic Factor ; Depression/drug therapy* ; Fluoxetine ; Mice ; Stress, Psychological ; Transcranial Magnetic Stimulation

Adolescent ; Altitude ; Brain ; drug effects ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Tablets

OBJECTIVETo investigate the effects of simple hypobaric hypoxia on parameters of hematology and blood rheology in order to establish a rat model of simulated high altitude polycythemia (HAPC) for the study of pathophysiologic mechanisms and medical prevention and treatment of HAPC.

METHODSForty-eight male Wistar rats were randomly divided into three normal control groups and three hypoxia model groups. Normal control group rats were bred in normoxia conditions, and hypoxia group rats were subjected to hypoxic exposure for 8 hours per day at simulated 5 500 m high altitude in a hypobaric chamber. After hypoxic exposure for 2, 4, 12 weeks, one group of normal control and hypoxia model rats were killed and blood was collected, respectively. Then parameters of erythrocyte and blood rheology were examined.

RESULTSMucous membrane of hypoxia model rats showed obviously cyanosis after 2 weeks hypoxic exposure. Hemoglobin concentration of hypoxia model rats were beyond 210 g/L after 2 weeks, 4 weeks and 12 weeks hypoxia exposure and significantly increased than that of normal control rats respectively. Besides, RBC counts, hematocrit, whole blood viscosity, erythrocyte aggregation index of hypoxia model rats were all notably higher than those of normal control rats respectively.

CONCLUSIONA rat model of high altitude polycythemia can be rapidly established by hypobaric hypoxia exposure at simulated 5 500 m high altitude for 8 hours daily.

Altitude ; Altitude Sickness ; Animals ; Disease Models, Animal ; Erythrocyte Count ; Hematocrit ; Hypoxia ; Male ; Polycythemia ; pathology ; Rats ; Rats, Wistar

China ; epidemiology ; Drug Resistance, Bacterial ; Dysentery, Bacillary ; epidemiology ; microbiology ; Humans ; Serotyping ; Shigella ; classification ; drug effects ; isolation & purification

BACKGROUND AND OBJECTIVEThe effect of gefitinib on advanced non-small cell lung cancer (NSCLC) was various. How to choose the sensitive patients and improve the effect was difficulty in clinic. This study was to assess the correlation of epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression with the effect of gefitinib on Chinese patients with advanced NSCLC.

METHODSFrom May 2002 to February 2005, a total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen were treated with gefitinib 250 mg once a day. The mutations in the exons 18-24 of EGFR gene were detected in the tumor tissues from 106 patients before the treatment of gefitinib, and HER2/3 expression in 84 tumor samples were detected by immunohistochemistry.

RESULTSMutation was identified in 32 (30.2%) tumor tissues. Overall remission rate was significantly higher in the HER2 high expression patients than in the HER2 low expression patients (36.8% vs 17.4%, P=0.044). HER2 and HER3 expression levels were not associated with time to progression (TTP) and overall survival (OS). The patients with HER2/3 single high expression had relatively longer TTP and OS than those with HER2/3 single low expression (6.1 vs 9.1 months, P=0.725; 6.1 vs 9.0 months, P=0.862), while those with concomitant HER2/3 high expression had significant longer TTP and OS. EGFR-mutated patients with HER2 expression or high HER2 and HER3 expressions were more sensitive to gefitinib.

CONCLUSIONEGFR mutations combined with HER2/3 expressions is a significant predictor for gefitinib efficacy on Chinese patients with advanced NSCLC.

Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; metabolism ; pathology ; Exons ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Remission Induction ; Survival Rate

OBJECTIVETo investigate the correlation between mutation in EGFR tyrosine kinase domain and tumor response as well as prognosis in advanced stage non-small cell lung cancer (NSCLC) treated with iressa.

METHODSFrom May 2002 to Feb. 2005, iressa was orally administered at a dose of 250 mg once daily for 106 advanced stage NSCLC patients until occurrence of disease progression or intolerable toxicity. Cancer tissue was obtained from these patients, and DNA was extracted for analysis of mutation in exon 18 to 24 of EGFR. Exon 18 to 24 of EGFR were amplified by nest PCR, sequenced and analyzed from both sense and antisence directions.

RESULTSPrimary NSCLC tissue specimens consisted of 25 frozen tissue blocks and 81 paraffin-embedded tumor tissue blocks from 106 consecutive NSCLC patients. Mutation was found to be more frequent in the adenocarcinoma than in the squamous cell carcinoma (35.9% vs 14.3%, P =0.033). Mutation was identified in 32 patients (30.2%). Response rate to iressa was 71.9% in the patients with EGFR mutation versus 13.5% in those without mutation (P <0.01). Compared with the patients without EGFR mutation, those with mutation had longer overall survival (median, 13.45 vs. 5.25 months; P<0.01) and median time to progression (median, 8.35 vs. 3.0 months; P <0.01).

CONCLUSIONEGFR mutation may be positively correlated with the response and survival in advanced stage Chinese NSCLC patient treated with iressa.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Exons ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Point Mutation ; Prognosis ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Sequence Deletion

Objective To investigate the effect of maternal infant separation stress on depression-like behavior in mother mice and further explore the underlying mechanism.Methods C57BL/6 mice were randomly divided into normal control group and model group,each group had ten mouse.Mice in model group were suffered with maternal infant separation stress (MISS) after delivery,namely,the pups were taken away from the mother mice for 3 hours per day for consecutive 14 days.While mice in normal control group did not conduct MISS.Depression-like behavior was evaluated by sugar consumption test and forced swimming test.The 5-hydroxytryptamine (5-HT) content in the brain tissue was determinate by HPLC-MS technology,and tryptophan hydroxylase expression in brain was detected by Western-blot.Results At 7 and 14 days after MISS,the percentage of sugar consumption in model group were (55.8 ± 15.7) ％ and (52.6 ± 10.5) ％,respectively;it significantly reduced compared to that of the normal control group (73.7±8.2)％ and (73.3 ± 11.7)％).And the immobility time of forced swim test in model group were significantly prolonged compared to that of the normal control group,it indicating that MISS can induced depression-like behavior in mother mice.The 5-HT content in cortex,hippocampus,and frontal lobe of model group were (4.68 ± 0.95),(8.12 ± 0.98),(6.46 ±0.72)ng ·mg-1,respectively;it markedly reduced when compared to that of the normal group.And the expression of tryptophan hydroxylasein cortex,hippocampus,and frontal lobe of model group were 0.86 ± 0.02,0.69 ± 0.02 and 0.87 ± 0.03,respectively;it also significantly lower compared to that of the normal group;it indicating that MISS can decrease 5-HT content and tryptophan hydroxylase expression in the brain tissue of mother mice.Compared with normal control group and model group,the above factors had significantly (P ＜ 0.01,P ＜ 0.001).Conclusion MISS can induce classical symptoms of depression in mother mice accompanied with decreased 5-HT synthesis and reduced 5-HT content in the brain tissue of stressed mice.