AIM: To investigate the effect of L-phenyla lanine on vascular remodeling in hypertensive rats. METHODS: Vascular remodeling was measured by laser scanning conf ocal microscopy (LSCM) in mesenteric resistance arteries isolated from spontaneo usly hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. The effect of L-phenylalanine on the hypertensive vascular remodeling was observed. The thi rd most distal first-order branches of mesenteric resistance arteries from SHR a nd WKY were studied. The arteries were fixed under pressure. The segments were s tained with the nuclear dye propidium iodide. The diameter, wall thickness and o rientation angle of smooth muscle cells were measured with LSCM. RESULTS: Compared with WKY, SHR arteries showed: (1) smaller lum en, (2) increased wall thickness, (3) disorganized orientation angle of smooth m uscle cells. L-phenylalanine treatment induced specific changes in the lumen, wa ll thickness and the orientation angle of smooth muscle cells. CONCLUSIONS: Hypertension induces vascular remodeling of the bra nches of mesenteric arteries from SHR. L-phenylalanine inhibits the vascular rem odeling process of hypertension.

Objective To analyze the epidemiologieal characteristics of the pre-hospital care cases in Shanghai in the year 2007. Method Based the demographic records in the year 2007, the cases which from the database of Shanghai pre-hospital care center with full items were analyzed. Chi-square test and exact probabilities were used to compete the consfituent ratio; and the method of circular distribution was used to calculate the peak time, date and month. Results There were 86 815 patients with pre-hospital care well documented from the ur-ban districts of Shanghai. The ratio of male to female was 3.89: 1. The senile patients accounted for 84.95% of all the pre-hospital care ones. The major causes of disease in patients with pre-hospital care were trauma, eere-brovascular disease,cardiac diseases, coma, high fever, tumor emergency, acute abodomen emergency,OB/GYN emergency and upper G1 tract bleeding in turn. During the daytime, the occurrence of those emergency patients with pre-hospital care usually peaked at 2:15 o' clock with the high frequency in the period of 5:45 to 17:45 o' clock.The top nine diseases had their own peak time and high frequency period, respectively. Within a year, no peak date occurrence of patients with prehospital care, in tolal, was found. Howerer, the occurrence of patients with high fever, acute abdomen and upper GI bleeding had specific peak dates within a year, respectively. Conclusioes The pre-hospital care eases in the urban of Shanghai have own epidemiologieal characteristics. Perfect the construc-tion of pre-hospital emergency care system, improving the professional training, and thereby meeting the require-ments are factors in the fundamental guarantee of improving the rescue full success rate of severe patients.

Objective:To establish an LC-MS/MS and HPLC assay for the determination of linezolid in human plasma to be used for the therapeutic drug monitoring ( TDM) and pharmacokinetic study. Methods:Acetontrile containing furazolidone ( internal stand-ard) as the protein precipitation agent was added to100 μl human plasma, and then vibrated and centrifuged for the precipitation of plasma protein. ① The supernatant was eluted on an Eclipse XDB-C18 (100mm × 2. 1mm,3. 5μm) column with acetontrile and water (80 :20) as the mobile phase at the flow rate of 0. 3 ml·min-1. The electrospray ionization (ESI) source was applied and operated in the positive ion mode. The multiple reaction monitoring (MRM) modes with the transition of m/z338. 1→296. 2 (linezolid) and m/z226.1→122.0 (furazolidone) were used for the quantification. ② The supernatant was eluted on an Eclipse Eclipse XDB -C18(250 mm × 4. 6 mm, 5μm) column with acetontrile and 0. 1% formic acid (20 :80) as the mobile phase at the flow rate of 1. 0 ml·min-1 and detected at 254 nm. The established assays were used for the determination of linezolid in the plasma samples after the administra-tion. Results:Linezolid was linear within the range of 0. 05-30 μg·ml-1 for LC-MS/MS, and 0. 25-30 μg·ml-1 for HPLC ( r2 >0. 999). The extraction recovery and the matrix effect respectively was 82. 1%-91. 3% and 74. 0%-82. 3%. The relative recovery of LC-MS/MS and HPLC was 91. 2%-106. 4% and 100. 1%-111. 6%, respectively. The intra-and inter-day RSDs were both lower than 20%. There was a good correlation between LC-MS/MS and HPLC. The trough concentration of 12 patients was (1. 77 ± 1. 23) g· ml-1 and the plasma concentration of 5 patients 2h after linezolid adminstration was (13. 36 ± 2. 63) g·ml-1 , respectively. Conclu-sion:The established assays are simple, rapid, specific, sensitive and accurate, which are suitable for the TDM and pharmacokinetic study of linezolid.

Objective:To establish an LC-MS/MS and HPLC assay for the determination of linezolid in human plasma to be used for the therapeutic drug monitoring ( TDM) and pharmacokinetic study. Methods:Acetontrile containing furazolidone ( internal stand-ard) as the protein precipitation agent was added to100 μl human plasma, and then vibrated and centrifuged for the precipitation of plasma protein. ① The supernatant was eluted on an Eclipse XDB-C18 (100mm × 2. 1mm,3. 5μm) column with acetontrile and water (80 :20) as the mobile phase at the flow rate of 0. 3 ml·min-1. The electrospray ionization (ESI) source was applied and operated in the positive ion mode. The multiple reaction monitoring (MRM) modes with the transition of m/z338. 1→296. 2 (linezolid) and m/z226.1→122.0 (furazolidone) were used for the quantification. ② The supernatant was eluted on an Eclipse Eclipse XDB -C18(250 mm × 4. 6 mm, 5μm) column with acetontrile and 0. 1% formic acid (20 :80) as the mobile phase at the flow rate of 1. 0 ml·min-1 and detected at 254 nm. The established assays were used for the determination of linezolid in the plasma samples after the administra-tion. Results:Linezolid was linear within the range of 0. 05-30 μg·ml-1 for LC-MS/MS, and 0. 25-30 μg·ml-1 for HPLC ( r2 >0. 999). The extraction recovery and the matrix effect respectively was 82. 1%-91. 3% and 74. 0%-82. 3%. The relative recovery of LC-MS/MS and HPLC was 91. 2%-106. 4% and 100. 1%-111. 6%, respectively. The intra-and inter-day RSDs were both lower than 20%. There was a good correlation between LC-MS/MS and HPLC. The trough concentration of 12 patients was (1. 77 ± 1. 23) g· ml-1 and the plasma concentration of 5 patients 2h after linezolid adminstration was (13. 36 ± 2. 63) g·ml-1 , respectively. Conclu-sion:The established assays are simple, rapid, specific, sensitive and accurate, which are suitable for the TDM and pharmacokinetic study of linezolid.

Objective:To explore the clinical value of procalcitonin (PCT) in predicting mortality of patients with acute biliary pancreatitis (ABP).Methods:The clinical data of 196 ABP patients admitted in the emergency department of Ruijin Hospital Affiliated to Shanghai Jiaotong University Medical College from January 2013 to June 2017 were analyzed retrospectively. The enrolled patients were divided into survival group ( n=176) and death group ( n=20) according to clinical outcome, and their clinical characteristics, laboratory results(including WBC, CRP, PCT), APACHEⅡ score, BISAP score, modified Marshall score, SOFA score and CTSI at admission were compared between two groups. The ROC curve and AUC were used to evaluate the effectiveness of PCT and multiple scoring systems in predicting mortality in ABP patients, and the Delong test was used to compare the predictive efficacy of various methods at 1-2 d, 3-4 d, and 5-7 d days after onset. Results:The PCT level, APACHEⅡ score, BISAP score, modified Marshall score, SOFA score, and CTSI of patients in the death group were significantly higher than those in the survival group [6.98(3.12, 13.64) μg/L vs 0.55(0.17, 1.74) μg/L, 12.00(6.00, 18.75) vs 6.00(3.00, 9.00), 3.20±1.47 vs 1.59±1.05, 2.85±0.37 vs 1.96±0.64, 5.50(4.00, 9.50) vs 2.00(1.00, 4.25), 5.05±2.33 vs 3.39±1.74], and all the differences were statistically significant (all P values <0.05). The AUC of PCT for predicting death was 0.881 (95% CI 0.820-0.938)and the cut-off value was 2.44. The predictive value of PCT was similar to that of the modified Marshall score, BISAP score and SOFA score, but higher than that of APACHEⅡ score and CTSI (all P values <0.05). The predictive AUC of PCT at 3-4 days after onset was higher than that of modified Marshall score, BISAP score and SOFA score, and were significantly higher than those at 1-2 days after onset. Conclusions:PCT can be used to predict the mortality of ABP within 7 days of onset. The predictive value of PCT was comparable to the modified Marshall score, BISAP score and SOFA score, and the best predictive time was 3-4 days after onset.

Objective To assess the predictive effect of myocardial injury biomarkers (proBNP, CK-MB, and cTnI) on the severity of acute pancreatitis (AP). Methods The records of 246 patients diagnosed with acute pancreatitis who were treated at Ruijin Hospital Emergency Department from January 2015 to December 2016 were retrospectively analyzed. According to the revised 2012 Atlanta guidelines, these patients were divided into the mild acute pancreatitis (MAP, n=47), moderately severe acute pancreatitis (MSAP, n=151) and severe acute pancreatitis (SAP, n=48) groups. The highest plasma levels of troponin I (cTnI), creatine kinase (CK)-MB, N-terminal B-type brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and procalcitonin (PCT) were recorded for comparison within 72 h after admission. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) score, sequential organ failure assessment (SOFA), bedside index for severity in acute pancreatitis (BISAP) and Balthazar computed tomography severity index (CTSI) were calculated at admission within 72 h. Whether there is an occurrence of organ dysfunction, and the organ types and persist time of organ dysfunction were recorded. The analysis of variance, SNK-q test and paired samples t test were used for the statistical analysis. Results The levels of proBNP, CK-MB, and cTnI were significantly higher in the SAP group than in the non-SAP group. The receiver operating characteristic (ROC) curve demonstrated cTnI had the maximum predictive power (AUC=0.872), while proBNP had the least predictive ability (AUC=0.763). The established model, which is to explore whether the myocardial injury markers had the predictive value, showed that the combination of myocardial injury indicators (CK-MB, cTnI) and traditional indicators had higher predictive value for SAP than traditional indicators alone (AUC=0.966 vs. AUC=0.945, P=0.04). Conclusions The elevated markers of myocardial injury had certain predictive value for severe acute pancreatitis.

OBJECTIVE: To investigate the effectiveness and safety of clinical pharmacists-directed vancomycin dosing and therapeutic drug monitoring (TDM), and to promote the individualized medication of vancomycin. METHODS: Information of hospitalized patients treated by vancomycin admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to October 2017 was collected retrospectively during study period, the patients were divided into pharmacists intervention and non-pharmacists intervention groups according to pharmacist-directed vancomycin dosing guideline or not. The individualized dosing regimen of vancomycin for the patients in pharmacists intervention group was guided by clinical pharmacists, this guideline was that pharmacists offered the TDM guidance, made the individualized dosage regimen of vancomycin, etc., which based on the patients' pathophysiology, condition, and the adjustments of increased dose or 24-hour continuous infusion vancomycin were made for patients if the steady-state trough concentrations fell below the target level. Vancomycin dosage was made for patients in the non-pharmacists intervention group by physicians only based on vancomycin instructions or clinical experience. The vancomycin dosing, TDM, microorganism culture, renal function, 30-day mortality rate, and length of hospital stay were recorded. The appropriateness of TDM for vancomycin was defined as a blood collection within 1 hour of the next scheduled dose after steady state achieved. The rationality of the initial dosing regimen was determined based on the vancomycin application guidelines issued by Infectious Diseases Society of America (IDSA) in 2009. RESULTS: A total of 258 patients were enrolled, and there were 158 patients in the non-pharmacists intervention group and 100 in pharmacists intervention group. The appropriateness of TDM for vancomycin in pharmacists intervention group was significantly improved as compared with that in non-pharmacists intervention group [87.0% (87/100) vs. 69.6% (110/158), P < 0.01], the percentage of first trough serum concentrations drawn on day 3 after steady state achieved was significantly increased [51.0% (51/100) vs. 37.3% (53/142), P < 0.05]. Compared with the non-pharmacists intervention group, the percentages of patients who received appropriate initial dosing and attained the initial target therapeutic range in pharmacists intervention group were significantly increased [87.4% (76/87) vs. 68.2% (75/110), 51.7% (45/87) vs. 30.9% (34/110), both P < 0.01], the percentage of patients whose vancomycin dosing regimen was adjusted based on TDM results was also significantly increased [54.0% (47/87) vs. 15.5% (17/110), P < 0.01], the rate of vancomycin serum concentrations reaching the standard was increased [70.1% (61/87) vs. 32.7% (36/110), P < 0.01], and a lower number of patients in sub- or supra-therapeutic range was observed in pharmacists intervention group [27.6% (24/87) vs. 46.4% (51/110), 2.3% (2/87) vs. 20.9% (23/110), both P < 0.01]. In addition, a lower incidence of vancomycin-induced acute kidney injury (AKI) was observed in pharmacists intervention group as compared with that in non-pharmacists intervention group [0 (0/87) vs. 6.4% (7/110), P < 0.01]. No significant difference was observed in the microorganism culture, 30-day mortality rate or length of hospital stay between the two groups. Among the 87 patients in pharmacists intervention group, the vancomycin dosing was adjusted for 42 patients who did not attain the target therapeutic range, increasing the dose of vancomycin was made for 22 patients, 24-hour continuous infusion was made for 20 patients. Compared with the only increasing vancomycin dose group, vancomycin continuous infusion for 24 hours could significantly increase the serum trough concentration (mg/L: 18.0±6.7 vs. 12.5±5.8, P < 0.05), and reduce daily dosage (mg/kg: 27.1±7.1 vs. 36.6±9.2, P < 0.01). CONCLUSIONS The implementation of a pharmacist-directed vancomycin dosing guideline based on TDM optimized vancomycin dosing regimen, improved the accuracy and timeliness of TDM for vancomycin, achieved a higher percentage of levels within the therapeutic range, and a lower incidence of vancomycin-induced AKI.
Anti-Bacterial Agents ; China ; Drug Monitoring ; Humans ; Pharmacists ; Retrospective Studies ; Vancomycin/administration & dosage*

Objective: To investigate the effectiveness and safety of clinical pharmacists-directed vancomycin dosing and therapeutic drug monitoring (TDM), and to promote the individualized medication of vancomycin. Methods: Information of hospitalized patients treated by vancomycin admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to October 2017 was collected retrospectively during study period, the patients were divided into pharmacists intervention and non-pharmacists intervention groups according to pharmacist-directed vancomycin dosing guideline or not. The individualized dosing regimen of vancomycin for the patients in pharmacists intervention group was guided by clinical pharmacists, this guideline was that pharmacists offered the TDM guidance, made the individualized dosage regimen of vancomycin, etc., which based on the patients' pathophysiology, condition, and the adjustments of increased dose or 24-hour continuous infusion vancomycin were made for patients if the steady-state trough concentrations fell below the target level. Vancomycin dosage was made for patients in the non-pharmacists intervention group by physicians only based on vancomycin instructions or clinical experience. The vancomycin dosing, TDM, microorganism culture, renal function, 30-day mortality rate, and length of hospital stay were recorded. The appropriateness of TDM for vancomycin was defined as a blood collection within 1 hour of the next scheduled dose after steady state achieved. The rationality of the initial dosing regimen was determined based on the vancomycin application guidelines issued by Infectious Diseases Society of America (IDSA) in 2009. Results: A total of 258 patients were enrolled, and there were 158 patients in the non-pharmacists intervention group and 100 in pharmacists intervention group. The appropriateness of TDM for vancomycin in pharmacists intervention group was significantly improved as compared with that in non-pharmacists intervention group [87.0% (87/100) vs. 69.6% (110/158), P < 0.01], the percentage of first trough serum concentrations drawn on day 3 after steady state achieved was significantly increased [51.0% (51/100) vs. 37.3% (53/142), P < 0.05]. Compared with the non-pharmacists intervention group, the percentages of patients who received appropriate initial dosing and attained the initial target therapeutic range in pharmacists intervention group were significantly increased [87.4% (76/87) vs. 68.2% (75/110), 51.7% (45/87) vs. 30.9% (34/110), both P < 0.01], the percentage of patients whose vancomycin dosing regimen was adjusted based on TDM results was also significantly increased [54.0% (47/87) vs. 15.5% (17/110), P < 0.01], the rate of vancomycin serum concentrations reaching the standard was increased [70.1% (61/87) vs. 32.7% (36/110), P < 0.01], and a lower number of patients in sub- or supra-therapeutic range was observed in pharmacists intervention group [27.6% (24/87) vs. 46.4% (51/110), 2.3% (2/87) vs. 20.9% (23/110), both P < 0.01]. In addition, a lower incidence of vancomycin-induced acute kidney injury (AKI) was observed in pharmacists intervention group as compared with that in non-pharmacists intervention group [0 (0/87) vs. 6.4% (7/110), P < 0.01]. No significant difference was observed in the microorganism culture, 30-day mortality rate or length of hospital stay between the two groups. Among the 87 patients in pharmacists intervention group, the vancomycin dosing was adjusted for 42 patients who did not attain the target therapeutic range, increasing the dose of vancomycin was made for 22 patients, 24-hour continuous infusion was made for 20 patients. Compared with the only increasing vancomycin dose group, vancomycin continuous infusion for 24 hours could significantly increase the serum trough concentration (mg/L: 18.0±6.7 vs. 12.5±5.8, P < 0.05), and reduce daily dosage (mg/kg: 27.1±7.1 vs. 36.6±9.2, P < 0.01). Conclusions The implementation of a pharmacist-directed vancomycin dosing guideline based on TDM optimized vancomycin dosing regimen, improved the accuracy and timeliness of TDM for vancomycin, achieved a higher percentage of levels within the therapeutic range, and a lower incidence of vancomycin-induced AKI.