A phase II trial of Doxorubicin HCl Liposome Injection in patients with advanced pancreatic adenocarcinoma

Summary We conducted a phase II study with doxorubicin encapsulated in a liposomal preparation (Doxorubicin HCl Liposome Injection) at a dose of 75 mg/m² administered as a one hour infusion once every three weeks. Sixteen patients were entered to the trial and 15 are evaluable for response. Hematologic toxicity was significant. The median white blood count was 1.6×10³/μl (range: 0.1–9.5), median absolute neutrophil count 0.6×10³/μl (range: 0–5.8) and median platelet count was 142.0×10³/μl (range: 20–327). Gastrointestinal toxicity was generally mild. Despite two minor responses in liver metastases with a significant decrease in CEA in one of these patients, no major responses were observed, excluding with 95% confidence, a response rate in excess of 20%.     

Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases

This study aimed to describe the occurrence and to evaluate the predictive factors of thrombocytopenia caused by parenteral linezolid in hospitalised patients without haemato‐oncologic diseases. Using electronic medical records, a retrospective safety evaluation was performed among all hospitalised adult patients who received parenteral linezolid therapy between January 2005 and June 2016. Of all identified 264 patients with an average age of 63.4 (SD 15.8) years, thrombocytopenia occurred at a rate of 29.2% after an average of 11.2 (SD 7.4) days of the initiation of linezolid therapy. Significant predictive factors for thrombocytopenia included the duration of linezolid therapy longer than or equal to 7 days (adjusted odds ratios [ORs] 7.25, 19.51 and 28.80; 95% confidence intervals [CIs] 1.92‐27.38, 4.76‐79.95 and 6.48‐127.92 for 7‐13 days, 14‐20 days and ≥21 days, respectively; P < 0.01 for all values), baseline platelet count <150 × 10³/mm³ (adjusted OR, 5.08; 95% CI, 2.06‐12.55; P < 0.001), creatinine clearance <30 mL/min (adjusted OR, 4.19; 95% CI, 1.59‐11.06; P = 0.004) and concurrent low‐dose aspirin therapy (adjusted OR, 2.99; 95% CI, 1.26‐7.08; P = 0.013). Baseline platelet count less than 150 × 10³/mm³ was an independent predictor of early‐onset (≤6 days) thrombocytopenia (adjusted OR, 5.07; 95% CI, 1.46‐17.58; P = 0.011). Closer monitoring of platelet count is required in patients who receive parenteral linezolid therapy for 7 days or more, and have low baseline platelet counts or impaired renal function.     

Octreotide‐Associated Neutropenia

Drug‐induced neutropenia and agranulocytosis are rare adverse events but can be fatal. Neutropenia can be induced by a myriad of drugs from almost every pharmacologic class. Octreotide is a somatostatin analog that has been used to treat variceal bleeding, acromegaly, and severe diarrhea associated with metastatic tumors, and to reduce symptoms in the setting of malignant bowel obstruction and pseudoobstruction. The most common adverse effects associated with octreotide include pain at the injection site and gastrointestinal effects such as loose stools, cramping, and nausea; neutropenia is not currently listed as an adverse effect of the drug. We describe the case of an 87‐year‐old man who developed neutropenia immediately after administration of three doses of subcutaneous octreotide. He presented to the hospital with a history of constipation and straining for 3 days. He was admitted, and laxatives, suppositories, and enemas were administered over the next 3 days to induce a bowel movement; however, they were ineffective. Bowel obstruction secondary to a mass was confirmed by computed tomography; the mass was eventually diagnosed as colon cancer. Octreotide 100 µg subcutaneously every 8 hours was started for the obstruction on the evening of hospital day 4. After the patient had received 3 doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 × 10³/mm³ (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 × 10³/mm³) on admission to 1.6 × 10³/mm³ (neutrophils 62%, ANC 0.99 × 10³/mm³) on day 5. Given the temporal relationship of octreotide and neutropenia as well as the lack of a reasonable alternative cause, it was suspected that octreotide was the most likely culprit of the patient's neutropenia. Octreotide was subsequently discontinued, and his WBC increased to 4.9 × 10³/mm³ (neutrophils 66.3%, ANC 3.2 × 10³/mm³) the next day. The remainder of the patient's hospitalization was not significant for any further hematologic abnormalities. His WBC and ANC (WBC 6.7 × 10³/mm³, neutrophils 83.2%, ANC 5.6 × 10³/mm³) remained stable 30 days after the incident. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient's development of neutropenia and octreotide therapy. To our knowledge, this report highlights the first case of octreotide‐associated neutropenia. Although the frequency of drug‐induced neutropenia remains rare outside of cytotoxic chemotherapy, the importance of recognizing this adverse effect cannot be understated given the mortality risks for neutropenic patients.     

Determination of urea in milk based on N-bromosuccinimide–dichlorofluorescein postchemiluminescence method

A new postchemiluminescence (PCL) reaction was observed when urea was injected into the reaction mixture after the CL reaction of N-bromosuccinimide and dichlorofluorescein. A possible reaction mechanism was proposed based on the studies of the CL kinetic characteristics, CL spectra, fluorescence spectra, and other experiments. A new flow injection CL method for the determination of urea was established based on the PCL reaction. The relative standard deviation for the determination of urea was 1.3% (n = 11, c = 5.0 × 10⁻⁸ g/mL). The CL intensity responded linearly to the concentration of urea in the range 2.0 × 10⁻⁹–1.0 × 10⁻⁶ g/mL (r = 0.9992). The detection limit was 7 × 10⁻¹⁰ g/mL. The method had been applied to the determination of urea in milk with satisfactory results.     

Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa

The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the P_eff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the P_eff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the P_eff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The P_eff of CHS‐IVa in the duodenum was 1.76 × 10^?3 to 2.00 × 10^?3 cm/min. The P_eff of CHS‐IVa in the jejunum was 1.26 × 10^?3 to 1.39 × 10^?3 cm/min. The P_eff of CHS‐IVa in the ileum was 1.25 × 10^?3 to 1.31 × 10^?3 cm/min. The P_eff of CHS‐IVa in the colon was 1.02 × 10^?3 to 1.08 × 10^?3 cm/min. There was no statistical difference of the P_eff in the four segments at different CHS‐IVa concentrations. The P_eff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported P_eff (3.00 × 10^?3 cm/min) in the jejunum. The P_eff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP.     

重组人血小板生成素对化疗所致血小板减少症的预防方案优化研究

目的 探讨重组人血小板生成素（rhTPO）对吉西他滨联合卡铂（GC）或吉西他滨联合顺铂（GP）方案化疗相关血小板减少症（CIT）二级预防的优化方案。方法 2019年3月—2020年6月,在内蒙古自治区人民医院、河南大学肿瘤医院共招募非小细胞肺癌（NSCLC）患者60例,此60例患者行GP/GC方案化疗,前1个化疗周期中血小板计数最低值<50×10⁹·L^-1,且经治疗已恢复正常,60例患者随机分为对照组和试验组,每组各30例,对照组患者在下1个化疗周期第2、4、6、9天预防性给予重组人血小板生成素（rhTPO）,试验组患者在下1个化疗周期第3、4、6天预防性给予rhTPO,监测两组患者的血小板计数变化,并进行对比分析。结果 试验组和对照组3度以上血小板减少症的发生率分别为40%、30%,两组比较差异无统计学意义;试验组血小板最低值为（38±13）×10⁹·L^-1,对照组为（45±17）×10⁹·L^-1,两组对比差异无统计学意义;试验组和对照组化疗后血小板计数低于100×10⁹·L^-1的持续时间分别为（9±3）、（7±4）d,两组比较差异显著（P<0.05）;试验组和对照组化疗后血小板低于50×10⁹·L^-1的持续时间分别为（4±3）、（3±2）d,两组比较差异无统计学意义。预防用药结束后,试验组有14例患者继续给予rhTPO治疗,rhTPO中位使用支数为3支（1～7支）;对照组有13例患者继续给予rhTPO治疗,rhTPO中位使用支数为3支（1～6支）,两组非参数秩和检验,差异无统计学意义。试验组有1例、对照组有2例患者血小板过低或伴有明显出血倾向,给予输注血小板。结论 rhTPO在吉西他滨联合铂类化疗方案的第3、4、6天3 d用药方案相较传统4 d方案,疗效及安全性无明显差异,但能减少患者住院天数,降低治疗费用。     

Monocyte and neutrophil direct counts correlate with C-reactive protein plasma concentration in patients with acute pancreatitis

Acute pancreatitis (AP) is associated with the intensive inflammatory response in white blood cells (WBC) and C-reactive protein (CRP). This paper presents the relationship between the CRP plasma concentration and the direct counts of peripheral WBC in AP during the initial five days. The study consisted of 56 patients with AP, 36 patients with mild form of AP and 20 patients with severe form of AP. ABX VegaRetic hematological analyzer was used to perform the count of blood cells, and the immunonephelometric method was performed to measure the CRP concentration levels. AP patients presented with WBC count values in the range of 3.2 − 22.4 × 10³/μl and CRP concentration levels in the range 3.3 − 599.8 mg/l. The WBC count correlates with CRP levels during the entire observation period. The relationship of CRP and WBC is expressed in the following regression equation: WBC (10³/μl) = 3.66 + 1.40 × log_eCRP (mg/l). The highest median neutrophil count (8.15 × 10³/μl) was observed on the first day. The count decreased to 5.27 × 10³/μl on the fifth day. The most substantial finding in this study involved the values found for the monocytes and CRP (r= 0.53; p<0.001). Day two and day three were the highest (r=0.59, p<0.001). On day two, the regression equation for this relationship is: Monocytes (10³/μl) = −0.34 + 0.21 × log_eCRP(mg/l). The correlation between direct monocyte count and plasma CRP concentration in AP reflect a CRP-dependent stimulation of IL-6 release from activated blood monocytes.     

Determination of doxorubicin in pharmaceutical preparation and rat plasma with luminol-K3Fe(CN)6 chemiluminescence system

A novel and rapid flow injection chemiluminescence (FI-CL) method was established for the determination of doxorubicin, which was based on the phenomenon that CL intensity of the reaction between K₃Fe(CN)₆ and luminol in alkaline solution could be strongly enhanced by doxorubicin. Under optimum conditions, the relative CL intensity of the system was linear with the concentration of doxorubicin in the range from 2.0 × 10^?9 g/mL to 5.0 × 10^?7 g/mL with a correlation coefficient of 0.9993 (n = 9). The detection limit (3σ) was 4.25 × 10^?10 g/mL, and the relative standard deviation (RSD) for 1.0 × 10^?7 g/mL doxorubicin (n = 11) was 0.33%. The method was applied to the determination of doxorubicin in pharmaceutical preparation and rat plasma, and the percentage recovery of doxorubicin in rat plasma was between 89.8% and 102.2%. The possible CL mechanism was also discussed briefly.     

Mechanistic study of absorption and first‐pass metabolism of GL‐V9, a derivative of wogonin

GL‐V9, a derivative of wogonin, has potent anti‐cancer activity. The absorption and metabolism of this compound have not been investigated systematically. This study aims to illustrate the pharmacokinetic characters of GL‐V9 by exploring its metabolic status under different administration routes. To further clarify the absorption mechanism of GL‐V9, an in situ single‐pass perfusion model and a Caco‐2 cell monolayer model were used. Meanwhile, a microsomal incubation system was used to evaluate the enzyme kinetic parameters. In vivo, the obtained gastrointestinal availability (F_a × F_g) was 21.28 ± 5.38%. The unmetabolized fraction in the gut wall (F_{gut wall}) was 98.59 ± 9.74%, while the hepatic bioavailability (F_h) was 29.11 ± 5.22%. These results indicated that poor absorption and extensive metabolism may contribute greatly to the low bioavailability of GL‐V9. The effective permeability (P_eff) in the duodenum and jejunum was 1.34 ± 0.50 × 10^?4 and 0.90 ± 0.27 × 10^?4 cm/s, respectively. The high permeability of GL‐V9 indicated that other unknown factors (such as metabolism) may account for its systemic exposure problem. Studies in rat liver microsomal (RLMs) confirmed this hypothesis, and the Cl_{int, CYP450s and UGT} of GL‐V9 was 0.20 ml/min/mg protein. In conclusion, these results suggest that GL‐V9 possesses higher permeability than wogonin and the metabolism of GL‐V9 is related to its disposition in rat intestine and liver.     

Circadian rhythm of white blood cells during clozapine treatment

Rationale: The atypical antipsychotic clozapine is effective in the treatment of patients with refractory schizophrenia. It carries a well-known risk of neutropenia and agranulocytosis, which necessitates the immediate discontinuation of clozapine. Objective: We report a patient who developed neutropenia on clozapine, but behind the cell count decrease showed to be a diurnal variation of the white blood cells (WBC). Methods: Due to the lack of efficacy of subsequent treatment of conventional and other atypical neuroleptics, treatment with clozapine was restarted after discontinuation. When the morning count of WBC began to fall, WBC count was repeated in the afternoons. Results: Careful blood cell monitoring showed a pronounced diurnal variation of WBC (2.9–4.2×10⁹/l in the morning and 3.6–7.1×10⁹/l in the afternoon) and granulocytes (0.8–1.4×10⁹/l and 2.9–5.5×10⁹/l, respectively). Conclusions: Some patients may thus have a spuriously low cell count and may be unnecessarily denied effective treatment. Received: 10 February 1999 / Final version: 22 March 1999     

Potentiometric monitoring of cobalt in beer sample by solid contact ion selective electrode

A new solid contact cobalt selective electrode was constructed with 4-tert-butylthiacalix[4]arene as ionophore. The best performance was observed with the membrane having an ionophore/polyvinyl chloride/sodium tetraphenylborate/nitrophenyl octyl ether ratio of 3.5:33:1.5:62 (w/w; mg). The electrode, under steady-state conditions, exhibited a working concentration range of 1 × 10⁻¹ – 1 × 10⁻⁶ mol/L with a near-Nernstian slope of 25.3 mV/decade and a detection limit of 3.5 × 10⁻⁷ mol/L. The electrode had a very short response time (<10 seconds) and good reproducibility at a working pH range of 4.0–6.5. The electrode was used for 4 months without any significant change in its sensitivity. The potentiometric performance of the electrode in partially nonaqueous medium [up to 20 % (v/v) alcohol] was found satisfactory. The performance of the prepared electrode for the analysis of beer samples using direct potentiometric method is very encouraging.     

Drug-induced thrombocytopenia: clinical data on 309 cases and the effect of corticosteroid therapy

Objective: To analyse the clinical picture and the course of thrombocytopenia induced by non-cytotoxic drugs, and to evaluate a possible therapeutic effect of corticosteroids. Methods: A retrospective analysis of 309 well-documented cases of drug-induced thrombocytopenia was performed. Data sources were reports from the files of the Danish Committee on Adverse Drug Reactions and discharge summaries. Results: The median length of exposure to the offending drug, before development of thrombocytopenia, was 21 days. The median nadir platelet count was 11 × 10⁹ · l⁻¹, and 74% of the patients had clinical haemorrhage. Bone marrow examination generally showed hyperplastic reactive changes and a variable number of megakaryocytes. Slight leucopenia was present in 6% of the patients and 16% were anaemic. Complete recovery was seen in 87% of cases, with a median recovery rate of 8 days. The standard treatment was corticosteroids, which were administered in 53% of the cases. No difference in recovery between corticosteroid-treated and untreated patients was observed. No other clinical parameter affected the recovery rate. The mortality rate due to haemorrhage was 3.6%. Conclusion: Thrombocytopenia induced by non-cytotoxic drugs is characterised by a heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due to the difficult initial differentiation between the two conditions. Received: 11 October 1996 / Accepted in revised form: 24 December 1996     

A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization

BackgroundRecombinant granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize haematopoietic stem cells. We compared the efficacy and safety of a biosimilar G-CSF (Zarzio^®, Sandoz Biopharmaceuticals) with the originator G-CSF (Neupogen^®, Amgen) in patients with haematological malignancies.MethodsA total of 108 patients were included in this study, 59 of whom were female (49 male), with an overall median age of 51 years (range 19–69). Patients had multiple myeloma (n = 46), non-Hodgkin's lymphoma (n = 28), Hodgkin's lymphoma (n = 26), or other diagnosis (n = 8). After administration of mobilizing regimens (primarily high-dose etoposide, high-dose cyclophosphamide, intermediate-dose Ara-C or ESHAP), patients were randomized to a standard daily 10 μg/kg dose of biosimilar G-CSF (n = 54) or originator G-CSF (n = 54).ResultsMedian duration of G-CSF administration was 8 days with both biosimilar G-CSF (range 4–17) and originator G-CSF (range 4–14). Both groups had a median of one apheresis with a median time until first apheresis of 11 days. There were no statistically significant differences between groups in the mean ± SD number of mobilized CD34+ cells/μL in peripheral blood or the number of CD34+ cells/kg body weight. Five patients (9%) in the originator G-CSF group and six patients in the biosimilar G-CSF group (11%) did not mobilize sufficient CD34+ cells. The adverse event profile was similar between groups.ConclusionsA biosimilar G-CSF (Zarzio^®) demonstrated similar efficacy and safety as the reference originator G-CSF (Neupogen^®) in hematopoietic stem cell mobilization in patients with haematological malignancies.     

The flavonolignan‐silymarin protects enzymatic,hematological, and immune system against γ‐radiation‐induced toxicity

The main focus of this study is evaluation of radioprotective efficacy of silymarin, a flavonolignan, against γ‐radiation‐induced damage to hematological, vital organs (liver and intestine), and immune system. Survival studies revealed that silymarin (administered orally for 3 days) provided maximum protection (67%) at 70 mg/kg body weight (b.wt.) against lethal 9 Gy γ‐irradiation (dose reduction factor = 1.27). The study revealed significant (p < 0.05) changes in levels of catalase (12.57 ± 2.58 to 30.24 ± 4.89 units), glutathione peroxidase (6.23 ± 2.95 to 13.26 ± 1.36 µg of reduced glutathione consumed/min/mg protein), glutathione reductase (0.25 ± 5.6 to 11.65 ± 2.83 pM NADPH consumed/min/mg protein), and superoxide dismutase (11.74 ± 0.2 to 16.09 ± 3.47 SOD U/mg of protein) activity at 30th day. Silymarin pretreated irradiated group exhibited increased proliferation in erythrocyte count (1.76 ± 0.41 × 10⁶ to 9.25 ± 0.24 × 10⁶), hemoglobin (2.15 ± 0.48g/dL to 14.77 ± 0.25g/dL), hematocrit (4.55 ± 0.24% to 37.22 ± 0.21%), and total leucocyte count (1.4 ± 0.15 × 10⁶ to 8.31 ± 0.47 × 10⁶) as compared with radiation control group on 15th day. An increase in CD4:CD8 ratio was witnessed (0.2–1%) at 30th day time interval using flow cytometry. Silymarin also countered radiation‐induced decrease (p < 0.05) in regulatory T‐cells (T_regs) (11.23% in radiation group at 7th day versus 0.1% in pretreated silymarin irradiated group at 15th day). The results of this study indicate that flavonolignan‐silymarin protects enzymatic, hematological, and immune system against γ‐radiation‐induced toxicity and might prove useful in management of nuclear and radiological emergencies. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 641–654, 2016.     

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na⁺, K⁺ and Ca²⁺, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10^?9 M/L to 1.4 × 10^?6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10^?8 M/L, r = 0.580, P < 0.05) (F = 2.980, df₁ = 6, df₂ = 28, P < 0.05). Paroxetine (from 1.2 × 10^?9 M/L to 5.1 × 10^?5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10^?8 M/L, r = 0.500, P < 0.05) (F = 2.350, df₁ = 9, df₂ = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.     

Electrochemical oxidation behavior of hydrochlorothiazide on a glassy carbon electrode and its voltammetric determination in pharmaceutical formulations and biological fluids

The electrochemical oxidation behavior of hydrochlorothiazide (HCT) on a glassy carbon as a working electrode was investigated in Britton–Robinson (B–R) buffer pH 3, by using anodic stripping voltammetry (ASV) and cyclic voltammetry (CV). This drug gave a well-defined voltammetric oxidation peak at + 1200 mV versus an Ag/AgCl reference electrode. The electrochemical oxidation process was shown to be irreversible and diffusion controlled, with adsorption characterized over the entire pH range. The optimized conditions, such as accumulation time and potential, scan rate, frequency, pulse amplitude, varying of working electrodes, and instrumental parameters were studied. The calibration graph for HCT was obtained from 4 × 10⁻⁶ to 4 × 10⁻⁵ M (correlation coefficient = 0.997) using the developed electroanalytical method (ASV). The detection limit of this drug was 4.3 × 10⁻⁹ M. ASV and CV techniques with adequate precision and accuracy have been developed and applied for direct determination of HCT in commercial tablets without separation or extraction procedures and biological fluids such as urine and plasma.     

腹水多形核细胞数量与自发性腹膜炎预后关系的研究

目的 评价腹水多形核细胞(PMN)数量与自发性腹膜炎(SBP)的预后关系。 方法 连续收集近2年间收治的291例SBP患者的临床资料。排除继发性、结核性腹膜炎,恶性腹水,并剔除未行腹穿或穿刺失败者40例,纳入研究的患者251例。以腹水PMN计数是否 >250×10⁶/L分为两组。比较两组间的一般情况、实验室检查、临床症状体征、合并症、治疗效果和生存率。 结果 在251例SBP患者中,PMN> 250×10⁶/L者63例(25%),PMN< 250×10⁶/L者188例(75%)。腹水细菌培养阳性的9例患者中,PMN> 250×10⁶/L者占77.8%(7/9),PMN< 250×10⁶/L者占22.2%(2/9)。两组患者在SBP主要症状体征方面无明显差别,均表现为有不同程度的发热、腹痛、腹胀,腹部张力增高,程度不等的压痛、反跳痛。抗菌药物治疗总有效率为67.3%(169/251),其中,PMN< 250×10⁶/L组抗菌药物治疗有效率为70.7%(133/188),PMN> 250×10⁶/L组为57.1%(36/63),两组比较差异有统计学意义(P <0.05)。在合并症方面,与PMN< 250×10⁶/L组比较,PMN> 250×10⁶/L组合并消化道出血、MODS、感染性休克较高(P均 <0.05),其住院病死率及其1年内病死率均较高,差异均有统计学意义(P <0.05)。结论 以PMN> 250×10⁶/L作为SBP的诊断标准,在SBP患者预后评估中具有重要意义。与PMN <250×10⁶/L的SBP患者比较,PMN> 250×10⁶/L的SBP患者抗菌药物治疗有效率低,合并症较高,预后较差。     

Electrochemical behavior of paclitaxel and its determination at glassy carbon electrode

The electrochemical behavior of paclitaxel drug was studied at a glassy carbon electrode in phosphate buffer solutions using cyclic and differential-pulse voltammetric techniques. The oxidation process was shown to be irreversible over the pH range (3.0–10.4) and was diffusion controlled. Effects of anodic peak potential (E_p), anodic peak current (I_pa), scan rate, pH, heterogeneous rate constant (k⁰), etc have been discussed. A possible electro-oxidation mechanism was proposed. An analytical method was developed for the determination of paclitaxel in phosphate buffer solution at pH = 7.0 as a supporting electrolyte. The anodic peak current varied linearly with paclitaxel concentration in the range 1.0 × 10⁻⁶ M to 1.0 × 10⁻⁵ M with a limit of detection (LOD) of 1.23 × 10⁻⁸ M and limit of quantification (LOQ) of 4.10 × 10⁻⁸ M. The proposed method was successfully applied to the determination of paclitaxel in pure and real samples.     

<Emphasis Type="Italic">TPMT</Emphasis> but not <Emphasis Type="Italic">ITPA</Emphasis> gene polymorphism influences the risk of azathioprine intolerance in renal transplant recipients

Purpose  Thiopurine drugs have to be withdrawn in 10–30% of cases due to side effects, and it has been presented that genetic factors may be responsible for some of reported toxicity cases. Among polymorphic enzymes of thiopurines’ metabolic pathway, thiopurine S-methyltransferase (TPMT) has been studied most extensively, and some recent studies point to inosine triphosphate pyrophosphohydrolase (ITPA) polymorphism as an additional toxicity risk factor. Methods  The aim of the current study was to evaluate an association between TPMT and ITPA gene polymorphisms and drug intolerance in a cohort of 157 renal transplant recipients treated with azathioprine (AZA). Each subject was genotyped for the presence of variant TPMT (*2, *3A, *3B, and *3C) and ITPA (94C>A and IVS2+21A>C) alleles. Results  Mean AZA dose, mean white-blood-cell count, and platelet count in the course of treatment were lower in carriers of variant TPMT alleles compared to patients with TPMT wild-type genotype. Leukocyte numbers fell below 4.0 × 10⁹/L in 41.2% of TPMT heterozygous renal transplant recipients, compared to only 18.0% of wild-type patients (P < 0.01). In contrast, ITPA genotype did not influence AZA dose, hematological parameters, or leucopenia risk. Conclusions  Our results suggest that routine genotyping of renal transplant recipients for TPMT variants may be useful in reducing the risk of AZA-related myelotoxicity, but there is not enough evidence to introduce ITPA testing into clinical practice.     

Voltammetric determination of chlorogenic acid in pharmaceutical products using poly(aminosulfonic acid) modified glassy carbon electrode

In this work, a poly(aminosulfonic acid) modified glassy carbon electrode was fabricated and the electrochemical behavior of chlorogenic acid (CGA) was studied by cyclic voltammetry. Compared with a bare glassy carbon electrode, the modified electrode exhibits excellent catalytic effect on the electrochemical redox of CGA. Utilizing this catalytic effect, a sensitive and selective electrochemical method for the determination of CGA was developed. The analytical parameters were optimized. Under the optimized conditions, the oxidation peak current is linearly proportional to the concentration of CGA in the range from 4.00 × 10⁻⁷ to 1.20 × 10⁻⁵ mol/L and the detection limit is 4.00 × 10⁻⁸ mol/L. Further, the performance of the proposed method has been validated in terms of linearity (r = 0.9995), recovery (96.3–102.8%), reproducibility (RSD ＜ 4.0%, n = 6) and robustness. The developed method has been successfully applied for the determination of CGA in a variety of pharmaceutical products.