Gender Affects the Median Effective Dose and 95% Effective Dose of Oxycodone for Blunting the Hemodynamic Response to Tracheal Intubation in Narcotic-Naïve Adult Patients.

BACKGROUND: Intravenous (IV) oxycodone has been used at induction to prevent an intubation reaction. The aims of the current study were to calculate the median effective dose (ED50) and the 95% effective dose (ED95) of an IV bolus of oxycodone that blunts the hemodynamic response to tracheal intubation with propofol according to gender and to observe the adverse events of induction-dose oxycodone. METHODS: Adult patients who required general anesthesia and tracheal intubation were enrolled. Tracheal intubation was performed using unified TD-C-IV video laryngoscopy and an ordinary common endotracheal tube. Dixon's up-and-down method was used to obtain ED50data for women and men separately. The initial dose of oxycodone was 0.2 mg/kg for women and 0.3 mg/kg for men (step size was 0.01 mg/kg). Next, a dose-response curve from the probit analysis was generated to determine the ED50and ED95to blunt the intubation reaction in female and male patients. Adverse events following oxycodone injection were observed for 5 min before propofol injection. RESULTS: Sixty-three patients were analyzed, including 29 females and 34 males. According to the probit analysis, the ED50 and ED95of oxycodone required to blunt the intubation reaction in women were 0.254 mg/kg (95% confidence interval [CI], 0.220-0.328 mg/kg) and 0.357 mg/kg (95% CI, 0.297-2.563 mg/kg), respectively. In men, the ED50 and ED95were 0.324 mg/kg (95% CI, 0.274-0.381 mg/kg) and 0.454 mg/kg (95% CI, 0.384-2.862 mg/kg), respectively. Men required 28% more oxycodone than women for induction (P < 0.01). The most common adverse events were dizziness (87.3%), vertigo (66.7%), sedation (74.6%), and respiratory depression (66.7%). CONCLUSIONS: Oxycodone can be used for induction to prevent intubation reactions. Gender affected the ED50and ED95of oxycodone for blunting the tracheal intubation reaction.

[Analysis of the prognosis of 111 patients with gastric cancer or adenocarcinoma of the esophagogastric junction combined with pleural or abdominal effusion].

OBJECTIVE: To explore the prognostic factors in patients with gastric cancer (GC) or adenocarcinoma of the esophagogastric junction (AEG) combined with malignant pleural and/or abdominal effusion. METHODS: Clinicopathological data of 111 GC or AEG patients with malignant pleural and/or abdominal effusion treated in our hospital from January 2001 to December 2010 were retrospectively analyzed. RESULTS: The median survival time for the whole group of 111 patients was 6 months. Effusion disappeared in 12 patients, was reduced in 36 cases, with no changes in 15 cases, and increased in 48 patients. The effusion control rate was 56.8%. Effusion was better controlled in female patients, with simple abdominal ascites, Karnovsky performance scores ≥ 80, with no liver metastases, effusion at initial diagnosis, and effective response to systemic chemotherapy.Univariate analysis showed that patients of female sex, Karnovsky performance scores ≥ 80, effusion present at initial diagnosis, simple abdominal ascites, minimal volume of effusion, absence of liver metastasis, control of effusion, initial treatment with effusions and effective response to systemic chemotherapy, normal hemoglobin, albumin, direct and indirect bilirubin levels showed better prognosis (all P < 0.05). Multivariate analysis showed that liver metastases, control of effusions were independent prognostic factors in patients with gastric cancer and adenocarcinoma of the esophagogastric junction (all P < 0.05). CONCLUSIONS: Female patients, simple abdominal ascites, KPS scores ≥ 80, ascites at initial diagnosis, no liver metastases and effective systemic chemotherapy seem to have a better control of the malignant effusion. Patients with no liver metastases and effective control of effusion have a longer survival time.

[In vitro effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide on differentiation from human adipose-derived mesenchymal stem cells to endothelial cells].

OBJECTIVE: To explore the effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide(W7) on the differentiation from human adipose-derived mesenchymal stem cells (hADSCs) to endothelial cells. METHODS: hADSCs were cultured with serum-free differential medium containing 40 ng/ml vascular endothelial growth factor (VEGF) and 10ng/ml basic fibroblast growth factor (bFGF). Cells were divided into control group (differential medium without W7), high-dose group (containing 30 µmol/L W7), medium-dose group (containing 20 µmol/L W7), and low-dose group ( containing 10 µmol/L W7). The hADSCs were cultured for 8 days, and then the changes in the phenotypes of von Willebrand factor (vWF) and vessel-selective cadherin (VE-Cadherin) were detected by flow cytometry (FCM). The intracellular Ca(2+) labeled with Fluo-3 was detected by laser confocal microscopy. After hADSCs planting on Matrigel, their angiogenic potentials were observed under the inverted phase contrast microscope, and the expression of extracellular regulated kinase (ERK) and phosphorylated extracellular regulated kinase (p-ERK) were evaluated by Western blot. RESULTS: After the hADSCs were cultured for 8 days, compared with the control group, the expressions of vWF and VE-Cadherin significantly increased along with the decrease of W7 level and the intracellular Ca(2+) also significantly increased (Pü0.01). Lumina-like vascular structure was formed in W7 treatment groups, but not in the blank control group. Compared with the blank control group, the expression of ERK showed no significant in W7 treatment groups (high-, medium-, and low-dose groups)(P>0.05); however, along with the decrease of W7 levels, the expression of p-ERK significantly increased(P<0.05). CONCLUSION: W7 in proper levels can effectively induce the differentiation from hADSCs to endothelium by increasing the intracellular Ca(2+) level and thus activating the ERK/MAPK pathway.

[Analysis of prognostic factors in 300 colorectal cancer patients with liver metastases].

OBJECTIVE: To analyse the clinical characteristics and potential prognostic factors of colorectal cancer patients with liver metastases. METHODS: The clinical and pathological data of 300 colorectal cancer patients with liver metastases were retrospectively reviewed and analyzed. RESULTS: The median survival time of these patients was 19.0 months. The 1-, 2- and 5-year survival rates after liver metastases were 79.0%, 29.0% and 3.0%, respectively. Univariate analysis revealed that performance status (KPS), histological grading, primary tumor, N status, lymphatic and vascular invasion, stage at diagnosis, the number, size and distribution of liver metastases and other accompanied metastases were prognostic factors. Multivariate analysis showed that KPS, lymphatic and vascular invasion, the number and size of liver metastases were independent prognostic factors of colorectal cancer with liver metastases. CONCLUSION: Performance status, lymphatic and vascular invasion, the number and size of liver metastases are independent prognostic factors of colorectal cancer with liver metastases.

[FOLFOX4 regimen versus DP(O)F regimen for advanced gastric cancer].

BACKGROUND & OBJECTIVE: Currently, there is no standard regimen for advanced gastric cancer. FOLFOX4 regimen [oxaliplatin(L-OHP) with 5-fluorouracil (5-FU)] and DP(O)F regimen [docetaxel (TXT), oxaliplatin (L-OHP)/cisplatin (DDP) with 5-FU] are usually used in treating gastric cancer with satisfactory efficacy. This study was to compare the efficacy, time to disease progression (TTP), overall survival (OS) and toxicity of the two regimens for advanced gastric cancer. METHODS: Clinical data of 70 chemotherapy-naive patients with advanced gastric cancer were analyzed. Of the 70 patients, 34 were treated with FOLFOX4 regimen, 36 were treated with DP(O)F regimen. The patients in FOLFOX4 group received intravenous infusion of L-OHP (85 mg/m(2)) at Day 1, bolus injection of 5-FU (400 mg/m(2)) at Days 1-2, and continuous intravenous infusion of 5-FU (600 mg/m(2)) for 22 h at Days 1-2; 14 days as one cycle. The patients in DP(O)F group received administration of TXT [20 mg x (m2 x w)(-1)], intravenous infusion of DDP (40 mg/m(2)) at Days 2-3 or L-OHP (100 mg/m(2)) at Day 2, and intravenous infusion of 5-FU (500 mg/m(2)) at Days 1-5; 21 days as one cycle. RESULTS: The objective response rates were 45.4% in FOLFOX4 group and 52.8% in DP(O)F group (P=0.628). The median TTP was 5.27 months in FOLFOX4 group and 4.70 months in DP(O)F group (P=0.848). The median survival time was 8.97 months in FOLFOX4 group and 12.17 months in DP(O)F group (P=0.095). The most frequent adverse events were nausea, vomit and hematologic toxicities. The occurrence rates of grade III-IV leukopenia and neutropenia were significantly lower in FOLFOX4 group than in DP(O)F group (11.8% vs. 36.1%, P=0.025; 17.6% vs. 41.7%, P=0.038). One patient in FOLFOX4 group died of liver function failure. CONCLUSION: Both FOLFOX4 and DP(O)F regimens are effective in treating advanced gastric cancer. The hematologic toxicities of DP(O)F regimen are worse than those of FOLFOX4 regimen.

[Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study].

OBJECTIVE: To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC). METHODS: 141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles. RESULTS: Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death. CONCLUSION: Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.

[10-hydroxy-camptothecin plus fluorouracil/leucovorin for the treatment of patients with advanced colorectal cancer].

OBJECTIVE: To evaluate the maximum tolerated dose and dose-limiting toxicity (DLT) of 10-hydroxy-camptothecin (10-HCPT) in HFL regimen for the treatment of advanced colorectal cancer (CRC). METHODS: 18 advanced CRC patients, 13 males and 3 females, aged 33 - 70, were randomly assigned to 6 groups to be treated with 10-HCPT 4, 6, 8, 10, 12, or 14 mg/m(2), and 5-fluoro-uracil (5-FU) 425 mg/m(2), and leucovorin (LV) 20 mg/m(2), all administered intravenously on days 1 - 5 with 4 weeks as one cycle. The efficacy and side-effect were evaluated. RESULTS: There were two patients with grade IV myelosuppression in the 10, 12, and 14 mg/m(2) groups each. The most dose-associated adverse reactions were myelosuppression and GI dysfunction. The DLT was myelosuppression, and the maximum tolerable dose of 10-HCPT is 10 mg/m(2) on days 1 - 5. CONCLUSION: HFL regimen is well tolerated in the patients with advanced CRC. The dosing regimen recommended in clinic trial is 8 mg/m(2).

[A randomized trial of irinotecan plus fuorouracil and leucovorin with thalidomide versus without thalidomide in the treatment for advanced colorectal cancer].

OBJECTIVE: To evaluate the efficacy, side-effects and quality of life in the advanced colorectal cancer patients treated by irinotecan plus fuorouracil and leucovorin with thalidomide or without thalidomide. METHODS: Eligible patients were randomly assigned to the treatment group and control group in a 1:1 ratio. In the treatment group, 32 evaluable patients were treated with irinotecan 180 mg/m2 i. v. on day 2, fuorouracil 400 mg/m2 bolus on day 1, 2 at a dose of 1200 mg/m2 civ. for 43 hours; leucovorin 200 mg/m2 i. v. on day 1, 2; thalidomide 300 mg, orally on day 1 - 14, two weeks as a cycle. In the control group, the regimen was the same as in the treatment group except oral intake of thalidomide. RESULTS: The response rate was 28.1% in the treatment group vs. 15.2% in the control group (P = 0.2034) with a median TTP of 3.8 months vs. 2. 5 months (P = 0.1312). Furthermore, there was no statistically difference either between two groups regarding to adverse effects. CONCLUSION: Irinotecan plus fuorouracil and leucovorin without oral intake of thalidomide is as effective and tolerable as irinotecan plus fuorouracil and leucovorin combined with oral thalidomide for advanced colorectal cancer.

[Influence of breast carcinoma cells on normal endothelial cells: experimental study with a co-culture system].

OBJECTIVE: To study the influence of breast carcinoma cells on normal endothelial cells. METHODS: Human endothelial cells were isolated from umbilical cord blood. Medium Z-MCF-7-EC was established and was used to co-culture the normal endothelium cells (ECs) and human breast cancer cells of the line MCF-7. Normal endothelial cells cultured by itself were used as control. Light microscopy and transmission electron microscopy were used to observe the morphology of the 2 kinds of endothelial cells. Expression of the genes ESM, IGFBP-3, alphavbeta3, VE-C, and Tie-2-2 was analyzed by semi-quantitative RT-PCR using a house-keeping gene beta(2m) as inner reference gene. RESULTS: The ECs co-cultured with MCF-7 breast cancer cells were abnormal in shape with increased size of nucleus and nucleolus, increased size ratio of nuclear to nucleoplasm, increased depth of surface fenestration, loosed and distorted endoplasm, increased size of cell-cell junctions, decreased number of surface microvilli, and tubules formed by ECs. The expression values of the genes ESM, IGFBP-3, alphavbeta3, VE-C, and Tie-2-2 in the ECs co-cultured with MCF-7 breast cancer cells were all up-regulated in comparison with those in the controls (P < 0.01, P < 0.05, P < 0.01, P < 0.01, and P < 0.05 respectively). CONCLUSION: Breast cancer cells promote formation of new vessels with endothelial cells different from the normal ECs in character and behavior.

Micro-vascular medicine and proteomics.

A new technique is sweeping the world, and changing the course of human work and life. It is impacting upon models, methods and the development of medical research. In the development of this new technique, a huge quantity of experimental research and clinical practice has proved that many human diseases have a close relationship to pathological changes that take place in the microvascular system. It has been proven that the microvascular system is the target for studying disease development and the treatment of disease. Many studies have shown that successful pathogenesis and pathological research must be aimed at understanding the key proteins in cells, organs and systems, as well as investigating their interaction, and finding out how these proteins change under disease conditions. This paper reviews the current status of microvascular medicine and proteomics.