Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis

The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.     

Poisoning by Datura leaves used as edible wild vegetables.

The causes of Datura intoxication include medication overdose, misuse of edible vegetables, deliberate abuse as a hallucinogen, homicidal or robbery and accidental intoxication from contaminated food. We report an incident of 14 people with Datura intoxication caused by ingesting wild Datura suaveolans for food. The incubation period was 15 to 30 min. The symptoms/signs were dizziness, dry mouth, flushed skin, palpitation, nausea, drowsiness, tachycardia, blurred vision, mydriasis, hyperthermia, disorientation, vomiting, agitation, delirium, urine retention, hypertension and coma. Three patients were hospitalized for 2-3 days. Thirteen persons received supportive fluid therapy. One patient did not receive medical therapy, he induced vomiting and drank a lot of water. Four patients presented with delirium/coma and 3 received physostigmine therapy with good response. One patient was intubated because of coma and respiratory depression. Three persons needed Foley catheterization for urine retention or coma status. One patient had a complication of urinary tract infection and antibiotic management. All patients recovered with no sequelae.     

神经生长因子对培养大鼠皮质神经元缺氧损伤的拮抗作用

AIM: To observe the effects of nerve growth factor (NGF) on neuronal hypoxic injury induced by sodium dithionite in primary cultures from gestation of 17-d rat fetal cerebral cortex. METHODS: Neuronal death and lactate dehydrogenase (LDH) efflux in the bathing medium were measured. The homogenate of cortical cells was used to determine malonyldialdehyde (MDA) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. RESULTS: When cultures were incubated for 24 h with sodium dithionite, efflux of LDH and MDA content increased while the number of surviving neurons decreased. NGF 100 micrograms.L-1 increased the number of surviving neurons to 85% +/- 9% of normoxia level under hypoxia. NGF 1-100 micrograms.L-1 concentration-dependently attenuated hypoxia-induced increase of efflux of LDH and MDA content, with IC50 of 27 and 49 (95% confidence limits: 18-49 and 29-110) micrograms.L-1. NGF 30 micrograms.L-1 induced a 3-fold increase in SOD and GSH-Px activities. The levels of SOD and GSH-Px activities in hypoxia group were increased 2.7-fold by NGF 100 micrograms.L-1. CONCLUSION: NGF prevented hypoxic insults in cultured cerebral cortical neurons by suppressing the generation of lipid peroxides and increasing the activities of antioxidant enzymes.     

氟伐他汀对自发性高血压大鼠阻力血管 功能的影响

AIM: To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor, on the alterations of structure and function of resistant vessels in spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric arteries isolated from rats. RESULTS: After 8 wk of treatment, histological examination showed that the wall-to-lumen area ratio was lower in SHRflu than that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P < 0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05]. CONCLUSION: Short-term treatment with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor; fluvastatin also attenuated the resistant vascular hypertrophy during the development of hypertension in SHR.     

促皮质素对甲醛引起大鼠脊髓内生长抑素的影响

目的：研究促皮质素（Ｃｏｒ）对甲醛引起大鼠脊髓内生长抑素及其合成的影响,方法：采用免疫组织化学,免疫组织化学双重染色法和原位杂交技术。结果：足底注射甲醛使大鼠脊髓背角内ＦＬＩ,ＳｏｍＬＩ,Ｓｏｍ－ＬＩ／ＦＬＩ和ＰＰＳ－ｍＲＮＡ神经元数均对较对照组显著增多,单独ｉｐＣｏｒ对脊髓背角ＦＬＩ和Ｓｏｍ－ＬＩ无明显影响。但是,ｉｐＣｏｒ显著抑制甲醛引起的背角内ＦＬＩ,Ｓｏｍ－ＬＩ,Ｓｏｍ－ＬＩ／ＦＬＩ和ＰＰ     

阿芙唑嗪及多沙唑嗪十二指肠给药及对猫尿道压的选择性作用

目的观察不同给药途径对芙唑嗪（Ａｌｆ）和多沙唑嗪（Ｄｏｘ）降尿道反压的选择性作用。方法 电刺激麻醉猫腹下神经以长高尿道压,比较十二指肠和静脉两种途径给药时,Ａｌｆ和Ｄｏｘ降低平均动脉血压（ＭＢＰ）及尿道压（ＵＰ）的作用。结果：相同电刺激条件（１０Ｈｚ,２５Ｖ）Ａｌｆ肠道给药与静脉给经时ＥＤ２０（ＢＰ）／ＥＤ５０（ＵＰ）比值为１０．９：４．３;Ｄｏｘ两种给药途径的比值为３．１：２．１,Ａｌｆ十二指肠     

复方云芝胶囊对丝裂霉素C诱发突变及老年自发突变的抑制作用

采用体外培养人淋巴细胞微核检测法,探讨复方云芝胶囊抗突变作用。结果表明,复方云芝胶囊（１０ｍｇ／Ｌ～５０ｍｇ／Ｌ）可显著抑制丝裂霉素Ｃ（ＭＭＣ）诱发的微核形成,并可拮抗老年人自发微核,增加细胞增殖活性。     

胰原性区域性门脉高压症血流动力学的临床研究

目的：研究胰原性区域性门脉高压症静脉血流动力学改变。方法：利用彩色多普勒及直接测量法测量血流动力学及脾静脉压力。结果：门静脉、肠系膜上静脉的血管直径、平均流速在两组间无差异。实验组脾静脉直径扩张,流速降低且静脉压力明显升高（Ｐ＜０．０５）。结论：胰原疾病可导致区域性门脉高压,正确的治疗方法是行脾脏切除术。     

Tissue potassium,selenium, and iron levels associated with gastric cancer progression

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe -spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.     

Renal vein thrombosis and selective arterial or venous thrombolytic therapy

Summary Background: Renal vein thrombosis (RVT) complicating the nephrotic syndrome is associated with a poor prognosis. Methods/Results: RVT was diagnosed in 12 of 60 patients with a diagnosis of nephrotic syndrome suggested by computed tomography (CT) and subsequently confirmed by selective renal angiography. Fifty patients carried a diagnosis of primary glomerulonephritis with various pathological findings, and 10 patients had lupus nephritis. Renal vein and peripheral vein blood samples were collected in the 12 patients with RVT and were assayed for fibrin(ogen) degradation products (FDP), antithrombin III (AT III), VIIIR:AG, and fibrinogen. The results suggested a state of hypercoagulation. Of these 12 patients, 7 were given 200,000 units of urokinase (UK) over 60 minutes in divided doses selectively via the renal vein. Five patients were given 200,000 units UK selectively into the renal artery. All patients also received 2.5 mg/day warfarin and 75 mg/day persantine. Except for three patients with focal glomerulosclerosis, all patients received 40 mg/day prednisone. After 1 month, the CT scan and blood samples for FDP, AT III, VIIIR:AG, and fibrinogen were repeated. Patients receiving intra-arterial UK had complete resolution of their thrombi. Complete resolution was also suggested in 2 of the 7 patients receiving UK by renal vein, and there was partial resolution in the other five. The hypercoagulation state decreased in all patients. Conclusions: We conclude that RVT is not an uncommon event in patients with nephrotic syndrome. The diagnosis can be supported reliably using abdominal CT scanning. Although a small number of patients were included in this nonrandomized study, it appeared that intra-arterial thrombolytic therapy yielded better results. The patients with minimal change disease have a good prognosis.