Patient-controlled epidural analgesia after abdominal surgery: ropivacaine versus bupivacaine.

UNLABELLED: In this randomized, double-blinded study we sought to assess the analgesic efficacy of ropivacaine and bupivacaine in combination with sufentanil and the efficacy of ropivacaine alone after major abdominal surgery. Sixty patients undergoing major abdominal surgery received standardized general anesthesia combined with epidural thoracic analgesia. They were allocated to one of three groups: the BS group received postoperative patient-controlled epidural analgesia with 0.125% bupivacaine plus 0.5 microg/mL sufentanil; the RS group received 0.125% ropivacaine plus 0.5 microg/mL sufentanil; and the R group received 0.2% ropivacaine, with the patient-controlled epidural analgesia device set at bolus 2-3 mL and background infusion 3-5 mL/h. Visual analog scale scores were significantly lower during coughing in the BS group compared with the RS and R groups and in the RS group compared with the R group. The BS group required significantly less local anesthetic (milligrams per day) during the first three postoperative days compared with the RS and R groups, and the RS group, significantly less than the R group. No major side effects were noted in any group. We conclude that, after major abdominal surgery, thoracic epidural analgesia was more effective with bupivacaine than with ropivacaine when these two local anesthetics are used in a mixture with sufentanil. Ropivacaine alone was less effective than ropivacaine in combination with sufentanil. IMPLICATIONS: After major abdominal surgery, thoracic epidural analgesia was more effective with 0.125% bupivacaine than with 0.125% ropivacaine when these two local anesthetics were used in a mixture with 0.5 microg/mL sufentanil. Ropivacaine 0.2% alone was less effective than 0.125% ropivacaine combined with sufentanil.

DNA intercalation, topoisomerase II inhibition and cytotoxic activity of the plant alkaloid neocryptolepine.

Cryptolepine and neocryptolepine are two indoloquinoline alkaloids isolated from the roots of the African plant Cryptolepis sanguinolenta. Both drugs have revealed antibacterial and antiparasitic activities and are strongly cytotoxic to tumour cells. We have recently shown that cryptolepine can intercalate into DNA and stimulates DNA cleavage by human topoisomerase II. In this study, we have investigated the mechanism of action and cytotoxicity of neocryptolepine, which differs from the parent isomer only by the orientation of the indole unit with respect to the quinoline moiety. The biochemical and physicochemical results presented here indicate that neocryptolepine also intercalates into DNA, preferentially at GC-rich sequences, but exhibits a reduced affinity for DNA compared with cryptolepine. The two alkaloids interfere with the catalytic activity of human topoisomerase II but the poisoning activity is slightly more pronounced with cryptolepine than with its isomer. The data provide a molecular basis to account for the reduced cytotoxicity of neocryptolepine compared with the parent drug.

Stimulation of topoisomerase II-mediated DNA cleavage by three DNA-intercalating plant alkaloids: cryptolepine, matadine, and serpentine.

Cryptolepine, matadine, and serpentine are three indoloquinoline alkaloids isolated from the roots of African plants: Cryptolepis sanguinolenta, Strychnos gossweileri, and Rauwolfia serpentina, respectively. For a long time, these alkaloids have been used in African folk medicine in the form of plant extracts for the treatment of multiple diseases, in particular as antimalarial drugs. To date, the molecular basis for their diverse biological effects remains poorly understood. To elucidate their mechanism of action, we studied their interaction with DNA and their effects on topoisomerase II. The strength and mode of binding to DNA of the three alkaloids were investigated by spectroscopy. The alkaloids bind tightly to DNA and behave as typical intercalating agents. All three compounds stabilize the topoisomerase II-DNA covalent complex and stimulate the cutting of DNA by topoisomerase II. The poisoning effect is more pronounced with cryptolepine than with matadine and serpentine, but none of the drugs exhibit a preference for cutting at a specific base. Cryptolepine which binds 10-fold more tightly to DNA than the two related alkaloids proves to be much more cytotoxic toward B16 melanoma cells than matadine and serpentine. The cellular consequences of the inhibition of topoisomerase II by cryptolepine were investigated using the HL60 leukemia cell line. The flow cytometry analysis shows that the drug alters the cell cycle distribution, but no sign of drug-induced apoptosis was detected when evaluating the internucleosomal fragmentation of DNA in cells. Cryptolepine-treated cells probably die via necrosis rather than via apoptosis. The results provide evidence that DNA and topoisomerase II are the primary targets of cryptolepine, matadine, and serpentine.

Ruptured abdominal aortic aneurysm: influence of intraoperative management on surgical outcome.

PURPOSE: This study was designed to determine the influence of changes in intraoperative management on the outcome of ruptured abdominal aortic aneurysm (RAAA). METHODS: Retrospective review of our surgical experience of RAAA identified 61 patients and was separated into two periods: 1986 to 1988 (group 1 [n = 21 patients]) and 1989 to 1994 (group 2 [n = 40 patients]). Since 1989 operations have been conducted by two vascular surgeons without systemic administration of heparin and with control of suprarenal aorta if extensive hematoma is present, use of collagen-impregnated grafts, preferential repair with aortoaortic grafting, and routine use of intraoperative autotransfusion. RESULTS: Factors differing between the groups were use of intraoperative autotransfusion (4.76% in group 1 vs 80% in group 2, p < 0.00001), repair with tube grafting (42.8% in group 1 vs 80% in group 2, p = 0.003), number of packed homologous red blood cells (7.5 +/- 5.2 units in group 1 vs 3.1 +/- 3.6 units in group 2, p = 0.008), postoperative blood loss (365 +/- 705 ml in group 1 vs 133 +/- 351 ml in group 2, p = 0.01). The intraoperative mortality rate was significantly lower in group 2 (5% vs 28.6%, p = 0.016). The only predictive factor was the use of intraoperative autotransfusion with a lower mortality rate in patients undergoing autotransfusion (p = 0.029). The postoperative mortality rate was significantly lower in group 2 (20% vs 52.4%, p = 0.009). Predictive factors were use of intraoperative autotransfusion (p = 0.0009), age of the patients (p = 0.0039), and repair with tube graft (p = 0.039). The odds ratio of postoperative death was 25 times higher without intraoperative autotransfusion and seven times lower when a tube graft was used. CONCLUSION: Continuing efforts to achieve improvement in surgical technique and use of intraoperative autotransfusion were important determinants in lowering the postoperative mortality rate of RAAA to 20%.

Psoralen--lexitropsin hybrids: DNA sequence selectivity of photoinduced cross-linking from MPE footprinting and exonuclease III stop assay, and mode of binding from electric linear dichroism.

The properties of certain hybrids 3 and 5 bearing a photoactivatable psoralen group attached to DNA sequence recognizing lexitropsin carriers have been examined. The hybrids bind to poly(dA-dT) with Kapp of 2.8 and 0.9 x 10(7) M-1, i.e. greater than or equal to that of netropsin (Kapp = 1.0 x 10(7) M-1), indicating that the psoralen moiety may contribute to binding in the case of 5. Photoinduced cross-linking of DNA by 3 and 5, while efficient, is less so than that of individual psoralens and reaches a maximum at a ligand to DNA base pair ratio (r) of 0.2. Complementary strand methidium-propyl-EDTA (MPE).Fe(II) footprinting demonstrated that, in the dark, the sequence preferential recognition of hybrids 3 and 5 is dominated by the lexitropsin moiety. Examination of 360 nm photoinduced DNA cross-linking by the hybrids 3 and 5 was carried out using an exonuclease III stop assay. This revealed that > 95% of the DNA remained double stranded, indicating that 3 and 5 generate primarily biadducts at AT-rich sequences. This assay also located individual monoadduct sites, some of which are remote from the dominant cross-linked sites. When the samples were exposed to 254 nm UV light before loading onto the gel to reverse the photoproducts, the pattern of the exonuclease III stop bands was not altered significantly compared with the experiment without 254 nm irradiation. It is concluded that these termination sites include both mono- and biadducts. Electric linear dichroism examination of the DNA complexes of hybrids 3 and 5 (without light activation) provides evidence that the lexitropsin portion binds in the minor groove, while the psoralen portion intercalates in a suitably located site for subsequent photoinduced cross-linking.