Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.

OBJECTIVES: The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting. BACKGROUND: Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices. METHODS: In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously). RESULTS: Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals. CONCLUSIONS: Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.

[Cocaine-body-packing. Infrequent indication for laparotomy]. / Kokain-body-packing. Seltene Indikation zur Laparotomie.

INTRODUCTION: Body-packers or "mules" are drug smugglers who swallow cocaine-filled condoms in order to conceal them during air travel. Body pushers hide drug packages in the rectum or vagina. In a cooperative effort between the Frankfurt Airport Clinic and the GIZ-Nord (Goettingen University poison control center), we performed a retrospective study and developed an algorithm for the problem of "rupture of a cocaine-filled condom in a body-packer." METHODS: In a retrospective analysis, the data of all cocaine body-packers and body pushers who were identified at Frankfurt International Airport from 1985 to 2001 were evaluated.Temporal development, demographic data, and surgical aspects were of special interest. RESULTS: From 1985 to 2001 a total of 280 body pushers and 2880 body-packers were identified: 63 "mules" (2.2%) developed symptoms of severe cocaine intoxication following rupture of a condom. Emergency laparotomy was performed on 20 patients (i.e., 32% of all symptomatic body-packers) and the condoms were removed, while 43 body-packers (68%) died before surgical therapy could be initiated. All operated patients survived. CONCLUSION: Severe cocaine intoxication is life threatening. Patients die from complications caused by generalized vasoconstriction. If the reason for severe cocaine intoxication is the rupture of a cocaine-filled condom,the only possible therapy consists of immediate laparotomy for removal of the condoms.

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells.

The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well. Induction of c-myc expression by serum stimulation of cells was blunted by the antisense oligonucleotide, as shown by immunoblotting. These results demonstrate that c-myc expression is an essential factor for proliferation of HSMCs after growth stimulation, and they show the potential of antisense technology for modulating gene expression of HSMCs in vitro.

Isolation of mammalian calelectrins: a new class of ubiquitous Ca2+-regulated proteins.

In a new approach to isolating proteins which participate in the Ca2+-dependent regulation of membrane traffic in animal cells, two new Ca2+-binding proteins (Mr 67 000 and 32 500) have been identified in and purified from bovine liver, brain, and adrenal medulla. These proteins specifically and reversibly bind to chromaffin granule membranes at low Ca2+ concentrations (half-maximal binding at 5.5 microM Ca2+) and greatly potentiate the Ca2+-induced aggregation of these membranes at higher concentrations (above 10 microM). In the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetate, the isolated proteins have Stokes radii of 3.40 nm (Mr 67 000) and 2.53 nm (Mr 32 500) as estimated by gel filtration and therefore occur as monomers. They are slightly acidic proteins with pI's of 5.85 and 5.60. In bovine tissues, both proteins and a third protein of Mr 35 000 cross-react immunologically with each other and with Torpedo calelectrin (Mr 34 000) and are therefore identified as mammalian calelectrins. In all tissues of Torpedo marmorata tested, only a single molecular mass form of calelectrin exists, whereas multiple forms of calelectrin exist in mammalian tissues, indicating gene duplication during evolution. We suggest that the evolutionary conservation and diversification, the high tissue concentrations, and the Ca2+-specific interactions of the calelectrins make them candidates for Ca2+-dependent regulators of membrane events in animal cells.