Lasting safe interruption of endarterectomy thrombosis by transiently infused antithrombin peptide D-Phe-Pro-ArgCH2Cl in baboons

To evaluate the relative antithrombotic efficacy and hemostatic safety of antithrombin therapy for vascular thrombus formation at sites of mechanical vascular injury, we administered the potent and specific irreversible synthetic antithrombin D-PHE-PRO-ARG chloromethyl ketone (D-FPRCH2Cl) after performing carotid endarterectomies in baboons. The continuous intravenous infusion of D-FPRCH2Cl, 100 nmol/kg per minute for 1 hour, abolished acute carotid endarterectomy thrombosis for at least 48 hours. The plasma level of D-FPRCH2Cl during the infusion was maintained steady at 7.2 +/- 0.9 mumol/L, but decreased rapidly after discontinuing its infusion (T50 17 minutes). Platelet deposition, measured in real time using autologous 111In-platelet scintillation camera imaging, was 1.51 +/- 0.40 x 10(8) platelet/cm in the 14 treated animals 90 minutes postoperatively, compared with 11.7 +/- 1.16 x 10(8) platelet/cm in 14 heparin-treated controls (P < .002). The antithrombotic benefit was equivalent for treatment begun either 5 minutes before (nine animals) or 15 minutes after (five animals) reestablishing flow in the operated vessel, ie, 1.59 +/- 0.36 x 10(8) platelet/cm versus 1.35 +/- 0.51 x 10(8) platelet/min, respectively; P > .5. Endarterectomy thrombosis remained decreased for at least 48 hours postoperatively, as determined by the ratio between net 111In- platelet radioactivity at the endarterectomized site versus whole blood (ratio 0.82 +/- 0.25 in the treatment group v 3.03 +/- 0.51 in heparin controls at 90 minutes, P < .005; and 0.85 +/- 0.23 v 3.25 +/- 0.48 at 48 hours, P < .002). The marked reduction in endarterectomy thrombosis in treated animals at 48 hours was confirmed by scanning electron microscopy. Thrombin activity formed rapidly and became immediately bound to thrombus on thrombogenic segments in untreated control studies; treatment with D-FPRCH2Cl irreversibly inactivated the thrombus-bound thrombin. Hemostatic function, as measured by bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) was impaired throughout the intravenous administration of D-FPRCH2Cl (BT > 30 minutes, APTT > 150 seconds, PT > 50 seconds); BT, APTT, and PT values were normal 30 minutes after discontinuing the infusions. As expected, blood loss into the surgical wound was substantial in nine animals receiving therapy initiated before restoring flow in the operated vessel (mean 95 mL, range 45 to 130 mL). By contrast, beginning D-FPRCH2Cl therapy in five animals 15 minutes after restoring arterial flow, a time when surgical hemostasis had been achieved, prevented excessive blood loss (mean 15 mL, range 10 to 35 mL; P < .01 compared with earlier treatment) without compromising the antithrombotic effects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Do Standard Monitoring Sites Reflect True Brain Temperature When Profound Hypothermia Is Rapidly Induced and Reversed?

Background: Brain temperature is closely approximated by most body temperature measurements under normal anesthetic conditions. However, when thermal autoregulation is overridden, large temperature gradients may prevail. This study sought to determine which of the standard temperature monitoring sites best approximates brain temperature when deep hypothermia is rapidly induced and reversed during cardiopulmonary bypass.

Methods: Twenty-seven patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest in order for each to have a giant cerebral aneurysm surgically clipped. Brain temperatures were measured directly with a thermocouple embedded in the cerebral cortex. Eight other body temperatures were monitored simultaneously with less invasive sensors at standard sites.

Results: Brain temperature decreased from 32.6 + 1.4 degrees Celsius (mean plus/minus SD) to 16.7 plus/minus 1.7 degrees Celsius in 28 plus/minus 7 min, for an average cerebral cooling rate of 0.59 + 0.15 degree Celsius/min. Circulatory arrest lasted 24 plus/minus 15 min and was followed by 63 + 17 min of rewarming at 0.31 plus/minus 0.09 degree Celsius/min. None of the monitored sites tracked cerebral temperature well throughout the entire hypothermic period. During rapid temperature change, nasopharyngeal, esophageal, and pulmonary artery temperatures corresponded to brain temperature with smaller mean differences than did those of the tympanic membrane, bladder, rectum, axilla, and sole of the foot. At circulatory arrest, nasopharyngeal, esophageal, and pulmonary artery mean temperatures were within 1 degree Celsius of brain temperature, even though individual patients frequently exhibited disparate values at those sites.     

EOE-13 in the detection of hepatosplenic lymphoma

Thirty-nine patients with lymphoma were evaluated prospectively to determine the usefulness of Ethiodol-Oil-Emulsion-13 (EOE-13) in the detection of hepatosplenic lymphoma by computed tomography. The detection rate in the spleen increased from 8% (before EOE-13 infusion) to 92% (after EOE-13 infusion). In ten of 39 patients (25%) in this series, lymphomatous disease was recognized only on the postinfusion computed tomographic scan. The postinfusion EOE-13 study demonstrated additional visceral abnormalities in 38% of the patients. The potential usefulness, limitations, and toxicity of this hepatosplenic-specific imaging agent are discussed.     

Estrogen stimulates von Willebrand factor production by cultured endothelial cells

Monolayers of cultured human umbilical vein endothelial cells were exposed to 17 beta-estradiol and compared to control cultures with respect to levels of von Willebrand factor (vWF) released into the media after 3-5 days of incubation. The amount of functional vWF activity was assessed by ristocetin-induced platelet aggregation and by a radioreceptor platelet assay. vWF antigen was quantitated by immunoassay. The DNA content of each monolayer was determined fluorometrically and used as a measure of cell number. By all assays, vWF levels in the media from the estradiol-treated endothelial cells were reproducibly and significantly higher when compared with control values. The amount of vWF produced by the cultured endothelial cells showed a dose-response effect to the estradiol added to the media. The estradiol-treated cells produced approximately 1.3 +/- 0.30 micrograms vWF/ml/micrograms DNA at 2 ng estradiol/ml, compared with control cultures that produced 0.75 +/- 0.16 microgram vWF/ml/micrograms DNA (p less than 0.001). The estradiol-treated monolayers consistently contained slightly greater amounts of DNA than control cultures: 2.0 +/- 0.10 micrograms versus 1.7 +/- 0.12 micrograms DNA (p less than 0.001). By multivariant analysis, however, the differences in cell number could only account for less than or equal to 10% of the elevation in the level of vWF that occurred in response to estradiol. By SDS-agarose electrophoresis and radioimmunoblotting, the vWF within the cytosol of the endothelial cells was found to possess a multimeric pattern similar to that found for either purified plasma vWF or vWF released into media overlying endothelial cell cultures. Our studies indicate that estrogen directly stimulates endothelial cells to increase their rate of production of vWF and, in addition, causes a slight increase in endothelial cell replication. These data may bear on the observation that administration of estrogen to some women with von Willebrand's disease causes an increase in their functional levels of vWF.     

“Is this a dagger I see before me?” — an audit of stabbings and gunshot wounds in Limerick

Background According to a recent study in Cardiff, the incidence of stab wounds is 14 per 100,000 population per annum. No such figures are available for Ireland. Aim To evaluate the incidence, type of injury, medical consequences and outcome of patients with stab or gunshot wounds presenting to the Mid-Western Regional Hospital, Limerick, over a 12 month period. Method A retrospective case study of all stab and gunshot wounds presenting over a 12 month period. Results Out of 62,000 new presentations to the Accident and Emergency (A&E) department, 101 (0.16%) were stabbings, giving an incidence of 33 per 100,000 population. Twenty-six patients required surgical intervention. There were three deaths. There were 10 gunshot wounds, of which 40% required surgical intervention, with no mortalities. Conclusion The incidence of stab wounds presenting to our institution is high. Although constituting a small percentage of presentations to the A&E department they result in considerable morbidity and surgical activity.     

Determinants of patient recruitment in a multicenter clinical trials group: trends,seasonality and the effect of large studies

Background

We examined whether quarterly patient enrollment in a large multicenter clinical trials group could be modeled in terms of predictors including time parameters (such as long-term trends and seasonality), the effect of large trials and the number of new studies launched each quarter. We used the database of all clinical studies launched by the AIDS Clinical Trials Group (ACTG) between October 1986 and November 1999. Analyses were performed in two datasets: one included all studies and substudies (n = 475, total enrollment 69,992 patients) and the other included only main studies (n = 352, total enrollment 57,563 patients).

Results

Enrollment differed across different months of the year with peaks in spring and late fall. Enrollment accelerated over time (+27 patients per quarter for all studies and +16 patients per quarter for the main studies, p < 0.001) and was affected by the performance of large studies with target sample size > 1,000 (p < 0.001). These relationships remained significant in multivariate autoregressive modeling. A time series based on enrollment during the first 32 quarters could forecast adequately the remaining 21 quarters.

Conclusions

The fate and popularity of large trials may determine the overall recruitment of multicenter groups. Modeling of enrollment rates may be used to comprehend long-term patterns and to perform future strategic planning.

     

新疆3城市青少年吸烟和饮酒行为调查

目的了解青少年吸烟和饮酒状况,为开展健康教育提供参考依据。方法采用多阶段随机抽样,从新疆3个城市选取不同学校类型的初中、高中和大学学生8869名进行问卷调查。结果35.2%的学生有吸烟行为,其中5.0%在7岁以前开始吸烟;58.3%的学生有饮酒行为,其中7.5%在7岁以前开始饮酒。结论随着年龄的增长,学生开始吸烟和饮酒的比例增高。应对学生加强健康教育,控制吸烟和限制饮酒。