Influence of heparin and a low molecular weight heparin fraction of the leukocytes in an experimental venous thrombosis model

A randomized study was performed to observe the effects induced by heparin and a low molecular weight heparin fraction (at different dosages) on the leukocytes of rats in the presence of experimental venous thrombosis. The experimentation was carried out on two series of animals: the first with a ligature of the inferior vena cava inducing the formation of a thrombus, the second without any ligature. The results show that the induction of thrombosis involves: in the blood, an increase of the number leukocytes, principally polymorphonuclear cells; in the thrombi, a significant rise in the total count of leukocytes, here mononuclear cells; the latter number increases with the dosages of the administered drugs.     

Clinical efficacy of low molecular weight heparin in postoperative thrombosis prophylaxis

Summary In a randomized controlled clinical trial, the efficacy and safety of two low molecular weight heparin (LMWH) fractions in the prophylaxis of deep vein thrombosis (DVT) were assessed. One hundred twenty-six patients undergoing major abdominal surgery received alternatively 2,500 APTT units b.i.d. of two LMWH fractions or 5,000 APTT units b.i.d. of an unfractionated sodium mucosal heparin (UFH). LMWH 2 differed from LMWH 1 by presenting a lower mean molecular weight and a higher anti-Xa/APTT ratio in vitro. Patients were randomly allocated to the three groups, and the development of DVT was studied with the¹²⁵I-fibrinogen uptake test (RFUT).The study was interrupted and the code broken prematurely because of otherwise unexplainable bleeding events.While no thrombosis and no severe bleeding were detected in the UFH group, three (7%) RFUT-positive DVT and two (5%) hemorrhagic complications occurred in the LMWH 1 group. No thrombosis and nine (22%) cases of severe bleeding were observed in the LMWH 2 group. Thus, the latter group differed significantly from the control group with regard to subjective and objective criteria for postoperative bleeding.Although these results do not allow general conclusions as to the value of LMWH fractions in the prevention of DVT, they indicate that these preparations just as ordinary heparin have a limited therapeutic range.Supported by a grant (Schm 345/4-2) from the Deutsche Forschungsgemeinschaft     

建立猪心大静脉阻塞的动物模型

心大静脉作为冠状静脉窦(简称冠状窦)系统的主要属支,在心脏血液循环中起重要的回流作用,也是现代心脏起搏技术常用的导管放置部位,新近研究发现,安装永久起搏器患者,电极所在静脉血栓发生率为30％。为进一步了解静脉管腔阻塞后心脏结构、功能及电生理参数的变化,指导临床工作,我们采用经皮穿刺技术,放置金属弹簧圈于猪心大静脉近中段,建立心大静脉阻塞的动物模型,并通过X线造影在不同时段进行评估。     

Creation and establishment of a respiratory liver motion simulator for liver interventions

Image-guided surgery and navigation have resulted from convergent developments in radiology, teletransmission, and computer science and are well-established procedures in the surgical routine in orthopedic, neurosurgery, and head-and-neck surgery. In abdominal surgery, however, these tools have gained little attraction so far. The inability to transfer the methodology from orthopedic or neurosurgery is mainly a result of intraoperative organ movement and shifting. To practice and establish navigated interventions in the liver, a custom-designed respiratory liver motion simulator was built which models the human torso and is easy to recreate. To simulate breathing motion, an explanted porcine or human liver is mounted to the diaphragm model of the simulator, and a lung ventilator causes a periodic movement of the liver along the craniocaudal axis. Additionally, the liver can be connected to a circulating pump device which simulates hepatic perfusion and provides real surgical options to establish navigated interventions and simulate management of possible complications. Respiratory motion caused by the simulator was evaluated with an optical tracking system and it was shown that in vitro movement and deformation of a liver mounted to the device are similar to the liver movements in human or porcine bodies. Based on the tests, it is concluded that the novel respiratory liver motion simulator is suitable for in vitro evaluation of navigated systems and interventional and surgical procedures.     

Influence of catheter intervention on platelet function and activation in a pig model for endovascular embolization of arteriovenous malformations

Catheter interventions are associated with the risk of thromboembolism; however, the extent of platelet activation is not known. Samples from an arteriovenous malformation model (n?=?21 pigs) were examined. The pigs received a continuous infusion of 66?IU?kg^?1?h^?1 (n?=?11) or 100?IU?kg^?1?h^?1 (n?=?10) heparin applied 20?min after an initial bolus of 100?IU/kg. Platelet aggregation according to Born and ADVIA 120? platelet activation indices were used to study platelet function and activation. Samples were taken previous to vascular puncture, following vascular puncture, 20?min after application of heparin bolus, following placement of microcatheters and after endovascular embolization. Reactivity of platelets was increased after puncture of the vessels (ADP: P?<?0. 0001, collagen: P?=?0.0053). Further on activity of platelets was constrained by heparinization (ADP: P?<?0.0001, collagen P?<?0.0001). It can be concluded that the puncture of vessels yields the highest risk of thromboembolic complications.     

Sutural growth restriction and modern human facial evolution: an experimental study in a pig model

Facial size reduction and facial retraction are key features that distinguish modern humans from archaic Homo. In order to more fully understand the emergence of modern human craniofacial form, it is necessary to understand the underlying evolutionary basis for these defining characteristics. Although it is well established that the cranial base exerts considerable influence on the evolutionary and ontogenetic development of facial form, less emphasis has been placed on developmental factors intrinsic to the facial skeleton proper. The present analysis was designed to assess anteroposterior facial reduction in a pig model and to examine the potential role that this dynamic has played in the evolution of modern human facial form. Ten female sibship cohorts, each consisting of three individuals, were allocated to one of three groups. In the experimental group (n = 10), microplates were affixed bilaterally across the zygomaticomaxillary and frontonasomaxillary sutures at 2 months of age. The sham group (n = 10) received only screw implantation and the controls (n = 10) underwent no surgery. Following 4 months of post‐surgical growth, we assessed variation in facial form using linear measurements and principal components analysis of Procrustes scaled landmarks. There were no differences between the control and sham groups; however, the experimental group exhibited a highly significant reduction in facial projection and overall size. These changes were associated with significant differences in the infraorbital region of the experimental group including the presence of an infraorbital depression and an inferiorly and coronally oriented infraorbital plane in contrast to a flat, superiorly and sagittally infraorbital plane in the control and sham groups. These altered configurations are markedly similar to important additional facial features that differentiate modern humans from archaic Homo, and suggest that facial length restriction via rigid plate fixation is a potentially useful model to assess the developmental factors that underlie changing patterns in craniofacial form associated with the emergence of modern humans.     

Effect of heparin reversal and fresh platelet transfusion on platelet emboli post-cardiopulmonary bypass in a pig model

Heparin reversal by protamine and fresh platelet transfusion may decrease bleeding complications post-cardiopulmonary bypass (CPB) and may increase the level of organ trapped platelet emboli. Platelet emboli were quantified in two groups of 12 Yorkshire pigs (30-35 kg), where 111indium labeled autologous platelets (INPLT: 850-1,200 microCi) were injected intravenously before and after CPB (BCPB, ACPB), and the platelet emboli level in intact organs and their samples (brain, heart, kidneys, lung, liver, and spleen) was quantified with an ion chamber and a gamma counter, respectively. All pigs were systemically heparinized (ACT > 400 sec). CPB was carried out at 2.5-3.5 L/min at 28 degrees C using a centrifugal pump, an oxygenator (OX:Bentley Univox 1.8 m2), an arterial filter (AF:0.25 m2), and a cardiotomy reservoir (CR: BMR 250) for 90 min. Heparin was reversed with an equivalent dose of protamine. The percent of INPLT dose (ID%, mean +/- SD) in organs of BCPB and ACPB pigs was calculated. The sequence of platelet emboli on a unit weight basis (ID%/g) had the following order: Spleen > Liver > Lung > Kidneys > Heart > Brain. The presence of significantly higher levels of emboli in brain, heart, and kidneys in the ACPB than the BCPB group suggest that platelet transfusion after heparin reversal with protamine may increase the risk of platelet emboli. However, it is an acceptable risk for patients having bleeding complications post-CPB.     

Low molecular weight heparin in prophylaxis of deep vein thrombosis in Asian general surgical patients: A Kashmir experience

Background and Objectives:

Deep vein thrombosis (DVT) occurs at a lower rate in Asia than in the rest of the world. We wanted to study the significance and efficacy of low molecular weight heparin (LMWH) in prophylaxis of DVT in major general surgical patients in the Kashmir Valley (India, Asia) so as to make it a routine in our patients.

Patients and Methods:

This was a prospective study in which the effect of LMWH was compared with no prophylaxis.

Results:

LMWHs are more effective than no prophylaxis in the prevention of DVT and pulmonary thromboembolism in highest-risk general surgical patients (odds ratio = 16.64; 95% confidence interval = 3.63–1130.03; P-value = 0.014).

Conclusion:

LMWHs have a significant prophylactic effect on DVT in general surgical patients, with a higher benefit to risk ratio, and, in spite of the low incidence of DVT in Asia, its prophylaxis should routinely be considered in this part of the world as well, preferably in the form of LMWHs.     

山羊颈椎能成为人类颈椎的良好模型吗?

目的比较山羊与人颈椎的体外三维生物力学特征.方法取新鲜成年人尸体与崇明山羊颈椎标本(C0～T1)各8具,在脊柱三维运动测试仪上检测两者屈曲、后伸、左右侧屈、左右轴向旋转等模式下的运动范围和中性区.结果在前屈运动方式下,山羊和人C1-2的ROM分别为16.9°±5.1°和14.3°±3.2°,超过其它节段.在后伸运动方式下,山羊与人C1-2的ROM分别为20.6°±4.8°和18.7°±3.7° C0-1的ROM分别为19.3°±4.7°和18.4°±4.3°,超过其它节段.在轴向旋转运动模式下,山羊与人C1-2的ROM分别为48.60±8.6°和56.3°±8.9°.除山羊C4-7左右侧屈的NZ与人相比有统计学差异(P＜0.05)外,其它节段前屈、后伸、轴向旋转及左右侧屈的ROM和NZ与人相比无统计学差异(P＞0.05).结论崇明山羊与人颈椎在前屈、后伸、左右侧屈和轴向旋转等运动模式下的ROM及NZ相近,可作为颈椎研究的良好动物模型.     

Advancement of prophylaxis and therapy for venous thromboembolism

Recently in Japan, venous thromboembolism (VTE) [deep vein thrombosis (DVT)/pulmonary thromboembolism (PTE)] has increased with the Westernization of eating habits and aging of society. In the West, the prophylaxis guidelines have been discussed for many years. Unfortunately, Japan falls far behind the West in this area. Therefore, the necessity of thromboprophylaxis in Japanese people should be emphasized based on reliable VTE studies in Japan. In orthopedic surgery, prospective multicenter studies in Japan indicate that the incidence of DVT/PTE in total hip or knee replacement surgery and hip fracture surgery were almost equal to those in Western people. Furthermore, a multi-center, prospective epidemiological study in Japan revealed that the incidence of VTE following major abdominal surgery was 24.3%. We developed Japanese Guidelines for VTE prophylaxis based on the 6th ACCP guideline in 2004. The incidence of perioperative PTE in Japan has been investigated by the Japanese Society of Anesthesiologists since 2002. The rate of perioperative PTE was estimated to be 4.41 per 10,000 operations in 2002, and 4.76 in 2003; however, it decreased to 3.61 immediately after the guideline for thromboprophylaxis was issued and the management fee for PTE prophylaxis became covered by health insurance in April 2004. Furthermore, it markedly decreased in 2005. However, mechanical prophylaxis is not sufficient to prevent PTE, and advanced prophylaxis by anticoagulants, such as low-molecular-weight heparin/selective Xa inhibitor along with unfractionated heparin (UFH)/vitamin K antagonists (VKA) will be essential. The advanced revised guidelines for VTE prophylaxis based on our clinical evidence will be established in the near future. As for treatment for VTE, anticoagulant and thrombolytic therapies are essential. In cases with VTE, UFH followed by VKA (INR: 1.5-2.5) is standard. In cases of PTE with shock, thrombolytic therapy such as tissue plasminogen activator or urokinase, catheter intervention, or surgical procedures under pericutaneous cardiopulmonary support should be selected based on the severity of PTE.     

A catheter tactile sensor for measuring hardness of soft tissue: measurement in a silicone model and in anin vitro human prostate model

Tissue hardness is related to tissue composition, and this is often changed by disease. It is therefore of interest to measure the hardness in an objective and non-invasive way. A tactile sensor based on a vibrating piezoelectric ceramic element in a feedback loop is described. When the sensor touches an object it produces a frequency shift related to the hardness of the object. The aim of this study was to develop an in vitro hardness measurement method using a catheter type version of the sensor. The method was evaluated in an established silicone tissue model and on human prostate tissue in vitro. A linear relationship was found with a high degree of explanation (R2 = 0.98) between a cone penetration hardness standard (DIN ISO 2137) applied to the silicone model and the corresponding frequency shift. The results from measurements on a human prostate tissue sample, fixed with formalin, showed that the relative hardness measured with the tactile sensor correlated (R = -0.96, p < 0.001, N = 60) with the proposed hardness related to the histological composition of the prostate tissue. The results indicated that hardness of prostate tissue, and maybe hardness of human tissue in general, can be expressed according to the cone penetration standard and that the hardness can be measured with this tactile sensory system. These findings hold the promise of further development of a non-invasive tool for hardness measurement in a clinical situation.     

Supportive accountability: a model for providing human support to enhance adherence to eHealth interventions

The effectiveness of and adherence to eHealth interventions is enhanced by human support. However, human support has largely not been manualized and has usually not been guided by clear models. The objective of this paper is to develop a clear theoretical model, based on relevant empirical literature, that can guide research into human support components of eHealth interventions. A review of the literature revealed little relevant information from clinical sciences. Applicable literature was drawn primarily from organizational psychology, motivation theory, and computer-mediated communication (CMC) research. We have developed a model, referred to as "Supportive Accountability." We argue that human support increases adherence through accountability to a coach who is seen as trustworthy, benevolent, and having expertise. Accountability should involve clear, process-oriented expectations that the patient is involved in determining. Reciprocity in the relationship, through which the patient derives clear benefits, should be explicit. The effect of accountability may be moderated by patient motivation. The more intrinsically motivated patients are, the less support they likely require. The process of support is also mediated by the communications medium (eg, telephone, instant messaging, email). Different communications media each have their own potential benefits and disadvantages. We discuss the specific components of accountability, motivation, and CMC medium in detail. The proposed model is a first step toward understanding how human support enhances adherence to eHealth interventions. Each component of the proposed model is a testable hypothesis. As we develop viable human support models, these should be manualized to facilitate dissemination.     

Evaluation of the silver iontophoretic catheter in an animal model

Silver iontophoretic catheters (SIC) were shown to be highly efficacious in preventing catheter infections in vitro and in a rabbit model (J. Infect. Dis. 173 (1996) 495). Furthermore, we sought to determine the safety and durability of SIC prior to use in humans. A total of 30 New Zealand white rabbits (3-4 kg) were randomly assigned to one of three groups whereby SIC or Arrow Guard (AG) catheters were tunneled and inserted in the jugular vein. All animals were followed for 2-12 weeks after catheter implantation. Blood was collected from each rabbit for assessment of toxicity and determination of silver levels. The electrical current generated by each SIC was measured once daily. At the end of the follow-up period, tissue samples were collected from the skin surrounding the catheter, the lungs, spleen, and liver. Microscopically, none of the tissues examined from any of the animals showed evidence of silver deposits, silver toxicity, thermal or electrical injury. The silver levels in the animals that received the SIC ranged from 0.1 to 2.23 microg/l with a mean of 0.62 (+/-0.44 SD). In conclusion SIC were safe with normal serum silver levels and were not associated with any local or systemic toxicity.     

Inhibition of human and guinea pig complement by heparin fractions differing in affinity for antithrombin III or in average molecular weight

Heparin comprises a mixture of structurally related molecules. Affinity for antithrombin III (AT III) is a prerequisite for its anticoagulant activity, which also is dependent on its molecular weight. In this study heparin fractions prepared by affinity chromatography on immobilized AT III and by gel filtration chromatography were compared for their ability to inhibit complement mediated haemolysis and both classical and alternative pathway C3 activation as measured by crossed immunoelectrophoresis. In normal human serum, inhibition of haemolysis and of heat-aggregated IgG (HAGG) as well as zymosan induced C3 activation by heparin was found to be independent of its AT III affinity and of its molecular weight (range 4800-17,000), on a weight basis. In guinea pig serum similar results were obtained for inhibition of HAGG induced C3 activation, but inhibition of haemolysis showed a marked molecular weight dependency and was also reduced for the fraction with low affinity for AT III. This may reflect a species difference in the haemolytic action of human and guinea pig complement. It is concluded that inhibition of human complement by heparin is independent of its anticoagulant activity and of its size and it is suggested that a fraction of heparin with reduced risk for bleeding and platelet aggregation is a potential anti-inflammatory agent.     

Assessment of a new hub design and the semiquantitative catheter culture method using an in vivo experimental model of catheter sepsis.

An in vivo model of hub-related catheter sepsis in rabbits is reported. The model was used to investigate the protection offered by a new hub design against external contamination by Pseudomonas aeruginosa or Staphylococcus epidermidis and to reassess the diagnostic value of the semiquantitative culture method in bacteremia of endoluminal origin. Contamination of conventional Luer-Lock connectors was followed by clinical sepsis, positive catheter segment cultures, or both, whereas contamination of the new hub was followed by complete protection. Clinical and bacteriological discrepancies observed between contamination with P. aeruginosa and S. epidermidis suggest that the virulence of microorganisms may account for differences in the natural history of hub-originated catheter sepsis. The semiquantitative extraluminal method for catheter culture yielded less than 15 CFU in three animals with proven bacteremia and should not be used as the "gold standard" to define catheter-related bacteremia.     

The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease

The biology of cells of the mononuclear phagocyte system has been studied extensively in the mouse. Studies of the pig as an experimental model have commonly been consigned to specialist animal science journals. In this review, we consider some of the many ways in which the innate immune systems of humans differ from those of mice, the ways that pigs may address the shortcomings of mice as models for the study of macrophage differentiation and activation in vitro, and the biology of sepsis and other pathologies in the living animal. With the completion of the genome sequence and the characterization of many key regulators and markers, the pig has emerged as a tractable model of human innate immunity and disease that should address the limited, predictive value of rodents in preclinical studies.