The report of an Italian family with heterozygous protein C deficiency

A heterozygote protein C deficit was found in 4 members of the same family. The propositus is a 40 year old male with a clear thrombotic tendency. This included repeated thrombophlebitis of the right leg, and one episode of pulmonary embolism. Arterial thrombosis was not noted. The anticoagulant therapy undertaken by the patient appears to be of some benefit in the sense that no recurrence of thrombotic manifestations occurred. One brother and two nephews of the propositus, even though asymptomatic showed reduced levels of Protein C both as activity and antigen. The parallel reduction of Protein C activity and antigen points towards a "true" deficit of Protein C. The normal, although reduced, pattern in the crossed immunoelectrophoresis supplies further confirmation to this interpretation.     

Postmenopausal hormone replacement therapy and venous thromboembolism

Background:Women taking hormone replacement therapy (HRT) have a 2- to 5-fold increased risk of venous thrombosis compared with nonusers. Increasingly, evidence has suggested that the size of the risk increase varies according to related factors, such as the type of estrogen used, the mode of delivery, and the presence of other predisposing factors.Objective:The aim of this study was to examine the current literature to assess the varying risk of venous thrombosis among women taking HRT.Methods:An extensive search was carried out on all major electronic databases including MEDLINE 1995 to October 2005 and BIS (EMBASE) 1980 to October 2005. Relevant keywords relating to thrombosis (venous thromboembolism, venous thrombosis, deep vein thrombosis, and pulmonary embolism) combined with hormones (hormone replacement therapy and estrogen) were used to capture all potentially relevant studies.Results:The increased risk of a first episode of venous thrombosis in women currently taking HRT compared with nonusers ranged from 1.22 (95% CI, 0.76–1.94) to 4.50 (95% CI, 1.30–15.10). Similar increases in risks for deep vein thrombosis and pulmonary embolism were found. The risk of venous thrombosis is the highest in the first year of therapy, durich which as much as a greater than 6-fold increase was found. Women taking estrogen-progestin HRT had a significantly greater risk of venous thrombosis than those using estrogen-only preparations (odds ratio [OR], 1.60; 95% CI, 1.13–2.26). Studies have also suggested a dose-related effect, suggesting high-dose estrogen therapy is associated with a greater increased risk of venous thrombosis than low-dose preparations. Comparisons between oral and transdermal HRT have shown a significant difference in the relative risk of venous thrombosis (OR, 4.0; 95% CI, 1.9–8.3) favoring the use of transdermal preparations. The presence of thrombophilia, particularly factor V Leiden, further amplifies the risk of venous thrombosis in women using HRT (OR, 13.16; 95% CI, 4.28–40.47). The presence of other risk factors, such as increasing age and being overweight, were all shown to be associated with a further increase in the risk of venous thrombosis.ConclusionsRecent studies have confirmed that current users of HRT are at increased risk of venous thrombosis. The increase in risk has been shown to vary according to duration of use, with the risk being greatest during the first year of use. Moreover, the increased risk varies according to the type of preparation and presence of additional risk factors such as increasing age, obesity, cancer, and recent surgery. Few studies have examined the relationship between thrombophilia, HRT and venous thrombosis; thus, more research is required in this area before accurate estimates of the risk can be made.     

Liver transplantation. Experience with 100 cases.

Between March 1988 and November 1989, 100 liver transplants were performed on 90 patients at Pacific Presbyterian (now California Pacific) Medical Center in San Francisco. The immunosuppressive regimen was a combination of prophylactic Minnesota antilymphocyte globulin, cyclosporine, and low-dose corticosteroids. Rejections were treated with OKT3, a monoclonal antibody, or corticosteroids. Of the 100 transplants, 32 were done on 30 children, 18 of whom weighed less than 10 kg and 9 of whom received livers that had been surgically reduced in size to fit the recipient. The overall patient survival at 2 years was 85%. Of 100 liver transplants, treatment was given for 80 (80%) for at least 1 episode of rejection. At least 1 episode of serious infection occurred in 34 of the 60 adult patients and 25 of the 30 children. Of the entire group, 2% had hepatic artery thrombosis, and 12% had biliary complications that necessitated reoperation. The quality of life has been good, with a follow-up from 1 to almost 3 years (mean = 22 months). Comparing these data with those of other published series shows a decreased incidence of surgical complications and a lower rate of fungal and viral infections. We attribute this to the reduction of steroid dosage during convalescence without jeopardizing patient or graft survival.     

Ambulant management of patients with recent myocardial infarction.

Thirty-two patients who had remained ambulant and active after suffering an acute myocardial infarction were observed for 6 months. Complications were present initially in 11 but proved transient. One patient died of a new coronary thrombosis 15 weeks after the initial episode. There were no recurrences among the 31 surviving patients. After the 6 months all but two patients were as well as before the attack; 21 were free of symptoms and there was no undue incidence of objective findings that could be attributed to failure to rest after the attack. It is therefore concluded that, for patients who suffer an acute myocardial infarction, immediate diagnosis and admission to a coronary care unit need not be equated invariably with immobilization in bed. Our experience suggests that selected patients can be allowed moderate activity without ill effects and thus avoid the undesirable consequences of enforced bed rest.     

Kidney transplantation in elderly patients

The Eurotransplant Senior Program (ESP) allocates kidneys from elderly donors to elderly recipients (> or = 65 years old). During the last 39 years, 922 kidney transplantations were performed in our transplant center. We retrospectively analysed patients included in the ESP from the our center. Eleven patients > or = 65 years old recieved kidney from donors 65 years old. Cold ischemia time was approximately 15 hours. Dual kidney transplantation was performed in one patient. Appropriate immunosuppressive protocol was given to all patients. Surgical complications were relatively common and included dissection of renal artery (1 patient), thrombosis of renal artery (1 patient), ureterovesical obstruction (1), lymphocele (1), bleeding (1), acute abdomen (2) and wound dehiscence (1). One rejection episode was registered. Delayed graft function was observed in the two patients with full recovery of kidney function. Seven patients until now have good functioning graft. Four kidneys were lost. One patient died because of pneumonia. Kidney transplantation in elderly is feasible procedure but with greater number of complications than usually.     

Relationship between Locomotor Activity and Monoamines Following Single and Double Transient Forebrain Ischemia in Gerbils

The relationship between locomotor activity and monoamine levels in gerbils after single and/or double forebrain ischemic insult was studied. Locomotor hyperactivity was observed after the first ischemic episode, but the gerbils failed to show hyperactivity after the second ischemic episode induced one week later. The monoamine levels were determined in order to clarify the biochemical basis of post-ischemic locomotor hyperactivity. Norepinephrine increased in response to first ischemic episode but remained at normal levels after the second episode of ischemia. Metabolites of dopamine and serotonin increased after both the first and second ischemic insults, which indicates that these monoamines do not play significant roles in post-ischemic locomotor activity. Therefore, increases in norepinephrine after first ischemic insult may play a role in increasing locomotor activity during the period following such an episode.     

Key Features of Human Episodic Recollection in the Cross-Episode Retrieval of Rat Hippocampus Representations of Space

Neurophysiological studies focus on memory retrieval as a reproduction of what was experienced and have established that neural discharge is replayed to express memory. However, cognitive psychology has established that recollection is not a verbatim replay of stored information. Recollection is constructive, the product of memory retrieval cues, the information stored in memory, and the subject''s state of mind. We discovered key features of constructive recollection embedded in the rat CA1 ensemble discharge during an active avoidance task. Rats learned two task variants, one with the arena stable, the other with it rotating; each variant defined a distinct behavioral episode. During the rotating episode, the ensemble discharge of CA1 principal neurons was dynamically organized to concurrently represent space in two distinct codes. The code for spatial reference frame switched rapidly between representing the rat''s current location in either the stationary spatial frame of the room or the rotating frame of the arena. The code for task variant switched less frequently between a representation of the current rotating episode and the stable episode from the rat''s past. The characteristics and interplay of these two hippocampal codes revealed three key properties of constructive recollection. (1) Although the ensemble representations of the stable and rotating episodes were distinct, ensemble discharge during rotation occasionally resembled the stable condition, demonstrating cross-episode retrieval of the representation of the remote, stable episode. (2) This cross-episode retrieval at the level of the code for task variant was more likely when the rotating arena was about to match its orientation in the stable episode. (3) The likelihood of cross-episode retrieval was influenced by preretrieval information that was signaled at the level of the code for spatial reference frame. Thus key features of episodic recollection manifest in rat hippocampal representations of space.     

小鼠体内血栓形成动物模型的建立及在抗血栓药物筛选中的应用

目的 :建立一种无创性小鼠体内血栓动物模型并应用于多种抗血栓药物的药效观察。方法 :用角叉菜胶建立了小鼠体内血栓动物模型。利用此模型观察潘生丁片 ,抗栓胶囊、复方丹参注射液、川芎嗪注射液对血栓形成的影响。结果及结论 :用角叉菜胶建立的小鼠体内血栓动物模型 ,无创伤性 ,操作简易方便。并可应用于多种抗血栓药物的药效观察 ,剂量的选择 ,药物的筛选。     

Genetic Polymorphism of NOS3 with Susceptibility to Deep Vein Thrombosis after Orthopedic Surgery: A Case-Control Study in Chinese Han Population

Deep vein thrombosis is one of the common complications of orthopedic surgery. Studies indicated that genetic factors played a considerable role in the pathogenesis of deep vein thrombosis. Endothelial nitric oxide synthase which encoded by nitric oxide synthase 3 (NOS3), can generate nitric oxide in endothelial cells. As a predominant regulator for vascular homeostasis, nitric oxide might be involved in the pathogenesis of thrombosis. It had been proved that the NOS3 polymorphism (rs1799983) was associated with the development of cardiovascular diseases. Our objective was to evaluate the association between the NOS3 polymorphism (rs1799983) and deep vein thrombosis after orthopedic surgery in Chinese Han population. The polymorphism was genotyped in 224 subjects with deep vein thrombosis after orthopedic surgery and 580 controls. Allele and genotype frequencies were compared between subjects with deep vein thrombosis and control subjects. The allele and genotype frequencies of the NOS3 polymorphism (rs1799983) were significantly different between subjects with deep vein thrombosis and control subjects. There were also significant differences when the subjects were stratified by gender, surgery type and hypertension status. These findings suggested that the NOS3 polymorphism (rs1799983) was associated with susceptibility to the deep vein thrombosis after orthopedic surgery in Chinese Han population, and NOS3 might play a role in the development of deep vein thrombosis after orthopedic surgery.     

The effect of established infection on microvascular surgery

The success of microvascular anastomoses in the presence of staphylococcal infection was studied using rat femoral arteries. There was a spontaneous thrombosis rate of 19 percent in normal vessels that traversed the area of infection. Vessels with an anastomosis outside the area of infection had a similar thrombosis rate, but if the anastomotic site was within the infected area itself, the thrombosis rate increased to 75 percent. Inflammatory changes with subsequent fibrosis in the media and adventitia appeared responsible for the thrombosis. The intima was unaffected by the presence of infection. This study suggests that when a microvascular anastomosis is necessary in the presence of infection, the anastomosis should be placed outside the area of infection with a pedicle to traverse the infected area.     

Involvement of bioantioxidants in thrombosis in mice

SUMMARY

An involvement of free radicals in thrombosis has been suggested previously. In order to further explore the role of free radicals and antioxidants in thrombosis, we have measured preventive (enzymes of the glutathione redox cycle) and chain-breaking antioxidants (vitamin E and C) in whole blood, platelets, neutrophils (PMNLs), heart and lung following collagen and adrenaline induced thrombosis in mice. A significant decrease in platelet glutathione (GSH) level (54%) and glutathione reductase activity was observed after thrombosis. In addition, GSH content in whole blood was also found to be reduced. In PMNLs, an increase in glutathione peroxidase activity and a four-fold elevation in vitamin C content was observed following thrombosis. However, levels of vitamin E and total thiol groups remained unchanged in both the cells and tissues. The results further suggest involvement of free radicals and PMNLs in thrombosis.     

Incidence of early post-operative iliofemoral thrombosis.

The doppler ultrasound probe was used to study 138 patients after major surgery to assess the incidence of iliofemoral thrombosis in the early postoperative period. The patients were simultaneously studied with the 125-I-fibrinogen uptake test. The accuracy of the ultrasonic technique was assessed concurrently by comparing its results with those of ascending phlebography in a separate group of patients. The ultrasound probe detected thrombus proximal to the calf but was inaccurate in locating its exact site. Of the 138 patients studied postoperatively 28 developed calf vein thrombosis detected istopically, but there was no evidence of iliofemoral thrombosis in any patient. Thus, spontaneous iliofemoral thrombosis in the early postoperative period is rare.     

支气管哮喘急性发作期超敏C-反应蛋白、白细胞、中性粒细胞比例检测的意义及比较

探讨超敏C-反应蛋白（hs-CRP）、血白细胞总数（WBC）、中性粒细胞比例（N％）在支气管哮喘（简称哮喘）急性发作期诊治中的临床意义。方法：分析60例患者治疗前及自觉症状缓解时hs—CRP、WBC、N％动态变化情况,观察上述指标在急性发作期的阳性率以及自觉症状缓解时的阴性率。结果：①hs-CRP、N％、WBC在自觉症状缓解时均明显低于哮喘急性发作期（P〈0．05）;②哮喘患者急性发作期hs—CRP、N％阳性率均高于WBC阳性率,且与后者比较均具有统计学差异（P〈0．05）;③哮喘患者经治疗自觉症状缓解时hs-CRP、WBC阴性率均高于N％阴性率,且与后者比较均具有统计学差异（P〈0．05）。结论-血清hs-CRP既可作为哮喘患者急性发作期感染的敏感指标,又是反映急性发作期治疗效果的早期评判指标,比WBC、N％更迅速、敏感。     

Superficial Siderosis of the Central Nervous System Induced by a Single-Episode of Traumatic Subarachnoid Hemorrhage: A Study Using MRI-Enhanced Gradient Echo T2 Star-Weighted Angiography

The purpose of this study was to examine whether a single episode of traumatic subarachnoid hemorrhage (tSAH) could cause superficial siderosis of the central nervous system (SS-CNS).This study was approved by the local ethics committee. Thirty-two patients with a history of a single episode of tSAH were enrolled in the study. An episode of tSAH was confirmed in patients based on a CT scan or a lumbar puncture, and a follow-up examination was conducted at least six weeks after the brain trauma. A follow-up MRI examination was performed, using enhanced gradient echo T2 star-weighted angiography (ESWAN) to detect hemosiderin deposition on the cortical surface. The extent to which hemosiderin deposition was associated with several clinical factors was investigated. Various degrees of hemosiderin deposition were detected in 31 of 32 (96.9%) single-episode tSAH patients. Analysis of contingency tables revealed an association between the regions of subarachnoid bleeding based on CT images and the regions of hemosiderin deposition based on ESWAN images (χ² = 17.73, P<0.05). SS-CNS was determined to be a common consequence after a single episode of tSAH. The extent of hemosiderin deposition is closely correlated with the initial bleeding sites and bleeding volume.     

Analysis of outpatient surgery center safety using an internet-based quality improvement and peer review program

Assessing the quality of care delivered in office-based outpatient surgery centers is difficult because formerly there was no central data collection system. The American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF), in its ongoing effort to assess and improve patient care, has developed an Internet-based quality improvement and peer review program to analyze outcomes for surgery centers it accredits. Reporting is mandatory for all surgeons operating in AAAASF-accredited facilities. Each surgeon must report all unanticipated sequelae and at least six random cases reviewed by an accepted peer review group biannually. A total of 411,670 procedures were analyzed during a 2-year period (from 2001 to 2002). There were 2597 sequelae reported during this period. The most common sequela was hematoma formation following breast augmentation. Infection occurred in 388 cases. Deep vein thrombosis, pulmonary embolism, and intraoperative cardiac arrhythmias were found to occur in a frequency consistent with previous reports. Significant complications (hematoma, hypertensive episode, wound infection, sepsis, and hypotension) were infrequent. A total of 1378 significant sequelae were reported for 411,670 procedures. This calculates to one unanticipated sequela in 299 procedures (an incidence of 0.33 percent). Seven deaths were reported. A death occurred in one in 58,810 procedures (0.0017 percent). The overall risk of death was comparable whether the procedure was performed in an AAAASF-accredited office surgery facility or a hospital surgery facility.This study documents an excellent safety record for surgical procedures performed in accredited office surgery facilities by board-certified surgeons.     

Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis.     

Diagnosis and treatment of venous thromboembolism by consultants in Scotland.

A questionnaire was sent to 508 consultants in Scotland likely to encounter deep vein thrombosis and pulmonary embolism to assess their current standard practice in diagnosis and treatment of these disorders. Replies were received from 358 (70.5%). In deep vein thrombosis 47% and in pulmonary embolism 33% of consultants usually depended on clinical observation alone for diagnosis. In deep vein thrombosis 37% used venography to supplement clinical diagnosis and in pulmonary embolism 13% used angiography and 53% used isotopic scanning. Almost all consultants treated deep vein thrombosis (95%) and pulmonary embolism (99%) with anticoagulants. Most consultants (81%) gave heparin by intravenous infusion. Although many consultants gave intravenous heparin for more than three days (49.5% in deep vein thrombosis and 61% in pulmonary embolism), 25% of these consultants did not use any laboratory monitoring of heparin''s effect. Large numbers of consultants gave warfarin for more than three months (20% in deep vein thrombosis and 47% in pulmonary embolism). There was a significant tendency to give heparin (p less than 0.01) and warfarin (p less than 0.001) for longer periods in pulmonary embolism than in deep vein thrombosis. This survey shows a widely varying practice and underlines the need for further controlled studies to provide clear guidance in the management of deep vein thrombosis and pulmonary embolism.     

Prevention of Deep Vein Thrombosis by Intermittent Pneumatic Compression of Calf

A consecutive, randomly allocated, controlled clinical trial of the prophylactic effect of intermittent pneumatic compression of the calf on the incidence of postoperative deep vein thrombosis showed that in patients without malignant disease there was a highly significant reduction in the incidence of thrombosis. In patients with malignant disease the incidence of thrombosis was higher than in those without, and there was no reduction in incidence by the application of intermittent compression. In the absence of malignant disease, severity of operation and the age of the patient were the most significant aetiological factors. We found no relation between the incidence of deep venous thrombosis and obesity, length of preoperative stay, location of hospital, or duration of anaesthesia. We suggest that intermittent pneumatic compression as used in this trial is a safe, effective, and extremely practical method of preventing postoperative deep vein thrombosis in patients not suffering from malignant disease.     

Episodic encoding is more than the sum of its parts: an fMRI investigation of multifeatural contextual encoding

Episodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced.