bluuebunny/crossref_metadata_2025 huggingface dataset:
State-of-the-Art Review : Antithrombotic Agents from Hematophagous Animals
Authors: Markwardt Fritz
Published: November 2007

Bloodsucking animals produce anticoagu lantly effective substances that are a challenge to coagu lation studies. In the past 40 years efforts have been fo cused on the isolation and chemical characterization of such agents as well as on the clarification of their modes of action. Following the success in the development of the anticoagulant agent hirudin from medicinal leeches, these naturally occurring anticoagulants were recently in vestigated as a source of antithrombotics for pharmaceu tical use. These polypeptides or miniproteins were shown to be specific inhibitors of certain coagulation factors that block either the formation or the effect of thrombin or are supported by substances that inhibit the aggregation and adhesion of blood platelets and by proteolytic enzymes with fibrinolytic activity. By advances in biotechnology of protein-like substances, especially gene technology, these antithrombotics have been obtained in amounts suf ficient for preclinical and clinical studies. Thus, the in vestigation of the anticoagulant agents from hematopha gous animals offers a new line of research in antithrom botic drugs. Key Words: Bloodsucking animals— Naturally occurring anticoagulants—Fibrinolytics and platelet inhibitors.
Functional Determination of Factor XII in Plasma
Authors: Schousboe Inger , Røjkær Rasmus , Lintner Rita
Published: November 2007

Clinical assays for factor XII determination are based on measurements of coagulation time in a mul tifactorial assay requiring the availability of factor XII deficient plasma, and the determination is affected by the presence of heparin. Another way of determining the amount of functionally active factor XII in plasma is to measure the amidolytic activity of factor XIIa in a chro mogenic assay. We describe such an assay, which in con trast to previously described chromogenic assays, is in dependent of the presence of prekallikrein. To prevent kallikrein from interfering with the assay, soy bean trypsin inhibitor was added to the plasma. Factor XII was autoactivated by addition of ZnCl2 and sulfatide. Sul fatide could be exchanged with acidic phospholipids but not with dextran sulfate. Linear standard curves were obtained whether the plasma was diluted with factor XII deficient plasma or a physiological buffer. The presence of a pharmacologic concentration of heparin did not affect the assay. In 37 plasma samples from healthy donors, a linear correlation was found between factor XII activity and the amount of factor XII antigen. Key Words: Factor XII—Hageman factor—Determination—Plasma.
State-of-the-Art Review : Prevention of Venous Thromboembolism in Major Orthopedic Surgery
Authors: Prandoni Paolo , Goldhaber Samuel Z. , Piccioli Andrea , Girolami Antonio
Published: November 2007

Venous thromboembolism continues to be a major source of morbidity and mortality in both elective and traumatic orthopedic surgery. Prevention of this complication has received much attention in the orthope dic literature in recent years. We reviewed the relative efficacy and safety of various agents in the prophylaxis of venous thromboembolism arising after major orthopedic surgery. In patients undergoing total hip replacement, low-molecular-weight heparin in fixed doses, adjusted doses of warfarin, and unfractionated heparin in adjusted doses are the most effective prophylactic agents and are highly recommended for routine use. Low-molecular- weight heparin or warfarin should be used in patients with hip fractures. Low-molecular-weight heparin, warfarin, or intermittent pneumatic compression should be used in patients undergoing major knee surgery. A number of questions still remain unanswered. In particular, further studies are needed to establish the optimal duration of prophylaxis.
State-of-the-Art Review : Activated Partial Thromboplastin Time in Heparinized Plasma: Influence of Reagent, Acute-Phase Reaction, and Interval Between Sampling and Testing
Authors: Strekerud Finn G. , Abildgaard Ulrich
Published: November 2007

Plasma samples from 10 healthy persons and 10 patients with acute-phase reaction were heparinized in vitro to obtain up to 0.70 U/ml. Activated partial throm boplastin time (APTT) was then determined using an op tical method (Automated Coagulation Laboratory or ACL Machine) and four different reagents (Actin, Ceph otest, Platelin, and Thrombosil). Heparin sensitivity var ied between individuals, and it was lower in acute-phase plasma than in healthy plasma. There was also a marked difference in heparin sensitivity among the different re agents; Actin was the least sensitive reagent, while Plate lin was the most sensitive reagent in healthy plasma and Thrombosil the most sensitive reagent in acute-phase plasma. Delay in testing prolonged the APTT values both in acute-phase and healthy heparinized plasma. With Ac tin and Cephotest, a delay of 90 min at 22°C resulted in 30-50% prolongation of APTT. A delay of 150 min caused a prolongation of 75-110% with Actin. Cephotest, Plate lin, and Thrombosil were less prolonged. Ex vivo samples from heparinized plasma showed similar degrees of pro longation. Storage at 4°C resulted in less prolongation. Assuming a therapeutic range of 0.35-0.70 U/ml of hep arin, the therapeutic APTT ratios in heparinized acute- phase plasma were 1.5-3.0 for Actin and 2.5-4.5 for Cephotest, Platelin, and Thrombosil. These results un derscore certain limitations in monitoring heparin therapy with the APTT system. Unless the assay is performed within 30 min after sampling, unduly prolonged APTT values will be recorded, which may lead to giving the patient an inappropriately small dose of heparin.
State-of-the-Art Review: The Preclinical and Clinical Pharmacology of Novastan (Argatroban): A Small-Molecule, Direct Thrombin Inhibitor
Authors: Schwarz Richard P. , Becker Jean-Claude P. , Brooks R. Lynn , Hursting Marcie J. , Joffrion James L. , Knappenberger Gary D. , Kogan Timothy P. , Kogan Patricia W. , McKinney Anthony A.
Published: November 2007

Because of the unsatisfactory options available for safe and effective antithrombotic therapy, recent, intense research and development efforts have been focused on direct thrombin inhibitors, also known as site-directed thrombin inhibitors. The intravenous agent Novastan (argatroban) is a small-molecule, reversible, direct thrombin inhibitor that is selective for the catalytic site of the thrombin molecule. Argatroban's molecular properties (small molecule; fast, selective, and reversible inhibition of the thrombin catalytic site; and similar in vitro potency for inhibiting both clot-bound and soluble thrombin) offer the potential for significant antithrombotic efficacy with minimal systemic anticoagulant ef fects. Its clinical pharmacologic properties offer the potential for minimal risk of bleeding, very rapid achievement of therapeutic antithrombotic efficacy, predictable dose-response, and rapid restoration of the hemostatic systems to normal upon termination of intravenous infusion. Argatroban is currently approved for clinical use in Japan for the treatment of peripheral arterial occlusive disease. It is in advanced clinical development in North America, South America, and Western Europe for several clinical indications, including (1) adjunctive therapy to thrombolytic agents in the treatment of acute myocardial infarction and (2) antithrombotic therapy for patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome. Key Words: Molecular properties—Novastan (argatroban)—Pharmacology—Thrombin inhibitor.
Arterial Damage, Triglycerides, Apolipoprotein, and Lp-(a) Values in PVD Patients
Authors: Catalano M. , Perilli E. , Carzaniga G. , Scandale G. , Carotta M.
Published: November 2007

The aim of the study was to provide a detailed apolipoproteic profile in stage II peripheral vascular disease (PVD) patients and to ascertain whether lower ankle/ arm pressure index (API) values were associated with a worse profile.

Apolipoproteins of 83 stage II PVD patients (average age 64.7 ± 9.3 years) were selected and compared with those of a group of 44 normal control subjects, similar in terms of age, sex, and smoking and eating habits. Neither PVD patients nor controls had ever received lipid-lowering agents or defined dietary treatment. A diagnosis of PVD was confirmed by an API of <0.85. Arteriopathic patients were also split into two groups, depending on their API values, similar in terms of age, sex and smoking habits: API values of one group (n = 38) were ≥0.6, those of the other group (n = 45) were <0.6. The following biohumoral parameters were considered: fasting glycemia, total cholesterol, triglycerides (TGs); high-density lipoprotein cholesterol (HDL-C); low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC)/HDL-C (TC/ HDL-C), Apoproteins (Apos) AI, AII, B, CII, CIII, and E; and lipoprotein a [Lp(a)].

HDL-C and Apo AI were lower ( p < 0.01), while TC/ HDL-C ratios, Apo B, and Apo CII were higher ( p < 0.01) in PVD patients compared with controls. The comparison between the two PVD groups with different API values showed higher blood TG and VLDL-C values for the patients with lower API values (p < 0.05), indicating a relationship between hypertriglyceridemia and greater arterial damage. Key Words: Peripheral arterial occlusive disease-Triglyceride-Lipoprotein a.
Relationship Between Activated Protein C Resistance and Central Venous Device-Related Complications
Authors: Keung Yi-Kong , Cobos Everardo , Barber Annabel , Ronaghan Cathy , Whitehead Robert , Staton Melody , Gilbert Mary , Morgan David
Published: November 2007

We studied the relationship between activated protein C (APC) resistance and the central venous devices (CVD)-related complications in 61 cancer patients (44 females `and 17 males, median age 50 years, 71 CVD) from November 1994 to November 1995. Two patients (3.3%) had APC resistance, i.e., APC ratio < 2. Twelve episodes of bactercmia, 8 site infections, 31 cases of CVD dysfunction requiring urokinase (UK), and 3 CVD-retated thromboses were noted. With Cox's proportional hazard models, low APC ratios and high d-dimer levels were significantly associated with CVD-related bacteremia (p = 0.0207 and 0.0210). Such an association was not observed with site infection and CVD dysfunction. The incidence of thrombosis was too low to be analyzed. However, one patient with APC resistance developed subclavian vein thrombosis, leading to eventual removal of the catheter. The prevalence of APC resistance in cancer patients and its association with bacteremia are discussed. Key Words : Activated protein C resistance—Central venous catheters—Bacteremia— Catheter site infection—Thrombosis.
Different Anticoagulant Response to Activated Protein C (APC test) and to Agkistrodon Contortix Venom (ACV test) in a Family with FV-R506Q Substitution
Authors: Gemrnati Donate , Serino Maria L. , Mari Rosella , Verzola Isabella , Moratelli Stefano , Ballerini Giorgio
Published: November 2007

To identify the defect(s) responsible for the thrombotic condition affecting a 55-year-old male and his family, we have utilized a new methodological approach (ProC Global®, Istituto Behring, Milan, Italy) to screen the global anticoagulant activity of the protein C pathway, a defect that accounts for the majority of inherited thrombophilias. The test is based on the activation of endogenous protein C in plasma by Protac®, derived from Agkistrodon contortix snake venom (ACV test). Nineteen members of the family were investigated, 11 showed low responsiveness to ACV (normalized ACV ratios < 0.66; normal > 1. 12); in these individuals specific assays of protein C (PC) and protein S (PS) levels and normalized activated protein C ratios (n-APC-r) were performed. A second test evaluating response to APC, using the classic commercial APC test (n-APC-r 1), detected only 10 subjects with abnormal responses : the propositus and two members of the family with n-APC-r 1 values < 0.54, indicating the homozygous state for the R506Q factor V gene mutation, and seven with values ranging 0.69-0.83, consistent with the heterozygous condition (normal > 0.85). Although only ten subjects presented with low n-APC-r 1 values, DNA analysis, in agreement with the ACV test, detected 11 individual with factor V-R506Q substitution (two homozygotes and nine heterozygotes). Thus the classical APC test failed to identify the APC resistance phenotype in two heterozygous subjects whose values were clearly normal (1.05) in the first case and homozygous (0.53) in the second. The ACV test, however, and the modified APC test with test plasma 1/5 diluted in factor V-deficient plasma (n-APC-r 2) completely matched the DNA analysis. A phenotype/genotype correlation was observed in dilutions higher than 1/3 test plasma factor V-deficient plasma. The presence of unknown mechanisms that influence plasma response to exogenous preformed APC (normal at high factor V-deficient plasma dilutions) but not endogenous ACV activated PC was suspected. The suspected low levels of proteins C and S found in several R506Q members of the family were excluded by reassaying the anticoagulant activities at higher plasma dilution ; this supports the known influence of factor V Leiden on functional PC and PS clotting activity. We conclude that the ACV test is appropriate to evaluate the APC resistance condition, but for a firm diagnosis DNA analysis together with the modified APC test are strongly advised even in the presence of unquestionable APC-r values. Key Words: APC resistance-Factor V Leiden-APC test-ACV test-Diagnosis-Inherited thrombophilia.
Thrombolysis, With or Without Heparin, During the First Nine Weeks After Acute Myocardiat Infarction
Authors: Pickering W. , Brozovic M. , Dancy M. , Cohen H.
Published: November 2007

The duration and characteristics of fibrinolytic "shut-down" were studied in 40 patients serially for a 9-week period after acute myocardial infarction (AMI). Patients were randomized into four equal groups to receive streptokinase (SK), SK plus heparin (SK + H), recombinant tissue plasminogen activator (rt-PA) or recombinant t-PA plus heparin (rt-PA + H). All patients received oral aspirin. Plasma fibrinolysis was assessed by performance of the following tests: fibrin plate lysis (FPL), tissue plas. minogen activator (t-PA) activity and t-PA antigen (Ag), plasminogen (plg) and α2-antiplasmin (α2-AP) activity, Clauss fibrinogen, and D-dimer. Prethrombolysis global fibrinolysis was normal in most patients, although plasminogen activator inhibitor (PAI) activity and PA inhibitor-1 antigen (PAI-I Ag) were increased 37.5% of the patients. Fibrin plate lysis was significantly decreased for the first 48 h in all four groups (p < 0.05-0.002) compared with normal controls (n = 10); the decrease persisted longest (5 days) in the group receiving rt-PA alone. The decreased fibrin plate lysis was accompanied by significantly increased D-dimer levels (p < 0.003-0.0002) as well as decreased plg and α2-AP activities (p < 0.05-0.0002), which persisted longer. (≤72 h) in patients receiving SK, indicating a more widespread activation of fibrinolysis in this group. Fibrinogen levels showed a rebound increase which began ≤24 h after thrombolysis while levels of plg and a2-AP were at their lowest. The fibrinogen rebound persisted for at least 6 weeks (p < 0.05-0.002). t-PA activity remained unchanged, and t-PA Ag levels were variable and showed no consistent pattern over the study period. PAI-1 Ag and PAI activity levels were significantly increased (p < 0.02-0.0005) in all four groups for the first 24 h, and individual patients showed increased levels at various times over the study period. The only significant prethrombolysis fibrinolytic change was increased PAI activity and PAI-1 Ag. The only significant effect of heparin was a shortening of the period of decreased global fibrinolysis observed in the rt-PA group from 5 to 2 days. Our findings show that the fibrinolytic shut-down after AMI in patients receiving thrombolysis is short-lived, lasting only a few days. Key Words : Thrombolysis—Myocardial infarction-Fibrinolysis-Heparin.
Antithrombin Concentrates: Clinical Indications
Authors: Vinazzer Helmut
Published: November 2007

Antithrombin (AT) is one of the most important inhibitors of activated clotting enzymes. It is a progressive inhibitor of factors thrombin, Xa, IXa, and XIa. Any diminu tion of activity of AT in plasma causes an increased risk of thrombosis. It is, therefore, important to detect such deficien cies. Congenital defects of AT activity cause a tendency toward venous thrombosis and pulmonary embolism, frequently begin ning between the ages of 10-15 years. In such cases a lifelong prophylaxis with oral anticoagulants is mandatory. In the case of surgery AT must be substituted to normal activity. Under this substitution an additional prophylaxis with low molecular weight heparin is also possible. In cases of pregnancy when oral anticoagulants cannot be given, substitution until delivery is necessary. Acquired AT deficiency in its most severe form is observed in consumption coagulopathy. In these cases it could be demonstrated that massive substitution of AT not only short ened the duration of this condition but was also frequently lifesaving. Antithrombin concentrates are, therefore, of consid erable importance under certain conditions. Antithrombin de ficiency is also found in the nephrotic syndrome due to massive losses of proteins. A diminished production of AT is observed in severe liver diseases. In these cases there is also a diminution of procoagulant factors and platelets resulting in a tendency toward a bleed instead of thrombosis.
Syndromes of Thrombosis and Hypercoagulability: Congenital and Acquired Thrombophilias
Authors: Bick Rodger L. , Kaplan Harold
Published: November 2007

This article stresses the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects apear to be APC-R, SPS, antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant (antiphospholipid antibodies). Therefore, these are the defects that should first be looked for in an individual with unexplained thrombosis. If these more common defects are not found, then the rarer defects including HC II, plasminogen or TPA deficiency, dysfibrinogenemia, el evated PAI-1 and hyperhomocysteinemia should be sought. The importance of finding these defects has significant impli cations for therapy of the individual patient and for institutions of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipopro tein (a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks of throm bosis. Finally, it must be recalled that a diagnosis of thrombo sis, like that of anemia, is only a generic and partial diagnosis; just as in the anemic patient, the etiology must be clearly de fined. Only in this manner can cost-effective and appropriate therapy for both primary treatment and secondary prevention be designed. In addition, the demonstration of a hereditary defect will allow primary prevention in afflicted family mem bers by allowing the choice of appropriate therapy.
Antiplatelet Agents in Cardiovascular and Cerebrovascular Diseases
Authors: Breddin Hans Klaus
Published: November 2007

Aspirin has become a widely accepted platelet function inhibitor and is used to prevent arterial occlusions in coronary cerebral and peripheral vascular disease. The results of clinical studies with aspirin in the area of peripheral arterial occlusive disease are critically reviewed. Two thienopyridine compounds, ticlopidine and clopidogrel, have been effectively used in the prevention of myocardial infarction and stroke in several clinical trials, especially in the recently published CAPRIE-trial. Potent new platelet function inhibitors recently were developed. Intravenous treatment with abciximab, a new platelet membrane glycoprotein IIb/IIIa-inhibitor, effectively prevented coronary reocclusions in patients with high-risk coronary events. A series of promising new oral IIb/IIIa- inhibitors have been developed and may become effective drugs in the prevention of reocclusions in patients with periph eral vascular disease and in coronary or cerebral vascular dis ease. Key Words: Antiplatelet agents—Aspirin—Peripheral arterial disease—Ticlopidine—Clopidogrel—GPIIb/IIIa inhibitor.
Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism: Current Recommendations
Authors: Hull Russell D. , Pineo Graham F.
Published: November 2007

Pulmonary embolism remains a major cause of death in high-risk medical and surgical patients. This is unfor tunate as effective measures for prevention of venous throm boembolism in such patients are now available. Based on Level 1 evidence from clincial trials and systematic reviews, recom mendations can be made for the prevention of venous throm boembolism in most situations. If such information is not avail able, recommendations based on extrapolation from similar risk situations or from consensus opinions must be used. Additional clinical trials are required to fill in such gaps in our knowledge and permit adequate protection against fatal pulmonary embo lism in most if not all medical and surgical patients. Key Words: Heparin—Low molecular weight heparin—Oral anti coagulants—Intermittent pneumatic compression—Graduated compression stockings—Deep vein thrombosis—Pulmonary embolism.
Pseudothrombocytopenia: A Rare Phenomenon
Authors: Makris Pantelis E. , Foka Zoi , Gerotziafas Grigoris T. , Kioumi Anna , Pithara Eleutheria
Published: November 2007

Thrombocytopenia is a serious situation that causes anxiety in doctors and patients due to its relationship with serious hemorrhagic manifestations. Pseudothrombocytopenia, however, is a situation without clinical interest because it is an in vitro decrease in platelet count. Pseudothrombocytopenia is related to the ethylenediaminetetraacetate (EDTA)-dependent exposure of antigenic determinants of platelet membrane gly coproteins gpIIb-IIIa and the subsequent reaction of common antibodies with these receptors. To our knowledge, a similar situation in Greece has not been reported. The main character istic of pseudothrombocytopenia due to EDTA is that the fall in platelet count is time-dependent and it disappears after the use of anticoagulant other than EDTA (e.g., citrate sodium or hep arin). We present seven cases of pseudothrombocytopenia re vealed when we used automatic hematologic analyzers and EDTA as an anticoagulant. After the use of another anticoagu lant (e.g., citrate sodium) the platelet count in the same hema tologic analyzer was normal.
Increased Plasma Soluble-adhesion Molecules in Thrombotic Thrombocytopenic Purpura and Disseminated Intravascular Coagulation
Authors: Shimura Minori , Wada Hideo , Hiyoyama Kazuyo , Nakasaki Takahiro , Takagi Mikio , Deguchi Akira , Mori Yositaka , Nisikawa Masakatu , Deguchi Katsumi , Shiku Hiroshi
Published: November 2007

We measured plasma-soluble adhesion molecules (granule membrane protein [GMP]-140, endothelial leukocyte adhesion molecule [ELAM]-1, intracellular adhesion molecule [ICAM]-1, and vascular adhesion molecule [VCAM]-1) in 21 patients with thrombotic thrombocytopenic purpura (TTP), 10 with mitomycin C-induced hemolytic uremic syndrome (MMC-HUS) and 59 with disseminated intravascular coagula tion (DIC) or pre-DIC. The plasma levels of soluble GMP-140 in the three groups were significantly higher than the levels in healthy volunteers, suggesting that platelets and vascular en dothelial cells are activated in these diseases. The plasma- soluble GMP-140 level of the DIC patients with nonhemato poietic malignancy was significantly higher than in the DIC patients with hematopoietic malignancy, perhaps due to the release of GMP-140 mainly from platelets. The plasma levels of soluble VCAM-1 in the TTP and DIC patients were signifi cantly higher than the levels in healthy volunteers. The plasma levels of ICAM-1 in DIC patients were significantly higher than those in healthy volunteers, but the levels in the TTP and MMC-HUS groups were not significantly high. The plasma ELAM-1 levels in the TTP and MMC-HUS groups were sig nificantly lower than those in healthy volunteers and DIC pa tients. Since elevated plasma cytokine levels have been ob served in TTP and DIC patients, the adhesion molecules might be upregulated in these diseases. However, plasma ELAM-1 is thought to be reduced in severe vascular endothelial cell dis eases such as TTP.
Anticardiolipin Antibodies in Hemophiliac and Nonhemophiliac Patients with Chronic Hepatitis C
Authors: Zanon Ezio , Pittoni Marina , Vaselli Giorgina , Tagariello Giuseppe , Girolami Bruno , Saracino Maria A. , Girolami Antonio
Published: November 2007

Anticardiolipin antibodies (ACA) have been de tected in a variety of infectious diseases, especially viral infec tions. ACA also have been described in human immunodefi ciency virus (HIV)-infected hemophiliacs. Recently the pres ence of ACA in hemophiliac and nonhemophiliac patients with chronic hepatitis C virus has been reported. We performed a case-controlled study to establish if ACA are present in hemo philia and if they are due to the hepatitis C infection; and to confirm the association between ACA and hepatitis C infec tions in nonhemophiliac patients. Anticardiolipin antibodies have been studied in the serum of 62 hemophiliacs with chronic hepatitis C virus and in the control group (70 hepatitis C- negative patients with hemophilia or other clotting disorders). ACA were positive in only three hepatitis C-positive hemo philiac patients and in three hepatitis C-negative patients with hemophilia or other coagulation defects (first control group). No significant statistical differences were found in the groups (OR = 1.1; 95% CI 0.2-7.4, p = .6). Sixteen of 111 nonhe mophiliacs with chronic hepatitis C were positive for ACA while in 100 matched hepatitis C-negative subjects (second control group) anticardiolipin antibodies were positive in 9 pa tients. ACA tended to be higher in hepatitis C-positive nonhe mophiliac patients than in the control group, but the difference between the two groups was not statistically significant (OR = 1.7, 95% CI 0.7-4.4, p = .3). ACA do not seem to be associ ated with the chronic hepatitis C virus.
Proposed Procedure for Evaluating Platelet Concentrate Units to Be Used for Transfusion
Authors: Speck Roy , Bonderman Dean , Cook Lloyd , Larison Joyce
Published: November 2007

Platelet concentrate samples from 100 units col lected by apheresis at The American Red Cross Blood Bank located at Columbia, S.C. and from 31 units collected by apher esis at The Santa Barbara Tri-County Blood Bank located in Santa Barbara, California were sent overnight to Fishers, Indi ana and tested for platelet factor 3 activity. The maximum dilution that would support normal clotting was determined for each unit. Units with maximum dilutions of 1:100 or greater were considered to have sufficient platelet factor 3 activity to be used for a transfusion. Ninety-six percent of the units sent from Columbia, South Carolina and 94.55% of the units sent from Santa Barbara, California were suitable for use based on their platelet factor 3 activity. This study shows the feasibility of sending platelet concentrates long distances and the impor tance of testing for platelet factor 3 activity.
Acute Budd-Chiari Syndrome Associated with Activated Protein C Resistance During Intravenous Anticoagulant Treatment
Authors: Yildiz Bülent O. , Oran Betül , Büyükaşik Yahya , Haznedaroglu brahim C. , Cekirge Saruhan , Kirazli Şerafettin
Published: November 2007

The Budd-Chiari syndrome is a rare but serious condition defined as hepatic venous outflow obstruction. This article presents a case of acute Budd-Chiari syndrome in a 43-year-old woman with activated protein C resistance while she was being treated with intravenous heparin infusion for previously documented deep venous thrombosis. Activated protein C resistance caused by factor V Leiden mutation has emerged as the most prevalent hereditary cause of venous thromboembolism and should be considered as an etiologic factor in patients with Budd-Chiari syndrome.
State-of-the-Art Review : Evaluation of the Clot Signature Analyzer as a Hemostasis Test in Healthy Volunteers Exposed to Low Doses of Aspirin
Authors: Igawa Takehiro , Kornhauser Robyn , Cilla Donald D. , O'Neal King Jennifer , Kambayashi Junichi
Published: November 2007

Several variables affect bleeding time that make it difficult to obtain consistent measurements. The Clot Signature Analyzer (CSA) has been developed to assess in vitro hemo stasis using well-controlled flow chambers. In this study, the equivalencies in the CSA parameters with the conventional bleeding time or platelet aggregation methods were evaluated in subjects exposed to aspirin. The CSA parameters, platelet hemostasis time (PHT) and collagen-induced thrombus forma tion (CITF), were compared to bleeding time (Surgicutt2®) and collagen-induced platelet aggregation, respectively. Fifty-three healthy volunteers were given two doses of aspirin (81 and 243 mg) in one day. Following the baseline period, the volunteers took 81 mg of aspirin and then took 243 mg 2 hours later. The changes in each value from the baseline to that at either aspirin dose (2 hours after dosing) were evaluated. Platelet hemostasis time and CITF correlated well with bleeding time and aggre gation, respectively, but PHT was not significantly increased after 81 mg of aspirin, whereas bleeding time was significantly increased. The variation in PHT was slightly higher than that of bleeding time. At 81 mg, CITF was significantly increased but aggregation was not, even though the variation was compa rable. This suggests that PHT and CITF can simulate the changes in bleeding time and aggregation, respectively, but the sensitivity of PHT for detecting the changes in bleeding time was no better than the conventional method. Also, CITF was more sensitive than aggregation in detecting platelet re sponse to collagen. In conclusion, the proposed CSA is not always suitable for detecting hemostatic abnormalities.
Thrombosis Involving the Major Veins with Heterozygote Factor V Leiden Mutation as the Only Risk Factor
Authors: Tokgözoğlu S. Lale , Açil Tayfun , Haznedaroglu Ibrahim C. , Aytemir Kudret , Batur Mustafa Kemal
Published: November 2007

A 27-year-old man was admitted to our hospital with the complaints of swelling of his face and lower limbs. Echocardiography showed minimal pericardial effusion accom panied by disordered diastolic function. Cardiac catheterization was performed to rule out constrictive pericarditis. Normal pressure tracings of the right heart rule out constrictive peri carditis, however, a narrowing of the inferior vena cava was observed. Venographies of the inferior and superior vena cavae showed extensive thrombotic involvement of these great veins. Protein C, protein S, anticardiolipin antibodies, fibrinogen, an tithrombin-III, activated protein C resistance, and factor V lev els were in normal limits. Heterozygosity for factor V Leiden mutation was detected. We conclude that factor V Leiden mu tation can cause extensive thrombotic involvement of major veins and should be considered in idiopathic thrombosis of them.
Central Retinal Vein Thrombosis Associated with Prothrombin 20210G/A Gene Variant
Authors: Vayá Amparo , López José Ma , Mira Yolanda , Ricart José Ma , Villa Piedad , España-Gregori Enrique , Estellés Amparo , Aznar Justo
Published: November 2007

We describe a patient with central retinal vein thrombosis associated with the prothrombin gene 20210G/A. The associated risk factors and the patient's personal and fam ily history of thrombosis are dealt with. In addition, the litera ture on the cases reported up to now is reviewed as is the prevalence of this new mutation in patients with central retinal vein thrombosis.
Review : Infertility after chemotherapy: A review of the risks and strategies for prevention
Authors: Lenz Kristi L. , Valley Amy W.
Published: November 2007

Purpose. Infertility as a late complication of cancer chemotherapy, focusing on specific drug-related ef fects, effects observed in the treatment of certain malignancies, and strategies for prevention is re viewed.

Data Sources. A MEDLINE search of articles from 1966 to present was conducted using the terms infertility, antineoplastics, amenorrhea, azospermia, oogenesis, and spermatogenesis. Additional refer ences were identified using review articles and phar macology textbooks.

Study Selection. All human studies reported in English language were included. Animal studies were included when human data were insufficient or un available.

Data Synthesis. Data on the infertility effects of individual antineoplastic agents are difficult to inter pret for several reasons, including small sample sizes, lack of prechemotherapy fertility assessment, inade quate long-term follow-up, and use of regimens in cluding multiple agents. In general, the incidence and severity of antifertility effects are dependent on the total dosage delivered, duration of therapy, and age at exposure. The alkylating agents have the most signif icant effects on fertility. Fertility outcomes have been reported for several different malignancies, especially in patients cured of Hodgkin's disease and testicular cancer. Information on specific antineoplastic agents and cancers are reviewed. Several methods have been employed to decrease gonadotoxic effects, but none have been effective.

Conclusions. Infertility is a common late com plication of cancer chemotherapy that is receiving increasing attention as the number of cancer survi vors increases. Health care professionals should be aware of infertility risks associated with antineoplastic agents and certain malignancies, and patients should be informed of these risks as treatment decisions are made.
Hypersensitivity after ifosfamide administration
Authors: Lakhi S.A. , Bais E.M. , Rutgers E.J.T. , Beijnen J.H.
Published: November 2007

The toxicity profile of the alkylating anti-cancer drug ifosfamide is quite well known. However, up to now only a few cases of hypersensitivity as an attributed adverse effect of ifosfamide have been described in literature.

This article describes the history of a woman suffering from a primary peripheral neuroectoder mal tumor (PNET) who was admitted to our hos pital for chemotherapy. Treatment was given ac cording to the EICESS-protocol (European Intergroup Cooperative Ewing's Sarcoma Study) with the following anti-cancer drugs: etoposide, doxorubicin, vincristine, and ifosfamide/mesna. Af ter ifosfamide administration an acute hypersensi tivity reaction was seen consisting of redness in the face and on the left arm, back and chest, and bronchoconstriction. Subsequent intravenous ad ministration of the anti-histaminic clemastine (2 mg) and dexamethasone (5 mg) before ifosfamide administration on a second occasion did not pre vent these reactions. After substituting cyclophos phamide for ifosfamide in consecutive courses no untoward reactions occurred.
Reduced pharmacy resource utilization associated with raltitrexed treatment of advanced colorectal cancer
Authors: Summerhayes Maxwell , Wanklyn Steven J , Shakespeare Roselyn A , Lovell Jacqueline
Published: November 2007

Objective. The pharmacy resources needed for prep aration of the direct, specific thymidylate synthase inhibitor raltitrexed (`Tomudex' ; Zeneca Pharmaceu ticals, Ltd., Macclesfield, UK); the Mayo, Machover, and De Gramont regimens of 5-fluorouracil (5-FU) and calcium leucovorin (LV); and continuous intravenous 5-FU for the treatment of advanced colorectal cancer were compared.

Design. The pharmacy time spent on prepara tion, the disposables used, and associated drug wast age were recorded and costed for a treatment cycle.

Patients. Colorectal cancer patients receiving standard treatment or included in a clinical trial in a large teaching hospital were considered.

Outcome Measures. The pharmacy preparative time, labor, disposable, and drug wastage costs per treatment cycle, prepared extemporaneously and us ing a batch process, were measured.

Results. A cycle of raltitrexed was much quicker to prepare than any other regimen (P < .05). The labor costs were significantly less (£2.87 for ralti trexed compared with £5.24-19.67 for the 5-FU regi mens) particularly with respect to the Machover regimen, which incurred costs seven times those of raltitrexed. The cost of disposables was significantly lower for raltitrexed, with continuously infused 5-FU incurring the greatest cost. As expected for a new treatment assessed within a clinical trial rather than in a routine setting, drug wastage was higher for ralti trexed (P < .05) except when compared with batch- preparation for the Machover regimen.

Conclusions. Raltitrexed was quicker and sim pler to prepare than 5-FU- based regimens for colo rectal cancer. This resulted in lower pharmacy labor and disposable costs, although in this study drug wastage was higher for raltitrexed prepared under clinical trial conditions.
Internet resources for oncology pharmacists
Authors: Hayes J Michael
Published: November 2007

The internet has allowed people to communicate easily and to retrieve a variety of information, including med ical information, very rapidly. Some functions of the internet include: sending and receiving electronic mail (e-mail); joining and participating in various discussion groups or newsgroups; exchanging (uploading or down loading) files via using various transfer protocols; logging into remote or host computers via telnet applications; connecting to thousands of computers worldwide using the gopher system; exploring the heart of the internet, the World Wide Web (WWW), via a commercially available browser; conversing electronically in real time with other people who are logged in to the same site and occupy the same "chat room" for "talking"; and, using the internet phone to talk to other people vocally, just as if you were using a regular phone.
Six lessons: cultural continuity in communicative language teaching
Authors: Holliday Adrian
Published: November 2007

Ideas about good teaching emerged from one-off ethnographic observations of six 'communicative' university English language classes in China and India. The lessons were all taught by non-native speakers in classes of between 25 and 45. Through analysis of the behaviour and physical environment of the culture of each classroom, it emerged that aspects of a popular view of 'communicative' connected with group- work, oral practice and teacher withdrawal may be questioned. Instead, cultural continuity between traditional and innovative forms emerges as an essential feature of successful communicative language teaching.
Emotional and rational product appeals in televised food advertisements for children: analysis of commercials shown on US broadcast networks
Authors: Page Randy M. , Brewster Aaron
Published: November 2007

The aggressive advertising and marketing of high caloric food products to children is implicated as a potential causative factor in the childhood obesity epidemic. This study analyzed 147 commercials appearing during children's programming on U.S. broadcast networks for a wide range of potential emotional and rational advertising appeals. The most prominent emotional appeals were fun/happiness and play followed by fantasy/ imagination, social enhancement/peer acceptance, and coolness/hipness. Many of the products used the term `super-charged' or a similar adjective to describe the powerful taste or other physical properties of the product. More than one-third of all the commercials used a fruit appeal or association. Statements or depictions that a product was healthy or nutritious were quite rare among the commercials. This seems to imply that health and nutrition claims are understood by food marketers to not be salient concerns among children and as such are not a selling point to children. Commercials for high sugar cereal products and fast food restaurants differed in several respects. This study can serve to guide child health care professionals and other child advocates in designing measures that counter food advertising messages directed at children.
Romancing the Sand: Constructions of Capital and Nature in Arid America
Authors: Henderson George L.
Published: November 2007

Hard upon the heels of a philosophy which glorifies success must follow a philosophy which rationalizes failure.1

Commodities borrow their aesthetic language from human courtship; but then the relationship is reversed and people borrow their aesthetic expression from the world of the commodity. 2
Oxygen Free Radicals and the Effect of a Free Radical Scavenger in Patients with Intermittent Claudication
Authors: Diamantopoulos Emmanuel J. , Charitos Dionisios , Georgopoulos Vassilios , Economou Emmanuel , Sfakianakis Michael , Toutouzas Pavlos , Raptis Sotirios
Published: November 2007

Oxygen free radicals (OFRs) are implicated in tissue injury during postischemic reperfu sion and play an important role in the pathogenesis of atherosclerosis. In patients with intermittent claudication the ischemia-reperfusion phenomenon could be reproduced after exercise, thus influencing the evolution of chronic peripheral arterial occlusive disease (CPAOD). The aim of this study was to investigate the behavior of OFRs and the effect of a free radical scavenger in patients with stage IIB CPAOD. Malondialdehyde (MDA), a reliable index of OFRs production, was measured in the serum of 19 patients with stage IIB CPAOD and 42 healthy controls. The blood samples were collected from a foot vein in resting condition and during reperfusion after 5 minutes of provoked ischemia. These measurements were repeated after 3 and 12 weeks of oral treatment with the free radical scavenger trimetazidine hydrochloride (60 mg daily). Statistical analysis of the findings revealed that resting MDA was significantly higher in claudicants when compared to the healthy controls (1.247 ±0.25 μmol/L vs 1.021 ±0.278 μmol/L, p<0.005). During postischemic reperfusion (PIR) the MDA levels were significantly increased in claudicants (resting vs PIR: 1.247 ± 0.25 vs 4.60 ± 0.86 μmol/L, p<0.001). The administration of trimetazidine led to a significant reduction of the PIR MDA levels (before treatment 4.60 ±0.86 μmol/L vs 3 weeks 3.93 ±0.63 μmol/L and vs 12 weeks of treatment 2.98 ±0.29 μmol/L, p < 0.001 and p < 0.001, respectively). These findings indicate that claudicants are at increased risk of oxidative damage after exercise. Long- term administration of the free radical scavenger trimetazidine attenuates reperfusion injury in patients with stage IIB CPAOD.
Pulmonary Artery Dissection and Rupture in Eisenmenger's Syndrome
Authors: Placik Branko , Rodbard Simon , McMahon Jeanine , Swaroop Satinder , Swaroop Satinder
Published: November 2007

A patient with ventricular septal defect and pulmonary arterial hyperten sion (Eisenmenger's syndrome) associated with aortic coarctation with fol low-up for 19 years, and with rupture of an aneurysmatic pulmonary artery is described. An incident of extreme fright with a possible transient systemic hypertension may have precipitated the dissection of the pulmonary arterial intima and the rupture.
Complications Encountered During Arterial Embolectomy with the Fogarty Balloon Catheter
Authors: Schweitzer Daniel L. , Aguam Abul S. , Wilder Joseph R.
Published: November 2007

The Fogarty arterial embolectomy catheter, while indispensible in the armamentarium of the vascular surgeon, is not an entirely benign instrument. A case is described in which the balloon was lost in its entirety from the catheter and immediately retrieved using a second identical instrument. A comprehensive survey of the literature reveals that a variety of arterial injuries have occurred during the use of the Fogarty catheter. Each of the major ones is discussed in depth. Amongst the most serious are arterial perforation and rupture occasionally followed by loss of the involved extremity.

All previously reported complications following use of the Fogarty catheter are tabulated and reviewed. Additionally, a formal classification of these complications is proposed.

Since the time of its introduction in 19631 the Fogarty balloon-tipped catheter has become an indispensible tool in the armamentarium of the vascular surgeon. Its use for arterial embolectomy has been responsible for the salvage of many thousands of limbs. Over the course of the past decade, however, a number of complications referable to this instrument have appeared in the literature. These include perforation of vessels, intimal disruption and foreign body embolization amongst others. To our knowledge, however, there has been only one reported case of a balloon having been lost intra-arterially in toto without obvious cause.2 It is the purpose of this paper to present the second such case where the balloon, which had separated entirely from the catheter during the course of an arterial embolectomy, was later retrieved by passage of a second Fogarty catheter. In addition, a comprehen sive review of the literature is undertaken, and all arterial complications reported to date summarized and tabulated.
Subclavian Steal Due to Hypoplasia of the Seventh Left Intersegmental Artery
Authors: Rees J. Richard , McQuarrie I. Bruce
Published: November 2007

Hypoplasia of the seventh left intersegmental artery resulted in a symptomatic subclavian steal syndrome in a 35-year-old white man. The lesion was successfully treated by aortosubclavian bypass.
Factors Predisposing to Development of Dissecting Aneurysm of the Aorta
Authors: Michal John A. , Jaffe Richard B.
Published: November 2007

Eighteen cases of dissecting aneurysm of the aorta are presented to illustrate the factors predisposing to this process. These factors, which include hypertension, arteriosclerosis, trauma, cardiovascular lesions, connective tissue diseases, inflammation, and pregnancy, cause disrup tion of the media of the aortic wall through abnormal hemodynamics, in herent defects in the aortic wall, or insult to a normal aortic wall. There was a close correlation between the predisposing factor and the type of dis section (ascending, descending, or dissection of the entire aorta). Distinc tive radiographic and angiographic features of some of these predisposing factors are reviewed to aid the radiologist in the diagnosis.
Diffuse Bilateral Coronary Artery Fistulae Entering the Left Ventricle: A Case Confirmed Surgically A Case Report
Authors: Berberich Stephen N. , Zager James R.S. , Herman N. Paul , Eslava Richard L.
Published: November 2007

A 65-year-old woman presented with intermittent left bundle branch block and angina pectoris. Cardiac catheterization demonstrated bilat eral coronary artery fistulae entering diffusely into the left ventricle with out evidence of major arterial-lumi nar shunt. A surgical procedure to reduce the arterial-to-cameral flow is discussed, and case reports are re viewed and discussed.
Myocardial Ischemia Caused By Coronary- Pulmonary Fistula and Coronary Atherosclerosis
Authors: Reza G. , Farsad H.
Published: November 2007

A 57-year-old woman suffered from atypical angina after a myocardial in farction. Coronary artery occlusive dis ease and fistula between the coronary artery and pulmonary artery was iden tified by cardiac catheterization. The result of medical treatment was border line, and she did not respond to nitro glycerin as is expected in coronary oc clusive disease. Following surgical clo sure of the fistula and myocardial re vascularization, her angina subsided and she was pain-free for more than 1 year.