bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Digoxin on Ventricular Remodeling and Responsiveness of β-Adrenoceptors in Chronic Volume Overload
Authors: Sullebarger J. Thompson , D'Ambra Paula M. , Clark Linda C. , Thanikarry Lisa , Fontanet Hector L.
Published: November 2007

Background: Digoxin improves baroreflex function and reduces neurohumoral activation in severe heart failure, but it is uncertain how digoxin affects ventricular remodeling and progression to left ventricular dysfunction. In addition, the effect of digoxin in in vitro β- adrenoceptor density and function, and contractile reserve in vivo is not well understood.

Methods and Results: To study this, we compared digoxin with placebo treatment in rats with chronic volume overload induced by aortocaval fistula and in sham-operated control animals. Left ventricular end-diastolic cavity dimensions (LVDd) and wall thickness were measured weekly by in vivo transthoracic echocardiography, and left ventricular mass (LVM) and percent fractional shortening (%FS) were calculated. Six weeks after fistula cre ation, simultaneous echocardiographic and invasive hemodynamic evaluation at rest and in response to incremental dobutamine (1-10 μg/kg/min intravenously) were measured. Myo cardial plasma membrane β-adrenoceptor density and maximal adenylate cyclase responses (Vmax) to isoproterenol, 5'-guanylylimi dodiphosphate, and forskolin were measured in vitro. Volume overload induced progressive increases in LVDd and LVM over the 6-week study period. Percent fractional shortening at rest. and the change in %FS in response to dobutamine stress were dramatically reduced 6 weeks after fistula creation. Although 6- week fistula animals had unchanged β-adrenoceptor density (Bmax) and binding affinity (Kd) as compared with controls, maximal adenylate cyclase responses to stimulation in vitro (V max) were markedly reduced. Digoxin treatment prevented this loss of responsiveness of adenylate cyclase but did not affect β-adrenoceptor density or affinity in vitro. Digoxin had no effect on LVDd, LVM, %FS, or the response to dobutamine infusion in vivo.

Conclusions: Although digoxin prevented β-adrenoceptor desensitization and improved in vitro myocardial adenylate cyclase response, the cardiac response to adrenergic stimulation in vivo was not significantly improved. These results suggest that the role of β-adrenoceptor desensitization in the progression from volume overload hypertrophy to left ventricular dysfunction and heart failure may be less important than previously thought. Furthermore, although digoxin treatment did produce modest hemodynamic benefits, it did not prevent progressive remodeling in this model.
Pharmacodynamics and Pharmacokinetics of Irbesartan in Patients With Mild to Moderate Hypertension
Authors: Marino Maria R. , Langenbacher Kathleen M. , Ford Neville F. , Raymond Ralph H. , Manning James , Vesterqvist Ole , Cooper Shamblen E. , Lasseter Kenneth C.
Published: November 2007

Background: The pharmacodynamics (plasma angiotensin II [AII], plasma renin activity [PRA], renal function, blood pressure [BP], urinary excretion of major metabolites of pros tacyclin [PGI 2-M], and thromboxane A2 [TXA2-M]) and pharmacokinetics of irbesartan were assessed in hypertensive patients.

Methods and Results: Twenty-four white patients with seated diastolic blood pressure 95 to 110 mmHg were randomized to double-blind irbesartan 300 mg or placebo once daily for 4 weeks, following a placebo lead-in. Irbesartan-treated patients had significantly greater 24- hour area under the curve values for mean change from baseline in AII and PRA versus pla cebo-treated patients on day B15 (AII [pg.h/mL]: 261 ± 515 vs 12 ± 51; PRA [(ng/mL/h).h]: 74 ± 162 vs -2 ± 14; P values < .05). Irbesartan significantly lowered BP without clinically important changes in renal function. Irbesartan had no effect on 24-hour urinary TXA2-M excretion, but significantly increased 24-hour PGI2-M excretion versus placebo on day B29 (20.7 ± 23 pg/mg creatinine vs -2.3 ± 43 pg/mg creatinine; P < .05). Pharmacokinetics were comparable to those from previous studies. The hourly relationship between plasma irbesartan concentration and antihypertensive effect indicated a broad, clockwise hysteresis, with peak concentration occurring at 1.5 hours, whereas peak antihypertensive effect occurred at 4 hours.

Conclusions: Irbesartan increases plasma AII and PRA and lowers BP consistent with AT1 receptor blockade, without clinically important effects on renal function.
Sustained Intramural Retention and Regional Redistribution Following Local Vascular Delivery of Polylactic-Coglycolic Acid and Liposomal Nanoparticulate Formulations Containing Probucol
Authors: Klugherz Bruce D. , Meneveau Nicolas , Chen Weiliam , Wade-Whittaker Fran , Papandreou George , Levy Robert , Wilensky Robert L.
Published: November 2007

Background: Probucol reduces restenosis after angioplasty, provided oral administration is begun 1 month before the procedure. Local vascular delivery of a nanoparticulate formula tion of probucol may obviate the need for drug loading by acutely raising arterial intramu ral concentration while providing sustained intramural retention. To test this hypothesis, we compared the retention and redistribution of 35S-probucol encapsulated in either liposomal or polylactic-coglycolic acid (PLGA) nanoparticles after local vascular delivery.

Methods: Nanoparticles were delivered using a Crescendo microporous infusion catheter (Cordis, Warren, NJ) after balloon angioplasty of rabbit iliac arteries (n = 12-18 arteries per formulation per time point). Animals were euthanized on day 0, 3, or 7 after delivery. Iliac arteries, perivascular fat, and downstream tissues were harvested and the radioactivity disintegrations per minute was measured. Autoradiographic and confocal microscopic anal yses of tissue sections were performed to evaluate intramural distribution of probucol.

Results: Immediately after delivery, radioactivity in the iliac arteries (log[dpm/mg], mean ± SEM) was greater with PLGA (2.72 ± 0.08) than with liposomal encapsulation (2.10 ± 0.08, P = 0.001). Intramural retention of probucol was 23% at 7 days using liposomes and 10% using PLGA, corresponding to a probucol concentration of 0.1 ng/mg tissue for both formulations. By the third day after delivery, radioactivity in peri-iliac fat, femoral arteries, and hindlimb muscle increased by 88%, 29%, and 154%, respectively. Thereafter, radioac tivity decreased to 56%, 43%, and 134% of initial dpm respectively, by day 7.

Conclusions: Although delivery efficiency was superior with PLGA encapsulation, intra mural probucol concentrations were similar on day 7 using both formulations. Radial and axial redistribution of probucol was observed, indicating that this technique can be exploited to increase adjacent tissue delivery.
Superoxide Anion Generation, Superoxide Dismutase Activity, and Nitric Oxide Release in Human Internal Mammary Artery and Saphenous Vein Segments
Authors: Schmalfuss Carsten M. , Chen Liying Y. , Bott Jeffrey N. , Staples Edward D. , Mehta Jawahar L.
Published: November 2007

Background: Internal mammary artery (IMA) as conduit for a coronary artery bypass graft (CABG) stays patent longer and more often than saphenous vein (SV). However, the pre cise differences in the biology of IMA and SV are unclear.

Methods and Results: To examine inherent difference in superoxide anion, superoxide dis mutase (SOD) and nitric oxide (NO) formation in IMA and SV as a basis for differences in patency rates, we measured these parameters in vascular segments of patients undergoing CABG. Superoxide anion generation was measured by lucigenin chemiluminescence and reduction of cytochrome c, SOD by inhibition of pyrogallol auto-oxidation, and NO as nitrite/nitrate fluorometrically using 2-3-diaminonaphthalene as a probe. Generation of superoxide anion, SOD activity, and NO formation were all greater in the IMA than in the SV segments (IMA:SV = 2.6:1, 2.9:1, 1, and 3.0:1, respectively, all P < .01). There was a pos itive correlation between superoxide anion generation and SOD activity ( r = 0.65, P < .05; r = 0.70, P < .05 in IMA and SV, respectively) and NO release ( r = 0.68, P < .05; r = 0.75, P < .03 in IMA and SV, respectively). Western blot analysis showed no differences in SOD and NO synthase protein expression in IMA and SV segment homogenates. To examine whether greater superoxide anion generation, SOD activity, and NO formation are unique to IMA, we studied pulmonary artery (PA) and pulmonary vein (PV) segments taken from patients undergoing lung resection. Superoxide anion generation, SOD activity, and NO formation were also found to be greater in PA than in PV segments.

Conclusions: Inherently greater superoxide anion generation and subsequently increased formation of SOD and NO release in IMA (vs SV) may be a factor in the greater patency of the former as CABG conduit. Because both IMA and PA are exposed to pulsatile stretch and carry blood at higher pressure than the SV and PV, it is likely that these 2 factors account for the observed differences.
Isoamyl Nitrite Depolymerized Heparin as a Universal Calibrator for Heparins and Low Molecular Weight Heparins
Authors: Ahsan Ahmad , Jeske Walter , Wolf Helmut , Fareed Jawed
Published: November 2007

Because the subcutaneous absorption of heparin depends on its molecular weight, high performance size exclu sion chromatography methods, among others, have been devel oped for its determination. Because heparin consists of polymer chains of varying lengths, a large number of calibrators, 19 in our work, are required for these molecular weight analyses. Because the preparation of that many calibrants is both time- consuming and expensive, other methods requiring fewer cali brants are being sought. In pursuit of these aims, a heparinase- degraded heparin has been accepted as the first international reference preparation low molecular weight heparin for mo lecular weight calibration. We have previously proposed an other calibrant, the Heparin Mass Calibrator. In this article, we introduce another calibrant, called the Heparin Molecular Mass Calibrant. It offers the advantage of a much wider availability because it is a commercial product. In addition to having a superior refractive index chromatography run profile, when used in combination with two Narrow Range Calibrators with molecular weights of 34.4 and 18.4 kDa, this new calibrant covers both the higher and the lower molecular weight ranges. Besides, ultraviolet detection is not needed for molecular weight calculations. Therefore, it is proposed that its feasibility as a universal reference calibrator for both heparins and low molecular weight heparins be considered.
Factor V Leiden and Prothrombin G20210A in Relation to Arterial and/or Vein Rethrombosis: Two Cases
Authors: Mira Yolanda , Todolí José , Alonso Rosario , Micó Ma Luisa , Vayá Amparo , Ferrando Fernando , Estellés Amparo , Villa Piedad , Aznar Justo
Published: November 2007

The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most common established genetic risk factors for deep vein thrombosis (DVT). However, the relationship. between these mutations and arterial thrombotic syndromes (coronary heart disease, myocardial infarction, stroke) has not been established. Some studies have suggested a relationship between them, but other authors have considered it unlikely that these anomalies are a major risk factor for arterial thrombosis. From the clinical point of view, a question arises concerning the risk of repeated thrombosis in patients carrying one of these two mutations. The question is whether the recurrence is attributable to the mutations or to the presence of additional circumstantial risk factors. As the risk of repeated thrombosis varies considerably from one patient to another, decisions about long-term treatment require weighing the persistence of risk factors for vascular disease (venous and arterial), especially in selected cases such as young patients or patients with thrombosis of unusual localization.
State-of-the-Art Review: Thrombophilia and Pregnancy: Review of the Literature and Some Original Data
Authors: Arkel Yale S. , Ku De-Hui W.
Published: November 2007

The association of thrombophilia with pregnancy complications has received increasing attention. It is now apparent that thrombophilia is respernsihle for a large number of the serious complications of pregnancy such as venous thrombosis, pulmonary embolism, fetal loss, pregnancy loss, intrauterine fetal demise, and preeclampsia. The inherited thrombophilia abnormalities, factor V Leiden mutation, prothrombin gene mutation 20210A, and antithrombin III, protein C, and protein S deficiency, and the acquired disorders, the anticardiolipin syndrome and lupus inhibitor, are responsible for a large share of the incidences of premature termination of pregnancy and many of the above complications. The normal physiology of pregnancy may be prothrombotic, with evidence for increased markers of activated coagulation and coagulation factors. There is a decrease in protein S and resistance to activated protein C occurs in a significant number of pregnancies in the absence of the factor V Leiden mutation. In the following article, we review some of the major studies that have correlated the thrombophilia and other acquired disorders that adversely impact pregnancies.
Purification and Properties of Human Melanoma Cell Tissue Factor
Authors: Siddiqui Farooq A. , Amirkhosravi Ali , Amaya Mildred , Desai Hina , Meyer Todd , Francis John L.
Published: November 2007

Tissue factor (TF) is a transmembrane glycoprotein that acts as a receptor for nonactivated and activated factor VII (FVII) and triggers the coagulation cascade. TF plays an important role in hemostasis, but may also have noncoagulation functions in vascular development, angiogenesis, and tumor cell metastasis. In tumor cells, analysis of the role of TF has been hampered by the lack of purified TF. In this study, TF antigen was identified on human A375 malignant melanoma cells using flow cytometry. We further purified TF apoprotein 2.000-fold to homogeneity from A375 melanoma cells using immunoaffinity chromatography. On SDS-polyacrylamide gel electrophoresis under reduction, purified TF apoprotein gave two major protein bands corresponding to molecular weights of 53 and 34 to 36 KD. The identity of these forms of TF was confirmed by Western blotting using a polyclonal antibody against human brain TF. Under reduction, the TF antibody bound with a monomeric form of TF (53 KD), and without reduction, to several forms of TF (34 to 128 KD). Preliminary carbohydrate analysis suggested that TF is a glycoprotein and contains about 22% total carbohydrates. The coagulant activity of the purified apoprotein was reconstituted by the addition of phospholipids. The effects of varying concentrations (0 to 8 μg) of polyclonal antibodies to TF and FVII on TF procoagulant activity were studied. Both antibodies inhibited more than 70% of the procoagulant activity of TF in an FX activation assay. The complex formation between purified TF apoprotein and FVlla was demonstrated by using an enzyme-linked immunosorbent assay. TF formed a complex with FVIIa in a concentration-dependent and saturable manner. We conclude that in human melanoma cells, TF occurs in monomeric and heterodimeric forms and appears to have similar properties as reported for TF from other sources.
Hereditary Protein C Deficiency: The Australian Experience
Authors: Doig Rowan G. , Begley C. Glenn , McGrath Katherine M.
Published: November 2007

Hereditary protein C deficiency (HPCD) is a recognized risk factor for thrombotic disease. To examine the underlying genetic defect in more detail, the protein C gene was examined in eight families from Australia. All exons and intron/exon boundaries containing the trans lated sequence of the protein C gene were amplified using the polymerase chain reaction (PCR) and sequenced di rectly. All families were identified because of a throm botic event in the proband. Six families had type I defi ciency and two had type II. Seven mutations were found in eight different families (two apparently unrelated fam ilies shared the same mutation). Five of them were point mutations leading to amino acid substitutions, most of which occurred in the serine protease domain of the ma ture protein. One mutation produced a premature stop codon, and another led to a putative splice site mutation. All of these mutations could be detected using restriction enzyme digestion or single-strand conformation polymor phism (SSCP) analysis of PCR-derived DNA. These re sults confirm the genetic heterogeneity of HPCD. Genetic diagnosis is feasible in families in whom the defect in the proband has been identified; it overcomes some of the limitations of protein-based diagnostic methods.
Overwhelming Sepsis and Bleeding in a Previously Splenectomized Patient
Authors: Messmore Harry L. , Nijm William , Gawlik Gerald , Fahey Patrick
Published: November 2007

The occurrence of overwhelming sepsis due to Streptococcus pneumoniae infection is a rare but well- known complication of splenectomy. Its occurrence 31 years postsplenectomy in a 35-year-old woman is the sub ject of this report. In spite of septic shock, disseminated intravascular coagulation, adult respiratory distress syn drome, gastrointestinal hemorrhage, and digital gangrene, the patient recovered with only minimal loss of parts of digits. The use of high-dose penicillin empirically in the emergency room along with liberal use of resuscitative fluids and dopamine may have been the major determi nants of her recovery. Intravenous corticosteroids, fresh- frozen plasma, and packed red blood cells appeared to be beneficial as well. A diagnosis of hereditary spherocyto sis was made following recovery. This case is discussed in the light of guidelines for prophylaxis of overwhelming sepsis in high-risk patients issued by the Centers for Dis ease Control of the National Institute of Health. Vacci nation with pneumococcal vaccine (23 valent) and men ingococcal vaccine is highly recommended for adults at high risk of overwhelming sepsis. This treatment should be repeated every 6 years. It is critical that the patient, the doctor, and emergency room physicians be aware of the importance of prompt aggressive antibacterial treat ment for any suspected infection.
Hypercoagulability in Children with Thalassemia Major
Authors: Kemahli Sabri , Gürman Ceyda , Egin Yonca , Yildirmak Yildiz , Sipahi Tansu , Uysal Zümrüt , Akar Nejat , Cin Şükrü , Arcasoy Ayten
Published: November 2007

Objective: We wished to determine the role of various factors causing hypercoagulability in thalassemia patients.

Methods: Forty-six homozygous β-thalassemia patients were investigated. Protein C, protein S, and antithrombin (AT) levels were measured and lupus anticoagulants (LA) were screened. D-Dimer and fibrinopeptide A ( FPA) levels were measured to show the activation of the fibrinolytic system. Ten healthy children served as controls.

Results: There was a marked decrease in protein C activity in 44.4% and in protein C antigen in 53.8% of the patients. Although no significant differences was noted between the mean values for protein S in the patient and control groups, protein S activity was <60% in 40% of the patients. AT levels were always normal. D-Dimer and FPA levels were increased, indicating the ongoing coagulation activation and fibrinolysis. Three patients had LA; which reflect the expression of phosphatidylserine on the outer surface of the erythrocyte membrane.

Conclusions: In thalassemic patients, there is activation of the coagulation and fibrinolytic system which is believed to be secondary to an underlying mechanism. The presence of LA in some patients, probably due to the expression of PS on the outer surface of the erythrocyte membrane, may be the initiating event. Key Words: Thalassemia-Hypercoagulability-Protein C—Protein S—Antithrombin—Antiphospholipid antibodies.
Tissue Factor Pathway Inhibitor is a Potent Inhibitor of Plasmin
Authors: Klauser Rainer J. , Hoppensteadt Debra , Fareed Jawed
Published: November 2007

Recombinant tissue factor pathway inhibitor (TFPI) was found to be a potent inhibitor of plasmin. In an amidolytic assay the inhibition constant K i was found to be 2.86 x 10-8 M. TFPI in the same concentration range also inhibited the activation of plasminogen by tissue plasminogen activator (tPA). The amidolytic activity of tPA was not inhib ited by TFPI. Other proteinases relevant to fibrinolysis such as urokinase, α-factor XIIa, and β-factor XIIa were not inhibited by TFPI. Plasma kallikrein was weakly inhibited by TFPI. When added to plasma, TFPI also prolonged the euglobulin lysis time. The interaction of TFPI with heparin and a muco polysaccharide polysulfuric ester, a heparin-like glycosamino glycan, was studied. Heparin augmented plasmin inhibition by TFPI, while mucopolysaccharide polysulfuric ester had no ef fect. Key Words: Tissue factor pathway inhibitor (TFPI)— Plasmin—Inhibition—Fibrinolysis.
The Effect of Hematopoietic Growth Factors on Platelet Aggregability
Authors: Kaplan Alexander , Kaplan Svetlana , Marcoe Karen F. , Sauvage Lester R. , Hammond William P.
Published: November 2007

We compared the in vitro effect of thrombopoietin (TPO) on platelet aggregation to other hematopoietic growth factors (HGFs): granulocyte colony stimulating factor (G- CSF), granulocyte macrophage colony stimulating factor (GM- CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), and erythro poietin (EPO). The platelet aggregation response of the venous blood of eight volunteers with differing aggregation patterns was characterized by a platelet aggregation (PA) score that provided numerical assessment of an individual's platelet ag gregation tendency to adenosine diphosphate (ADP). The method for analysis of the data included constructing regres sion lines for each participant's PA score versus the HGF con centration (range of 0.5 nG/mL to 100 nG/mL) and calculating the regression coefficients for the slope and the Y axis inter cept. We demonstrated that the proposed method resulted in accurate assessment of the HGF effect or lack of it on the platelet aggregation response. Within the concentration range evaluated, the influence of IL-6 and G-CSF on platelet aggrega bility was insignificant and the effects of GM-CSF and IL-3 were almost undetectable. In contrast, the potentiating effect of TPO on platelet activation was dose dependent with significant enhancement for all responder types. The concentrations of TPO utilized in our in vitro experiments were in pathophysi ological range, indicating that its impact on platelet aggregation may have clinical relevance, and that monitoring platelet func tion in conjunction with TPO treatment might be advisable. Investigation of the possible synergistic effect of HGF combi nations is warranted.
Diminished Platelet Aggregation in Patients with Iron Deficiency Anemia
Authors: Çalişkan Ümran , Öner Ahmet Faik , Kabakuş Nimet , Koç Hasan
Published: November 2007

To evaluate platelet function in iron deficiency anemia, using impedance (in whole blood) and optic (in plate let-rich plasma methods, platelet aggregation analyses were performed in 42 children with iron deficiency anemia at the time of diagnosis and after iron therapy. Collagen-induced platelet aggregation was decreased in patients before therapy compared to after therapy and control levels as indicated by the two methods while adenosine diphosphate (ADP)-induced platelet aggregation was decreased only by the whole blood method. Platelet aggregation with epinephrine, performed only by the optic method, was not altered in patients with iron de ficiency anemia. Platelet counts were found to be increased in patients with iron deficiency anemia, and decreased with therapy. These results indicate that some platelet functions are decreased in patients with iron deficiency anemia. These de creased functions may be compensated by increased platelet numbers.
Familial Association of Hypoplasminogenemia and Heterozygous Factor V Deficiency
Authors: Sartori Maria Teresa , Patrassi Giovanni Maurizio , Theodoridis Panagiotis , Danesin Cristina , Abati Carlo , Girolami Antonio
Published: November 2007

The coinheritance of hypoplasminogenemia and heterozygous factor V deficiency in a relative with thrombotic disease and no hemorrhagic tendency is described. The proposita, a 28-year-old woman, suffered from neurologic dis turbances due to two ischemic cerebral lesions confirmed by nuclear magnetic resonance scan. She was found to be affected with heterozygous plasminogen deficiency in a coagulation study for inherited thrombophilia. Moreover, she disclosed a prolongation of prothrombin time and activated partial throm boplastin time, which was compatible with heterozygous factor V deficiency. Her father, with a history of deep vein thrombo sis, was also affected with plasminogen deficiency, as well as three brothers and one sister who were asymptomatic. The mother of the proposita showed borderline or slightly decreased factor V levels and normal plasminogen levels; she was there fore considered to be heterozygous for factor V deficiency. Heterozygous factor V deficiency was also found in one brother and one sister of the proposita, and they were both asymptomatic. Among the other available family members, one brother and one sister of the proposita, all asymptomatic for either thrombotic or bleeding events, showed a normal clotting and fibrinolytic profile. To our knowledge, this is the first case of combined heterozygous plasminogen and factor V defi ciency in the same family. Two of six patients with hypoplas minogenemia showed thrombotic events, and in one of these symptomatic cases the coexistence of factor V deficiency did not prevent the occurrence of thrombosis. As expected, no hemorrhagic tendency was observed in patients with heterozy gous factor V deficiency, who may be mildly symptomatic only in 10% of cases.
Quality control in a centralized reconstitution unit of cytotoxic agents: Determination of etoposide using high-performance thin-layer chromatography
Authors: Beaupin Cécile M. , Darmanaden Roland
Published: November 2007

Introduction. The introduction of a Quality Assur ance Program in the Centralized Reconstitution of Cytotoxic Drugs Unit (CRCDU) at the Arnaud de Villeneuve Hospital Medical Center of Montpellier (France) led to revising our procedures and guide lines. On the average, 170 cytotoxic agents are pre pared weekly, including 20 to 30 preparations of ETOPOSIDE (VP 16). As a quality indicator, we chose etoposide concentration in the final product prepara tion because this drug is viscous and homogenizes poorly in solution. We therefore assumed that etopo side preparation quality should reveal good manufac turing guideline compliance.

Methods. A High-Performance Thin Layer Chro matography (HPTLC) method was selected because it's simple, results can be obtained rapidly, and does not require destruction of a whole preparation. Con centrations were determined by a technique using Silica gel plates (MERCK 60 F 254). Migration solvent was composed of ethyl acetate, methanol, dichloro methane, and aqueous ammonia (170:30:20:10). An optical scanning photodensitometer was set at 220 nm. Each sample was determined in duplicate. Devi ations between theoretical and actual doses were evaluated in terms of pharmaceutical quality related with clinical significance. Results are discussed weekly to determine whether guidelines are consis tent or if a change is necessary.

Results. Eighteen months after implementing, this procedure, its viability as a quality control was tested. 75.9% of samples showed less than 10 percent deviation from theoretical dosage concentration and this is considered a clinically tolerated error by the physicians of our hospital.

Conclusion. In consequence, we feel that using this method is an appropriate quality indicator.
Raltitrexed and the treatment of advanced colorectal cancer
Authors: Summerhayes Maxwell
Published: November 2007

Objective. Colorectal cancer is the second largest cause of death from malignant disease in Western countries. Although surgical resection is the preferred treatment in early disease, chemotherapy has an important role to play both as an adjunct to surgery and in the palliation of advanced disease. For many years 5-fluorouracil (5-FU) has been the only cyto toxic drug with significant activity in this condition and, recently, considerable effort has been directed toward enhancing its activity and finding better, alternative agents. Recently, raltitrexed (Tomudex; Zeneca Pharmaceuticals), the first of a new class of cytotoxic drugs, the selective, direct, thymidylate synthase inhibitors, received its first regulatory ap proval for the first-line treatment of advanced colo rectal cancer. The purpose of this review is to con sider the efficacy, toxicity, and resource implications of using this new antineoplastic agent, alongside developments that have been made in the more effective use of fluoropyrimidines, and the place of drug treatment in the management of colorectal cancer.

Data Sources. A variety of sources were used, including manual and on-line (Medline and Pharm- line) literature searching. Approved and other drug names were used as primary search terms, linked with colorectal cancer where limitation was required. The medical information department of Zeneca Pharma ceuticals also was used where appropriate.

Study Selection. Particular attention was di rected to randomized clinical trials, but nonrandom ized and preclinical studies were considered where appropriate.

Conclusions. Although colorectal cancer is in herently resistant to cytotoxic chemotherapy, such treatment now has an established role as an adjunct to surgery and in the palliation of advanced disease. The optimum 5-FU- based regimen has yet to be estab lished with certainty, although in advanced disease a four-times-weekly, 5-day regimen of 5-FU and low- dose folinic acid is probably the best of those fully evaluated to date. Raltitrexed seems to be as effective as this combination while having definite advantages in terms of toxicity and the resources required for its preparation and administration, although it remains to be seen to what extent these and other resource benefits will be offset by its higher cost and how its efficacy and tolerability will compare with other 5-FU- based regimens in ongoing clinical trials.
Review : p53 in the pathogenesis, diagnosis, and treatment of cancer
Authors: Perz Elizabeth , Kuhn John G.
Published: November 2007

Objective. The cellular functions of p53, the conse quences of the loss of p53 function, and the potential impact of p53 in oncology are reviewed within the framework of an overview of the molecular basis of cancer and cell cycle control.

Data Sources. A MEDLINE search of articles from 1976 to the present was conducted using the terms p53 protein and p53 gene. The search was restricted to the English language. Oncology and molecular biology textbooks were used as additional references.

Data Extraction. We reviewed the literature to discuss the cellular function of p53, the mechanisms of p53 inactivation, the cellular consequences of the loss of p53 function, the role of p53 loss in tumori genesis, and the potential applications of this knowl edge.

Data Synthesis. p53 mutations are found in ~ 50% of human cancers. Knowledge of p53 functions and defects provides the basis for potential applica tions in the areas of cancer epidemiology, cancer diagnosis, and determination of prognosis. An under standing of the functions and defects of p53 also presents a host of opportunities for the design of novel cancer therapies. Therapeutic approaches be ing studied include the restoration of p53 by gene therapy, the alteration of mutant p53 expression by antisense therapy, and the use of p53 mutations as a target for directing therapy to cancer cells; some of these approaches are already under phase I investiga tion. As knowledge of p53 unfolds, additional thera peutic approaches will certainly be developed. The story of p53 illustrates that the manipulation of mo lecular interactions is a new frontier in therapeutics and offers an additional role for oncology pharmacy specialists.
Reorienting the teaching universe: the experience of five first-year English teachers in Hong Kong
Authors: Pennington Martha C. , Richards Jack C.
Published: November 2007

This article reports on the experience of five Cantonese-dominant secondary English teachers in Hong Kong during their first year of teaching after graduation from a BA course in TESL. The report investigates the extent to which the teachers implemented the principles they were exposed to in their university education. The findings demonstrate that these teachers coped with their instructional contexts by abandoning much of what they were taught in the BA course and by reorienting their teaching universe away from communicative teaching principles and practices and towards product- oriented teaching principles and practices. This reconfiguring of their teaching model involved (i) a focus on order and control and (ii) shifts in: (a) procedural orientation, from teaching language communicatively to covering the required syllabus and materials; (b) interpersonal orientation, from developing the teacher's role and relationship with the students to establishing the teacher's authority; and (c) conceptual orientation, from viewing English as the medium of instruction and communication to viewing English as curriculum content. Reasons for these shifts in orientation are explored, and suggestions are offered for improving the experience of graduates of the course.
Politeness and pragmatic competence in foreign language education
Authors: LoCastro Virginia
Published: November 2007

Anecdotal evidence indicates that some native speakers of English are uncomfortable with what they perceive to be the lack of linguistic politeness forms in the speech of some Japanese speakers of English. A common example is found in the expression of desires and wants, when a Japanese speaker will say 'I want you to do X', rather than 'I'd like you to do X'. As it is possible the learning materials Japanese students used in secondary school EFL had an influence on their ability to use politeness markers in their L2, this paper will report on an analysis of evidence of politeness in senior high school textbooks. First, in order to go beyond the anecdotal evidence, there is a review of some of the relevant literature on linguistic politeness. The analysis follows in which it will be seen that there is a noticeable absence of politeness. Finally, five speculations on explanations for the absence of linguistic politeness markers are suggested in an effort to raise the awareness of language educators about this component of pragmatic competence.
Carotid Endarterectomy Based on Duplex Ultrasonography: A Safe Approach Associated with Long-term Stroke Prevention
Authors: Samson Russell H. , Bandyk Dennis F. , Showalter David P. , Yunis Jonathan P.
Published: November 2007

To evaluate the short-term and long-term safety of carotid endarterectomy (CEA) based on duplex ultrasound without confirmatory diagnostic arteriography.

A 4-year retrospective review of CEA based on duplex ultrasound alone (n = 653) or with confirmatory arteriography (n = 118) was performed in 244 women and 458 men whose ages ranged from 39 to 92 years (mean, 70 years). Practice patterns, perioperative morbidity, and stroke rate (life-table analysis) of a community-based and university- based vascular surgical practice were analyzed and compared.

Surgical intervention based on duplex ultrasound was judged possible in 85% of the patients (community, 93%; university, 55%). Indications for arteriography included: testing completed prior to surgical consultation (44%), nonfocal extracranial carotid stenosis (23%), nonhemispheric symptoms (13%), and prior stroke (9%). This approach was safe (with a combined operative mortality and neurologic morbidity of 1.8%), asso ciated with long-term stroke prevention (a 95% stroke-free survival at 4 years), and yielded results similar to CEA with arteriography (operative morbidity, 2.6%; 91% stroke- free survival). The incidence and nature of late neurologic deficits were similar after CEA with and without arteriography. Twenty-three (4%) of the patients who underwent CEA based on duplex ultrasound developed late neurologic symptoms including 9 contralat eral and 4 ipsilateral strokes; and 4 ipsilateral and 4 contralateral transient ischemic attacks (TIAs). Cardiac embolism from atrial fibrillation accounted for 6 strokes, lacunar infarct associated with hypertension (3 strokes), intracranial atherosclerosis (3 strokes), and contralateral internal carotid artery (ICA) occlusion (1 stroke). Forty patients (6.8%) died predominantly from cardiac events. After CEA with arteriography 6 (5%) of the patients died. Six late strokes (4 contralateral, and 2 ipsilateral hemisphere) occurred as a result of progressive, untreated ICA stenosis (n = 3), and lacunar infarct (n = 3). Overall, 11% of the patients underwent contralateral CEA for progressive ICA stenosis.

CEA, based on duplex scanning, is safe and applicable for the majority of patients undergoing surgical evaluation. Short-term and long-term outcomes were similar to outcomes in patients having CEA based on diagnostic arteriography.
Constrictive Pericarditis Following Aortocoronary Bypass Surgery
Authors: Samant Anil R. , Romney David , Brown Lee B. , Desser Kenneth B. , Benchimol Alberto
Published: November 2007

A 61-year-old man had progressive dys pnea along with signs and symptoms sug gesting severe right heart failure following aortocoronary bypass surgery. He was ini tially treated with indomethacin, digoxin, and furosemide, but with no major change in his condition. Four months after opera tion the patient presented with clinical find ings compatible with the postpericardiotomy syndrome and hemodynamic evidence of constriction. Pericardiectomy resulted in a marked improvement in his functional ca pacity. The possible mechanism for peri cardial constriction following open heart surgery is discussed.
Restenosis After Carotid Endarterectomy
Authors: Terrence C.F. , Rao G.R.
Published: November 2007

The recurrence of transient ischemic attacks (TIA's) after carotid endarterectomy is an unusual occurrence. We recently studied a patient who had restenosis and recurrence of TIA's months to years after three different carotid endarterectomies, all done on the same carotid bifurcation. This unusual case represents an extreme example of the association between hyperlipidemia and an increased risk of restenosis after carotid endarterectomy.
Spontaneous Dissecting Subclavian Aneurysm — A Case Report
Authors: Quinones William , Reuter Victor E. , Smullens Stanton N.
Published: November 2007

Dissecting aneurysms of the peripheral arteries are rare lesions. In 1969, Wychulis reviewed the medical literature and found one hundred and eight reported cases of primary dissecting aneurysms of peripheral arteries and added two cases of his own.1Of these, only one case of primary dissecting aneurysm of the subclavian artery was reported. This one was associated with trauma.

In 1968, Persaud reported the first case of dissecting aneurysm of the subclavian artery secondary to idiopathic cystic medial necrosis (ICMN).2Later in 1968, Fee reported a case of dissecting aneurysms of both subclavian arteries also associated with ICMN.3

To our knowledge, there has been no reported cases of primary dissecting aneurysms of the subclavian artery occurring spontaneously without associated recognizable trauma, ICMN, syphilis, or congenital defects. Such a case is the subject of this report. Plain x-rays and angiographic presentation, intra-operative appearance, and management are presented. Histologic findings are briefly discussed.
Basic Vascular Access for Hemodialysis
Authors: Strate Richard G.
Published: November 2007

Vascular access for acute or chronic hemodialysis can be relatively simple or present a significant surgical challenge. The patient about to undergo acute dialysis is frequently suffering from multi-system disease and renal failure is just one component of his illness.

Hemodialysis may need to be initiated on an emergent basis because of life threatening chemical abnormalities, drug intoxication, or fluid overload. Semi-emergent dialysis may be required when a rising serum creatinine indi cates that renal function is deteriorating at a rapid rate. The acute dialysis patient not uncommonly becomes a candidate for chronic dialysis and consid eration must be given to establishing some form of permanent access. The need for chronic dialysis, however, may often be anticipated and access created many weeks before the first dialysis is actually required allowing sufficient time for maturation of an arterio-venous fistula.
Exclusion Technique for Abdominal Aortic Aneurysm and Horseshoe Kidney
Authors: Shuman Robert L.
Published: November 2007

An exclusion technique was utilized in dealing with an abdominal aortic aneurysm with an overlying horseshoe kidney. Use of this technique rather than symphysiotomy was necessitated by 1) a primative collecting system which joined together anteriorly to form a single midline ureter, and 2) a large anomalous renal artery which supplied the mid portion of the horseshoe kidney. The lack of filling of the excluded segment indicated that the lumbar arteries supplied little retrograde flow and therefore the subsequent risk of late rupture of the excluded segment was nil.
Tracheo-Innominate Artery Fistula: Successful Surgical Repair Using a Portion of the Thymus as an Arterial Wrap
Authors: Rubio Pedro A. , Farrell Edward M. , Alvarez B. Antonio
Published: November 2007

A 40-year-old postcraniotomy patient was undergoing comprehensive reha bilitation at our hospital when he suddenly had massive bleeding from a tra cheo-innominate artery fistula that complicated a low tracheostomy. Successful surgical repair was achieved with an arterial wrap fashioned from a portion of the thymus. To our knowledge, this technique has never been used before.
Limb Salvage in Two Cases With Unusual Reconstruction of the Profunda Femoris Artery and Reimplantation of a Large First Branch
Authors: Rubio Pedro A.
Published: November 2007

Two patients with complex histories of coronary artery disease and periph eral vascular disease underwent reconstruction of the common femoral, superfi cial femoral, and profunda femoris arteries after previously implanted prosthetic grafts had failed. In both cases, the diseased segment was removed, a new prosthetic graft was inserted, and the profunda femoris artery was recon structed, with reimplantation of its large first branch. This unusual approach may prove valuable in similar cases that do not lend themselves to traditional methods of repair.
Frequency of Thrombus on Non-Pathologic and Atherosclerotic Intima of Human Aorta — Thrombosis as a Pathogenesis of Atherosclerosis
Authors: Tanimura Akira , Hayashi Itsuro , Nakashima Teruyuki
Published: November 2007

Forty-four aortas dissected from human subjects were sliced into 30-50 se rial sections and studied morphologically for the presence of thrombi. A total of 569 thrombi were found histologically in 1,400 sections. The frequency of thrombosis was 7% for subjects under 30 years-old. However, with increasing age, the frequency rose to 8% in the third decade, 9% in the fourth decade, 13.5% in the fifth decade, 10.5% in sixth decade, 25.5% in the seventh decade and 33.5% for subjects over 80 years-old.

Thrombi were morphologically classified into three types: (1) microthrombi (2) membranous thrombi, and (3) large massive thrombi. The latter were rarely found on the intima, and no sclerotic lesions were observed.

The frequency of thrombosis on non-pathologic areas was 11 %, and almost all of them were microthrombi. The thrombi on the areas of cloudy thickening was 47% with 6% of them being classified as membranous thrombi or large massive thrombi. The thrombi on atherosclerotic lesions was 42%, unusually high compared with the other categories and 32 % of them were membranous or large massive thrombi.

In each region of thoracic and abdominal aorta, thrombi were apt to be more on abdominal aorta than that on thoracic aorta.
Aortic Aneurysm and Ureteral Obstruction Associated with Retroperitoneal Fibrosis and Arteritis. A Case Report and Literature Survey
Authors: Harjula A.L.J. , Harjola P.-T. , Heikkilä L. , Somer T. , Nordling S.
Published: November 2007

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease of unknown etiol ogy. The disease is related to some therapeutic agents. Previously only in two cases methylopa has been associated with IRF. 4,5 The reported patient, a 56- year-old woman had suffered from arterial hypertension for 20 years and the only medication used was methyldopa for two years. A low back pain and a feeling of heaviness in her lower abdomen resulted in clinical examinations and an abdominal aortic aneurysm with moderate hydronephrosis on the right-hand side was found. IRF was revealed at operation. A ureterolysis and an aorto-iliac reconstruction were made using prosthesis. Postoperative recovery was un eventful.

An inflammatory reaction in the outer part of the media and in the adventi tia of the aortic wall was found. The inflammatory cells were mostly lympho cytes and plasmacells but also some areas with heavy eosinophilic infiltrates were present. Vasculitis was seen in small vessels.

Eleven cases of IRF associated with arteries from the previous literature are described.
Abdominal Aortic Aneurysms in Elderly Patients
Authors: Walker John T. , Johnson Brad , Fitz William , Vaccaro Patrick S. , Smead William L. , Cooperman Marc
Published: November 2007

A retrospective review of the morbidity and mortality of repair of abdominal aortic aneurysms in elderly patients was performed. Between 1975 and 1984, 104 patients older than 70 years of age (average 76.3 years) were operated upon for abdominal aortic aneurysm. Of these, 65 had elective operations, 16 had expanding aneurysms, and 23 had ruptured aneurysms. Most of those undergo ing elective operations had an asymptomatic pulsatile mass. In contrast, all those with expanding or ruptured aneurysms had abdominal or back pain, and most of those with ruptured aneurysms were in shock. The mortality rates for the elective, expanding, and ruptured groups were 4.6%, 12.5%, and 60.8% respectively. The most common cause of death in those undergoing elective op eration was myocardial infarction, while the most common cause of death from a ruptured aneurysm was multisystem failure. Improved mortality rates for the second five-year period (1980-1984) were noted and may reflect improved pre operative preparation and postoperative monitoring. It appears that elective aneurysmorrhaphy can be accomplished with relative safety in elderly patients, but that rupture carries high morbidity and mortality.
Iloprost, a Prostacyclin Analog in the Treatment of Advanced Peripheral Arterial Disease
Authors: Pessi Teuvo , Kaukinen Seppo , Ylitalo Pauli , Reinikainen Pekka , Vapaatalo Heikki
Published: November 2007

Iloprost (ZK 36 374), a derivative of carbaprostacyclin, was infused intravenously for seventy-two hours to 10 patients with advanced obliterative peripheral arterial disease. Nine patients reported subjective improvement after the treatment. In 6, the effect lasted for up to two months. In 2, chronic crural ulcers healed for at least a year and a half. In objective circulatory parameters (angiography, plethysmography, ankle blood pressure), no uniform findings could be registered. The possible role of vasodilative, antiaggregative, or micro-circulatory actions of iloprost remains an open question. If the dose is kept in the range of 2ng · kg-1 min-1, iloprost is generally well tolerated, except for its side effects originating from vasodilation or stimulation of the motility of the gastrointestinal tract. No serious side effects were observed. In selected, not very advanced cases, iloprost offers a new approach in the treatment of peripheral arterial disease.