bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenomedullin Does Not Inhibit Human Platelet Aggregation
Authors: Schiller N.K. , Champion Hunter C. , Hugghins S.Y. , Timothy A.M. , Murphy W.A. , Coy D.H. , Peter J.R. , Kadowitz Philip J. , McNamara D.B. 
Published: November 2007

Background: Adrenomedullin (ADM) is a hypotensive peptide isolated from human pheo chromocytoma extracts discovered in 1993 using an assay system designed to monitor its ability to increase rat platelet adenosine 3',5'-cyclic monophosphate (cAMP) levels. Physio logical mediators that elevate cAMP levels, such as prostaglandin (PG)E1 and PGI2, have also been shown to inhibit platelet aggregation. Therefore, we have chosen to investigate the effect of ADM, a peptide shown to increase platelet cAMP levels, on human platelet aggregation. Methods and Results: Platelet-rich plasma prepared from blood donors was incubated with ADM (10-9-10-6 M) for 1 min at 37°C before the addition of a submaximal dose of adeno sine 5'-diphosphate (ADP). ADM did not alter the platelet aggregatory response to ADP. PGE1, a substance known to inhihit ADP-induced human platelet aggregation (10-6 M), however, inhibited ADP-induced platelet aggregation. In addition, the ADM induced a dose-dependent relation in rings of human chorionic arteries. Conclusions: These data may be interpreted to suggest that human platelets do not possess a functional ADM receptor couple with adenylate cyclase.
Pharmacokinetics of Catecholamines During Hemofiltration in Pediatric Patients
Authors: Freter Anne E. , Husayni Tarek S. , Reyes Gerardo 
Published: November 2007

Background: Continuous hemofiltration is used in pediatric patients with acute renal fail ure. Many of these patients are treated with catecholamines for hemodynamic instability. The authors studied the pharmacokinetics of dopamine and dobutamine on patients under going continuous venovenous hemofiltration. Methods and Results: Three critically ill pediatric patients with acute renal failure and car diovascular instability treated with hemofiltration and intravenous infusion of dopamine and/or dobutamine were entered into the study. Blood samples were drawn at steady-state levels from the arterial port (inflow) of the hemofilter, from the venous port (outflow) of the hemofilter, and from the ultrafilter. Sixteen (n = 16) pharmacokinetic measurements were made, six (n = 6) for dopamine and 10 (n = 10) for dobutamine. The clearance of dopamine by the hemofilter was 0.078 ± 0.011 mL/kg/min, and for dobutamine it was 0.036 ± 0.008 mL/kg/min. On the average, 0.56% of the dopamine dose and 0.13% of the dobutamine dose was removed by the hemofilter. Conclusions: The pharmacokinetics of dopamine and dobutamine at the dosage range of 5- 25 μg/kg/min are not altered by continuous hemoliltration. Relative to total plasma clear ance. negligible amounts of the drug were removed. The dosage of these catecholamines need not hc adjusted during continuous hemofiltration.
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.
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.
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.
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.
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.