bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelium-Independent Relaxation of Vascular Smooth Muscle by 17β-Estradiol
Authors: Gonzales Rayna J. , Kanagy Nancy L. 
Published: November 2007

Background: Estrogens directly dilate arteries, and this acute relaxation of vascular smooth muscle (VSM) may contribute to the cardioprotective effect of this important hormone. However, the mechanism by which estrogens relax VSM is not clear. Methods and Results: Based on observations in isolated smooth muscle cells, we hypothe sized that 17β-estradiol (E 2) causes dilation through receptor-mediated activation of K+ channels in VSM cells. To test this hypothesis, E2-relaxation was studied in arteries from male Sprague-Dawley rats. We observed that the estrogen receptor antagonist, tamoxifen (3 μmol) attenuated E2 relaxation, suggesting that at least a portion of the relaxation depends on activation of E2 receptors. The nitric oxide synthase inhibitor, Nω-nitro-L-arginine (100 μmol) did not affect E2 relaxation in either denuded or endothelium-intact arterial strips. Furthermore, inhibition of guanylyl cyclase with LY83583 (10 μmol) had no effect on the relaxation, suggesting that nitric oxide does not contribute to this relaxation. Vascular seg ments contracted with 90 mmol KCl to disrupt the K+ gradient had a similar E2 relaxation to segments contracted with phenylephrine (10 -6 mol/L) indicating that E2 relaxation does not require K+-channel activation. Finally, E2 pretreatment inhibited contraction of arterial segments depleted of intracellular calcium but in the presence of extracellular calcium. However, E2 did not affect contraction of strips in calcium-free solution. Conclusions: These final experiments suggest that E2 inhibits Ca2+ influx but not intracellu lar calcium release. Together, these studies establish that E2 causes receptor-mediated relax ation of peripheral resistance arteries through inhibition of calcium entry independent of nitric oxide production, guanylyl cyclase stimulation, and K+-channel activation.
Primary Hyperparathyroidism and Polymorphic Ventricular Tachycardia
Authors: Speakman Mark T. , Ostrzega Enrique 
Published: November 2007

Background: Primary hyperparathyroidism is a rare but important cause of ventricular arrhythmias. Methods and Results: The medical records of a patient with primary hyperparathyroidism and polymorphic ventricular tachycardia was reviewed. The patient was serially interviewed and examined before and after parathyroidectomy. A literature search was performed. The association of primary hyperparathyroidism and polymorphic ventricular tachycardia is rare. Hypokalemia and hypomagnesemia occur infrequently in primary hyperparathyroidism. Conclusions: The potential for malignant ventricular arrhythmias in the setting of primary hyperparathyroidism must be recognized.
Value of Prothrombin Fragment 1.2 (F 1.2) in the Diagnosis of Stroke in Young Patients With Antiphospholipid Antibodies
Authors: Ellis Martin H. , Kesler Anat , Friedman Ziva , Drucker Ilana , Radnai Yehudit , Kott Edna 
Published: November 2007

The presence in the serum of antiphospholipid an tibodies (aPL) is associated with venous and arterial thrombo sis. This observation has led to the search for these antibodies in young patients with ischemic neurologic syndromes. How ever, 1% to 5% of healthy people may be found to have cir culating aPL without necessarily being at increased risk of thromboembolism. Thus, the finding of APLA in a patient with cerebral ischemia does not necessarily provide an explanation for the etiology of the clinical syndrome. The aim of this study was to determine whether the presence of aPL in young patients with stroke or transient ischemic attacks represents a possible cause of hypercoagulability as defined by ongoing thrombin formation with resultant elevation of prothrombin fragment 1.2 (F1.2) levels. This was a retrospective, case-control study involving 57 subjects. Twenty-seven patients had a recent cerebrovascular ischemic event—either TIA or a stroke. Fifteen were positive for aPL, and 12 were aPL-negative. Thirty subjects, matched for age and sex with no history of cerebrovascular disease, served as controls. Of this group, 20 were aPL-positive and 10 were aPL-negative. Causes of hy percoagulability other than aPL were excluded by laboratory testing. A positive test for aPL was repeated after a 6-week interval and two positive tests were required for a patient to be regarded as being aPL-positive. Levels of F1.2 were measured by an ELISA technique. There was a significant difference ( p < 0.05) in the mean F1.2 levels between the aPL-positive group with a history of cerebrovascular disease (mean F1.2 = 2.3733) and each of the other study groups. There was no statistically significant dif ference between any of the other study groups. Our findings suggest that F1.2 levels are elevated in young patients with cerebrovascular syndromes who have aPL and in whom other causes of hypercoagulability and atherosclerotic vascular disease are absent. Elevated F1.2 in these patients may be a potential marker of the hypercoagulable state associated with aPL.
Coronary and Peripheral Thrombolysis: Current Status and Recommendations
Authors: Gensini Gian Franco , Comeglio Marco , Colella Andrea 
Published: November 2007

Thrombolytics are mainly indicated in acute myo cardial infarction (AMI), with limited evidence of usefulness in stroke and acute peripheral arterial occlusion (PAO). Throm bolytics can successfully dissolve thrombi in any vessel, but clinical benefit varies according to the involved vascular bed. The anticipated clinical benefit of thrombolytics in treating AMI, stroke, and PAO must be carefully balanced against the risk of bleeding (especially intracranial hemorrhage). In AMI, fibrinolytic agents reduce mortality rates by as much as 30% when started within 6 h of symptom onset and by as much as 50% if given within 1 to 2 h. Therefore, the timing of fibrino lytic therapy largely determines the magnitude of reduction in mortality after AMI. Streptokinase is a well-documented treat ment for AMI, with r-TPA plus IV heparin enabling better results, specially in anterior MI and in the elderly. Reteplase was not superior to alteplase in GUSTO-III and TNK-TPA is in the early phase of investigation. However their ease of admin istration and potential for more potent and specific clot lysis may prove advantageous. In acute stroke, the most recently reported phase III trials of streptokinase and recombinant tissue plasminogen activator (r-TPA) have stressed the importance of the clinical benefit/hemorrhage risk balance. These studies sup ported the viewpoint that the use of fibrinolytic agents for stroke must be limited to r-TPA in well-characterized patients and with a narrow time window. Finally, local administration of thrombolytic agents in acute arterial thrombosis, mainly in the limbs, is commonly used by interventional radiologists. Goods results have been reported in terms of safety and effec tiveness in the treatment of acute lower extremity ischemia. The preliminary results of the Thrombolysis or Peripheral Ar terial Surgery (TOPAS) trial suggest that recombinant uroki nase therapy (4,000 IU/min) is associated with limb salvage and patient survival rates similar to those achieved with sur gery, concurrent with a reduced need for complex surgery after thrombolytic intervention. In summary, AMI represents the most important indication for thrombolysis, with large amounts of data supporting its use. In acute stroke, there is less evidence of efficacy and it is limited to a few well-characterized patients, whereas local ad ministration in patients with acute PAO may favorably affect patient outcome despite of the absence of evidence of improved limb salvage. Key Words: Thrombolysis—Myocardial infarc tion—Stroke—Acute peripheral arterial occlusion.
Factor V Antigen Is Decreased in Both Types of Combined Factor V and Factor VIII Congenital Defects
Authors: Girolami Antonio , Zanon Ezio , Gavasso Sabrina , Girolami Bruno , Zerbinati Patricia 
Published: November 2007

Factor V antigen was evaluated in four patients with combined factor V and factor VIII deficiency. Two of these patients belonged to type I combined defect (pure asso ciation between factor V deficiency and hemophilia A). The other two belonged to type II (common defect of factor V and VIII). Factor V antigen was low in all patients and compared well with factor V activity levels. Factor VIIIc coagulant was low in all patients. On the con trary Von Willebrand factor (vWF) was normal in all patients. The presence of low factor V antigen in type I combined factor V and factor VIII disease had never been described be fore even though it could have been anticipated on theoretical grounds. Heterozygous for true factor V deficiency are known in fact to have a parallel decrease of activity and antigen level.
Conversion of etoposide phosphate to etoposide under ambulatory infusion conditions
Authors: Webster Lorraine K. , Crinis Nicholas A. , Davis Jillian R. , Millward Michael J. 
Published: November 2007

Objective: To determine the extent of conversion of etoposide phosphate, a water-soluble prodrug for etoposide, to etoposide at concentrations and temper atures likely to occur during ambulatory infusion. Design: Etoposide phosphate solutions were prepared at equivalent etoposide concentrations of 15 and 1.5 mg/mL in ambulatory infusion cassettes and stored protected from light at 18 to 20°C and 37°C. Daily samples were taken for 7 days. Main Outcome Measure: Instability was as sessed as percentage conversion of etoposide phos phate to etoposide. Both drugs were measured using high-performance liquid chromatography. Results: At room temperature, there was less than 2% conversion of etoposide phosphate to etopo side. At 37°C, there was a cumulative conversion to etoposide of 6.6% after 7 days at both the low and high concentrations. Conclusion: Etoposide phosphate displays a temperature-dependent, concentration-independent conversion to etoposide over 7 days of less than 7%. Previous studies have confirmed the chemical stabil ity of etoposide up to 96 hours but have suggested that the maximum recommended etoposide concen tration to prevent crystal formation in infusion solu tions is 0.4 mg/mL. To be conservative, if the maxi mum conversion of etoposide phosphate to etoposide over 7 days is estimated to be 10%, and 0.3 mg/mL is selected as the maximum etoposide concentration, then the maximum concentration of etoposide phos phate should be the equivalent of 3.0 mg/mL etopo side. Therefore, prepared under aseptic conditions in a laminar flow cytotoxic safety cabinet, up to 3.0 mg/mL etoposide as etoposide phosphate in 0.9% sodium chloride can be delivered by ambulatory infusion, protected from light, over 96 hours. This will permit therapeutic doses of etoposide, as etopo side phosphate, to be delivered continuously by ambulatory infusion. Given that the extent of conver sion to etoposide was temperature dependent, it is recommended that the infusion cassette remain be low 37°C and preferably as close to room temperature as possible.
Prolonged response to flutamide withdrawal and initiation of aminoglutethimide in a patient with metastatic prostate cancer
Authors: Middleman Matthew N. , Lush Richard M. , Sartor Oliver , Reed Eddie , Figg William D. 
Published: November 2007

Objective. To present a patient with metastatic pros tate cancer who has experienced an extended re sponse to the withdrawal of flutamide and the con comitant initiation of aminoglutethimide. Case Summary. A 73-year-old male was diagnosed with advanced metastatic prostate cancer. He received treatment with suramin, leuprolide, and flutamide. After progressing on this regimen his flutamide was discon tinued and aminoglutethimide was initiated. His re sponse to this treatment has reached almost 3 years, with no evidence of progression. Discussion. The response to the withdrawal of flutamide is thought to arise from a mutated androgen receptor that recognizes hydroxyflutamide, the active metabolites of flutamide, as an agonist. The receptor continues to recognize endogenous steroids as agonists. The addition of the adrenal steroid synthesis inhibitor, aminoglutethimide may play a role in enhancing this response phenomenon. Conclusions. This patient is progression free for approximately 3 years following the withdrawal of flutamide. This maneuver has been found to have activity in a subset of patients who have been treated for metastatic prostate cancer with combined andro gen blockade.
A phase I trial of recombinant gamma interferon administered intravenously on a daily × 5 schedule
Authors: Koeller Jim , Brown Thomas D. , Beougher Kenneth , Golando James , Bonnem Eric M. , VonHoff Daniel D. 
Published: November 2007

Objective: To determine the maximally tolerated dose and associated toxicity of r-γ-IFN. In addition, to evaluate the development of serum IFN neutralizing factors. Design: This is an open-labeled, Phase I dose escalating trial. Setting: This trial was carried out at a Veteran's Administration and Army hospital. Patients: Patients with advanced malignancies for whom no known effective therapy is available were eligible. Patients must have adequate organ function, a performance status of 2 or lower and a minimal life expectancy of 2 months. Intervention: Patients received escalating doses of r-γ-IFN (0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0 X 106 IU/m2) daily for 5 days given intravenously over 2 hours every other week. Main Outcome Measures: Tumor response was followed clinically, with radiographic support when appropriate. Toxicity was evaluated using the World Health Organization (WHO) standard toxicity grading guidelines. Serum samples were used to monitor and evaluate the IFN neutralizing factors.
Pancreatitis and fatal ARDS following high-dose cytarabine induction for acute myelogenous leukemia
Authors: Wittbrodt Eric T , Aviles Victor M 
Published: November 2007

Objective. To describe a case of fatal acute respira tory distress syndrome (ARDS) and pancreatitis aris ing from high-dose cytarabine induction therapy. Case Summary. A 50-year-old male without a history of hepatobiliary disease and with a diagnosis of acute myelogenous leukemia was treated with high-dose cytarabine therapy. Tumor lysis occurred promptly; the white cell count reached a nadir of 100/mm 3 3 days after initiation of therapy. Severe mid-epigastric pain, fever, hypotension, and increased lipase and amylase occurred on the 6th day of cytara bine therapy. Cytarabine was discontinued 6 days after initiation. Serum amylase and lipase were persis tently elevated; respiratory failure due to ARDS ensued, and the patient expired of refractory hypoxemia. Discussion. Cytarabine-associated pancreatitis is a rare occurrence. Literature reports have described pancreatitis after high-dose cytarabine therapy for induction of remission of ALL and acute myelogenous leukemia. Pancreatitis resolved in all reported cases on discontinuation of cytarabine. In our patient, drug-induced pancreatitis likely provoked the onset of ARDS, which concluded with fatal respiratory failure. The absence of positive cultures decreased the likeli hood of sepsis-induced ARDS; the time course of cytarabine administration was temporally associated with the development of pancreatitis. Conclusions. Acute pancreatitis is a rare but potentially fatal event associated with high-dose cy tarabine therapy.
Extravasation of topotecan, a report of two cases
Authors: Oostweegel Lonneke MM , van Warmerdam Laurence JC , Schot Margaret , Dubbelman Ria C , Ten Bokkel Huinink Wim W , Beijnen Jos H 
Published: November 2007

Objective. Extravasations of anticancer agents may give serious complications and specific therapy might be needed. Topotecan is a new cytotoxic drug and is used in many clinical studies. In our clinic two extravasations of topotecan occurred, and the clinical consequences are discussed. Clinical Features. The extravasations oc curred in two patients who were receiving topo tecan intravenously because of ovarian carcinoma stage III. The patients experienced some discom fort caused by the expansion of soft tissue. How ever, no serious complications were observed. Case Progress and Outcome. Both patients received all further courses of topotecan without any negative effects. Conclusion. In conclusion, besides stopping the injection, trying to aspirate the fluid, keeping the arm high, and cooling the swelling, we advise no specific measures to be taken after extravasa tion of topotecan.
Human resource issues in cytotoxic drug dispensing
Authors: Roos Ian , Makela Tuija 
Published: November 2007

Introduction. The human resource issues for phar macists manipulating and dispensing cytotoxic drugs in safety cabinets and clean rooms, in accordance with Australian Standards, have been investigated. The technology is regulating, resulting in very formal procedures and work practices. Often staff work under conditions of restricted environmental stimula tion that can have effects on cognitive functioning and reduce efficiency for demanding tasks. Methods. Discussions were held with senior staff of twenty hospitals treating patients with cancer, one manufacturing facility, and one research laboratory, regarding work in cytotoxic drug suites. A survey was administered to staff working in these facilities. Issues explored included: work practices; rosters; cleaning; work flow; ergonomics; quality of work environment; clothing; certification of facilities, and training. Results and Discussion. The survey shows that the major stressors for people working in the facilities are the physical conditions, especially the tempera ture, and the lack of control over workflow. It confirms the importance of windows in the working environment and the need for communication facili ties. Design deficiencies in the technology that impact the quality of the work environment are identified. There are age differences with regard to perceptions of risk from cytotoxic drugs. The study identifies the need for further training, both in technique and understanding of the technology. Conclusion. Whilst minimising risk to staff, the adoption of the technology has had an impact on environment. Identification of these issues should enable improved facilities and work environment.
Review : Topoisomerase I inhibitors: 2. Irinotecan
Authors: Skirvin J. Andrew , Relias Valerie 
Published: November 2007

Purpose. The primary objective of this article is to discuss the pharmacology, pharmacokinetics, clinical use, and adverse effects of the approved topoisomer ase I inhibitors. This is the second in a series of two articles and will focus on irinotecan. Data Sources. We reviewed the literature through a MEDLINE search of English language arti cles from 1985 through 1998. Relevant articles cited in the titles obtained from the MEDLINE search were also used. The following terms were used for purpose of conducting the MEDLINE search: topoisomerase inhibitors, irinotecan, topoisomerase I, camptosar, and CPT-11. Data Extraction. We have reviewed the current literature to discuss the pharmacology, pharmacokinet ics, clinical use, toxicity, drug interactions, indications, formulation, dosage and administration, and pharmaceu tical issues surrounding the use of irinotecan. Data Synthesis. The topoisomerase I inhibitors are new antineoplastic agents with a unique mechanism of action. Promising areas of application include colo rectal cancer, non-small-cell lung cancer, small-cell lung cancer, cervical cancer, and lymphomas. Clinical trials detailing the activity of topoisomerase I inhibitors in these areas are presented.
Review : Statistical methods in clinical research: A review for pharmacists
Authors: Dranitsaris George 
Published: November 2007

Objective. Pharmacists have been recognized as both clinicians and researchers. As clinicians, they have to be able to critically review the results of clinical trials and to determine whether the fmdings of these studies were justified based on the methodology. As investigators, pharmacists must select the appropriate research design to answer the main study hypothesis. This paper will review basic statistical concepts that the oncology pharmacist can use to evaluate clinical trials and to design research studies. Data Sources. A variety of articles accessed from a MEDLINE search and statistical reference texts were used. Data Extraction. The information was re viewed, and statistical concepts relevant to oncology pharmacy practice were included. Data Synthesis. The concepts of descriptive and inferential statistics are presented. Detailed nu merical examples of how differences between two independent groups can be evaluated for statistical significance are provided. Similarities and differences between hypothesis testing and estimation are also highlighted.
Fatal Hemorrhage as a Complication of Neurofibromatosis
Authors: Leier Carl V. , Dewan Charles J. , Anatasia Louis F. 
Published: November 2007

Rupture of a major artery occurred in a patient with Von Recklinghausen's disease. The adventitia and media of the artery in the region of the rupture were invaded by neurofibroma. Numerous cases of hemorrhage into neurofibromata have been reported1 2, 3, several of these with a fatal outcome. Cases have been reported describing neurofibromatous involvement of the adventitia of blood vessels with the devel opment of aneurysms 4, 5 and hypertension 5,6. In 1882, Frederick Von Reckling hausen reported a case of neurofibromatosis with rupture of a pulmonary artery aneurysm 7, 8. Unfortunately, microscopic examination of the vessel was not performed. We report a fatal case of rupture of a major artery secondary to neurofibromatous involvement of the adventitia and media of the vessel.
Statement of Policy
Authors: Boyd A. Michael , Friedmann Lawrence W. 
Published: November 2007

As a new policy of the Journal, the Board of Editors have decided to invite views of noted experts in the field of actual and controversial problems in vascu lar diseases. These views will be presented as "special editorials." These editorials do not necessarily reflect the consensus of the Board of Editors of the Journal, and the Board will make no efforts to impose its views on them. They are intended to present individual opinions from the leaders of our profession. We will also invite and, if possible, provide a place in the Journal for the expression of opposite viewpoints.
Statement of Policy
Authors: Boyd A. Michael 
Published: November 2007

As a new policy of the Journal, the Board of Editors have decided to invite views of noted experts in the field of actual and controversial problems in vascu lar diseases. These views will be presented as "special editorials." These editorials do not necessarily reflect the consensus of the Board of Editors of the Journal, and the Board will make no efforts to impose its views on them. They are intended to present individual opinions from the leaders of our profession. We will also invite and, if possible, provide a place in the Journal for the expression of opposite viewpoints.