bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Heparin versus Lepirudin Flushes to Prevent Withdrawal Occlusion of Central Venous Access Devices
Authors: Horne McDonald K. , McCloskey Donna Jo , Calis Karim , Wesley Robert , Childs Richard , Kasten‐Sportes Claude
Published: September 2006

Study Objective. To determine whether lepirudin flushes are more effective than heparinized saline in preventing withdrawal occlusion of central venous access devices.

Design. Randomized, double‐blind clinical trial.

Setting. Research institution‐tertiary referral center.

Patients. Forty‐nine adults undergoing bone marrow transplantation for hematologic malignancies or metastatic solid tumors.

Intervention. Twenty‐four patients received heparin and 25 received lepirudin flushes. The heparin dose was 3 ml of porcine heparin 100 U/ml (300 U) per catheter lumen at least once/day; the lepirudin dose was 3 ml of lepirudin 100 μg/ml (300 μg) per catheter lumen at least once/day After 3–4 weeks, all 49 patients received the heparin flushes.

Measurements and Main Results. Efficacy was assessed by the frequency with which the patients were treated with alteplase instillations for withdrawal occlusion of their central venous access devices during the first 4 months of catheterization. Three (12.5%) patients treated with heparin alone and five (20%) treated initially with lepirudin required alteplase instillations for an estimated relative risk with lepirudin versus heparin of 1.6 (95% confidence interval [CI] 0.40–13.86, p=0.70).

Conclusion. Lepirudin was not more effective than heparin, which may have been related to the conservative dose of lepirudin administered. However, higher lepirudin doses are likely to incur an unacceptable risk of systemic anticoagulation.
Analysis of the Psychoactive Terpenoid Salvinorin A Content in Five Salvia divinorum Herbal Products
Authors: Wolowich William R. , Perkins Alisha M. , Cienki John J.
Published: September 2006

Study Objective. To determine the content of the hallucinogen salvinorin A in a variety of Salvia divinorum herbal products and to compare the content with the label claims of potency and purity.

Design. Laboratory analysis.

Setting. University‐affiliated laboratory.

Samples. Five herbal products containing Salvia divinorum.

Measurements and Main Results. The samples were purchased from the Internet and local drug paraphernalia shops (“head shops”). High‐performance liquid chromatography and thin‐layer chromatography–gas chromatography–mass spectroscopy were used for the analysis. All five samples contained salvinorin A, a psychoactive compound found in Salvia divinorum; however, the salvinorin A concentrations we measured were much lower than those claimed on the product label. Vitamin E was also found in two samples and caffeine in one sample.

Conclusion. The five salvinorin A herbal products were found to be subpotent, and three products contained adulterants. Any discrepancy between the advertised salvinorin A concentration and their actual concentration may pose a potential risk of both misuse and overdose. These concerns, and the recently reported teenage suicide that could have been related to salvia consumption, underscore the need for practitioners to become familiar with the signs and symptoms of salvia use.
Treatment Options for Nausea and Vomiting During Pregnancy
Authors: Badell Martina L. , Ramin Susan M. , Smith Judith A.
Published: September 2006

Nausea and vomiting, common symptoms during pregnancy, often are regarded as an unpleasant but normal part of pregnancy during the first and early second trimesters. Nausea and vomiting of pregnancy (NVP) occurs in approximately 75–80% of pregnant women. The exact etiology and pathogenesis of NVP are poorly understood and are most likely multifactorial. Some theories for the etiology of NVP are psychological predisposition, evolutionary adaptation, hormonal stimuli, and Helicobacter pylori infection. Treatment ranges from dietary and lifestyle changes to vitamins, antiemetics, and hospitalization for intravenous therapy. Treatment generally begins with nonpharmacologic interventions; if symptoms do not improve, drug therapy is added. Although NVP has been associated with a positive pregnancy outcome, the symptoms can significantly affect a woman's life, both personally and professionally. Given the substantial health care costs, as well as indirect costs, and the potential decrease in quality of life due to NVP, providers need to acknowledge the impact of NVP and provide appropriate treatment.
Statin Withdrawal: Clinical Implications and Molecular Mechanisms
Authors: Cubeddu Luigi X. , Seamon Matthew J.
Published: September 2006

Retrospective analyses of data from the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM), the National Registry of Myocardial Infarction 4, and the Global Registry of Acute Coronary Events (GRACE) trials revealed that the benefits of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) on acute coronary outcomes are rapidly lost and outcomes worsened if statins are discontinued during a patient's hospitalization for an acute coronary syndrome. Withdrawal of statin therapy in the first 24 hours of hospitalization for non–ST‐elevation myocardial infarction increased the hospital morbidity and mortality rate versus continued therapy (11.9% vs 5.7%, p<0.01). Data from the Treating New Targets (TNT) study, however, suggested that short‐term discontinuation of statin therapy in patients with stable cardiac conditions may not substantially increase the risk of acute coronary syndromes. In patients with acute coronary syndromes who discontinue statins, the rapid increase in risk of an event may result not only from the lost benefits from the therapy, but also from rebound inhibition of vascular protective substances and activation of vascular deleterious substances. Statins inhibit cholesterol synthesis in vascular cells. By reducing levels of isoprenoid intermediates, statins increase the production of nitric oxide and downregulate angiotensin II AT1receptors, endothelin‐1, vascular inflammatory adhesion molecules, and inflammatory cytokines. These benefits are rapidly lost and often transiently reversed when statins are acutely discontinued. Acute removal of pleiotropic effects and rebound vascular dysfunction may be more important in an acute coronary event, where inflammation promotes rupture of atherosclerotic plaques and inflammatory and prothrombosis markers are present in high concentration, than in stable chronic vascular disease. In the absence of data from randomized controlled trials, current information suggests that statin therapy should be continued, and possibly boosted, during hospitalization for an acute coronary syndrome. Because statins are discontinued during the early hospitalization of many patients, practitioners must ensure that statins are not omitted, unless contraindicated, from the treatment of patients with acute coronary syndromes.
Interaction Between Selective Serotonin Reuptake Inhibitors and Nonsteroidal Antiinflammatory Drugs: Review of the Literature
Authors: Mort Jane R. , Aparasu Rajender R. , Baer Rebecca K.
Published: September 2006

Objective. To evaluate the evidence of an interaction between selective serotonin reuptake inhibitors (SSRIs) and nonsteroidal antiinflammatory drugs (NSAIDs) producing an increased risk for gastrointestinal adverse outcomes such as bleeding.

Methods. We searched MEDLINE for English‐language literature published between 1966 and August 2005. All studies examining gastrointestinal adverse effects from an SSRI‐NSAID combination were included.

Data Synthesis. Four retrospective studies examined gastrointestinal adverse outcomes from the combination of SSRIs and NSAIDs. The risk ratio for an upper gastrointestinal bleed from this drug combination (compared with not receiving either agent) ranged from 3.3–15.6, and the risk ratio for gastrointestinal adverse effects was 12.4. Two studies found that the risk for an upper gastrointestinal bleed from the drug combination exceeded the additive risk of the agents alone. The risk ratio for an upper gastrointestinal bleed from an SSRI‐aspirin interaction was 1.9–7.2. In addition, the number needed to harm in terms of an upper gastrointestinal bleed from an SSRI‐NSAID combination ranged from 62–75 patient‐years, and the number needed to harm for gastrointestinal adverse effects was 2 patient‐years.

Conclusion. Concurrent use of an SSRI and NSAID increases the risk of gastrointestinal adverse outcomes such as bleeding. Clinicians must take care to avoid these negative outcomes by altering NSAID or SSRI therapy, or by providing ulcer‐protective drugs.
Interaction Between Warfarin and Cranberry Juice
Authors: Aston Jonathan L. , Lodolce Amy E. , Shapiro Nancy L.
Published: September 2006

Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0–3.0 for most indications or 2.5–3.5 for high‐risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction. Clinicians should be aware of this potential interaction and monitor and counsel patients accordingly.
Application of Antimicrobial Pharmacodynamic Concepts into Clinical Practice: Focus on β‐Lactam Antibiotics
Authors: Lodise Thomas P. , Lomaestro Ben M. , Drusano George L.
Published: September 2006

In recent years there have been tremendous strides in understanding the relationship between the pharmacodynamics of β‐lactams and microbiologic response. For β‐lactams, in vitro and animal studies suggest that the amount of time in which free or non–protein‐bound antimicrobial concentration exceeds the minimum inhibitory concentration (MIC) of the organism (fT>MIC) is the best predictor of bacterial killing and microbiologic response. Using population pharmacokinetic modeling and Monte Carlo simulation, it is possible to integrate pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate empiric β‐lactam dosing strategies that maximize the likelihood of achieving fT>MIC associated with near‐maximal bactericidal effect against the range of pathogens encountered in clinical practice. At Albany Medical Center Hospital, these mathematical modeling techniques were used to devise alternative dosing schemes for piperacillin‐tazobactam, meropenem, and cefepime. These alternative schemes optimized fT>MIC at a lower total daily dose than would be employed with traditional dosing methods. Moreover, they achieved the targeted fT>MIC with less administration time/day than would be needed for continuous infusion.
Coronary Artery Disease and Hypertension: Outcomes of a Pharmacist‐Managed Blood Pressure Program
Authors: McConnell Karen J. , Zadvorny Emily B. , Hardy Angela M. , Delate Thomas , Rasmussen Jon R. , Merenich John A. ,   Clinical Pharmacy Cardiac Risk Service Study
Published: September 2006

Study Objective. To assess the effectiveness of a pharmacist‐managed service in improving hypertension control among patients with coronary artery disease.

Design. Prospective cohort study

Setting. Health maintenance organization.

Patients. Three hundred seventy‐six patients with uncontrolled hypertension and coronary artery disease.

Intervention. Pharmacist‐managed, physician‐supervised population‐management approach to optimize evidence‐based drug management.

Measurements and Main Results. Blood pressure reduction and control were evaluated, as well as the use of angiotensin‐converting enzyme inhibitors and generic antihypertensive drugs during 7‐month follow‐up. At baseline, mean ± SD age was 70.4 ± 8.8 years, 247 (65.7%) were men, 201 (53.5%) had a history of myocardial infarction, and 237 (63.0%) had diabetes mellitus. Baseline mean systolic blood pressure was 151 mm Hg, and none had achieved their blood pressure goal. During follow‐up, mean systolic blood pressure decreased 16.1 mm Hg overall (p<0.001), and 179 (47.6%) patients achieved their goal blood pressure (p<0.001). Blood pressure reductions were 14.7 and 18.4 mm Hg in patients with and patients without diabetes, respectively (p<0.001). The target dose for angiotensin‐converting enzyme inhibitors was achieved in 252 (67.0%) patients compared with 102 (27.1%) at baseline (p<0.001). Generic fill rates for antihypertensive drugs continued to be higher than 95% during follow‐up (p=0.723).

Conclusion. A pharmacist‐managed, physician‐supervised population‐management approach in patients with coronary artery disease significantly improved blood pressure control. Clinically meaningful reductions in blood pressure were achieved by using evidence‐based, cost‐effective drug regimens.
Effectiveness of a Two‐Part Educational Intervention to Improve Hypertension Control: A Cluster‐Randomized Trial
Authors: Hennessy Sean , Leonard Charles E. , Yang Wei , Kimmel Stephen E. , Townsend Raymond R. , Wasserstein Alan G. , Ten Have Thomas R. , Bilker Warren B.
Published: September 2006

Study Objective. To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control.

Design. Cluster‐randomized trial.

Setting. Academic health system using an ambulatory electronic medical record.

Subjects. A total of 10,696 patients with a diagnosis of hypertension cared for by 93 primary care providers.

Intervention. Academic detailing, provision of provider‐specific data about hypertension control, provision of educational materials to the provider, and provision of educational and motivational materials to patients.

Measurements and Main Results. The primary outcome was blood pressure control, defined as a blood pressure measurement below 140/90 mm Hg, and was ascertained from electronic medical records over 6 months of follow‐up. We determined the adjusted odds ratio for the association between the intervention and the achievement of controlled blood pressure. When we accounted for clustering by provider, this adjusted odds ratio was 1.13 (95% confidence interval 0.87–1.47). Adjusted odds ratios were 1.03 (95% confidence interval 0.78–1.36) in patients whose blood pressure was controlled at baseline and 1.25 (95% confidence interval 0.94–1.65) in those whose blood pressure was not. These odds ratios were not significantly different (p=0.11).

Conclusions. These results were consistent with no effect or, at best, a relatively modest effect of the intervention among patients with hypertension. Had we not included a concurrent control group, the data would have provided an unduly optimistic view of the effectiveness of the program. The effectiveness of future interventions may be improved by focusing on patients whose blood pressure is uncontrolled at baseline.
Probable Association Between Ziprasidone and Worsening Hypertension
Authors: Villanueva Noemi , Markham‐Abedi Courtney , McNeely Connie , Diaz Francisco J. , de Leon Jose
Published: September 2006

According to premarketing studies, at least 1% of ziprasidone‐treated patients exhibited hypertension; however, this figure is not necessarily attributable to the drug. A PubMed/MEDLINE search yielded no articles describing hypertension as a possible adverse event associated with oral ziprasidone therapy. We describe a 53‐year‐old African‐American woman with hypertension and schizophrenia whose blood pressure increased during ziprasidone therapy. She experienced no similar blood pressure increases during therapy with four other atypical antipsychotics. Her mean systolic blood pressure during ziprasidone treatment (158 mm Hg) was significantly higher than before (141 mm Hg) and after (135 mm Hg) treatment. Also, her mean diastolic blood pressure during ziprasidone treatment (88 mm Hg) was significantly higher than after treatment (79 mm Hg). Linear regression analysis demonstrated that the patient's systolic blood pressure increased significantly with ziprasidone dose (regression coefficient [B] = 0.22 mm Hg x day/mg, 95% confidence interval 0.10–0.34, p=0.001). Thus, after adjusting for the effect of antihypertensive doses, an increase of 40 mg/day in ziprasidone yielded an increase of 8.8 mm Hg in systolic blood pressure. For unknown (perhaps genetic) reasons, this patient may have been particularly sensitive to ziprasidone. Clinicians prescribing ziprasidone in patients with hypertension should be aware that their hypertension could worsen with the addition of ziprasidone. If this occurs, replacement of ziprasidone with a different antipsychotic should be considered.
Quantitative Ultrasound Imaging of Healthy and Reconstructed Cleft Lip: A Feasibility Study
Authors: van Hees Nancy J. M. , Thijssen Johan M. , Huyskens Rinske W. , Weijers Gert , Nillesen Maartje M. , de Korte Chris L. , Katsaros Christos
Published: September 2006

Objective:

To investigate the feasibility of echographic imaging of healthy and reconstructed cleft lip and to estimate tissue dimensions and normalized echo level.

Methods:

Echographic images of the upper lip were made on three healthy subjects and two patients using a linear array transducer (7 to 11 MHz bandwidth) and a noncontact gel coupling. Tissue dimensions were measured using calipers. Echo levels were calibrated and were corrected for beam characteristics, gel path, and tissue attenuation using a tissue-mimicking phantom.

Results:

At the central position of the philtrum, mean thickness (SD) of lip loose connective tissue layer, orbicularis oris muscle, and dense connective layer was 4.0 (0.1) mm, 2.3 (0.7) mm, and 2.2 (0.7) mm, respectively, in healthy lip at rest; and 4.1 (0.9) mm, 3.8 (1.7) mm, and 2.6 (0.6) mm, respectively, in contracted lip. Mean (SD) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was −19.3 (0.6) dB and −10.7 (4.0) dB, respectively, in relaxed condition and −20.7 (1.5) dB and −7.7 (2.3) dB, respectively, in contracted state. Color mode echo images were calculated, showing lip tissues in separate colors and highlighting details like discontinuity of the orbicularis oris muscle and presence of scar tissue.

Conclusions:

Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper echographic equipment calibration. Diagnostic potentials of this method for noninvasive evaluation of cleft lip reconstruction outcome are promising.
Adjuvant Therapy with Trastuzumab for HER-2/neu-Positive Breast Cancer
Authors: Gonzalez-Angulo Ana M. , Hortobágyi Gabriel N. , Esteva Francisco J.
Published: September 2006

Learning Objectives

After completing this course, the reader will be able to: Select appropriate adjuvant therapy for patients with HER-2/neu-positive breast cancer.Monitor trastuzumab therapy for cardiac toxicity.Discuss the controversies that remain in the treatment of HER-2/neu-positive breast cancer.

Access and take the CME test online and receive 1 AMA PRA category 1 creditTM at CME.TheOncologist.com

Breast cancer is the most common cancer in women in the U.S. and western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. In experimental models, transfection of the her-2/neu gene results in transformation of mammary epithelial cells. In human breast cancer, amplification of the her-2/neu gene results in protein over expression and poor prognosis. Patients whose tumors have her-2/neu gene amplification have a shorter disease-free survival time than patients whose tumors exhibit a normal her-2/neu gene copy number. her-2/ neu gene amplification identifies a biologically unique subset of aggressive breast tumors that are sensitive to growth inhibition and apoptosis induced by anti-HER-2/neu-targeted therapies. The first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with metastatic HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. However, potential cardiotoxicity requires careful patient selection. Here, we review the recently completed clinical trials of adjuvant trastuzumab in the adjuvant setting. HER-2/neu testing, patient selection, cardiotoxicity, duration of therapy, and directions for future research are discussed.
Molecular Classification of Breast Cancer: Limitations and Potential
Authors: Pusztai Lajos , Mazouni Chafika , Anderson Keith , Wu Yun , Symmans W. Fraser
Published: September 2006

Learning Objectives

After completing this course, the reader will be able to: Discuss the technical variables that affect accuracy of estrogen receptor immunohistochemistry.Describe emerging methods to quantify estrogen receptor expression and predict the prognosis of estrogen receptor-positive patients.Discuss limitations of current gene expression-based molecular classification of breast cancer.Explain the conceptual differences between unsupervised molecular class discovery methods and supervised clinical outcome prediction models such as multigene prognostic signatures.Interpret results of DNA microarray literature as they relate to diagnosis and prognosis of breast cancer.

Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com

Reverse transcription polymerase chain reaction and DNA microarrays are increasingly used in the clinic and in clinical research as prognostic or predictive tests. Results from these tests led to novel risk stratification methods and to new molecular classification of breast cancer. Some of these tools already complement existing diagnostic tests and can aid medical decision making in some situations. Better understanding of the molecular classes of breast cancer, independent of their prognostic and predictive values, may also lead to new biological insights and eventually to better therapies that are directed toward particular molecular subsets. However, there is substantially less experience with these emerging technologies than with the more established methods, the accuracy of which is often overestimated. This review discusses some of the limitations and strengths of current gene expression-based molecular classification of breast cancer. To provide context for this discussion, we also briefly examine the performance of estrogen receptor immunohistochemistry, which represents an essential part of the routine diagnostic workup for all breast cancer patients.
Thymoma: Benign Appearance, Malignant Potential
Authors: Riedel Richard F. , Burfeind William R.
Published: September 2006

Thymoma is a rare tumor with a largely indolent growth pattern. It does, however, have malignant potential as a result of its ability to invade locally and metastasize regionally. Often associated with a number of immune- and nonimmune-mediated paraneoplastic syndromes, patient outcomes are directly related to stage of disease and the ability to achieve a complete surgical resection. Surgery is the mainstay of treatment, with adjuvant radiation recommended for invasive thymoma. Sensitive to both chemotherapy and radiation, durable responses are achievable in incompletely resected and inoperable patients. We present two cases of thymoma followed by a general discussion with an emphasis on treatment for both early and advanced-stage disease.
Role of Minimally Invasive Surgery in Gynecologic Cancers
Authors: Schlaerth Alan C. , Abu-Rustum Nadeem R.
Published: September 2006

Learning Objectives

After completing this course, the reader will be able to: Describe the different minimally invasive surgical options for patients diagnosed with cervical, endometrial, or ovarian cancer.List the benefits and limitations of a minimally invasive surgical approach in patients with gynecologic cancers.Identify the clinical criteria that are useful in determining whether a patient with a gynecologic cancer is an appropriate candidate for a minimally invasive surgery.

Access and take the CME test online and receive 1 AMA PRA category 1 creditTM at CME.TheOncologist.com

The role of minimally invasive surgery in the management of gynecologic cancers continues to expand. Radical vaginal trachelectomy with laparoscopic pelvic lymphadenectomy has emerged as a safe, reasonable option for women with early-stage cervical cancer desiring fertility preservation. Similarly, laparoscopically assisted radical vaginal hysterectomy has been systematically described, is feasible, and can be offered to women with early-stage cervical cancer who do not desire future childbearing. In the treatment of early-stage endometrial cancer, the surgical approach of laparoscopic hysterectomy, peritoneal washings, and pelvic and para-aortic lymph node dissection, with or without an omentectomy, is being compared with the same surgery performed via laparotomy in the cooperative Gynecologic Oncology Group LAP 2 study, which has completed accrual, and appears to be a reasonable surgical option. In ovarian cancer, minimally invasive surgery has been incorporated to manage early-stage, advanced-stage, and recurrent disease, as well as second-look procedures. Hand-assisted laparoscopy has also recently been described in managing larger volume primary and recurrent gynecologic cancers. Extraperitoneal laparoscopy for para-aortic and pelvic lymph node dissections has been shown to yield adequate nodal counts and to be safe and feasible in the management of gynecologic cancers.
What Is the Current State-of-the-Art Imaging for Detection and Staging of Cholangiocarcinoma?
Authors: Slattery James M. , Sahani Dushyant V.
Published: September 2006

Cholangiocarcinoma is an adenocarcinoma that arises from the bile duct epithelium and is the second most common primary hepatobiliary cancer, after hepatocellular cancer, with approximately 2,500 cases annually in the U.S. However, cholangiocarcinoma remains a relatively rare disease, accounting for <2% of all human malignancies. Although the entire biliary tree is potentially at risk, tumors involving the biliary confluence or the right or left hepatic ducts (hilar cholangiocarcinoma) are most common and account for 40%–60% of all cases. Most patients present with advanced disease that is not amenable to surgical treatment. The median survival time for patients with intrahepatic cholangiocarcinoma without involvement of the hilum varies among centers from 18–30 months. The median survival time for patients with perihilar cholangiocarcinoma is slightly less, varying from 12–24 months. Despite the overall poor prognosis, survival after surgical treatment of hilar cholangiocarcinoma has improved during the past 10–15 years. This review highlights the imaging features of cholangiocarcinoma, with particular emphasis on the imaging techniques that can best assess tumor resectability and guide the surgeon regarding the potential extent of resection required in operable candidates.
Disseminated Intravascular B-Cell Lymphoma: Clinicopathological Features and Outcome of Three Cases Treated with Anthracycline-Based Immunochemotherapy
Authors: Bouzani Maria , Karmiris Themis , Rontogianni Dimitra , Delimpassi Susanna , Apostolidis John , Mpakiri Maria , Nikiforakis Emmanuel
Published: September 2006

The purpose of this study was to evaluate the use of combination anthracycline-based immunochemotherapy in intravascular lymphoma (IVL). This is an extremely rare, disseminated, and aggressive extranodal CD20+ non-Hodgkin's lymphoma (NHL) with poor outcome following anthracycline-based chemotherapy. From a population of 700 newly diagnosed patients with NHL who were registered and followed up at our unit between 1990 and 2005, three cases (0.4%) have been classified as IVL. Among the patients, there were two men and one woman, with a median age of 52 years. We have assessed the clinicopathological characteristics, response to therapy, and outcome. All patients presented with systemic symptoms and disseminated disease. All patients received anthracycline-based chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab (immunochemotherapy). Complete remission was achieved in all three patients, and currently all remain progression free with a follow-up of 24–45 months. In conclusion, anthracycline-based immunochemotherapy induces durable remissions in patients with IVL, an ultimately fatal disease, suggesting that the clinical course of this disease may be altered with immunochemotherapy.
Advances in the Therapy of Chronic Idiopathic Myelofibrosis
Authors: Arana-Yi Cecilia , Quintás-Cardama Alfonso , Giles Francis , Thomas Deborah , Carrasco-Yalan Antonio , Cortes Jorge , Kantarjian Hagop , Verstovsek Srdan
Published: September 2006

Learning Objectives

After completing this course, the reader will be able to: Discuss the clinical manifestations of myelofibrosis with myeloid metaplasia and recent developments in the understanding of its pathogenesis.Discuss the most recent clinical trials involving novel therapies for myelofibrosis with myeloid metaplasia.Propose an algorithm-based approach to the treatment of patients with myelofibrosis with myeloid metaplasia.

Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com

The molecular basis of chronic idiopathic myelofibrosis (CIMF) has remained elusive, thus hampering the development of effective targeted therapies. However, significant progress regarding the molecular mechanisms involved in the pathogenes is of this disease has been made in recent years that will likely provide ample opportunity for the investigation of novel therapeutic approaches. At the fore front of these advances is the discovery that 35%–55% of patients with CIMF harbor mutations in the Janus kinase 2 tyrosine kinase gene. Until very recently, the management of patients with CIMF involved the use of supportive measures, including growth factors, transfusions, or interferon, and the administration of cyto-reductive agents, such as hydroxyurea and anagrelide. However, several trials have demonstrated the efficacy of antiangiogenic agents alone or in combination with corticosteroids. In addition, the use of reduced-intensity conditioning allogeneic stem cell transplantation has resulted in prolonged survival and lower transplant-related mortality.
Prophylaxis of Irinotecan-Induced Diarrhea with Neomycin and Potential Role for
UGT1A1*28
Genotype Screening: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: de Jong Floris A. , Kehrer Diederik F. S. , Mathijssen Ron H. J. , Creemers Geert-Jan , de Bruijn Peter , van Schaik Ron H. N. , Planting André S. Th. , van der Gaast Ate , Eskens Ferry A. L. M. , Janssen Jos Th. P. , Ruit Jan B. , Verweij Jaap , Sparreboom Alex , de Jonge Maja J. A.
Published: September 2006

Objective. Delayed-type diarrhea is a common side effect of irinotecan and is associated with a bacterial-mediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestine. Based on a pilot study, we hypothesized that concomitant administration of the antibiotic neomycin would diminish exposure of the gut to SN-38 and ameliorate the incidence and severity of diarrhea.

Patients and Methods. Patients were treated with irinotecan in a multicenter, double-blind, randomized, placebo-controlled trial. Eligible patients received irinotecan (350 mg/m2 once every 3 weeks) combined with neomycin (660 mg three times daily for three consecutive days, starting 2 days before chemotherapy) or combined with placebo. Blood samples were obtained for additional pharmacokinetic and pharmacogenetic analyses.

Results. Sixty-two patients were evaluable for the toxicity analysis. Baseline patient characteristics, systemic SN-38 exposure, and UGT1A1*28 genotype status (i.e., an additional TA repeat in the promoter region of uridine diphosphate-glucuronosyltransferase isoform 1A1) were similar in both arms. Although distribution, severity, and duration of delayed-type diarrhea did not differ significantly between arms, grade 3 diarrhea tended to be less frequent in the neomycin arm. The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2–3 diarrhea. In the neomycin arm, grade 2 nausea was significantly more common.

Conclusion. Our results do not suggest a major role for neomycin as prophylaxis for irinotecan-induced delayed-type diarrhea. It is suggested that the UGT1A1*28 genotype status could be used as a screening tool for a priori prevention of irinotecan-induced delayed-type diarrhea.
A Short‐Term Clinical and Microbial Evaluation of Periodontal Therapy Associated With Amalgam Overhang Removal
Authors: Roman‐Torres Caio Vinicius Gonçalves , Cortelli Sheila Cavalca , de Araujo Marcelo Werneck Barata , Aquino Davi Romeiro , Cortelli José Roberto
Published: September 2006

Background: This study evaluated the effect of periodontal therapy plus amalgam overhang removal (PT+AOR) on periodontal status and the presence of Actinobacillus actinomycetemcomitans and Streptococcus mutans and compared two microbiological sampling techniques.

Methods: Molar teeth with Class II overhang restorations were selected as the test group, and homologous sound teeth were selected as the control group. Periodontal probing depth (PD), clinical attachment level (CAL), and plaque and gingival indices were measured, and restorations were evaluated using radiographs and clinical exploration at baseline (T1) and 90 days after PT+AOR (T2). Microbial samples were taken with dental floss and paper points at T1 and T2. S. mutans and A. actinomycetemcomitans were detected using culture and commercial kits.

Results: Mean values of plaque and gingival indices did not show statistically significant differences between test and control teeth between T1 and T2. At T2, the mean CAL decreased among test teeth, and the number of test teeth positive for A. actinomycetemcomitans showed a decrease, whereas positive samples for S. mutans increased. At T1, an association between the two sampling techniques for both bacteria was found. At T2, dental floss presented low sensitivity values for A. actinomycetemcomitans, whereas paper points showed low sensitivity for S. mutans.

Conclusions: PT+AOR showed a beneficial effect on clinical parameters and a decrease of A. actinomycetemcomitans. At T1, both sampling techniques showed appropriate results. At T2, the use of paper points was a more sensitive sampling technique for isolate A. actinomycetemcomitans, whereas dental floss was found to be an alternative sampling method for isolate S. mutans.
Additional Effect of Dentifrices on the Instant Efficacy of Toothbrushing
Authors: Paraskevas S. , Timmerman M.F. , van der Velden U. , van der Weijden G.A.
Published: September 2006

Background: Inconclusive evidence exists in the literature with regard to the additional effect of the use of dentifrice on plaque removal. The present study was undertaken to test whether the use of dentifrice during toothbrushing contributes to the instant cleaning efficacy of the brushing procedure.

Methods: Three groups of patients, 40 subjects each, were randomly assigned to one of three dentifrices that differed with respect to the relative dentin abrasivity (RDA) value. After a 48‐hour plaque accumulation, subjects brushed under supervision in a split‐mouth order with or without the use of dentifrice (total time = 2 minutes).

Results: Plaque reductions varied between 51% and 58% for the three dentifrices. The overall analysis showed a mean difference of 3% in plaque reduction in favor of brushing without dentifrice (P = 0.017). The type of dentifrice did not influence this observed difference (P = 0.506). Also, the order of the brushing procedure (starting the brushing procedure with or without dentifrice) had no interaction with the effect of dentifrice on the brushing (P = 0.187).

Conclusions: The use of dentifrice does not contribute to the instant mechanical plaque removal during manual toothbrushing. A higher dentifrice abrasivity does not seem to contribute to increased plaque removal with a manual toothbrush. It appears that the mechanical action provided by the use of a toothbrush is the main factor in the plaque‐removing process.
Relationship Between Salivary Melatonin and Severity of Periodontal Disease
Authors: Cutando Antonio , Galindo Pablo , Gómez‐Moreno Gerardo , Arana Carlos , Bolaños Jorge , Acuña‐Castroviejo Darío , Wang Hom‐Lay
Published: September 2006

Background: Melatonin possesses antioxidant, free‐radical scavenging, and immunoenhancing properties that promote fibroblast activity and bone regeneration. The aim of this study was to examine the possible links between salivary melatonin levels and the severity of periodontal disease using the community periodontal index (CPI).

Methods: Thirty‐seven patients with different degrees of periodontal disease were studied. Salivary and plasma melatonin levels (by radioimmunoassay), salivary/plasma melatonin ratio, and CPI status were collected for each patient. The Spearman correlation coefficient was used to analyze relationships among variables.

Results: Data showed a significant correlation between CPI and salivary/plasma melatonin ratios. When saliva volume was controlled for, a significant correlation (P <0.05) was found between lower salivary melatonin and a worse CPI. This finding suggests that melatonin may act as a protector against free radicals produced by inflammatory periodontal diseases.

Conclusions: Salivary melatonin levels varied according to the degree of periodontal disease. As the degree of periodontal disease increased, the salivary melatonin level decreased, indicating that melatonin may act to protect the body from external bacterial insults. Therefore, melatonin may be potentially valuable in the treatment of periodontal diseases, although further research is required to validate this hypothesis.
Superior Effect of MD05, Beta‐Tricalcium Phosphate Coated With Recombinant Human Growth/Differentiation Factor‐5, Compared to Conventional Bone Substitutes in the Rat Calvarial Defect Model
Authors: Poehling Sylke , Pippig Susanne D. , Hellerbrand Klaus , Siedler Michael , Schütz Andreas , Dony Carola
Published: September 2006

Background: MD05 consists of beta‐tricalcium phosphate (β‐TCP) coated with recombinant human growth/differentiation factor‐5 (rhGDF‐5) and is under evaluation as an osteoinductive and osteoconductive bone graft material for use in dental and maxillofacial applications. The objective of this study was to compare the bone regenerative properties of MD05 with those of conventional commercially available bone substitutes.

Methods: Full‐thickness, 6‐mm diameter, calvarial critical‐size defects (two per animal) were created in adult Sprague‐Dawley rats. Groups of rats were implanted with the following: 1) MD05; 2) bovine bone mineral; 3) bovine bone mineral with collagen; 4) bovine bone mineral with synthetic peptide, 5) β‐TCP (from two different manufacturers); or 6) no filling material (sham controls). Blinded macroscopic analysis, histopathologic analysis, and histomorphometric analysis were carried out 6 weeks after implantation.

Results: New bone formation assessed histomorphometrically was about five times greater with MD05 than with the other bone substitutes tested, and bone repair was well advanced in MD05‐filled defects after 6 weeks. The extent of fibrous tissue and residual implant were significantly lower in the MD05 group. In contrast to the other materials, the use of MD05 was associated with the complete osseous bridging of the defect and with the presence of normal bone marrow. The osteoinductive effect of rhGDF‐5 was apparent from the more pronounced bone ingrowth observed with MD05 compared to the β‐TCP carrier alone. All implants showed good biocompatibility.

Conclusion: MD05 achieved superior bone regeneration compared to conventional materials and is a promising new bone substitute for dental and maxillofacial applications.
Impaired Masticatory Behavior in Subjects With Reduced Periodontal Tissue Support
Authors: Johansson Anders S. , Svensson Krister G. , Trulsson Mats
Published: September 2006

Background: Mechanoreceptors situated in the periodontal ligament provide detailed information about intensive and spatial aspects of tooth loads, which support the neural control of masticatory forces. We asked whether a reduced periodontal ligament due to periodontitis, and, thus, an altered mechanoreceptive innervation of the teeth, would affect masticatory behavior when subjects used incisors to hold and split food.

Methods: We tested 11 subjects with reduced periodontal tissue support that rendered 30% to 70% alveolar bone loss for at least one pair of opposing anterior incisors. Forces were recorded when subjects used their affected incisors to hold half of a peanut for ∼4 seconds and then split it. Age‐ and gender‐matched healthy subjects served as the control group. None of the participants showed acute oral symptoms or massive periodontal inflammation.

Results: The test group used greater force when holding food between the teeth (1.1 ± 0.4 N [ mean ± 1 SD]) compared to the control group (0.4 ± 0.2 N). Hold forces used by subjects in the test group were also more variable, both within and between trials. The increase in bite force applied to split the peanut was slower and more hesitant for subjects in the test group compared to the control group.

Conclusions: Reduced periodontal tissue support accompanies impaired regulation of masticatory forces. Faulty mechanoreceptive innervation of the periodontal ligament explains the elevated hold force, whereas a change in biting strategy due to the weakened support of the teeth may account for the more defensive food‐splitting behavior.
Reevaluation of Initial Therapy: When Is the Appropriate Time?
Authors: Segelnick Stuart L. , Weinberg Mea A.
Published: September 2006

The concept of periodontal reevaluation of initial therapy needs to be revisited. From interviewing selective periodontists and reviewing the literature, it is apparent that the time period to perform a reevaluation is an ambiguous topic. This seems to be a dichotomy because today everything in dental medicine and medicine is evidence based. When reviewing selective literature sources, it was found that either a time period for reevaluation was given that was different in almost every publication, or a time period was not given but the subject of reevaluation was addressed. The objective of this commentary is to define reevaluation and to determine the best time interval after initial therapy to perform a reevaluation based on classic and current literature. Some questions that need to be addressed are the following: 1) Does too short of a time frame for reevaluation lead to the overtreatment of patients? 2) Is there a danger in reevaluating over too long of a time frame that will lead to disease progression and the return of pathogenic microbial flora? This would mean unnecessary periodontal breakdown could be occurring without appropriate further treatment. Many concerns need to be addressed, including when the appropriate time period is to measure the effects of initial therapy. After this time period, the stability of the periodontium should be evaluated rather than the effects of therapy.
Microbiota of the Dorsum of the Tongue After Plaque Accumulation: An Experimental Study in Humans
Authors: Faveri Marcelo , Feres Magda , Shibli Jamil Awad , Hayacibara Roberto F. , Hayacibara Mitsue M. , de Figueiredo Luciene Cristina
Published: September 2006

Background: The purpose of the present investigation was to determine the effect of the absence of tongue hygiene on the microbiota of the dorsum of the tongue.

Methods: Ten volunteers (aged 19 to 22 years) entered the study at baseline and were instructed to abstain from tongue cleaning for 7 days, followed by a period of 3 days without any kind of oral hygiene. Subsequently, a period of 21 days of washout was employed, and this protocol was repeated three times. Microbiological samples were obtained from the dorsum of the tongue at baseline and at the end of the period of coating accumulation and analyzed using the checkerboard DNA‐DNA hybridization technique.

Results: The species found in highest mean counts at baseline and day 10 were Prevotella melaninogenica and Veillonella parvula. The mean bacterial total counts enhanced significantly during the study (from 17.1 × 106 to 33.7 × 106). Proportions of red and blue complexes and levels of 18 species also increased after the period of coating accumulation, including several periodontal pathogens, such as Prevotella intermedia, Prevotella nigrescens, Streptococcus constellatus, Tannerella forsythensis, Porphyromonas gingivalis, Treponema denticola, and P. melaninogenica.

Conclusion: The tongue surface could be an important reservoir for periodontal pathogens and may play a role in the recolonization of tooth surfaces and in the etiology of oral halitosis.
Salivary Histamine Level as a Predictor of Periodontal Disease in Type 2 Diabetic and Non‐Diabetic Subjects
Authors: Venza Mario , Visalli Maria , Cucinotta Maria , Cicciù Domenico , Passi Pietro , Teti Diana
Published: September 2006

Background: Some previous investigations underscored the role of histamine in periodontal disease, especially in diabetic patients, but the behavior of this inflammatory mediator in the early phases of periodontal involvement remains unclear. The aim of the present study was to correlate the presence of histamine in saliva with clinical parameters in healthy, periodontitis‐affected, and diabetic subjects to ascertain whether this amine may serve as a predictive index of periodontal risk.

Methods: For this purpose, subjects were selected as follows: 1) with newly diagnosed type 2 diabetes mellitus; 2) with neither diabetes nor periodontitis; 3) with no diabetes but with chronic, untreated periodontal disease. Histamine salivary levels were measured at the initial time (T0) and after 6, 12, and 24 months using high‐performance liquid chromatography. The main periodontal indexes were recorded at the same time intervals.

Results: At T0, a very typical shape of the histamine chromatogram was found for all patients of the three groups; at this time, the salivary histamine levels of diabetic patients were increased and comparable to those of healthy patients with periodontal disease, whereas healthy subjects with no periodontitis showed reduced histamine levels. Further controls at 6, 12, and 24 months showed a statistically significant correlation between the increase of salivary histamine and the worsening of the periodontal indexes in diabetic and non‐diabetic subjects.

Conclusion: These results suggest that salivary histamine may serve as a predictive index in the prevention of periodontal disease.