bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenovirus-Mediated Expression of Human Prorelaxin Promotes the Invasive Potential of Canine Mammary Cancer Cells
Authors: Silvertown Josh D. , Geddes Brad J. , Summerlee Alastair J. S.
Published: April 2003

This study reports the characterization of a recombinant adenoviral vector containing a tetracycline-regulatable promoter, driving the bicistronic expression of the human H2 preprorelaxin (hH2) cDNA and enhanced green fluorescent protein, via an internal ribosomal entry site. An hH2 ELISA was used to measure the secreted levels of recombinant hH2 in transfected canine (CF33.Mt) and human (MDA-MB-435) mammary cancer cell lines over a 6-d period; secreted peptide peaked on d 2 and 4 for the canine and human cell types, respectively. An unprocessed hH2 immunoreactive form of approximately 18 kDa was identified by Western blotting analysis and confirmed by mass spectrometry, suggesting that prorelaxin remains unprocessed in these cell types. The biological activity of the adenovirally expressed human prorelaxin was measured in the established human monocytic cell line THP-1 cAMP ELISA and in an in vitro Transwell cell migration system. Exogenous recombinant hH2 and adenovirally-mediated delivery of prorelaxin to CF33.Mt cells conferred a significant migratory action in the cells, compared with controls. Cell proliferation assays were performed to discount the possibility that the effect of relaxin was mitogenic. Thus, we have demonstrated that prorelaxin has the ability to facilitate cell migration processes exclusive of its ability to stimulate cell proliferation. In validating this adenovirus-based system, we have created a potential tool for further exploration of the physiology of relaxin in mammalian systems.
Statistical Analysis of Computational Tests of Algorithms and Heuristics
Authors: Coffin Marie , Saltzman Matthew J.
Published: April 2003

Statistical analysis is a powerful tool to apply when evaluating the performance of computer implementations of algorithms and heuristics. Yet many computational studies in the literature do not use this tool to maximum effectiveness. This paper examines the types of data that arise in computational comparisons and presents appropriate techniques for analyzing such data sets. Case studies of computational tests from the open literature are re-evaluated using the proposed methods in order to illustrate the value of statistical analysis for gaining insight into the behavior of the tested algorithms.
Parallelizing the Dual Simplex Method
Authors: Bixby Robert E. , Martin Alexander
Published: April 2003

We study the parallelization of the steepest-edge version of the dual simplex algorithm. Three different parallel implementations are examined, each of which is derived from the CPLEX dual simplex implementation. One alternative uses PVM, one general-purpose System V shared-memory constructs, and one the PowerC extension of C on a Silicon Graphics multi-processor. These versions were tested on different parallel platforms, including heterogeneous workstation clusters, Silicon Graphics multi-processors, and an IBM SP2. We report on our computational experience.
When Does a Dynamic Programming Formulation Guarantee the Existence of a Fully Polynomial Time Approximation Scheme (FPTAS)?
Authors: Woeginger Gerhard J.
Published: April 2003

We derive results of the following flavor: If a combinatorial optimization problem can be formulated via a dynamic program of a certain structure and if the involved cost and transition functions satisfy certain arithmetical and structural conditions, then the optimization problem automatically possesses a fully polynomial time approximation scheme (FPTAS). Our characterizations provide a natural and uniform approach to fully polynomial time approximation schemes. We illustrate their strength and generality by deducing from them the existence of FPTASs for a multitude of scheduling problems. Many known approximability results follow as corollaries from our main result.
A Minimal Algorithm for the Bounded Knapsack Problem
Authors: Pisinger David
Published: April 2003

The Bounded Knapsack Problem (BKP) is a generalization of the 0-1 Knapsack Problem where a bounded amount of each item type is available. Currently, the most efficient algorithm for BKP transforms the data instance to an equivalent 0-1 Knapsack Problem, which is solved efficiently through a specialized algorithm. However, this paper demonstrates that the transformation introduces many similarly weighted items, resulting in very hard instances of the 0-1 Knapsack Problem.

To avoid these problems, we propose a specialized algorithm that solves an expanding core problem through dynamic programming such that the number of enumerated item types is minimal. Sorting and reduction is done by need, resulting in very little effort for the preprocessing. Compared to other algorithms for BKP, the presented algorithm uses tighter reductions and enumerates considerably less item types. Computational experiments are presented, showing that the presented algorithm outperforms all previously published algorithms for BKP.
Gabapentin and Posttraumatic Stress Disorder
Authors: Malek-Ahmadi Parviz
Published: April 2003

OBJECTIVE:

To report the effects of gabapentin in a patient with concurrent depression and posttraumatic stress disorder (PTSD) and review the use of antiepileptic drugs (AEDs) in PTSD.

CASE SUMMARY:

A 37-year-old Latin American woman was being treated for major depression and PTSD. While the depressive symptoms were in remission, she reported a significant reduction in the frequency of her flashbacks after gabapentin was added to venlafaxine. She did not receive any type of psychotherapy. The flashbacks recurred after she discontinued gabapentin.

DISCUSSION:

While the improvement reported by the patient may have been related to a placebo effect or spontaneous recovery, treatment with gabapentin may have played a role in alleviating the flashbacks. Other published reports suggest that AEDs have a beneficial effect on some PTSD symptoms.

CONCLUSIONS:

AEDs may be of some therapeutic value in patients with PTSD. Future controlled studies are warranted to investigate the effectiveness of these agents.
Topiramate Titration to Response: Analysis of Individualized Therapy Study (TRAITS)
Authors: Dodson W Edwin , Kamin Marc , Kraut Lesley , Olson William H , Wu Shu-Chen
Published: April 2003

OBJECTIVE:

To evaluate the relationship between baseline seizure frequency and stabilized topiramate dosage and the effect of individualized treatment on tolerability in adults with partial-onset seizures receiving other antiepileptic drugs (AEDs).

METHODS:

In this 20-week, open-label trial, dosages of medications were adjusted according to clinical response. Dosage and seizure response data were analyzed for 2 groups defined by baseline seizure frequency: <4 and ≥4 seizures per month.

RESULTS:

In the outcome evaluable population (n = 471), the mean ± SEM stable topiramate dosage was 303 ± 139 mg/d when baseline seizure frequency was <4 seizures/month and 341 ± 153 mg/d when baseline seizure frequency was ≥4 seizures/month (p = 0.005). The most common adverse events were somnolence (8.5%), fatigue (7.3%), nausea (5.3%), and dizziness (5.0%). Cognitive complaints were reported by <3% of patients. When concomitant AED dosages were reduced, 14% of patients discontinued topiramate due to adverse events compared with 23% if the concomitant AED dosage was unchanged or increased.

CONCLUSIONS:

When clinicians individualize topiramate dosage according to clinical response, the stabilized topiramate dosage as add-on therapy is influenced by baseline seizure frequency. Topiramate tolerability is improved when dosages of concomitant AEDs are reduced.
An Interventional Program to Improve Antibiotic Use
Authors: Feucht Cynthia L , Rice Louis B
Published: April 2003

BACKGROUND:

Large volume and often inappropriate use of specific antimicrobial agents increase selective pressure for emergence of resistant bacteria and place strain on the pharmacy budget.

OBJECTIVE:

To initiate a multidisciplinary program designed to align intravenous vancomycin and fluoroquinolone prescribing practices with guidelines for appropriate use of these agents.

METHODS:

A multidisciplinary, prospective interventional program was implemented to encourage early discontinuation of inappropriate vancomycin and fluoroquinolone therapy and decrease inappropriate duplicative gram-negative coverage using fluoroquinolones. A computerized review was performed for patients receiving intravenous vancomycin and fluoroquinolones for 1998 in a Veterans Affairs Medical Center. In June 1999, guidelines were disseminated and an interventional program was initiated, with a monthly conference for medical residents regarding antimicrobial resistance and local hospital practices. Concurrently, a prospective review of new orders was assessed by the clinical pharmacist and interventions performed when inappropriate use occurred.

RESULTS:

The interventional program was successful in reducing unnecessary duplicative gram-negative coverage with intravenous fluoroquinolones by 26% (p < 0.001) from 1998 to 2001. Overall, a 43% reduction in the number of courses of intravenous fluoroquinolones was seen during these 4 years. Courses lasting >5 days were reduced by 22% (p < 0.001). Vancomycin prescriptions deemed inappropriate that were administered >5 days were reduced by 16% (p < 0.001) during the same time period. The interventions performed by the clinical pharmacist were deemed successful, with a 76% acceptance rate by providers.

CONCLUSIONS:

Education of physicians through monthly conferences and personal interventions resulted in an increase in appropriate empiric antibiotic use, a decrease in the duration of inappropriate use, and a decrease in duplicate gram-negative coverage.
Excessive Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia
Authors: Reichert Marc G , MacGregorew A , Kincaid Edward H , Dolinski Sylvia Y
Published: April 2003

OBJECTIVE:

To report 4 patients who became excessively anticoagulated with the recommended or lower starting doses of argatroban during treatment for heparin-induced thrombocytopenia type II (HIT-II) in a cardiothoracic intensive care unit.

CASE SUMMARY:

Four patients were treated with argatroban after confirmation of HIT-II after cardiac surgery. In 3 patients, argatroban was initiated at the recommended starting dose of 2 μg/kg/min; in 1 patient, therapy was initiated at 1 μg/kg/min. All patients had relatively normal hepatic function. In all cases, the resulting activated partial thromboplastin time was supertherapeutic and exceeded 100 seconds in 3 patients. Additionally, argatroban clearance appeared to be prolonged upon discontinuation.

DISCUSSION:

Argatroban pharmacokinetics in critically ill patients have not been investigated. Our case series demonstrates the potential over-anticoagulation that can occur in this patient population despite relatively normal hepatic function. An objective causality assessment revealed that the adverse drug event in these patients was probably caused by administration of argatroban.

CONCLUSIONS:

Formal pharmacokinetic studies of argatroban are needed in critically ill patients in order to optimize therapy.
Acute Tumor Lysis Syndrome Secondary to Hydroxyurea in Acute Myeloid Leukemia
Authors: Seki Jack T , Al-Omar Hamad M , Amato Dominick , Sutton David MC
Published: April 2003

OBJECTIVE:

To report 2 cases of acute tumor lysis syndrome (ATLS) associated with hydroxyurea treatment.

CASE SUMMARY:

A 79-year-old woman diagnosed with chronic lymphocytic leukemia presented with an acute blastic transformation. She was promptly hydrated, started on allopurinol, and treated with hydroxyurea. About 24 hours later, her biochemistry panel showed parameters consistent with ATLS when compared with pretreatment levels. The second case was a 76-year-old man newly diagnosed with acute myeloid leukemia presenting with high blast fraction. He was given appropriate hydration and allopurinol prophylaxis, and was started on high-dose hydroxyurea treatment. He became symptomatic after 12 hours and results of his blood work were consistent with ATLS.

DISCUSSION:

ATLS is a well-known metabolic disturbance that occurs after cell destruction of rapidly growing tumors. In standard doses, hydroxyurea leads to cell death in the S phase and is not thought to cause significant cell lysis. However, in large doses, it possibly acts by a different mechanism and had a direct cytolytic effect associated with ATLS in our patients.

CONCLUSIONS:

Although ATLS caused by hydroxyurea appears to be rare, patients at risk should be closely monitored for this complication. An objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction was probable between ATLS and hydroxyurea therapy in these 2 patients.
Comparing Therapies for Postmenopausal Osteoporosis Prevention and Treatment
Authors: Eichner Samantha F , Lloyd Kimberly B , Timpe Erin M
Published: April 2003

OBJECTIVE:

To review the literature concerning the efficacy of calcium, hormone replacement therapy (HRT), bisphosphonates, selective estrogen receptor modulators, and calcitonin in the prevention and treatment of postmenopausal osteoporosis.

DATA SOURCES:

Articles were identified through searches of the MEDLINE (1966–July 2002), EMBASE (1980–July 2002), and International Pharmaceutical Abstracts (1970–July 2002) databases using the key words osteoporosis, postmenopausal, fracture, calcium, vitamin D, hormone replacement therapy, bisphosphonates, alendronate, risedronate, raloxifene, and calcitonin. Additional references were located through review of the bibliographies of the articles cited. Searches were not limited by time restriction, language, or human subject.

STUDY SELECTION AND DATA EXTRACTION:

Experimental and observational studies of the use of calcium and antiresorptive therapies for the prevention and treatment of postmenopausal osteoporosis were selected. Articles evaluating bone mineral density (BMD) or fracture efficacy were included in this review.

DATA SYNTHESIS:

HRT, bisphosphonates, raloxifene, and calcitonin have demonstrated stabilization of and improvement in BMD. Randomized clinical trials have shown fracture risk reduction with bisphosphonates, raloxifene, HRT, calcium, and calcitonin. The largest risk reductions have been reported with use of bisphosphonates in several trials.

CONCLUSIONS:

Several therapeutic options with well-documented improvements in BMD and reductions in fracture risk are available to women for the prevention and treatment of postmenopausal osteoporosis.
Octreotide as a Therapeutic Option for Management of Chylothorax
Authors: Al-Zubairy Sulaiman A , Al-Jazairi Abdulrazaq S
Published: April 2003

OBJECTIVE:

To report a case of post-cardiac surgery–induced chylothorax treated with octreotide and review the literature on octreotide efficacy.

CASE SUMMARY:

A 5-month-old boy with Down syndrome was admitted for atrioventricular canal repair. On admission, he was taking captopril and furosemide. On postoperative day 4, he exhibited signs of chest wheezing and crackles, but was without cough or fever. Chest X-ray revealed a moderate right-sided pleural effusion. Accordingly, a pleural catheter was inserted and drained an average of 7.14 mL/h of chylous fluid that day. Laboratory analysis of the pleural fluid revealed a triglyceride level of 89 mg/dL, without bacterial growth. Based on those findings, the diagnosis was chylothorax. Because of the continuous extensive tube drainage, octreotide 3.5 μg/kg/h was begun. The average daily chyle drainage was reduced from 7.14 one day before octreotide initiation to 0.83 mL/h on day 4 of octreotide therapy. After 4 days of therapy (postoperative day 8), octreotide was discontinued because of the satisfactory response and the pleural catheter was removed.

DISCUSSION:

In our case and the other few cases reported, octreotide showed acceptable efficacy in the management of chylothorax. The mechanism by which octreotide decreases chyle production includes reducing the intestinal absorption of fats, mainly triglycerides, and increasing fecal fat excretion.

CONCLUSIONS:

Octreotide may have reduced chyle production in our patient. Further reports and studies assessing octreotide efficacy in the management of chylothorax are warranted.
Extended-Release Metoprolol Succinate in Chronic Heart Failure
Authors: Tangeman Heather J , Patterson J Herbert
Published: April 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and tolerability of extended-release (ER) metoprolol succinate and its role in the management of chronic heart failure.

DATA SOURCES:

A MEDLINE search of English-language literature (1990–October 2002) was conducted using congestive heart failure and metoprolol CR/XL or metoprolol CR/ZOK as search terms to identify pertinent studies.

STUDY SELECTION/DATA EXTRACTION:

All of the articles identified from the data sources were evaluated, with priority given to randomized, double-blind, placebo-controlled studies.

DATA SYNTHESIS:

ER metoprolol succinate is a controlled-release tablet designed to produce even and consistent β1-blockade throughout the 24-hour dosing interval, with less fluctuation in metoprolol plasma concentrations compared with immediate-release metoprolol. Three randomized, double-blind, placebo-controlled trials have evaluated the efficacy of ER metoprolol succinate in the treatment of patients with chronic heart failure. The MERIT-HF (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure) study, the largest of these trials and the largest randomized mortality trial with β-blockers in heart failure to date, demonstrated that ER metoprolol succinate reduced the relative risk of all-cause mortality by 34% versus placebo. Furthermore, the relative risk of the combined endpoint of mortality plus all-cause hospitalizations was reduced by 19% and sudden death was reduced by 41%. The benefits of therapy were evident in various patient subgroups, including elderly patients and those with diabetes mellitus. ER metoprolol succinate was generally well tolerated, with a similar proportion of patients discontinuing therapy due to adverse events relative to placebo (9.8% and 11.7%, respectively).

CONCLUSIONS:

ER metoprolol succinate therapy provides substantial mortality and morbidity benefits in patients with New York Heart Association class II and III heart failure who are stabilized on angiotensin-converting enzyme inhibitors and diuretics. ER metoprolol succinate is administered once daily, is well tolerated, and provides consistent β1-blockade over the 24-hour dosing interval.
Autoimmune Thrombocytopenia Due to Chronic Lymphocytic Leukemia Treated with Fludarabine
Authors: Wells Tiffany , Kovacs Michael J
Published: April 2003

OBJECTIVE:

To report a case of autoimmune thrombocytopenia due to chronic lymphocytic leukemia (CLL) treated with fludarabine.

CASE SUMMARY:

A 68-year-old white woman with CLL was treated with oral chlorambucil. She subsequently presented with severe autoimmune thrombocytopenia purpura (ITP). Intravenous gammaglobulin was administered without response, and a therapeutic splenectomy produced only a temporary response, with platelets reaching 65 times 103/mm3. Four weeks later, the platelet level was below 10 times 103/mm3. At that time, the woman was treated with fludarabine. The platelet count 4 weeks later was normal (270 times 103/mm3) and has been sustained for over 22 months.

DISCUSSION:

Fludarabine has been reported to be causative in the onset of autoimmune cytopenias with CLL. Our case cautiously suggests fludarabine as a potential treatment for cases of CLL-associated ITP refractory to standard therapy.

CONCLUSIONS:

Fludarabine could be considered as treatment of ITP in CLL refractory to standard treatment.
Aripiprazole: A New Atypical Antipsychotic Drug
Authors: Bowles Toya M , Levin Gary M
Published: April 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of aripiprazole for the treatment of schizophrenia.

DATA SOURCES:

Information was selected from MEDLINE (1995–August 2002). Abstracts, scientific posters, and presentations were also used.

STUDY SELECTION/DATA EXTRACTION:

All published information regarding the pharmacokinetic, pharmacodynamic, and clinical characteristics of aripiprazole was considered. Studies providing a comprehensive description of aripiprazole were selected.

DATA SYNTHESIS:

Aripiprazole is a dopamine partial agonist and a serotonin-2A antagonist; it is dosed 10–30 mg/d, with no initial titration necessary. Short-term clinical trials demonstrated efficacy in acute exacerbations, and long-term studies showed that aripiprazole can maintain remission of schizophrenia. Most adverse events were mild. The incidence of extrapyramidal symptoms was low, with akathisia being the most common.

CONCLUSIONS:

Aripiprazole currently demonstrates comparable efficacy and safety for use in schizophrenia.
Composition and Cost of Drugs Stored at Home by Elderly Patients
Authors: Wasserfallen Jean-Blaise , Bourgeois Robert , Büla Christophe , Yersin Bertrand , Buclin Thierry
Published: April 2003

BACKGROUND:

Elderly people often have multiple chronic diseases, are frequently treated by several physicians, and also use over-the-counter medications. Excessive prescribing, imperfect therapeutic adherence, treatment modifications after hospitalization, and oversized drug packages result in home storage of leftover drugs, resulting in a waste of healthcare resources.

PATIENTS AND METHODS:

All patients aged ≥75 years hospitalized for >24 hours during a 6-month period in an urban teaching hospital in Switzerland were eligible for inclusion in a study collecting sociodemographics, medical, functional, and psychosocial characteristics. Six months later, a research nurse visited the patients at home and recorded the names, number of tablets, and expiration dates of all open or intact drug packages, and the doses actually taken. Acquisition costs of these drugs were computed.

RESULTS:

One hundred ninety-five patients were included (127 women; mean age 82.2 ± 4.8 y, range 75–96). They had a total of 2059 drugs (mean per patient 10.3 ± 6.7, range per patient 1–42), corresponding to a total cost of (US) $62 826 (mean per patient 322 ± 275, range per patient 10–1571). Self-reported drug intake was regular for 36% of the drugs (46.5% of total costs) and occasional for 11% (6.1%), whereas 35.7% (30.1%) had been stopped during the last month. Cardiovascular drugs amounted to 36.6% of the drugs and 55.5% of the costs. None of the patients' characteristics was significantly associated with a greater number of drugs and higher costs.

CONCLUSIONS:

Drugs stored at home by elderly patients were worth about $320 per patient. Only about one-third of these drugs were regularly taken. In the context of resources shortage, innovative solutions should be found to reduce the waste linked with drugs stopped in previous months.
Zolpidem-Induced Distortion in Visual Perception
Authors: Huang Chiung-Lei , Chang Ching-Jui , Hung Chi-Feng , Lin Hsi-Yen
Published: April 2003

OBJECTIVE:

To describe a patient who developed visual perception distortion after a single dose of zolpidem.

CASE SUMMARY:

A 50-year-old Asian woman had been prescribed conjugated estrogen 1 tablet daily for hormone replacement therapy and tricalcium phosphate twice daily for osteoporosis. One day, she took zolpidem 10 mg for insomnia as well as acetaminophen 500 mg for headache at bedtime and began to have visual perception distortion (e.g., the shapes of objects were twisted, houses were crooked) within 20 minutes, lasting for approximately 30 minutes, and then her vision returned to normal. She only partially recalled the event. She had never taken zolpidem before, and she had not had any such disturbances in the past.

DISCUSSION:

There have been 21 case reports of zolpidem-related psychotic symptoms in the literature; however, the exact mechanism by which zolpidem may cause visual perception changes is undetermined. Many factors have been correlated with zolpidem-induced visual experiences, such as pharmacokinetic factors, gender, age, and hypoalbuminemia. This patient shared certain similarities such as gender, dosage, and time of onset and duration of adverse reactions.

CONCLUSIONS:

An objective causality assessment revealed that the zolpidem-induced visual perception distortion in this patient was probable. Clinicians should be aware of the potential for visual perception distortion, as this is an uncommon adverse effect.
Combined Furosemide and Human Albumin Treatment for Diuretic-Resistant Edema
Authors: Elwell Rowland J , Spencer Ann P , Eisele George
Published: April 2003

OBJECTIVE:

To evaluate the clinical usefulness of combined furosemide and human albumin for the treatment of diuretic-resistant edema in patients with nephrotic syndrome and cirrhosis.

DATA SOURCES:

Clinical literature was accessed through MEDLINE (1966–May 2002). Key search terms included furosemide, albumin, human albumin solution, nephrotic syndrome, and cirrhosis.

DATA SYNTHESIS:

Hypoalbuminemia, edema, and ascites are often manifestations of nephrotic syndrome and cirrhosis of the liver. Many patients with these conditions are resistant to the effects of diuretics. The combination of furosemide and human albumin solution is occasionally used in these patients. An evaluation of published studies focusing on combined furosemide and albumin in the management of nephrotic syndrome and cirrhosis was conducted.

CONCLUSIONS:

Published studies report conflicting results regarding the efficacy of combined furosemide and albumin. Although it is difficult to generate firm conclusions, it appears the combination may provide clinical benefits for select patients. Given these findings, we believe that the addition of albumin to enhance diuretic efficacy should be reserved for patients with recalcitrant edema or ascites in whom diuretic doses have been maximized and those with severe hypoalbuminemia.
Role of Ethnicity in Predicting Antipsychotic Medication Adherence
Authors: Opolka Jayme L , Rascati Karen L , Brown Carolyn M , Gibson P Joseph
Published: April 2003

BACKGROUND:

Clinicians treating schizophrenia face increasingly diverse ethnic populations. Ethnic groups may have different approaches to the management of schizophrenia, which could impact antipsychotic medication adherence.

OBJECTIVE:

To examine the association between adherence and ethnicity or the specific medication used after controlling for other factors.

METHODS:

Texas Medicaid claims were retrieved for persons aged 21–65 years, diagnosed with schizophrenia or schizoaffective disorder, after initiating treatment with olanzapine (n = 1875), risperidone (n = 982), or haloperidol (n = 726) between January 1997 and August 1998. The association between ethnicity (African American, Mexican American, white) or medication and days' use of the medication in the year following initiation was assessed using multivariate linear regression. Covariates included other patient demographics, region, comorbid mental health conditions, and prior medication and healthcare resource use.

RESULTS:

African American and Mexican American patients were significantly less adherent than white patients (19 d less, p < 0.001 for African Americans; 18 d less, p = 0.003 for Mexican Americans). For patients of all ethnicities, olanzapine was associated with 23 more adherent days than risperidone and 55 more adherent days than haloperidol (p < 0.001 for each comparison).

CONCLUSIONS:

When other factors were controlled for, ethnicity was a significant predictor of medication adherence following initiation on an antipsychotic medication, and patients of all ethnicities were most adherent when taking olanzapine, less adherent when taking risperidone, and least adherent when taking haloperidol.
Cutaneous Dalteparin Reactions Associated with Antibodies of Heparin-Induced Thrombocytopenia
Authors: Payne Sonja M , Kovacs Michael J
Published: April 2003

OBJECTIVE:

To report widespread cutaneous lesions due to low-molecular-weight heparin therapy associated with heparin-induced thrombocytopenia (HIT), but without evidence of thrombocytopenia, and to review previously reported cases of skin reactions related to heparin therapy.

CASE SUMMARY:

A 59-year-old white man with a subtotally resected glioblastoma developed febrile neutropenia and pneumonia secondary to chemotherapy. The development of an upper extremity thrombosis, following insertion of a peripherally inserted central venous catheter, was treated with subcutaneous dalteparin. Cutaneous lesions developed distant from the site of injection. The diagnosis of HIT was confirmed despite stable platelet counts. Dalteparin therapy was discontinued immediately, and anticoagulation was maintained with warfarin. The skin lesions resolved without further complications.

DISCUSSION:

Numerous cases of heparin-induced cutaneous reactions have been reported. The majority of these describe a local reaction at the heparin injection site with or without associated thrombocytopenia. The case presented here is unique in that the observed skin reaction was distant to the injection site and occurred without thrombocytopenia, but with detectable heparin-dependent antibodies.

CONCLUSIONS:

Although a skin reaction is a rare complication of heparin therapy, it can be a clinical indicator of HIT despite normal platelet counts. Patients who develop skin lesions should have their heparin therapy discontinued and a diagnosis of HIT investigated.
HOPE Study Impact on ACE Inhibitors Use
Authors: Hemels Michiel EH , Bennett Heather A , Bonari Lori , Han Donald , Traverso Maria L , Einarson Thomas R
Published: April 2003

BACKGROUND:

Angiotensin-converting enzyme (ACE) inhibitors are used to treat cardiovascular diseases, major causes of death in Canada. The HOPE (Heart Outcomes Prevention Evaluation) study showed that ramipril benefits patients at high risk for cardiovascular disease. We analyzed ACE inhibitor use and costs in Canada before and after publication of HOPE.

METHODS:

We obtained pharmacy and hospital sales data for 1985–2001 from IMS Canada for all ACE inhibitors (Anatomical Therapeutic Category code C09A0) and for the 3 largest provinces (i.e., British Columbia, Quebec, Ontario). Prescription numbers, total costs, cost/prescription, and market share of individual ACE inhibitors were plotted over time and analyzed using regression. Canadian dollars were used to report costs.

RESULTS:

We examined 10 drugs; captopril was the first, introduced in 1985. Overall, prescriptions increased consistently from 356 000 in 1985 to 11.5 million in 2001, representing an annual increase of 660 000 (y = 661 410x–510 360; r2 = 0.99). Total costs increased linearly from 1985 ($14.5 million) to 2001 ($513 million): Y = 29.3•106x − 29.9•106; r2 = 0.99. Provincial utilization patterns were also similar. Ramipril's national use increased dramatically from 1999 (822 000 prescriptions, 9.2% of all ACE inhibitors) to 2001 (3.8 million, 32.8% of all ACE inhibitors). National costs for ramipril increased exponentially (y = 1.08e0.6248x) to a total of $157 million in 2001, with the 3 major provinces accounting for 78.9%. Costs per prescription followed no observable trend (range $39.45–46.20).

CONCLUSIONS:

The number of prescriptions and the total cost of ACE inhibitors increased over the period studied. Ramipril use increased in concert with publication of the HOPE trial, while the growth rates of other ACE inhibitors remained constant.
Effect of Chronic Probenecid Therapy on Cefazolin Serum Concentrations
Authors: Spina Sean P , Dillon Edward C
Published: April 2003

OBJECTIVE:

To prospectively assess the effectiveness of probenecid at maintaining therapeutic serum concentrations of cefazolin at steady-state by comparing cefazolin serum concentrations produced by intravenous cefazolin 2000 mg every 8 hours with concentrations produced by once-daily administration of intravenous cefazolin 2000 mg plus oral probenecid 500 mg 4 times daily.

METHODS:

Patients in this prospective, nonrandomized, unblinded study were identified after an order was written for intravenous cefazolin 2000 mg every 8 hours or once daily plus oral probenecid 500 mg 4 times daily in the emergency department. For both study arms, a peak cefazolin serum concentration was obtained 1 hour after the infusion was started and 23 hours later, prior to the next scheduled dose. Doses of cefazolin for days 2–4 were then administered as ordered. On day 5, peak and trough serum concentrations were drawn 1 hour after the infusion started and 23 hours later, respectively.

RESULTS:

A total of 26 patients were prospectively assessed from April 2000 to October 2001. In patients who received cefazolin once daily, the average serum peak and trough concentrations on day 1 were 146.53 and 2.02 mg/L, respectively. Peak and trough concentrations on day 5 were 148.30 and 2.67 mg/L, respectively. In patients who received cefazolin every 8 hours, peak and trough concentrations were 122.15 and 18.65 mg/L on day 1 and, on day 5, 136.51 and 16.98 mg/L, respectively.

CONCLUSIONS:

Probenecid 500 mg given orally 4 times daily was effective in maintaining therapeutic serum concentrations of cefazolin at steady-state when given with intravenous cefazolin 2000 mg once daily.
Nicardipine to Control Neonatal Hypertension During Extracorporeal Membrane Oxygen Support
Authors: McBride Brian F , White C Michael , Campbell Margaret , Frey Bruce M
Published: April 2003

OBJECTIVE:

To describe the clinical course of a newborn (gestational age 38 wk, 6 d) administered intravenous nicardipine to control hypertension while on extracorporeal membrane oxygen (ECMO) support.

SETTING:

Urban, university teaching hospital.

CASE SUMMARY:

A 1-day-old male neonate presenting with a left congenital diaphragmatic hernia developed a sustained elevation in blood pressure following a change of ECMO tubing. After several unsuccessful treatment regimens, nicardipine was started at a rate of 0.5 μg/kg/min and aggressively titrated to 1.5 μg/kg/min. Nicardipine produced a sustained antihypertensive effect that was noticed 8 hours after the start of the infusion. The infusion was continued through postoperative day 2. Following a second circuit change, nicardipine was discontinued and sodium nitroprusside therapy was started. Treatment with nitroprusside failed to lower the blood pressure.

DISCUSSION:

Nicardipine is an effective antihypertensive agent for neonates receiving ECMO therapy. However, the expanded volume of distribution caused by the ECMO circuit may result in a reduced serum concentration and a reduced antihypertensive effect.

CONCLUSIONS:

We recommend a conservative initial dose of nicardipine of 0.5 μg/kg/min that is aggressively titrated to reduce blood pressure effectively in neonates receiving ECMO therapy.
Effects of Subclinical Hypothyroidism and Its Treatment on Serum Lipids
Authors: Ineck Beata A , Ng Tien MH
Published: April 2003

OBJECTIVE:

To determine whether the literature supports an effect of subclinical hypothyroidism on serum lipids and, if so, what are the effects of thyroxine replacement therapy.

DATA SOURCES:

Articles were identified on MEDLINE using the MeSH terms hypothyroidism, lipids, or cholesterol.

DATA SYNTHESIS:

The majority of studies that determined the prevalence of lipid abnormalities in subclinical hypothyroidism and studies that evaluated the effects of thyroxine replacement on lipids were small, uncontrolled, and varied in inclusion criteria. Six randomized, placebo-controlled trials were identified that evaluated the effect of levothyroxine on lipids in subclinically hypothyroid patients.

CONCLUSIONS:

Subclinical hypothyroidism can potentially contribute to a pro-atherogenic lipid profile, with effects being greater at higher thyroid-stimulating hormone levels. Thyroxine replacement reduces total cholesterol and low-density lipoprotein cholesterol, with no effect on triglycerides. Effects on high-density lipoprotein, lipoprotein (a), and apolipoproteins A1 and B require further study. Larger prospective studies are needed to clarify many issues.
A Cost-Effectiveness Analysis of Stress Ulcer Prophylaxis
Authors: Schupp Kelly N , Schrand Linda M , Mutnick Alan H
Published: April 2003

OBJECTIVE:

To evaluate the efficacy, safety, and cost of using cimetidine, famotidine, and lansoprazole for stress ulcer prophylaxis (SUP) at our institution and determine which agent was most cost-effective.

METHODS:

An observational study of adults admitted to the medical, surgical, or cardiovascular intensive care unit was conducted to compare the cost and effectiveness of cimetidine, famotidine, and lansoprazole for SUP. Patients were identified for inclusion during three 2-week periods in 2000. Medical record reviews were conducted to gather data regarding the costs associated with the administration of SUP drugs and the treatment of any adverse events or therapeutic failures. Decision analysis was used to determine the average cost per patient for each treatment arm. A cost-effectiveness analysis was then conducted to determine which of the SUP agents was associated with the least cost without adversely affecting patient outcomes. A sensitivity analysis was applied to determine the robustness of the data.

RESULTS:

Eighty-eight patients were included in the analysis. Five of the patients started on cimetidine experienced therapeutic failure, whereas no patients receiving lansoprazole experienced therapeutic failure. For these reasons, and because lansoprazole is an oral agent, the average costs associated with lansoprazole use were lower than with the use of cimetidine. Lansoprazole was found to be the most cost-effective therapy.

CONCLUSIONS:

This study showed that lansoprazole is a cost-effective agent for the use of SUP at our institution. However, due to the higher cost of intravenous pantoprazole, the model demonstrates that, assuming equal effectiveness, intravenous pantoprazole would not be cost-effective when compared with cimetidine.
Phenytoin–Diazepam Interaction
Authors: Murphy Andrea , Wilbur Kerry
Published: April 2003

OBJECTIVE:

To report a case of phenytoin toxicity potentially associated with concurrent diazepam therapy.

CASE SUMMARY:

A 44-year-old First Nations man presented to the emergency department with headache, nystagmus, diplopia, and ataxia. Apart from a long-standing seizure disorder, his past medical history was unremarkable. The antiepileptic drug regimen of phenytoin, phenobarbital, and lamotrigine had been unchanged for almost 5 months. Total phenytoin serum concentration reported 2 weeks prior to hospital admission was 8 μg/L. Two days prior to admission, he was prescribed amoxicillin and diazepam; he denied use of nonprescription or herbal medications. The serum phenytoin concentration drawn in the hospital was 37 μg/mL. Both phenytoin and diazepam were stopped, and the symptoms resolved. His neurologic abnormalities were attributed to phenytoin toxicity caused by an interaction with diazepam.

DISCUSSION:

The literature documenting a potential interaction between diazepam and phenytoin is conflicting. Case reports and controlled studies have demonstrated both increases and decreases in serum phenytoin concentrations when these agents were administered concomitantly. Phenytoin induces the metabolism of drugs that are substrates of CYP2C, CYP2D, and CYP3A; however, phenytoin is eliminated predominantly by CYP2C9-and CYP2C19-dependent hepatic metabolism. Diazepam is one example of a drug that is extensively metabolized by CYP2C19 and could potentially influence phenytoin elimination by acting as an alternate substrate for this isoenzyme. In our patient, the timing of drug administration, clinical and physical examination findings, and laboratory data suggest that diazepam therapy resulted in phenytoin toxicity. Use of the Naranjo probability scale indicated a probable relationship between the adverse clinical effects observed and phenytoin and diazepam coadministration in this patient.

CONCLUSIONS:

Phenytoin is a known inducer of drugs metabolized by CYP2C, CYP2D, and CYP3A, but its own metabolism may be altered by drugs influencing CYP2C9 or CYP2C19, such as diazepam. Agents not acting as enzyme inhibitors or inducers, but instead behaving as alternate substrates for enzyme-binding sites, may produce clinically relevant drug interactions through an underrecognized mechanism.
Skin Breakdown and Blisters from Senna-Containing Laxatives in Young Children
Authors: Spiller Henry A , Winter Mark L , Weber Julie A , Krenzelok Edward P , Anderson Deborah L , Ryan Mark L
Published: April 2003

BACKGROUND:

At the direction of the Food and Drug Administration, phenolphthalein was removed from all over-the-counter laxatives in 1999. Phenolphthalein was then replaced in most laxative products with the natural product senna from Cassia acutifolia Delile, which contains various anthraquinones. No data are available on the safety of senna use in children <6 years of age.

OBJECTIVE:

To describe the clinical outcomes of exposure to unintentional ingestion of senna-containing laxatives in young children.

METHODS:

All ingestion exposures of senna-containing laxatives in children <5 years of age from 6 poison centers over a 9-month period were evaluated. Inclusion criteria required 24-hour follow-up and the presence of diarrhea to confirm ingestion. Parents were told routinely that severe diaper rash was possible and to protect the perianal area with frequent cleansing and a barrier ointment if the child was wearing diapers.

RESULTS:

During the study period, 111 cases were reported: 19 children experienced no diarrhea, 4 were lost to follow-up, and 88 exposures were evaluated. Fifty-two children (59%) were ≤2 years old. Fifty children remained in diapers, 28 children were fully toilet trained, and 10 wore diapers (pull-up pants) overnight. Twenty-nine children (33%) experienced severe diaper rash. The mean ± SD time to recognition of the diaper rash was 15.6 ± 8.6 hours. Ten children (11%) had blisters and skin sloughing. There was a significant increase in severe diaper rash (p < 0.05) and onset of blisters and skin breakdown (p < 0.05) in children wearing diapers versus those who were fully toilet trained. The mean time to onset of blisters was 14.5 ± 6.8 hours. Skin burns and loss were seen primarily on the buttocks and perineum, loosely following the diaper area.

CONCLUSIONS:

Unintentional ingestion of senna-containing laxatives in young children may potentially cause severe diaper rash, blisters, and skin sloughing.
Radikalreaktionen in Ethylen‐Vinylacetat‐Copolymeren
Authors: Taplick Thomas , Rätzsch Manfred
Published: April 2003

Unter Bezug auf frühere Untersuchungen an Polyethylen und Polyvinylacetat wird gezeigt, daß in UV‐bestrahlten Ethylen‐Vinylacetat‐Copolymeren neun unterschiedliche Radikale, für die eine Strukturzuordnung getroffen wird, mit Hilfe der ESR beobachtet werden können. Bei der Diskussion der Reaktionsmechanismen wird der Acylradikal‐bildung besondere Aufmerksamkeit geschenkt, die nicht auf eine Kohlenmonoxidanlagerung zurückgeführt wird.
Neuere Ergebnisse zum Mechanismus der kationischen Polymerisation von Vinylmonomeren. Fortschrittsbericht
Authors: Heublein G.
Published: April 2003

Es wird über einige in den letzten Jahren erreichte Fortschritte auf dem Gebiet der kationischen Polymerisation von Vinylmonomeren berichtet. Neuere Ergebnisse der Initiierung durch Protonsäuren, Lewis‐Säuren und stabile Salze werden diskutiert. Weiterhin werden aus der unterschiedlichen Natur der Kettenträger und der Gegenionen resultierende Probleme der Wachstumsreaktion sowie neuere Vorstellungen zu kettenlimitierenden Reaktionen erörtert.
Oxacycloalkane in der polymerchemie. I
Authors: Frommelt H. , Rübner J.
Published: April 2003

Oxacycloalkane (cyclische Acetale, Formale) erfahren während der Lagerung eine Änderung ihrer Eigenschaften (Viskosität, IR‐Absorption). Am Beispiel des 1,3,6‐Trioxacyclooctans (Diethylenglykolformal) wird nachgewiesen, daß diese Eigenschaftsveränderungen eine Verringerung der durchscnittlichen Monomerreaktivität hervorrufen. Die Geschwindigkeit der kationisch initiierten Polymerisation und Oligomereigenschaften werden beeinträchtigt. Als Ursache dieser änderungen wird eine Autopolymerisation erkannt, die bei Wasserstoffionenkonzentrationen > 10−5 g/l zu einem weiteren Anstieg des Polymerisationsgrades führt. Die damit gegebene Instabilität der cyclischen Acetale ist abhängig von der Lagerungsdauer, der bestehenden Wasserstoffionenkonzentration, der Lagerungstemperatur und der Struktur der entsprechenden Verbindungen.
Zur Veresterung und Auflösung der Cellulose mit Säureanhydriden und Säurechloriden des Schwefels und Phosphors
Authors: Wagenknecht W. , Philipp B. , Schleicher H.
Published: April 2003

Die Lösewirkung von Systemen aus Säreanhydrid beziehungsweise Särechlorid des Schwefels oder Phosphors und polarer organischer Flüssigkeit beziehungsweise aus Säureanhydrid oder ‐chlorid, aliphatischem Amin und polarer organischer Flüssigkeit gegenüber Cellulose wurde verglichen. Es wurde festgestellt, daß sich im Gegensatz zu den entsprechenden Schwefelverbindungen mit PCl3, POCl3 und P2O5 keine Lösungsmittelsysteme für Cellulose aufbauen lassen. Die Untersuchung der Veresterung der Cellulose mit Säurechloriden des Schwefels und des Phosphors in DMF und in Formamid als Reaktionsmedien ergab einen ausgeprägten Lösungsmitteleinfluß hinsichtlich selektiver Einführung von P und S einerseits, Cl andererseits in die Cellulosekette.
Über den Einsatz von Polymeren in der Heterogen‐ und Homogenkatalyse. Fortschrittsbericht. Teil 6b
Authors: Dawydoff W.
Published: April 2003

Der vorliegende Bericht befaßt sich mit den in den Jahren 1975 bis 1977 veröffentlichten Arbeiten über die Anwendung von Polymerträgern in der Katalyse.
Studien zur Verzweigung von Kettenmolekülen. X. Untersuchungen des Lösungszustandes von Polyethylen mittels Lichtstreuungsmessungen
Authors: Schröder E. , Arndt K. F.
Published: April 2003

Von fraktionierten und unfraktionierten Polyethylenproben wurden in unterschiedlichen Lösungsmitteln und bei verschiedenen Temperaturen Mw, 〈r2〉z und A2 bestimmt. Die Molmassenzunahme bei Annäherung der Meßtemperatur an die Ausfälltemperatur und das Verhalten des 2. Virialkoeffizienten weisen aus, daß Polyethylen in einem schlechten Lösungszustand vorliegt und große Polymermoleküle kugelförmig sind.
Fibride aus Aromatischen Polyamiden
Authors: Gohlke U. , Baum E.
Published: April 2003

Über die Herstellung, Charakterisierung und Verarbeitung von Fibriden aus aromatischen Polyamiden wird berichtet. Das Haupteinsatzgebiet für diese Fibride ist die Herstellung von Elektroisolierpapieren mit hoher Dauerwärmebeständigkeit.
Copolymerisation von Butadien/Styrol mit anionischen Emulgatoren
Authors: Hühn G. , Singer H.
Published: April 2003

Es werden Untersuchungen über den Einfluß der Struktur einiger wichtiger anionischer Emulgatoren der Carboxyl‐Sulfat‐ und Sulfonatreihe auf die Emulsionscopolymerisation von Butadien/Styrol mitgeteilt. Die Verbindungen üben, in Abhängigkeit von der Kettenlänge ihres Alkyl‐ bzw. Alkylarylrestes, einen unterschiedlichen Einfluß auf die Bruttoreaktionsgeschwindigkeit vBr der Emulsionscopolymerisation aus. Dieser Einfluß zeigt sich besonders in der Teilchenbildungsperiode. Es wurden weiterhin Einflüsse auf den Kaliumperoxodisulfatzerfall in Abhängigkeit von der Carboxyl‐, Sulfat‐ bzw. Sulfonatgruppe gefunden. Ein Einfluß der C‐Atomzahl in der Alkylkette von Carbonsäuresalzen (C12C18) war nicht zu erkennen.
Über Streulichtmessungen an Lösungen von Butadien‐Acrylnitril‐Copolymeren mit Mikrogelgehalt. II. Auswertungen im ZIMM‐Diagramm
Authors: Francuskiewicz F. , Glöckner G.
Published: April 2003

Bei Streulichtuntersuchungen an mikrogelhaltigen Butadien‐Acrylnitril‐Copolymer‐Lösungen treten gekrümmte ZIMM‐Diagramme auf. Bei niedrigen Mikrogelanteilen können die Komponenten im ZIMM‐Diagramm getrennt bestimmt werden. Das Verhältnis zwischen rel. Molekülmasse und Trägheitsradius gestattet die Unterscheidung von mikrogelfreier Komponente und Mikrogel. Die Abhängigkeit der Gestalt der ZIMM‐Diagramme vom Mikrogelanteil wird untersucht.