bluuebunny/crossref_metadata_2025 huggingface dataset:
An introduction to ALS-inhibiting herbicides
Authors: Whitcomb Carl E.
Published: January 2007

Herbicides that inhibit acetolactate synthase (ALS), the enzyme common to the biosynthesis of the branch-chain amino acids (valine, leucine, and isoleucine), affect many species of higher plants as well as bacteria, fungi, yeasts, and algae. The novel mechanism of action attributed to ALS inhibitors, their effect on the reproduction of some plant species, their potency at extremely low concentrations, and the rapid evolution of resistance to these herbicides in some plants and microorganisms are characteristics that set ALS inhibitors apart from their predecessors. This class of chemicals affects seedling growth. Older plants exhibit varied signs of malformation, stunting, and reduced seed production. These herbicides are so potent that they can affect plants at levels that are undetectable by any standard chemical protocol. Weeds quickly become resistant to ALS inhibitors, presumably because these herbicides have a single mode of action and because many have long residual activity. Concern now is directed towards developing the technology to detect very low concentrations of ALS inhibitors in the environment and their indirect effects on plant and animal health.
The Environmental Exposure and Sensitivity Inventory (EESI): a standardized approach for measuring chemical intolerances for research and clinical applications
Authors: Miller Claudia S. , Prihoda Thomas J.
Published: January 2007

The lack of a generally accepted case definition for multiple chemical sensitivity (MCS) and the absence of a standardized approach for measuring salient aspects of chemical sensitivity that would permit cross-comparison of findings by different investigators have hindered progress in this area. Based upon findings from an earlier study of 112 persons with self-reported chemical sensitivity who attributed their chemical sensitivity to a well-defined exposure event, we developed an instrument with self-rating scales to assess Symptom Severity, Chemical (Inhalant) Intolerances, Other Intolerances (e.g., foods, medications, alcohol), Life Impact, and Masking (a measure of ongoing chemical exposures). When administered to four patient groups and controls, the scales showed good reliability and validity overall ( n=421) and in each group. Used together, the scales provided sensitivity of 92% and specificity of 95% in differentiating chemically sensitive persons from controls. Our results support use of these scales individually or collectively for a variety of applications including the selection of chemically sensitive subjects and controls for research, assessment of chemical sensitivity in various study populations, cross-comparison of groups studied by different investigators, pre- and post-assessment of therapeutic interventions, clinical evaluation of complex patients who report intolerances, and teaching medical residents and students how to evaluate patients for chemical sensitivity and MCS.
A controlled comparison of symptoms and chemical intolerances reported by Gulf War veterans, implant recipients and persons with multiple chemical sensitivity
Authors: Miller Claudia S. , Prihoda Thomas J.
Published: January 2007

Using the Environmental Exposure and Sensitivity Inventory (EESI), a standardized instrument for measuring chemical sensitivity, weobtained and compared ratings of symptoms, chemical (inhalant) intolerances, other intolerances (e.g., drugs, caffeine, alcohol, skin contactants), lifeimpact, and masking (ongoing exposures) in five populations: multiple chemical sensitivity (MCS) patients who did ( n=96) or did not ( n=90) attribute onset of their illness to a specific exposure event, patients with implanted devices ( n=87), Gulf War veterans ( n=72), and controls ( n=76). For each patient group, mean scores on the first four scales were significantly greater than for controls. MCS patients reported avoiding more chemical exposures (were less masked) than the other groups. Across groups, for a given level of symptoms, as masking increased, mean scores on the Chemical Intolerance Scale decreased. In contrast, mean scores on the Other Intolerance Scale appeared to be less affected by masking. These findings suggest that some patients with antecedent chemical exposures, whether exogenous (chemical spill, pesticide application, indoor air contaminants) or endogenous (implant), develop new chemical, food, and drug intolerances. Reports of new caffeine, alcohol, medication, food, or other intolerances by patients may signal exposure-related illness. Masking may reduce individuals' awareness of chemical intolerances, and, to a lesser degree, other intolerances.
Odor sensitivity and respiratory complaint profiles in a community-based sample with asthma, hay fever, and chemical odor intolerance
Authors: Baldwin Carol M. , Bell Iris R. , O'Rourke Mary Kay
Published: January 2007

This is a community-based study of odor sensitivity and respiratory complaints for persons reporting asthma ( n=14/141), hay fever ( n=72/140), and chemical odor intolerance (CI) ( n=41/181). CI, a symptom of multiple chemical sensitivity (MCS), was determined from self-ratings of feeling `moderately' to `severely' ill using the Chemical Odor Intolerance Index (CII). Index odors included perfume, pesticide, drying paint, new carpet odor, and car exhaust. Six additional odors [natural gas, disinfectants, chlorinated water, room deodorizers, and environmental tobacco smoke (ETS)] were also assessed in the health and environment survey. Asthmatics reported feeling `frequently' to `almost always' ill from the CII index odors of drying paint, new carpet odor, perfume, and cleaning agents compared to nonasthmatics. People with hay fever documented feeling `frequently' to `almost always' ill from pesticides, drying paint, and car exhaust compared to individuals without hay fever. The CI cited illness from air freshener, natural gas and chlorinated water, in addition to the index odors of perfume, paint, pesticides, new carpeting and auto exhaust. All three groups were significantly more likely to report feeling ill from ETS. People with asthma were significantly more likely to report lower lung complaints, such as wheeze and dyspnea. People with hay fever cited more chest tightness. The CI were significantly more likely to report upper and lower respiratory symptoms. Given this overlap in respiratory complaints, it could be that CI may serve to amplify these traditional immune-related disorders and/or suggest that having asthma or hay fever could make one more vulnerable to CI.
Psychiatric illness in the first-degree relatives of persons reporting multiple chemical sensitivities
Authors: Black Donald W. , Okiishi Christopher , Gabel Janelle , Schlosser Steven
Published: January 2007

The multiple chemical sensitivities (MCS) syndrome is characterized by unexplained physical and psychiatric complaints attributed by patients and some of their physicians to low-level chemical exposures. In this study, we interviewed 15 subjects with MCS and 21 controls about their first-degree relatives using the Family History-Research Diagnostic Criteria (FH-RDC). Subjects with MCS were more likely than controls to report their relatives to have major depression, alcoholism, panic disorder, obsessive-compulsive disorder, and antisocial personality disorder. They were also likely to have past suicide attempts, and to have received some form of psychiatric treatment (hospitalization, medication or electroconvulsive therapy, or counseling). Nearly 30% of the relatives of subjects with MCS were reported to have MCS themselves. Possible reasons for the findings are discussed.
Developing a pesticide policy for individuals with multiple chemical sensitivity: considerations for institutions
Authors: Brown Amy E.
Published: January 2007

Institutions are increasingly being asked to accommodate individuals with multiple chemical sensitivity (MCS). Most establishments have chosen to provide such accommodations on a case-by-case basis only. This paper investigates feasible actions that may be taken by institutions to reduce exposure of MCS individuals as well as the general institutional population to pesticides and other substances. Emphasis is placed on procedures that can be instituted on a regular basis and may be combined with case-by-case management for better resolution of problems.
Cardiovascular effects of odors
Authors: Smith Carr J. , Scott Sandra M. , Ryan Brett A.
Published: January 2007

Several occupational and residential settings can expose both normal and sensitive human subjects to odors and irritants. These settings include intensive agricultural operations housing swine and poultry, cigarette-smoke-filled bars, landfills and manufacturing processes. The literature suggests that adverse sensory reactions to strong odors and irritants may lead to the release of catecholamines and stress hormones. Physiological and biochemical measurements related to cardiovascular risk, e.g., blood pressure, heart rate, high-density lipoprotein (HDL) cholesterol level and serum triglyceride level, may be altered as a result of exposure to odor and irritant-induced release of catecholamines. Further work in the form of field studies and chamber exposure protocols is required to determine whether the physiological and biochemical changes observed to date represent an increase in cardiovascular risk, or are reversible changes within the normal homeostatic range.
The cost of blood transfusions in cancer patients: a reanalysis of a Canadian economic evaluation
Authors: Dranitsaris George
Published: January 2007

Background. Cancer patients undergoing chemotherapy are at an increased risk for anemia. Hence, they are high consumers of allogenic blood transfusions. In 1997, an economic evaluation was undertaken at the Princess Margaret Hospital to estimate the cost of a transfusion in cancer patients. The analysis relied on published costing information and on an internal review of patient resource utilization. Overall, the cost of a blood transfusion was estimated at Can$599. Since 1997, there have been some major changes in the management of Canada's blood supply and within the Princess Margaret Hospital.

Methods. In order to evaluate how these changes affected the cost of a transfusion in cancer patients, the original 1997 economic database was reanalyzed using updated 1999 costing information obtained from Canadian Blood Services (CBS) and from the Princess Margaret Hospital.

Results. The reanalysis suggested that the cost of a blood transfusion in cancer patients increased from Can$599 in 1997 to Can$731 in 1999. The major incremental costs responsible for this increase were additional screening tests, increased opportunity costs for donors and a modest rise in distribution and administration within the hospital. Costs that were no longer relevant in 1999 were the cost of treating transfusion-related infections.

Conclusions. These results support the findings of the original publication that a unit of blood is a highly resource intensive commodity which requires that each blood unit be used appropriately. Therefore, preventative strategies that would reduce the use of blood products have to be identified and implemented.
Reproducibility of treatment methodologies detailed in contemporary clinical trial reports
Authors: Dooley Michael Joseph , Vernon Joanne
Published: January 2007

Objective. To assess the reproducibility of treatment methodology detailed in contemporary published clinical trial reports.

Design. Published articles focusing on clinical trials involving the administration of chemotherapy for the treatment of cancer were selected. The data required for the administration of chemotherapy was determined by an experienced oncology pharmacist.

Outcome measures. The degree of potential impact of the omission of relevant detail was assessed. The overall reproducibility of the methodology was then classified as reproducible, reproducible with further literature evaluation, or not reproducible without communication with the authors.

Results. Ninety-two articles were reviewed. Ninety percent of articles omitted data required to enable reproduction of the methodology. Of these, 5.4% omitted essential data which could only be obtained by communication with the authors. Over 57% of articles required further detailed literature evaluation before the methodology could be reproduced. A number of articles contained errors or ambiguity.

Discussion. The focus of the article and journal contributed to the completeness of the methodology. Guidelines for the preparation of manuscripts for publication in biomedical journals need to be reviewed. Practitioners and editors must be cognizant of the limitations of published methodologies.

Conclusion. A significant number of articles contained omissions, ambiguity and even errors, which would prevent the methodology being reproduced. The majority of methodologies could be reproduced with the interpretation of an experienced oncology pharmacist, or by utilising resources for detailed literature evaluation.
A multidisciplinary approach to ensure safety in the prescribing and administration of chemotherapy
Authors: Roscoe Juliet C , Goransson Elke , Slancar Michael , Smith Janine , Taylor Sue , Tyson Sue
Published: January 2007

Contemporary cancer treatment requires a multidisciplinary approach in order to ensure the safe prescribing and administration of chemotherapy. The increasing complexity of drug regimens and the introduction of new cytotoxic agents, combined with the inexperience of medical staff in this area, highlighted the need for a comprehensive educational reference tool. Our experience highlighted inconsistencies in prescribing anti-emetics and hydration regimens and the need for ongoing education.1 A multidisciplinary team was established to address these issues and develop a Chemotherapy Practice Manual which consists of chemotherapy protocols, administration guidelines including cost-effective premedication recommendations and supportive therapy such as hydration regimens. It also includes patient monitoring parameters for before, during and after treatment and protocol specific patient education. Preprinted prescription charts were designed to aid the medical officer in prescribing the chemotherapy and include discharge medication to ensure appropriate post treatment therapy. These have been incorporated into a computer-generated prescribing program. The introduction of the manual to the oncology unit has proved beneficial: prescriptions are legible and include all supportive treatment and follow up medication. The nursing staff now have guidelines regarding chemotherapy administration and patient education. By working together and combining our knowledge we have provided a complete package that ensures safety in prescribing and administration of chemotherapy as well as an educational reference tool. Other benefits include both time and cost savings.
Dual topoisomerase I/II inhibitors
Authors: van Gijn R , Lendfers RRH , Schellens JHM , Bult A , Beijnen JH
Published: January 2007

Topoisomerase (topo) I and II are nuclear enzymes, which play a major role in the topological rearrangement of DNA during replication and transcription processes. In the course of years, many different agents have been found which can inhibit the topos and thereby exploit cytotoxicity, also against tumour cells. Selective inhibition of the topo I enzyme can, however, induce a reactive increase in topo II levels, and vice versa. This mechanism is associated with the development of drug resistance. Dual inhibition of both topo I and II may, theoretically, overcome this resistance problem. In this review, the most important and promising dual topo I/II inhibitors designed as anticancer agents will be discussed. Thus far, only the indolyl quinoline derivative TAS-103, the 7 H-benzo [ e] pyrido [4,3- b] indole derivative intoplicine, and the acridine derivative PZA have been shown to be dual topo inhibitors with high cytotoxicity.
Irinotecan: a new treatment in metastatic colorectal cancer
Authors: Douillard Jean-Yves
Published: January 2007

Objective. Historically, outcomes of metastatic colorectal cancer therapy have been disappointing, with fluorouracil (5-FU) producing response rates of no more than 15%. The addition of leucovorin increases response rates; however, survival rates are largely unaffected. Recently, the topoisomerase I inhibitor, irinotecan, has proved active in metastatic colorectal cancer and is indicated as second-line therapy following disease recurrence or progression after 5-FU-based therapy. More recently, irinotecan plus 5-FU-LV was compared with 5-FU-LV as first line treatment of colorectal cancer, showing impressive results. This article discusses the role of irinotecan, as a single agent and in combination with 5-FU-LV, in the treatment of advanced colorectal cancer.

Data sources. A MEDLINE search was conducted using 5-fluorouracil, irinotecan, leucovorin, and metastatic colorectal cancer as primary search terms. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the European Society for Medical Oncology annual meetings were also identified and reviewed. Clinical literature was reviewed and analyzed.

Data synthesis. Results of studies comparing irinotecan with continuos infusion 5-FU or best supportive care suggest that irinotecan is superior to either treatment as second-line therapy of metastatic colorectal cancer. Based on these study results, along with irinotecan's lack of cross-resistance with other chemotherapy agents and mechanism of action that differs from 5-FU, phase III trials evaluating the use of irinotecan in combination with 5-FU-LV as first-line treatment for advanced colorectal cancer were conducted. The results of a pivotal trial evaluating irinotecan plus 5-FU-LV in this setting show superior response rates (RRs), time to tumor progression (TTP), and median survival times (MSTs) when compared with 5-FU-LV alone. This combination represents a major advance in the treatment of metastatic colorectal cancer and should be considered the first-line treatment standard.
Introduction to taxane pharmacokinetics and pharmacodynamics
Authors: Frame David
Published: January 2007

Objective. To compare the pharmacokinetics and pharmacodynamics of the taxanes, paclitaxel and docetaxel.

Data sources. A MEDLINE search was conducted using docetaxel, dose, drug interactions, liver dysfunction, liver impairment, mechanism of action, paclitaxel, pharmacodynamics, pharmacokinetics, and schedule as search terms. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the American Association for Cancer Research annual meetings were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed.

Data synthesis. The taxanes, paclitaxel and docetaxel, are a novel class of antineoplastic drugs that provide notable activity, and produce high response rates but minimal side effects. These agents share a similar mechanism of action, but several important pharmacokinetic and pharmacodynamic differences exist. The higher tubulin affinity, slower efflux from cells, triphasic elimination, and prolonged drug exposure of docetaxel confer pharmacokinetic and pharmacodynamic advantages over paclitaxel. The nonlinear pharmacokinetics of paclitaxel may result in disproportionate increases in plasma concentrations and AUCs; however, several safe and effective paclitaxel regimens are currently used. Because the taxanes are metabolized extensively in the liver by cytochrome P-450 enzymes, patients with hepatic impairment have reduced total body clearance that may result in increased toxicity. Additionally, drugs that induce, inhibit, or compete with microsomal enzymes known to metabolize the taxanes, can result in clinically significant drug interactions. These pharmacokinetic differences should be carefully considered when dosing and scheduling paclitaxel or docetaxel in clinical practice.
Prospective evaluation of a policy of early discontinuation of antibiotics and discharge from hospital in children with cancer who develop fever
Authors: Wiernikowski John T. , Barr Ronald D. , Pennie Ross
Published: January 2007

Objective. To prospectively evaluate a set of clinical care schemata that would facilitate early discontinuation of antibiotics and hospital discharge in children with cancer admitted for management of infection.

Methods. Based on recent published studies identifying children with fever and neutropenia who are at ‘‘low risk’’ for infection, and studies where antibiotics were discontinued quickly in such populations. We developed a set of four clinical schemata by which children with cancer would be managed at our institution. The schemata were prospectively evaluated over a period of 15 months.

Results. The schemata were evaluated in 103 consecutive admissions in 69 children with cancer, admitted for treatment of presumed infection. In 61% of cases, children could be discharged home within 5 days of admission; only 9% was re-admitted within 7 days of discharge. In 77% of cases, children could be sent home on no antibiotics; in the remaining 23%, antibiotics could be narrowed in spectrum, and the majority sent home on an oral agent. Median length of stay for the entire cohort of patients was 5 days. In children receiving prophylactic G-CSF, the use of this agent did not impact on the length of stay, the need for subsequent re-admission, or the requirement for antibiotics at time of discharge.

Conclusions. Early discontinuation of antibiotics and discharge from hospital is safe, provided that the child is clinically well and afebrile. Children with a clinical or microbiologic focus can have their spectrum of coverage narrowed, and can be safely discharged on oral agents. J Oncol Pharm Practice (2001) 6, 131-137.
Cancer gene therapy update
Authors: Smith Judith A , Goldspiel Barry R
Published: January 2007

Objective. To provide an update about gene marking and gene therapy trials in cancer patients.

Data Sources. A MEDLINE search using the term “gene therapy” was conducted for the period 1985 to 1998. The reference lists from retrieved articles were reviewed. Meeting abstracts from the American Society of Clinical Oncology annual meeting (published in their proceedings) and the Annual Cancer Gene Therapy Symposium (published in Cancer Gene Therapy) that concerned gene therapy in cancer patients were also included.

Data Extraction. Both authors reviewed the retrieved material and included preclinical data, case reports, and clinical trials related to gene transfer or gene therapy in cancer patients.

Data Synthesis. There are several possible approaches to using gene therapy for the diagnosis and treatment of cancer and for the monitoring of cancer therapy. Exogenous genes may be used to mark cells to help better understand cancer biology or may be used directly for cancer treatment. Gene-marking trials have already provided new information about cancer biology and have demonstrated that reinfused progenitor cells may be a source of relapse in patients with acute or chronic myelogenous leukemia and neuroblastoma.

Approaches using gene therapy for cancer treatment include: using lymphocytes as gene carriers, using foreign genes to increase tumor immunogenicity, introducing tumor regression antigen genes into viruses, introducing “sensitivity” genes to produce new cytotoxic agent(s) within tumors, producing new protein product(s) to protect normal cells, replacing missing or mutant tumor suppressor genes, and inactivating oncogenes. Clinical trials using these strategies have demonstrated that gene transfer is feasible (albeit with low transduction efficiency) and that gene expression occurs; in addition, clinical responses have been noted.
Response and prediction of response to recombinant human erythropoietin in patients with solid tumors and platinum-associated anemia
Authors: Fjornes Tom
Published: January 2007

Objective. Anemia is commonly observed in tumor patients and may be worsened by the concomitant administration of chemotherapy with platinum. Recombinant human erythropoietin (rhEPO) is able to improve the chemotherapy-associated anemia and the quality of life in patients with solid tumors. The most effective dose, route, and frequency of administration of rhEPO in anemic cancer patients has not yet been determined.

The purpose of this review is to describe the results obtained up to now concerning the response and prediction of response to rhEPO in anemic patients with solid tumors undergoing platinum-based chemotherapy. In particular, the renal function conditions in this patient group were examined.

Data sources. The literature was reviewed through a MEDLINE search covering 1987 to 1997. Relevant articles were additionally obtained by the systematic examination of article references. We searched the following terms: rhEPO, tumor, anemia, cisplatin, carboplatin, and renal failure.

Study Selection. The current literature was reviewed with regard to both the pathophysiology of platinum-induced anemia and the clinical use, indications, and dosage of rhEPO in anemic tumor patients undergoing platinum therapy. Particular attention was directed to the prediction criteria of this drug.

Conclusions. The rhEPO response rates in patients with solid tumors and platinum-associated anemia vary widely in the current literature and range from 36% to 82%. Unfortunately, no strong predictor of response can be recommended at the present time. Clinical studies support findings concerning a reduction in renal function parameters and a blunted erythropoietin response in patients with platinum-induced anemia. It is possible that a baseline serum erythropoietin concentration in conjunction with the serum creatinine concentration or the creatinine clearance value can serve as a prognostic indicator for rhEPO therapy response in this patient group.
Treatment of hormone-refractory prostate cancer
Authors: Medina Patrick J , DiPaola Robert S , Goodin Susan
Published: January 2007

Objective. An increasing number of patients with prostate cancer develop hormone-refractory disease after standard treatment modalities. In these patients, early clinical trials with chemotherapy produced disappointing response rates. However, clinical trials that employ response criteria such as prostate-specific antigen (PSA) and clinical benefit response have produced encouraging responses. This article reviews current and future treatment options for the management of hormone-refractory prostate cancer.

Data Sources. A MEDLINE search for the years 1978 to 1998 was completed. The following terms were used in our search: prostate cancer, hormone-refractory, treatment, and chemotherapy. Relevant articles referenced in the literature obtained in our MEDLINE search were reviewed.

Study Selection. Randomized and nonrandomized clinical trials were used in our review. Clinical trials using prostate-specific antigen or a palliation of symptoms as primary criteria for response were given priority.

Data Synthesis. Several genetic alterations, including the overexpression of bcl-2 or mutations in p53, may lead to the development of hormone-refractory prostate cancer. Agents such as estramustine and taxanes, which affect microtubule function and potentially modulate bcl-2, appear to be particularly active in the treatment of hormone-refractory prostate cancer. In addition, mitoxantrone as well as other agents has been shown to be beneficial in improving the quality of life in patients with hormone-refractory prostate cancer.

Conclusion. Hormone-refractory prostate cancer is not a chemotherapy-resistant disease as once believed; significant progress in the treatment of hormone-refractory prostate cancer has been made with new combinations of chemotherapy agents. Promising new treatments are currently under evaluation to assess their potential benefit over the standard treatment modalities that are currently available.
Clinical pharmacy services in oncology clinics
Authors: Wong Shirley W , Gray Elizabeth S
Published: January 2007

Objective. To describe the implementation and evaluation of clinical pharmacy services in ambulatory hematology-oncology clinics.

Design. A prospective study was conducted to evaluate the impact of the clinical pharmacist in outpatient clinics.

Setting. The clinical pharmacist is available to patients and health care professionals for drug consultations in adult hematology-oncology, cancer pain, surgical oncology, pediatric hematology-oncology, and gastrointestinal tumor clinics. The pharmacist also participates in a cancer outreach program in an off-site rural clinic.

Interventions. A chart review, pharmacy patient profile review, and patient interview were performed to obtain medication histories. Drug-related problems were identified, resulting in interventions. Patient outcomes were evaluated by follow-up phone calls or by patient interviews on the following clinic visit.

Results. A total of 211 interventions were documented within 36 days. The most frequent activity was patient counseling followed by therapeutic recommendations. A majority of the interventions were not related to chemotherapy. The physician acceptance rate was 94.5%. Most of the problems were of high and moderate clinical significance, with positive clinical outcomes after pharmacy interventions.

Conclusion. Hematology-oncology clinics provide an excellent opportunity to involve pharmacists. A clinical pharmacist has a significant role in outpatient clinics and can potentially lead to an overall decrease in health care costs and to an improvement of the quality of patient care.
Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices
Authors: Krämer Irene , Thiesen Judith
Published: January 2007

Purpose. The purpose of this study was to determine the physicochemical stability of topotecan after reconstitution and after further dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in both polyvinylchloride (PVC) bags and elastomeric portable infusion devices.

Methods. Each vial of topotecan (Hycamtin®) was reconstituted with sterile water for injection, yielding a nominal concentration of 1 mg/mL. Topotecan infusion solutions were aseptically prepared by further dilution of reconstituted topotecan solutions with either 0.9% sodium chloride or 5% dextrose in both PVC bags and portable elastomeric infusion devices, in amounts yielding topotecan concentrations of 10 µg/mL, 25 µg/mL, or 50 µg/mL. Test solutions were stored light-protected at room temperature (25°C) or under refrigeration (2-8°C) in parallel. One test solution of the nominal concentration of 10 µg/mL topotecan in a 0.9% sodium chloride PVC infusion bag was stored under ambient light conditions (mixed daylight and normal laboratory fluorescent light) at room temperature. Topotecan concentrations were obtained periodically throughout a 4-week storage period via a stability-indicating high performance liquid chromatography assay with ultra-violet detection. In addition, measurements of pH values were performed regularly, and test solutions were visually examined for colour change and precipitation.

Results. The stability tests revealed that the currently available topotecan formulation is stable (at a level of ≥90% topotecan) after reconstitution and dilution, independent of temperature (refrigerated, room temperature), the vehicle (0.9% sodium chlo-ride, 5% dextrose), the concentration (10 µg/mL, 25 µg/mL, or 50 µg/mL), or the container material (PVC bags, elastomeric portable infusion devices). The results were obtained over a test period of ≥4 weeks. Topotecan infusion solutions exposed to daylight were stable for only 17 days.

Conclusions. Reconstituted and diluted topotecan infusion solutions are shown to be physicochemically stable for 4 weeks. Light protection during administration is not necessary.
Oncology pharmacy in the new millennium
Authors: Sewell Graham J
Published: January 2007

It is almost impossible, with any degree of certainty, to predict the progress of oncology pharmacy in the next millennium. As a relatively new field, it is perhaps most instructive to look at the foreseeable future, the next 20 years. The following is an attempt to broadly outline the trends for oncology pharmacy in the coming years, and identify those issues that will be key for the practising oncology pharmacist.
Targeted toxins
Authors: Brok M W J den , de Gast G C , Schellens J H M , Beijnen J H
Published: January 2007

Objective. Current modalities used in the treatment of cancer often cause unacceptable damage to normal tissue. Toxins targeted toward tumor cells by antibodies or growth factors have the potential to selectively kill tumor cells while leaving normal tissue intact. The purpose of this review is to provide background information on targeted toxins and current clinical studies for this new class of anti-cancer compounds.

Data sources. A MEDLINE search was conducted using the term “immunotoxins.” Relevant articles were also obtained by the systematic examination of article references.

Data synthesis. The toxins Pseudomonas exotoxin, diphtheria toxin, and ricin toxin are often used as targeted toxins. Deletion or mutation of the binding domains of these toxins decreased binding of the toxins to normal tissues. Antibodies or growth factors can be used as targeting moiety, and the resulting agents are called immunotoxins or fusion proteins, respectively. DNA technology and chemical modifications of the toxin as well as the antibody moiety led to smaller and less immunogenic targeted toxins. Smaller targeted toxins are less toxic and penetrate further into the tumor. The summary of several targeted toxins elicited during clinical trials in this review makes it clear that several targeted toxins are potential agents for the treatment of various cancers, although some problems still need to be overcome. These problems include toxicity, immunogenicity, cross-reactivity of the targeted toxin with life-sustaining tissue, heterogenicity of tumor cells, and limited tumor penetration.
Protein kinase C as a target for new anti-cancer agents
Authors: van Gijn Roel , Zuidema Xander , Bult Auke , Beijnen Jos H.
Published: January 2007

Cancer joins the category of diseases involving abnormalities in the rate of proliferation of cells and is associated with uncontrolled cell division, where cells either generate their own growth-promoting stimuli or neighboring cells or do not respond to growth inhibitory signals. Protein kinase C (PKC) is one of the key elements in the tumor growth signal transduction pathways and is found to be overexpressed in several malignant cell types. A way to control cell proliferation and cell differentiation is by influencing signal transduction pathways by modulation of PKC. PKC encloses 12 different isoenzymes, and each isoenzyme is found to have a different functional property. Because specific PKC isoenzyme types are present in different (malignant) cell species, they may be an attractive target in the development of anti-cancer agents. Classification and identification of the available PKC isoenzymes in different tumor cells could be useful in targeting specific tumors. PKC also tends to be overexpressed in association with the multidrug resistance pheno-type. This concise review deals with the role of PKC isoenzymes in (tumor) cell biology and evaluates the antineoplastic agents interacting on PKC isoenzymes.
Thalidomide does not interfere with graft-versus-leukemia reactivity in mice
Authors: Kapelushnik Joseph , Weiss Lola , Pappo Orit , Okon Eliezer , Or Reuven
Published: January 2007

Objective. To determine whether thalidomide is an effective prophylactic agent against acute graft-versus-host disease (GVHD) and whether it exerts an effect on graft-versus-leukemia (GVL) reactivity, the drug was administered to leukemic mice that were exposed to allogeneic bone marrow transplantation.

Methods. Mice (BALB/c 3 C57BL/6) F1 were inoculated with 107 B cell leukemia cells (BCL1) and conditioned with total body irradiation followed by reconstitution with bone marrow plus splenic cells harvested from C57BL/6 mice. After transplant, mice were treated with oral thalidomide (20 mg/kg/day) for a period of 10 days.

Results. Stable chimerism was documented in all recipients with $73% (mean) donor-type C57 cells. In this semi-allogeneic murine model, thalidomide failed to prevent or alleviate the acute GVHD symptoms; however, the drug did not impair GVL reactivity. The antileukemia allogeneic effect was similar in the thalidomide and non-thalidomide-treated animals. Comparison of the GVL reactivity occurring in the allogeneically transplanted groups with that in the syngeneic recipients revealed a significant difference ( P 5 0.001).

Conclusions. Although thalidomide did not exert any effect against acute GVHD, the fact that the GVL reactivity was spared holds promise for its use as a treatment modality in chronic GVHD.
Agent-Based Modeling: A New Approach for Theory Building in Social Psychology
Authors: Smith Eliot R. , Conrey Frederica R.
Published: January 2007

Most social and psychological phenomena occur not as the result of isolated decisions by individuals but rather as the result of repeated interactions between multiple individuals over time. Yet the theory-building and modeling techniques most commonly used in social psychology are less than ideal for understanding such dynamic and interactive processes. This article describes an alternative approach to theory building, agent-based modeling (ABM), which involves simulation of large numbers of autonomous agents that interact with each other and with a simulated environment and the observation of emergent patterns from their interactions. The authors believe that the ABM approach is better able than prevailing approaches in the field, variable-based modeling (VBM) techniques such as causal modeling, to capture types of complex, dynamic, interactive processes so important in the social world. The article elaborates several important contrasts between ABM and VBM and offers specific recommendations for learning more and applying the ABM approach.
The Moderating Role of Familiarity in Fairness Perceptions of Revenue Management Pricing
Authors: Wirtz Jochen , Kimes Sheryl E.
Published: January 2007

Perceived fairness of revenue management (RM) pricing is a serious concern, as RM uses different prices for fundamentally the same service. The authors examine the effects of familiarity with an RM pricing practice, framing of prices, and fencing condition (i.e., whether a respondent was advantaged or disadvantaged by an RM price) on fairness perceptions. The authors conduct two experiments and find that familiarity moderated the effects of framing and fencing condition on consumers’ fairness perceptions. Specifically, framing and fencing condition had strong effects on perceived fairness when respondents were less familiar with a pricing practice. However, when familiarity was high, neither the framing nor fencing condition effect was significant. Our findings suggest that familiarity may be a boundary condition for prospect theory.
How Embarrassing! An Exploratory Study of Critical Incidents Including Affective Reactions
Authors: Grace Debra
Published: January 2007

Using Critical Incident Technique, data are collected from 166 respondents who related incidents involving embarrassment experienced over a total of 44 different service environments. In applying a functional analysis, a number of embarrassment antecedents in the form of sources (e.g., customer, service provider, others present) and stimuli (e.g., criticism, awkward acts, image appropriateness, forgetfulness/lack of knowledge/error, environment/surroundings, and violations of privacy) are identified. Embarrassment was found to be manifested by emotional, physiological, and behavioral reactions, and its long-term consequences include both positive and negative behavioral intentions and word-of-mouth communications. The Functional Analysis of Consumer Embarrassment provides an informative framework to enhance our understanding of affective reactions in service encounters and provides a solid foundation for future research.
Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis
Authors: Zhang G X , Baker C M , Kolson D L , Rostami A M
Published: January 2007

In recent years we have seen growing evidence for the role of chemokines in the pathogenesis of several infectious and non-infectious inflammatory CNS disease states, including Multiple Sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). An increase in proinflammatory chemokines has been associated with demyelinating lesions and clinical neurological dysfunction in patients with MS; these chemokines could be potential targets for MS therapy. Besides a clearly defined role in mediating leukocyte migration, these and other chemokines may act as immunoregulatory molecules in the driving to Th1/Th2 responses, switch of cytokine profiles, and the induction of tolerance. Since chemokine receptors have now been identified on macrophages, microglia, astrocytes, and endothelial cells as well as neurons in the CNS, chemokine/receptor interactions may mediate functional responses in a variety of CNS cell types during the course of inflammatory disease states. Therefore, clarification of the roles of chemokines and their receptors in the pathogenesis of EAE and MS will be useful in establishing immunotherapeutic strategies for these neurological autoimmune disorders.
Positive association between blood brain barrier disruption and osmotically-induced demyelination
Authors: Adler S , Martinez J , Williams D S , Verbalis J G
Published: January 2007

Rapid correction of chronic hyponatremia can cause osmotic brain demyelination in animals and humans. Why demyelination develops is unknown, but blood brain-barrier disruption might expose oligodendrocytes to substances normally excluded from the brain. To test this hypothesis, chronic hyponatremia was induced and corrected using a new, reproducible rat model for producing osmotic brain demyelination. Blood brain barrier integrity was assessed by NMR imaging at either 3, 16 or 24 h during the first day of correction. Demyelination was determined histopathologically 5-6 days later. Of 96 rats studied, demyelination developed 5-6 days later in 37 rats, 89% of whom showed barrier disruption. In the 59 rats who did not develop demyelination, 45 (76%) had no barrier disruption. Thus, blood-brain barrier disruption during the first 24 h of correction was associated with a 70% risk of developing demyelination. By contrast, the risk of developing subsequent demyelination was only 8% when the barrier was intact. This strong association between barrier disruption and subsequent demyelination provides new insights into the role of blood brain barrier function in demyelinative disorders such as the osmotic demyelination syndrome and by extension to other demyelinative disorders such as multiple sclerosis.
Polymorphisms of apolipoprotein E; outcome and susceptibility in multiple sclerosis
Authors: Weatherby S JM , Mann C LA , Davies M B , Carthy D , Fryer A A , Boggild M D , Young C , Strange R C , Ollier W , Hawkins C P
Published: January 2007

Allelic variants of the apolipoprotein E (APOE) gene influence the course of several neurological diseases. In multiple sclerosis the concentration of APOE in cerebrospinal fluid and its intrathecal synthesis is reduced. Specific isoforms of APOE may also be important and it has been suggested that possession of the e4 allele may be associated with a more aggressive disease process. These data prompted us to re-examine, in a large group of patients with multiple sclerosis, the proposal that allelism in the apolipoprotein gene influences disease course. Genotypes were determined in a well-defined group of 370 unrelated Caucasians with clinically definite multiple sclerosis and in 159 healthy controls. Age at onset, sex, disease duration, disease subtype were recorded. Disability was measured using the Kurtzke expanded disability status score in patients with a disease duration of 10 years or greater. There was no significant difference in APOE allele or genotype frequencies between patients and controls, between disease subtypes or between genders. APOE genotype did not significantly influence age of onset, and no significant relationship between genotype, allele frequency and disease severity was found. This study suggests that individual APOE alleles or genotypes do not determine disease susceptibility or the clinical course of multiple sclerosis.
Macrophages: their myelinotrophic or neurotoxic actions depend upon tissue oxidative stress
Authors: Bartnik B L , Juurlink B HJ , Devon R M
Published: January 2007

There are still questions regarding whether macrophages found in MS lesions are agents of recovery or of destruction. To address this, we examined in aggregate cultures prepared from dissociated embryonic spinal cord tissue, with or without addition of exogenous macrophages, the effect of menadione-induced oxidative stress. Similar to findings of other laboratories, we observed that in the absence of oxidative stress macrophage enrichment promoted myelinogenesis. In macrophage-poor cultures, menadione at 5 μM had very little effect upon the status of the aggregate cultures; however, increasing this to 10 and 20 μM did result in some damage to axons and myelin. By contrast, in macrophage enriched cultures, menadione at a concentration as little as 5 μM caused the complete destruction of the aggregates. We suggest that in neural tissues that have sufficiently high macrophage numbers, oxidative stress results in a positive inflammatory feedback loop that results in massive tissue destruction. We further suggest that what we see in macrophage-enriched aggregates subjected to oxidative stress may represent what happens in the Marburg-type of MS lesion.
Contrast-enhanced magnetic resonance activity in relapsing remitting multiple sclerosis patients: a short term natural history study
Authors: Bagnato F , Tancredi A , Richert N , Gasperini C , Bastianello S , Bash C , McFarland H , Pozzilli C , Frank J A
Published: January 2007

Magnetic resonance imaging (MRI) has been used to study the history of multiple sclerosis (MS). We analyze the relationship between MRI activity in the first scan compared to the subsequent five scans, and we evaluate whether a shorter observation period of 3 months may predict the subsequent 3 months. Monthly enhanced MRI was performed in 103 relapsing remitting (RR) MS patients for 6 months. Thirty-five per cent of patients had an inactive scan on the initial examination. More than 80% of them developed MRI activity during the following 5 months. Eighteen per cent of patients had three consecutive inactive scans; 65% of them had at least one active scan on the subsequent 3 monthly MRI's. The relationship between the first scan and all subsequent scans demonstrates a clear weakening over time. Eighty-two per cent of patients had at least one active scan during the initial 3 consecutive months, the chance of becoming inactive decreased from 23% to 0% over the subsequent 3 months, according with the mean number of enhancing lesions during the first 3 months. These results suggest that neither a single scan nor a short baseline of 3 months may adequately describe the natural history of disease in an individual RRMS patient.