bluuebunny/crossref_metadata_2025 huggingface dataset:
Burden of Methicillin‐ResistantStaphylococcus aureus: Focus on Clinical and Economic Outcomes
Authors: Lodise Thomas P. , McKinnon Peggy S.
Published: June 2007

Infections caused by methicillin‐resistantStaphylococcus aureus(MRSA) are a major public concern. Hospital‐acquired MRSA rates have steadily increased over the past 25 years, and the bacterial strain is making inroads to the community. The morbidity and mortality burden of MRSA infection is compounded by delayed or inappropriate antibiotic treatment, taking a toll on health care resources that are already stretched thin. Vancomycin has historically been the drug of choice for this pathogen because its broad spectrum can address the multidrug resistance of most MRSA infections. Despite its sustained in vitro microbiologic inhibitory activity, researchers are beginning to question the continued utility of vancomycin for MRSA infections. Evidence against vancomycin is most notable with regard to nosocomial pneumonia and skin and soft tissue infections. In addition, because vancomycin must be administered intravenously, patients typically require prolonged hospitalization, which further increases the cost of MRSA treatment and exposes patients to additional nosocomial infections. Recent studies have shown that antibiotics with good bioavailability, such as linezolid, can be given orally to facilitate early hospital discharge, thus alleviating the economic burden of MRSA infections. Several agents have been developed over the past decade that have excellent in vitro activity against MRSA. Further studies are needed to determine if these drugs can better eradicate MRSA than vancomycin and remedy the adverse outcomes frequently observed with this organism.
Safety of Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis
Authors: Munzenberger Paul J. , Montejo Jenny M.
Published: June 2007

Atopic dermatitis is a chronic, highly pruritic, and frequently recurring inflammatory skin disease that can be burdensome to affected individuals as well as to their family members, the health care system, and society as a whole. Immunomodulatory agents, such as topical corticosteroids and topical calcineurin inhibitors (TCIs), target the underlying immunopathology of atopic dermatitis and are the foundation of pharmacologic treatment for disease exacerbations. Recent recommendations from the United States Food and Drug Administration prompted the addition of a black‐box warning and medication guide for tacrolimus ointment and pimecrolimus cream (both TCIs). The recommendations were based on a theoretical risk of malignancy derived from safety profiles, animal data, and reported cases of malignancy from clinical trials and postmarketing safety surveillance of oral calcineurin inhibitors. We know of no data that suggest that TCI use increases the risk of malignancy. Several dermatologic associations have issued statements supporting the safety of TCIs, and independent oncology experts have concluded that reported lymphomas were not related to TCI use. The black‐box warning added to the TCI prescribing information also states that no causal link has been established. Effective treatment of atopic dermatitis can help alleviate the burden this disease imposes, and TCIs remain important treatment options.
Clostridium difficile: Recent Epidemiologic Findings and Advances in Therapy
Authors: McMaster‐Baxter Nicole L. , Musher Daniel M.
Published: June 2007

Clostridium difficile–associated disease (CDAD) has become an important public health problem. The causative organism is acquired by the oral route from an environmental source or by contact with an infected person or a health care worker who serves as a vector. Disruption of the bowel microflora, generally by antibiotics, creates an environment that allows C. difficile to proliferate. Organisms produce toxins A and B, which cause intense inflammation of the colonic mucosa. The syndrome that results includes severe diarrhea, fever, abdominal pain, and leukocytosis. A new strain of C. difficile has become prevalent in the United States, Canada, and the United Kingdom. Identified by pulsed‐field gel electrophoresis (PFGE), this strain is called North America PFGE type 1, abbreviated as NAP‐1. Clostridium difficile NAP‐1 characteristically generates large amounts of toxins A and B, as well as an additional binary toxin and is associated with enhanced morbidity and a poor response to antibiotic therapy. Mild cases of CDAD may respond to cessation of antibiotic therapy, perhaps related to antibody production by the infected person, but most infected persons require antimicrobial therapy. Vancomycin has been approved by the United States Food and Drug Administration for treatment of CDAD, but reluctance to use this antibiotic in the hospital setting has led to reliance on metronidazole as first‐line therapy. Recent studies show a high rate of failure, due either to infection by NAP‐1 or to the presence, in hospitals, of older and sicker adults who have been treated with many broad‐spectrum antibiotics. Nitazoxanide, bacitracin, teicoplanin, and fusidic acid are additional agents that have published efficacy for this indication in humans. Rifaximin and PAR‐101 are under investigation. Other therapies, including polymers that bind C. difficile toxin and monoclonal antibodies to toxins, and preventive measures such as toxoid vaccines are also under study.
Tobacco Interventions Delivered by Pharmacists: A Summary and Systematic Review
Authors: Dent Larry A. , Harris Kari Jo , Noonan Curtis W.
Published: June 2007

Background. As one of the most accessible health care professionals, pharmacists are in an ideal position to provide tobacco‐cessation and prevention services. Although there is growing interest in expanding the pharmacist's role in tobacco treatment, few published studies have assessed the efficacy or effectiveness of tobacco‐cessation services delivered by pharmacists in the United States.

Objective. To summarize and critique studies that examined pharmacist‐delivered tobacco‐cessation services.

Methods. Articles written in English that appeared in peer‐reviewed journals were identified from a systematic review of literature published from 1980–2006. Publications were selected for review if the interventions were delivered by pharmacists, if the intervention included United States Food and Drug Administration—approved drugs (if drug therapy was used), and if smoking‐cessation rates could be calculated.

Results. Fifteen studies met inclusion criteria. Fourteen of the studies targeted smoking, and one targeted spit (chewing) tobacco. Five studies were controlled, and 10 were uncontrolled. One of the controlled studies (chewing tobacco) and eight of the uncontrolled studies were conducted in the United States. Findings of the uncontrolled U.S. studies suggest that pharmacists can deliver smoking‐cessation services. Three of the controlled studies found statistically significant differences between the pharmacist‐based intervention and the control group, and the trend in the other two studies was toward the effectiveness of the pharmacist‐delivered intervention. Only six of the 15 studies reviewed used biochemical measures to verify self‐reported cessation.

Conclusion. The uncontrolled and controlled studies reviewed demonstrate that pharmacists can deliver tobacco‐cessation interventions, and the evidence strongly suggests that they are effective in helping smokers to quit. Future studies conducted in the United States that are well controlled and include biochemical verification of smoking status are needed to provide definitive confirmation that pharmacist‐delivered interventions are effective for smoking cessation. With the availability and expanded training of pharmacists, this is an opportune time for testing and disseminating evidence‐based research evaluating the effectiveness of pharmacist‐delivered tobacco‐cessation services.
Health Outcomes and Economic Impact of Therapy Conversion to a Biphasic Insulin Analog Pen Among Privately Insured Patients with Type 2 Diabetes Mellitus
Authors: Cobden David , Lee Won Chan , Balu Sanjeev , Joshi Ashish V. , Pashos Chris L.
Published: June 2007

Study Objective. To evaluate claims‐related treatment adherence, health care resource utilization, and associated costs of therapy conversion from an insulin vial and syringe to a premixed biphasic insulin analog pen device among privately insured patients with type 2 diabetes mellitus.

Design. Retrospective, longitudinal, intrapatient (before and after) analysis.

Data Source. PharMetrics database of medical and pharmaceutical claims from 57 commercial health plans across the United States.

Patients. Four hundred eighty‐six adult patients with a confirmed diagnosis of type 2 diabetes who converted from an insulin analog vial and syringe (233 patients) or a human insulin vial and syringe (253 patients) to a biphasic insulin analog pen device between July 1, 2001 and December 31, 2002.

Measurements and Main Results. All patients had no previous use of the pen device. Primary end points were medication possession ratio (MPR), a measure of adherence; hypoglycemic events; associations between treatment adherence and hypoglycemic events, and adherence and all‐cause health care costs; and all‐cause—attributable, hypoglycemia‐attributable, and other diabetes‐attributable costs. After conversion, MPR increased significantly from 59% to 68% (p<0.01). A significant decrease in the likelihood of experiencing a hypoglycemic event was also observed after conversion (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.27–0.61, p<0.05), with hypoglycemic occurrences reduced nearly two thirds among subjects with optimal adherence indicated by an MPR of 80% or greater (incidence rate ratio 0.36, 95% CI 0.11–0.76, p<0.05). Significant decreases in hypoglycemia‐attributable emergency department visits (OR 0.36, 95% CI 0.16–0.84, p<0.05) and physician visits (OR 0.39, 95% CI 0.20–0.77, p<0.05) were observed. Total mean all‐cause annual treatment costs were reduced by $1748/patient (p<0.01), hypoglycemia‐attributable costs were reduced by $908/patient (p<0.01), and other diabetes‐attributable costs were reduced by $643/patient (p<0.01). Patients with an MPR of 80% or greater were associated with significant reductions in all‐cause health care costs (OR 0.55, 95% CI 0.31–0.80, p<0.05).

Conclusion. Privately insured patients with type 2 diabetes may exhibit considerable improvements in clinical and economic outcomes after insulin therapy conversion from vial and syringe to a premixed biphasic insulin analog pen device.
Institutional Experience with Voriconazole Compared with Liposomal Amphotericin B as Empiric Therapy for Febrile Neutropenia
Authors: Shehab Nadine , DePestel Daryl D. , Mackler Emily R. , Collins Curtis D. , Welch Kathleen , Erba Harry P.
Published: June 2007

Study Objective. To assess the effectiveness, safety, and cost of empiric treatment of febrile neutropenia before and after implementing an algorithm in which voriconazole was substituted for liposomal amphotericin B (L‐AmB).

Design. Retrospective cohort analysis.

Setting. An 850‐bed tertiary care hospital, which is also a referral site for patients with acute leukemia.

Patients. Fifty‐five adult patients who started empiric antifungal therapy for febrile neutropenia between January 1, 2002, and December 31, 2003, encompassing 58 treatment episodes (defined as a hospitalization during which empiric antifungal therapy was administered).

Measurements and Main Results. Medical charts, including patients' pharmacy and laboratory data, were reviewed. Twenty‐six and 32 episodes of L‐AmB and voriconazole use, respectively, were identified. No significant differences between the L‐AmB and voriconazole groups were noted at baseline. Rates of fever resolution (54% vs 59%, p=0.791) and breakthrough invasive fungal infections (11% vs 12%, p>0.999) were similar for the L‐AmB and voriconazole episodes. Premature drug discontinuation due to the prescriber's perceived lack of efficacy occurred most frequently in the voriconazole group (25% vs 8%, p=0.160). Survival was significantly higher in the voriconazole than in the L‐AmB group (100% vs 77%, p=0.006). Adverse effects that were significantly more common in the L‐AmB group than in the voriconazole group were elevated serum creatinine levels (27% vs 3%, p=0.017) and electrolyte disturbances (19% vs 0%, p=0.014). Adverse effects reported more frequently in the voriconazole group than in the L‐AmB group were visual disturbances (9% vs 0%, p=0.245) and elevated hepatic enzyme levels (9% vs 8%, p>0.999). Mean drug expenditures/episode for initial empiric antifungal therapy were lower for voriconazole than for L‐AmB ($1593 vs $4144, or $153 vs $380/day).

Conclusion. Our institution's algorithm incorporating voriconazole into the empiric management of febrile neutropenia was associated with effectiveness outcomes comparable to those observed with L‐AmB as well as a lower frequency of adverse effects and overall expenditures for antifungal drugs.
Aprotinin Use in Cardiac Surgery Patients at Low Risk for Requiring Blood Transfusion
Authors: Kristeller Judith L. , Stahl Russell F. , Roslund Brian P. , Roke‐Thomas Marie
Published: June 2007

Study Objectives. To determine if aprotinin is safe and effective in patients at low risk for requiring blood transfusion after cardiac surgery by evaluating whether there is any significant difference in blood product use or other significant clinical outcomes between patients who received aprotinin versus those who did not.

Design. Retrospective review.

Setting. Inpatient community nonteaching hospital.

Patients. Three hundred thirty‐five patients who underwent primary cardiac surgery involving cardiopulmonary bypass between November 1, 2003, and December 31, 2005, and were considered at low risk for requiring postoperative blood transfusion; 162 patients received aprotinin and 173 patients received aminocaproic acid (control).

Measurements and Main Results. Comparison of patients in the aprotinin group versus those in the aminocaproic acid group revealed no difference in total donor exposures to blood products (1.86 vs 1.16 units/patient, p=0.07), total packed red blood cells (PRBCs) received (1.25 vs 0.86 units/patient, p=0.09), postoperative donor exposures to blood products (0.91 vs 0.48 unit/patient, p=0.13), or postoperative PRBCs received (0.61 vs 0.40 unit/patient, p=0.23). No difference was noted in any other clinical outcome in the aprotinin group versus the aminocaproic acid group, including postoperative azotemia (13.0% vs 10.4%, p=0.46), new onset of atrial fibrillation (14.8% vs 15.0%, p=0.95), myocardial infarction, stroke, or death. Mean ± SD total hospital length of stay was similar in the aprotinin group versus the aminocaproic acid group (8.1 ± 3.8 vs 7.4 ± 2.8 days, p=0.08), but length of stay from surgery to discharge was longer in the aprotinin group than in the aminocaproic acid group (5.9 ± 0.17 vs 5.4 ± 0.12 days, p=0.032).

Conclusion. Although aprotinin appeared to be safe in this low‐risk patient population, it was not more effective than aminocaproic acid in reducing blood product use after cardiac surgery. More robust evidence is needed from a controlled randomized trial to demonstrate the safety, efficacy, and pharmacoeconomic benefit of aprotinin.
Chondrocyte Viability After Intra-articular Calcaneal Fractures in Humans
Authors: Ball Scott T. , Jadin Kyle , Allen R. Todd , Schwartz Alexandra K. , Sah Robert L. , Brage Michael E.
Published: June 2007

Background: Chondral damage from the impact of injury may contribute to the high incidence of post-traumatic arthritis after calcaneal fractures, but this has yet to be proven. We sought to study the effect of intra-articular calcaneal fractures on chondrocyte viability and to correlate these effects with injury severity, time from injury to surgery, and patient age and co-morbidities. Methods: Irreducible osteochondral fragments from 12 patients undergoing operative treatment for intra-articular calcaneal fractures were analyzed. Control cartilage was obtained from four tissue donors who died of unrelated causes. The cartilage was assessed for chondrocyte viability through the full thickness of tissue using a Live/Dead assay followed by laser scanning confocal microscopy. Patient demographics including injury classification and severity, time from injury to surgery, and patient age were recorded. Results: Chondrocyte viability from fracture patients averaged 72.8% ± 12.9% (range 53% to 95%), which was significantly lower than the 94.8% ± 1.5% viability observed in the control specimens ( p = 0.005). Chondrocyte viability declined with higher energy injuries ( p = 0.13), time from injury to surgery ( p = 0.07), and increasing patient age ( p = 0.07). However, none of these factors reached a level of statistical significance. Conclusions: A significant decline in chondrocyte viability occurs after intra-articular fractures of the calcaneus. This may contribute to the development of post-traumatic arthritis.
Foot and Ankle Problems of Aboriginal and Non-Aboriginal Diabetic Patients with End-Stage Renal Disease
Authors: McIntyre Ian , Boughen Cindy , Trepman Elly , Embil John M.
Published: June 2007

Background: There is little information available about the profile of lower extremity morbidity in diabetic patients with end-stage renal disease (ESRD) in the Canadian Aboriginal and non-Aboriginal population. Method: A retrospective review of medical records in 127 diabetic patients on hemodialysis at a tertiary health care center was performed. Patient interviews and physical examinations were performed in 77 of these patients (36 Aboriginal, 41 non-Aboriginal), and followup evaluation was done in 39 patients at an average of 1 year later. Results: Aboriginal patients were an average of 7 years younger than non-Aboriginal patients. Comorbidities of diabetes and ESRD were frequent. Peripheral neuropathy and inability to occlude the vessels were present in the majority of feet. Lower extremity complications were frequent, including prior foot ulcer in the majority of patients and an amputation in more than one fourth of the patients. Aboriginal patients had a significantly greater frequency of prior foot ulcer, mean number of foot ulcers per patient, amputation, prior osteomyelitis, and Charcot foot than non-Aboriginal patients. Almost all patients were at risk for future foot ulcer, but many patients did not inspect their feet daily. Home care was significantly less frequently available for Aboriginal than non-Aboriginal patients. The majority of patients had inadequate custom or prefabricated shoes and did not wear insoles on the day of examination. Aboriginal patients cited financial cost, insufficient family support, and language barriers as reasons for inadequate foot care and footwear more frequently than non-Aboriginal subjects. A significantly smaller frequency of Aboriginal patients had good knowledge of footwear or diet than non-Aboriginal patients. Conclusions: Lower extremity complications were significantly more frequent in Aboriginal than non-Aboriginal diabetic patients with ESRD. Financial cost and knowledge deficit were barriers to adequate foot care and footwear. These findings support the need for a formal foot care and footwear program for this high-risk population.
Forefoot Amputation with Limb Revascularization: The Effects of Amputation, Timing, and Wound Closure on the Peripheral Vascular Bypass Graft Site
Authors: Steel Maxwell W. , DeOrio James K.
Published: June 2007

Background: Much has been written about the effects of successful arterial bypass on forefoot surgery for ulceration and gangrene. This study examined the effects of the amputation site and timing on the arterial bypass graft site. Methods: We reviewed the records of all patients who had successful vascular bypass graft surgery and amputation at our institution, between October, 1995 and May, 2002. Thirty-eight procedures in 35 patients fit the criteria and were included in the study. Results: Thirty-five patients had successful vascular bypass graft surgery and forefoot amputation for gangrene or nonhealing ulceration. Three of these patients developed gangrene on the contralateral side and received similar treatment for that side. All of the wounds eventually healed. Healing time, rate of graft infection, and rate of wound dehiscence did not differ noticeably between patients with amputation immediately after arterial bypass and patients with amputation one or more days after arterial bypass. Infection at the bypass site occurred in two patients; their amputation sites were closed primarily. Wound dehiscence developed at the bypass site in one patient whose amputation site was closed by secondary intention. Although not statistically significant, the median healing time in patients treated with primary closure (37 days) was less than that in patients treated with closure by secondary intention (61 days; p = 0.09), and rates of graft infection and wound dehiscence did not differ between these two groups of patients. Conclusions: Amputation site wound closure may adversely affect the bypass graft, but results were not statistically significant. Treatment requires a closely coordinated team approach between the vascular surgeon and the orthopedic surgeon.
A Randomized Controlled Trial of Two Types of In-Shoe Orthoses in Children with Flexible Excess Pronation of the Feet
Authors: Whitford Deirdre , Esterman Adrian
Published: June 2007

Background: Orthoses for children with flexible excess pronation are estimated to cost Australian parents millions of dollars per year; however, there is no high-level evidence that orthoses improve function or reduce pain. Methods: A randomized parallel, single-blinded, controlled trial of custom-made and ready-made orthoses was conducted in children between the ages of 7 and 11 years with bilateral flexible excess pronation. The diagnosis was based on calcaneal eversion and navicular drop. Outcomes included gross motor proficiency, self-perception, exercise efficiency, and pain. Measurements were taken at baseline, and at 3 and 12 months. Of the 178 children who participated at baseline, 160 continued to the end of the trial. Results: After randomization, baseline characteristics were similar between the three treatment groups (custom-made, ready-made, and control). Statistical modeling demonstrated that although for most outcome measures there were statistically significant trends over time, none of the group comparisons were statistically significant. A sub-group analysis of those presenting with pain found no significant differences at 3 or 12 months. Conclusions: This study found no evidence to justify the use of in-shoe orthoses in the management of flexible excess foot pronation in children.
Capitalisation, Commoditisation and Obligation among Ethiopia's Afar Pastoralists
Authors: Davies Jonathan
Published: June 2007

This paper on the Afar pastoralists of north-eastern Ethiopia examines their livelihood goals to understand how they view the institutions that are central to their existence. The paper examines the choices made in allocating livestock resources to accumulate different forms of capital. Using qualitative and quantitative research the paper considers the value of internal livestock exchange for accruing insurance and the impact that such value has on the commoditisation of livestock.
Characterization of Histaminergic Receptors
Authors: Strakhova Marina , Esbenshade Timothy A.
Published: June 2007

This unit describes radioligand binding protocols for histamine H1, H2, H3, and H4receptors. Because these receptors demonstrate low amino acid sequence homology and divergent pharmacological characteristics, assay conditions vary for each. These protocols can be employed in high‐throughput screening programs aimed at identifying selective agonists and antagonists for these sites.
Murine and Canine Models of Appendicular Osteosarcoma
Authors: Fan Timothy M.
Published: June 2007

Appendicular osteosarcoma (OSA) is a primary bone sarcoma affecting humans during their second decade of life. Despite aggressive surgical and chemotherapeutic interventions, 30% of patients will experience progressive metastatic disease within 5 years of diagnosis. Understanding the biology of pediatric OSA and potential targets for therapeutic development remains an area of focus for both basic scientists and clinical oncologists. The identification and study of relevant comparative tumor models in mice and canines may allow for a better understanding of OSA biology, and permit the rapid investigation of novel therapeutic strategies for managing this metastatic bone sarcoma. This unit provides a protocol for using an orthotopic, syngeneic murine model of appendicular OSA as an investigative tool for the study of OSA biology. Additionally, the comparative relevance of spontaneously occurring appendicular OSA in canines for the study of pediatric bone sarcomas is discussed.
Carcinogen‐Induced Animal Models of Head and Neck Squamous Cell Carcinoma
Authors: Bassi Daniel E. , Klein‐Szanto A.J.P.
Published: June 2007

This unit provides two models of oral carcinogenesis (hamster cheek pouch and rat tongue), as well as more simple procedures to induce squamous cell carcinomas (SCCs) in mouse skin. The most significant usage of these models has been their application in studying the molecular pathology of the genesis and multi‐step progression of tobacco‐associated SCC. Nevertheless, these protocols have been used frequently as in vivo bioassays to demonstrate the chemopreventive and, to a lesser extent, the chemotherapeutic effects of numerous compounds. Several examples, using four different carcinogenesis protocols, are presented with detailed steps on how to elicit squamous lesions and when and how to apply test compounds that could have either cancer chemopreventive or chemotherapeutic effects.
Orthotopic Model of Human Pancreatic Ductal Adenocarcinoma and Cancer Cachexia in Nude Mice
Authors: Jones‐Bolin Susan , Ruggeri Bruce
Published: June 2007

Pancreatic ductal adenocarcinoma (PDAC) represents the fourth leading cause of cancer‐related deaths in the United States, with a 5‐year survival rate of only 2% to 10%. This tumor is aggressive, often metastasizing to distant sites (liver, lung, and adjacent intestines) by the time of diagnosis. Treatment options are limited, and the disease carries a grave prognosis for most patients. An orthotopic model of human PDAC in nude mice provides an excellent way to evaluate the pathogenesis of tumor growth and metastasis in order to develop therapies, to better define the underlying biology of tumor growth and metastasis, and to identify new molecular targets. This unit describes an orthotopic model of human PDAC in athymic nude mice that closely mimics the human condition. It is characterized by diffuse peritoneal, lymphatic, and hepatic metastatic spread and manifestations of a cancer cachexic phenotype.
Orthotopic Models of Human Gastric Carcinoma in Nude Mice: Applications for Study of Tumor Growth and Progression
Authors: Jones‐Bolin Susan , Ruggeri Bruce
Published: June 2007

Gastric carcinoma (GC) remains a leading cause of cancer related deaths worldwide with the 5‐year survival rate in the U.S. at ∼5% to 15% with existing therapies. This tumor is aggressive and has often metastasized to distant sites (liver, lung, and adjacent intestine) by the time of diagnosis. Treatment options (surgery, radiation, and chemotherapy) are limited and the disease carries a grave prognosis for most patients (50% 5‐year survival for distal GC; 10% 5‐year survival for proximal GC). An orthotopic model of human GC in nude mice provides an excellent way to evaluate the pathogenesis of tumor growth and metastasis in order to develop effective therapies, as well as to better understand the underlying biology of gastric tumor growth and metastasis. The protocol described in this unit details the development and characterization of an orthotopic model of human GC in athymic nude mice with diffuse lymphatic and hepatic metastatic spread. This model closely mimics the course of the human disease.
Solid‐Phase Oligonucleotide Labeling with DOTA
Authors: Jaakkola Lassi , Ylikoski Alice , Hovinen Jari
Published: June 2007

This unit describes a method to construct oligonucleotide conjugates labeled with 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) on a solid support. A nucleosidic phosphoramidite that contains a protected DOTA ligand compatible with normal chain assembly is prepared first. As the chain assembly is completed, the oligonucleotide is deprotected and converted to the corresponding gadolinium(III) chelate, resulting in an oligonucleotide conjugate containing the chelate at the 5′‐terminus.
Biophysical Analysis of Triple‐Helix Formation
Authors: Boutorine Alexandre S. , Escudé Christophe
Published: June 2007

Two methods for DNA triple‐helix analysis are described in this unit: a gel‐shift assay based on the slower electrophoretic migration of a triplex in a polyacrylamide gel under nondenaturing conditions, and an optical method in which the thermal denaturation of the triple helix is followed by UV spectrophotometry. Both methods give valuable information on the characteristics of DNA triple‐helix formation and triplex stability under different conditions.
Synthesis of Cidofovir and (S)‐HPMPA Ether Lipid Prodrugs
Authors: Beadle James R.
Published: June 2007

Cidofovir [(S)‐1‐(3‐hydroxy‐2‐phosphonomethoxypropyl)cytosine] and (S)‐HPMPA [(S)‐9‐(3‐hydroxy‐2‐phosphonomethoxypropyl)adenine] are potent nucleoside phosphonate antiviral agents that are not orally bioavailable unless one or both of their negative charges are masked. This unit describes the synthesis of hexadecyloxypropyl esters of cidofovir and (S)‐HPMPA. These prodrugs are readily absorbed after oral administration and are converted intracellularly to the corresponding diphosphates. The hexadecyloxypropyl esters of cidofovir and (S)‐HPMPA are orally active in animal models of viral infection. Two synthetic strategies are employed. In the first, cyclic cidofovir is coupled to 3‐hexadecyloxy‐1‐propanol using the Mitsunobu reaction (triphenylphosphine, DIAD), followed by basic hydrolysis of the cyclic ester. In the second, the lipid moiety is incorporated into a phosphonate synthon and a stepwise approach is used to assemble the (S)‐HPMPA analog.
Using geneid to Identify Genes
Authors: Blanco Enrique , Parra Genís , Guigó Roderic
Published: June 2007

This unit describes the usage of geneid, an efficient gene‐finding program that allows for the analysis of large genomic sequences, including whole mammalian chromosomes. These sequences can be partially annotated, and geneid can be used to refine this initial annotation. Training geneid is relatively easy, and parameter configurations exist for a number of eukaryotic species. Geneid produces output in a variety of standard formats. The results, thus, can be processed by a variety of software tools, including visualization programs. Geneid software is in the public domain, and it is undergoing constant development. It is easy to install and use. Exhaustive benchmark evaluations show that geneid compares favorably with other existing gene finding tools.
Transfection ofWolbachia pipientisintoDrosophilaEmbryos
Authors: Dobson Stephen L.
Published: June 2007

Wolbachiais a genus of obligate intracellular Alpha‐Proteobacteria represented by the type speciesWolbachiapipientis(Dumler et al., 2001).Wolbachiacommonly reside within cytoplasmic vacuoles of arthropods and helminths (Werren and Windsor, 2000; Casiraghi et al., 2004); vertebrate infections have not been identified.Wolbachiaare maternally transmitted from mothers to offspring though the embryonic cytoplasm.Wolbachiaare able to induce a diverse range of phenotypes in their invertebrate hosts, ranging from classical mutualism to reproductive parasitism. Examples of the latter include male killing, host feminization, parthenogenesis, and cytoplasmic incompatibility (reviewed in Dobson, 2003a). CurrentWolbachiaresearch foci include examining the impacts ofWolbachiainfection on host evolution, characterizing the mechanisms by whichWolbachiamanipulate invertebrate hosts, and developing applied strategies that employWolbachiafor pest and disease control.Wolbachiatransfection has proven a useful technique for addressing questions within each of these research foci. This unit describes a method forWolbachiatransfection via embryonic microinjection.
Genetic Manipulation of Porphyromonas gingivalis
Authors: Bélanger Myriam , Rodrigues Paulo , Progulske‐Fox Ann
Published: June 2007

Porphyromonas gingivalis, an oral anaerobic bacterium, is an important etiological agent of periodontal disease and may contribute to cardiovascular disease, preterm birth, and diabetes as well. Therefore, genetic studies are of crucial importance in investigating molecular mechanisms of P. gingivalis virulence. Although molecular genetic tools have been available for many bacterial species for some time, genetic manipulations of Porphyromonas species were not developed until more recently and remain limited. In this unit, current molecular genetic approaches for mutant construction in P. gingivalis using the suicide vector pPR‐UF1 and the transposon Tn4351 are described, as are protocols for performing electroporation and conjugation. Furthermore, a technique to restore the wild‐type phenotype of the mutant by complementation using vector pT‐COW is provided. Finally, a description of a noninvasive reporter system allowing the study of gene expression and regulation in P. gingivalis completes this unit.
Preparation and Electroporation of Oat Protoplasts from Cell Suspension Culture
Authors: Rakotondrafara Aurelie M. , Jackson Jacquelyn R. , Kneller Elizabeth Pettit , Miller W. Allen
Published: June 2007

Protoplasts provide a convenient system for introduction of nucleic acids into plant cells. Protoplasts allow rapid assays of gene expression and virus replication, with advantages for plant biology similar to those of cultured animal cells for the study of animal systems. Traditionally, preparation and handling of protoplasts has been as much art as science, requiring a special touch by the user. The purpose of this unit is to lay out in clear detail all the methods and nuances involved in protoplast preparation using a robust, reliable system that does not require skills beyond those expected of an unspecialized molecular biologist. Because dicots and monocots differ in many biological properties, and because different procedures may work better for different plants, separate units in this chapter are devoted to protoplast preparation from dicots (Arabidopsis, tobacco; refer to UNITS 16D.1 & 16D.4) and from a monocot (oat). This unit describes methods for preparation and transfection by electroporation of protoplasts derived from an oat suspension culture.
Cover Picture: Magnetorheological Fluids Based on Ionic Liquids (Adv. Mater. 13/2007)
Authors: Guerrero‐Sanchez C. , Lara‐Ceniceros T. , Jimenez‐Regalado E. , Raşa M. , Schubert U. S.
Published: June 2007

The use of ionic liquids as carriers of magnetorheological fluids is described by Schubert and co‐workers on p. 1740. Combining the properties of ionic liquids with magnetorheological technology may lead to new, “smart” fluids for application in medical therapies, engineering devices, or multiphase biological and chemical systems. In the presence of a magnetic field the fluids behave as solids owing to a stronger interaction between their suspended magnetic particles. In the absence of the magnetic field, they become liquids again in a fully reversible process.
Extended work hours and risk of acute occupational injury: A case‐crossover study of workers in manufacturing
Authors: Vegso S. , Cantley L. , Slade M. , Taiwo O. , Sircar K. , Rabinowitz P. , Fiellin M. , Russi M.B. , Cullen M.R.
Published: June 2007

Objective

This study was designed to determine whether injury risk among manufacturing workers was related to hours worked during the previous week.

Methods

A case‐crossover design was utilized to contrast hours worked prior to an injury shift with those worked prior to a non‐injury shift for hourly workers. Paired t‐tests were used to determine significance of the difference. Conditional logistic regression was used to assess dose–response.

Results

Hours worked prior to injury significantly exceeded hours during the control week. Workers who worked more than 64 hr in the week before the shift had an 88% excess risk compared to those who worked 40 hr or fewer, P < 0.05.

Conclusion

The study provides evidence that injury risk is related to time worked during the previous week. Control of overtime in manufacturing may reduce risk of worker injury. Am. J. Ind. Med. 50:597–603, 2007. © 2007 Wiley‐Liss, Inc.
Effect of vibration extrusion on high‐density polyethylene
Authors: Gao Xueqin , Zhang Jie , Chen Changsen , Shen Kaizhi
Published: June 2007

A new type of extrusion apparatus with a hydraulic vibration field was self‐developed to study the effects of vibration on the rheological behavior, mechanical properties, and morphology of high‐density polyethylene (HDPE) during the process of extrusion. In the research, the morphology and mechanical properties of specimens produced by conventional extrusion molding were used for comparison with specimens obtained via vibration extrusion molding. The research showed that the extrusion property of the HDPE melt was improved under a vibration field, and the apparent viscosity decreased. The maximum decrement of the apparent viscosity was 37.98%. The change in the apparent viscosity of the HDPE melt corresponded to the vibration frequency and amplitude, die temperature, and rotational speed of the extruder screw. Both the longitudinal and transverse yield strengths of the HDPE specimens increased under the vibration field. The increment of the longitudinal yield strength (11.5%) was bigger than that of the transverse yield strength (6.9%). According to scanning electron microscopy micrographs, the vibration field made the crystallites orient and become smaller, and the crystal size became more homogeneous. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Synthesis of liquid crystalline–amorphous block copolymers by the combination of atom transfer and promoted cationic polymerization
Authors: Demirhan S. , Serhatli İ. E. , Önen A.
Published: June 2007

Block copolymers of liquid crystalline 6‐(4‐cyanobiphenyl‐4′‐oxy) hexyl acrylate (LC6) and cyclohexene oxide (CHO) were obtained by the combination of atom transfer radical polymerization (ATRP) and promoted cationic polymerization (PCP). In the first part, a bifunctional initiator containing benzoin and halide groups in the same structure was used as an initiator in ATRP of LC6, in diphenyl ether in conjunction with CuBr/N,N,N′,N″,N″‐pentamethyldiethylenetriamine as a catalyst. The obtained photoactive liquid crystalline polymers poly[6‐(4‐cyanobiphenyl‐4′‐oxy)hexyl acrylate] (PLC6), were used to induce polymerization of CHO through formation of electron donor polymeric radicals upon photolysis and subsequent oxidation to corresponding carbocations in the presence of onium salt. The spectral, thermal and optical measurements confirmed a full combination of ATRP and PCP, which resulted in the formation of AB‐type block copolymers. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Removal of residual lignin of ethanol‐based organosolv pulp by an alkali extraction process
Authors: Zhang Meiyun , Xu Yongjian , Li Kecheng
Published: June 2007

Organosolv pulps usually have high kappa number. This research investigated an alkaline extraction method prior to bleaching for reducing the kappa number of organosolv pulp. Ethanol wheat straw pulp with a kappa number of 58.2 was extracted with 1% NaOH solution. The results show that the ethanol pulp has a large amount of lignin particles on the fiber surface. After 1 min alkali extraction, the kappa number of the ethanol pulp is reduced by 60%, to 22.2, and both the number and the size of the lignin particles on the fiber surface are significantly reduced. In comparison with a further ethanol washing/extraction, the alkali extraction is much more effective in terms of lignin removal. X‐ray photoelectron spectroscopy results show that a thin layer of lignin remained on the fiber surface after alkli extraction, but this did not reduce the internal bond strength. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Chain extension of polybutylene adipate and polybutylene succinate with adipoyl‐ and terephthaloyl‐biscaprolactamate
Authors: Zhao Jing Bo , Li Kai Yong , Yang Wan Tai
Published: June 2007

HO‐terminated polybutylene adipate (HO‐PBA‐OH) with molecular weight from 1040 to 3540 and HO‐terminated polybutylene succinate (HO‐PBS‐OH) with intrinsic viscosity of 0.37 dL/g were synthesized through melt condensation polymerization from adipic acid or succinic acid with excess of butanediol. Chain extension of HO‐PBA‐OH or HO‐PBS‐OH with adipoyl biscaprolactamate and terephthaloyl biscaprolactamate was carried out at 200–240°C under reduced pressure. At the optimal conditions, chain‐extended PBA with Mn up to 50,700, and Mw up to 125,700 was synthesized, and the chain‐extended PBS with intrinsic viscosity of 1.25 dL/g was obtained. Meanwhile, p‐toluenesulfonic acid, SnCl4 and zinc acetylacetonate catalyzed chain‐extending reaction of HO‐PBA‐OH and HO‐PBS‐OH was also studied. The chain‐extended polyesters were characterized by IR spectra, 1H‐NMR spectra, and differential scanning calorimetry (DSC). The chain extension proceeds through the elimination of caprolactam rings in the chain‐extenders, the adipoyl groups or the terephthaloyl groups couple the hydroxyl‐terminated polyesters together and make the molecular weight of PBA or PBS increased, whether the acid catalyst such as p‐toluenesulfonic acid was present or not. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Preparation and properties of PC/SAN alloy modified with styrene‐ethylene‐butylene‐styrene block copolymer
Authors: Yin Nianwei , Zhang Yinxi , Zhang Yong , Zhang Xiangfu , Zhou Wen
Published: June 2007

A polycarbonate (PC)/ poly (styrene‐co‐acrylonitrile) (SAN) alloy modified with styrene‐ethylene‐butylene‐styrene (SEBS) block copolymer was prepared and the influence of SEBS content, PC content, and types of modifier on Izod notched impact strength, tensile strength, flexural strength, and Vicat softening temperature was studied. The results showed that the addition of SEBS could obviously increase the Izod notched impact strength and the elongation at break and decrease the tensile and flexural strength and Vicat softening temperature. PC/SAN alloy modified with SEBS had better mechanical properties than the PC/SAN alloy modified with ABS. DSC analysis and SEM photographs revealed that the SEBS was not only distributed in the SAN phase but also distributed in PC phase in a PC/SAN/SEBS alloy while the ABS was mainly distributed in SAN phase in a PC/SAN/ABS alloy. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Catalytic hydrogenation of nitrile rubber using palladium and ruthenium complexes
Authors: Schulz Gracélie A. S. , Comin Edson , de Souza Roberto F.
Published: June 2007

The catalytic hydrogenation of acrylonitrile‐butadiene copolymer (nitrile rubber, NBR) using Pd(OAc)2 or RuCl2(PPh3)3 catalysts has been investigated in order to produce a totally saturated nitrile rubber. The hydrogenation of NBR is effective with both catalysts and achieved total conversion under the appropriate reaction conditions. In the case of palladium the effects of reaction parameters such as reaction temperature, pressure, time, catalyst concentration, and NBR concentration have been investigated. Even though both ruthenium‐ and palladium‐based catalysts are effective in the production of HNBR, the former requires harsh reaction conditions and has the drawback of gel formation under high conversion, motivating the migration to RuCl2 (PPh3)3 as an alternative catalyst. The degree of hydrogenation was determined by IR and NMR spectroscopy. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Synthesis and characterization of novel poly(arylene ether)s based on 9,10‐bis‐(4‐fluoro‐3‐trifluoromethylphenyl) anthracene and 2,7‐bis‐(4‐fluoro‐3‐trifluoromethylphenyl) fluorene
Authors: Salunke Arun K. , Ghosh Anindita , Banerjee Susanta
Published: June 2007

Two new bisfluoro monomers 9,10‐bis‐(4‐fluoro‐3‐trifluoromethylphenyl) anthracene and 2,7‐bis‐(4‐fluoro‐3‐trifluoromethylphenyl) fluorene have been synthesized by the cross‐coupling reaction of 2‐fluoro‐3‐trifluoromethyl phenyl boronic acid with 9,10‐dibromo anthracene and 2,7‐dibromo fluorine, respectively. These two bisfluoro compounds were used to prepare several poly(arylene ether)s by aromatic nucleophilic displacement of fluorine with various bisphenols; such as bisphenol‐A, bisphenol‐6F, bishydroxy biphenyl, and 9,9‐bis‐(4‐hydroxyphenyl)‐fluorene. The products obtained by displacement of the fluorine atoms exhibits weight‐average molar masses up to 1.5 ×105 g mol−1 and number average molecular weight up to 6.8 × 104 g mol−1 in GPC. These poly(arylene ether)s show very high thermal stability even up to 490°C for 5% weight loss occurring at this temperature in TGA in synthetic air and showed glass transition temperature observed up to 310°C. All the polymers are soluble in a wide range of organic solvents, e.g., CHCl3, THF, NMP, and DMF. Films cast from DMF solution are brittle in nature. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Ursachen der Blasenbildung bei Reaktionsharzbeschichtungen auf Beton – Welche Rolle spielt die Osmose?
Authors: Wolff Lars , Raupach Michael , Hailu Kidist
Published: June 2007

Polymere Beschichtungen werden heutzutage standardmäßig für verschiedene Bauwerke eingesetzt. Sie dienen entweder der Sicherstellung der Dauerhaftigkeit der Konstruktion z. B. als Schutz vor eindringenden Chloriden aus winterlichem Tausalzeinfluss oder sind für die Nutzung des Bauwerks z. B. bei der Halbleiterproduktion in Reinsträumen unersetzbar.

Das Phänomen der “osmotischen Blasenbildung” bei derartigen Beschichtungen ist seit Anfang der 1970er Jahre bekannt. Unmittelbar nach Auftrag der Beschichtung oder einige Wochen bis Monate später können i. d. R. flüssigkeitsgefüllte Blasen in der Beschichtung von einigen Millimeter bis Zentimeter Durchmesser entstehen. Bisher ging man bei der Ursache dieser Blasen von osmotischen Vorgängen aus, bei denen sich infolge einer semipermeablen Membran in der Kontaktzone Beton – Grundierung ein osmotischer Druck aufbauen kann.

In einem von der Deutschen Forschungsgemeinschaft DFG geförderten Forschungsvorhaben zu den Mechanismen dieser Blasenbildung konnte anhand von Laborversuchen und Analysen von Schadensfällen gezeigt werden, dass die Kontaktzone Beton – Grundierung im Bereich vorhandener Blasen für die wesentlichen Inhaltsstoffe der Blasenflüssigkeiten permeabel ist. Gleichzeitig zeigen Untersuchungen, dass Wechselwirkungen zwischen dem flüssig aufgetragenen Epoxidharz und dem mineralischen Untergrund zu Fehlstellen und Vernetzungsstörungen innerhalb der Epoxidharzgrundierung führen können. Die für die Blasenbildung erforderlichen Drücke basieren daher nicht, wie bisher angenommen, auf osmotischen Vorgängen sondern vielmehr auf im Wesentlichen feuchte‐ und temperaturbeeinflussten Druckschwankungen innerhalb des Kapillarporengefüges des Betons.
Tragfähigkeit von Spannbeton‐Fertigdecken auf biegeweichen Auflagern
Authors: Schnell Jürgen , Ackermann Florian P. , Nitsch Andreas
Published: June 2007

Spannbeton‐Fertigdecken, die in Deutschland unter der Bezeichnung “Spannbeton‐Hohlplatten” durch allgemeine bauaufsichtliche Zulassungen geregelt sind, werden in rund 100 m langen Produktionsbahnen mit Spannstahl ohne weitere Betonstahlbewehrung hergestellt. Bei der Begrenzung der Plattenbreite auf 1,20 m kann die Querbewehrung entfallen. Während die Querverteilung geregelt ist, stellt sich bei der Auflagerung auf biegeweichen Trägern und Unterzügen die Frage nach der Querkrafttragfähigkeit in Zusammenhang mit einer möglichen Rissbildung durch die aufgezwungen Verformungen. Um die genauen Versagensmechanismen und den Einfluss auf Tragfähigkeit zu untersuchen, wurde an der TU Kaiserslautern, Fachgebiet Massivbau und Baukonstruktion, ein Großversuch durchgeführt.