bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)
Authors: Ejlertsen Bent , Mouridsen Henning T. , Langkjer Sven T. , Andersen Jorn , Sjöström Johanna , Kjaer Mogens
Published: June 2004

Purpose

To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer.

Patients and Methods

A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses.

Results

Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms.

Conclusion

Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.
Capecitabine Plus Paclitaxel As Front-Line Combination Therapy for Metastatic Breast Cancer: A Multicenter Phase II Study
Authors: Gradishar William J. , Meza Luis A. , Amin Bipinkumar , Samid Dvorit , Hill Todd , Chen Yin-Miao , Lower Elyse E. , Marcom P. Kelly
Published: June 2004

Purpose

The goal of this multicenter, open-label phase II study was the clinical evaluation of combination therapy with the oral fluoropyrimidine capecitabine and the taxane paclitaxel in patients with metastatic breast cancer (MBC).

Patients and Methods

Forty-seven patients with MBC received oral capecitabine at 1,650 mg/m2/d (825 mg/m2 twice daily) on days 1 through 14, and intravenous infusion of paclitaxel at 175 mg/m2 on day 1 of each 21-day treatment cycle. Treatment continued until disease progression, intolerable toxicity, or patient's decision to discontinue. Patients (35 to 76 years old) had a median Karnofsky performance status of 90%. Forty-four patients (94%) received study treatment as first-line therapy for metastatic disease.

Results

Objective responses occurred in 24 (51%) patients; seven (15%) complete responses and 17 (36%) partial responses. Stable disease lasting 180 days or more was observed in nine (19%); the clinical response rate was 70%. Median duration of response was 12.6 months, median time to disease progression was 10.6 months, and median overall survival time was 29.9 months. The most common treatment-related adverse events, regardless of severity, were alopecia, hand-foot syndrome, nausea, and fatigue. Neutropenia (15%), alopecia (13%), and hand-foot syndrome (11%) were the only grade 3 or 4 treatment-related adverse events that occurred in more than 10% of patients.

Conclusion

The combination of capecitabine plus paclitaxel is a highly active and generally well-tolerated regimen for first-line treatment of MBC.
Differential Activation of Epidermal Growth Factor (EGF) Receptor Downstream Signaling Pathways by Betacellulin and EGF
Authors: Saito Tsugumichi , Okada Shuichi , Ohshima Kihachi , Yamada Eijiro , Sato Minoru , Uehara Yutaka , Shimizu Hiroyuki , Pessin Jeffrey E. , Mori Masatomo
Published: June 2004

To determine the downstream signaling pathways regulated by betacellulin (BTC) in comparison with epidermal growth factor (EGF), we used Chinese hamster ovary cells overexpressing the human EGF receptor (ErbB1/EGFR). The overall time-dependent activation of EGFR autophosphorylation was identical in cells treated with 1 nm BTC or 1.5 nm EGF. Analysis of site-specific EGFR phosphorylation demonstrated that the BTC and EGF tyrosine phosphorylation of Y1086 was not significantly different. In contrast, the autophosphorylation of Y1173 was markedly reduced in BTC-stimulated cells, compared with EGF stimulation that directly correlated with a reduced BTC stimulation of Shc tyrosine phosphorylation, Ras, and Raf-1 activation. On the other hand, Y1068 phosphorylation was significantly increased after BTC stimulation, compared with EGF in parallel with a greater extent of Erk phosphorylation. Expression of a dominant interfering MEK kinase 1 (MEKK1) and Y1068F EGFR more efficiently blocked the enhanced Erk activation by BTC, compared with EGF. Interestingly BTC had a greater inhibitory effect on apoptosis, compared with EGF, and expression of Y1068F EGFR abolished this enhanced inhibitory effect. Together, these data indicated that although BTC and EGF share overlapping signaling properties, the ability of BTC to enhance Erk activation occurs independent of Ras. The increased BTC activation results from a greater extent of Y1068 EGFR tyrosine phosphorylation and subsequent increased recruitment of the Grb2-MEKK1 complex to the plasma membrane, compared with EGF stimulation. The increased Erk activation by BTC associated with antiapoptotic function.
Ovarian Follicle Development Requires Smad3
Authors: Tomic Dragana , Miller Kimberly P. , Kenny Hilary A. , Woodruff Teresa K. , Hoyer Patricia , Flaws Jodi A.
Published: June 2004

Smad3 is an important mediator of the TGFβ signaling pathway. Interestingly, Smad3-deficient (Smad3−/−) mice have reduced fertility compared with wild-type (WT) mice. To better understand the molecular mechanisms underlying the reduced fertility in Smad3−/− animals, this work tested the hypothesis that Smad3 deficiency interferes with three critical aspects of folliculogenesis: growth, atresia, and differentiation. Growth was assessed by comparing the size of follicles, expression of proliferating cell nuclear antigen, and expression of cell cycle genes in Smad3−/− and WT mice. Atresia was assessed by comparing the incidence of atresia and expression of bcl-2 genes involved in cell death and cell survival in Smad3−/− and WT mice. Differentiation was assessed by comparing the expression of FSH receptor (FSHR), estrogen receptor (ER) α, ERβ, and inhibin α-, βA-, and βB-subunits in Smad3−/− and WT mice. Because growth, atresia, and differentiation are regulated by hormones, estradiol, FSH, and LH levels were compared in Smad3−/− and WT mice. Moreover, because alterations in folliculogenesis can affect the ability of mice to ovulate, the number of corpora lutea and ovulated eggs in response to gonadotropin treatments were compared in Smad3−/− and WT animals. The results indicate that Smad3 deficiency slows follicle growth, which is characterized by small follicle diameters, low levels of proliferating cell nuclear antigen, and low expression of cell cycle genes (cyclin-dependent kinase 4 and cyclin D2). Smad3 deficiency also causes atretic follicles, degenerated oocytes, and low expression of bcl-2. Furthermore, Smad3 deficiency affects follicular differentiation as evidenced by decreased expression of ERβ, increased expression of ERα, and decreased expression of inhibin α-subunits. Smad3 deficiency causes low estradiol and high FSH levels. Finally, Smad3−/− ovaries have no corpora lutea, and they do not ovulate after ovulatory induction with exogenous gonadotropins. Collectively, these data provide the first evidence that reduced fertility in Smad3−/− mice is due to impaired folliculogenesis, associated with altered expression of genes that control cell cycle progression, cell survival, and cell differentiation. The findings that Smad3−/− follicles have impaired growth, increased atresia, and altered differentiation in the presence of high FSH levels, normal expression of FSHR, and lower expression of cyclin D2, suggest a possible interaction between Smad3 and FSH signaling downstream of FSHR in the mouse ovary.
The Role of Uncoupling Protein 1 in the Metabolism and Adiposity of RIIβ-Protein Kinase A-Deficient Mice
Authors: Nolan Michael A. , Sikorski Maria A. , McKnight G. Stanley
Published: June 2004

Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.
Desmoplakin is required for microvascular tube formation in culture
Authors: Zhou Xuan , Stuart August , Dettin Luis E. , Rodriguez Gisela , Hoel Bonnie , Gallicano G. Ian
Published: June 2004

Desmoplakin (DP) is a key component of cellular adhesion junctions known as desmosomes; however, recent investigations have revealed a novel location for DP in junctions separate from desmosomes termed complexus adherens junctions. These junctions are found at contact sites between endothelial cells that line capillaries. Few studies have focused on the function of DP in de novo capillary formation (vasculogenesis) and branching (angiogenesis) during tumorigenesis, embryonic development, cardiovascular development or wound healing. Only recently have investigations begun to determine the effect the loss of DP has on capillaries during embryogenesis (i.e. in DP–/– mice). Evidence shows that the loss of desmoplakin in vivo results in leaky capillaries and/or capillary malformation. Consequently, the goal of this study was to determine the function of DP in complexus adherens junctions during capillary formation. To accomplish this goal, we used siRNA technology to knock down desmoplakin expression in endothelial cells before they were induced to form microvascular tubes on matrigel. DP siRNA treated cells sent out filopodia and came in close contact with each other when plated onto matrigel; however, in most cases they failed to form tubes as compared with control endothelial cells. Interestingly, after siRNA degradation, endothelial cells were then capable of forming microvascular tubes. In depth analyses into the function of DP in capillary formation were not previously possible because the tools and experimental approaches only recently have become available (i.e. siRNA). Consequently, fully understanding the role of desmoplakin in capillary formation may lead to a novel approach for inhibiting vasculo- and angiogenesis in tumor formation.
Rab11 regulates the recycling and lysosome targeting of β2-adrenergic receptors
Authors: Moore Robert H. , Millman Ellen E. , Alpizar-Foster Estrella , Dai Wenping , Knoll Brian J.
Published: June 2004

The pericentriolar recycling endosome (RE) may be an alternative compartment through which some β2-adrenergic receptors (β2ARs) recycle from early endosomes to the cell surface during prolonged exposure to agonist. For the transferrin receptor, CXCR2, and the M4-muscarinic acetylcholine receptor, trafficking through the RE and receptor recycling is regulated by the small GTPase rab11. The precise role of the RE and rab11 in regulating the cellular trafficking of the β2AR is not understood. We therefore monitored trafficking of β2ARs in HEK293 cells following the modulation of rab11 activity. Expression of a rab11 mutant deficient in GTP binding (as a fusion between enhanced green fluorescent protein (EGFP) and the rab11S25N mutant) significantly slowed receptor recycling to the cell surface from dispersed transferrin-positive peripheral vesicles following a brief exposure to agonist. The agonist was applied at a time when receptors have undergone only one or two rounds of endocytosis and recycling. In cells overexpressing wild-type rab11, β2ARs localized to a rab11-positive compartment and the rate of β2AR recycling to the cell surface was reduced, but only after prolonged exposure to agonist and multiple rounds of receptor endocytosis and recycling. This effect was associated with impaired β2AR trafficking to lysosomes and receptor proteolysis, whereas the sorting of low-density lipoprotein from transferrin-positive vesicles to late endosomes and lysosomes was not affected. These data highlight a pivotal role for rab11 in regulating the traffic of a G protein-coupled receptor at the level of the RE, where modulation of rab11 activity dictates the balance between receptor recycling and downregulation during prolonged exposure to agonist.
Synaptotagmin V and IX isoforms control Ca2+-dependent insulin exocytosis
Authors: Iezzi Mariella , Kouri Georgia , Fukuda Mitsunori , Wollheim Claes B.
Published: June 2004

Synaptotagmin (Syt) is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic β-cell is an example of a Ca2+-dependent secretory process. Previous studies have yielded conflicting results as to which Syt isoform is present on the secretory granules in the native β-cell. Here we show by western blotting and RT-PCR analysis, the presence of both Syt V and Syt IX in rat pancreatic islets and in the clonal β-cell line INS-1E. The subcellular distribution of the two Syt isoforms was assessed by confocal microscopy and by sedimentation in a continuous sucrose density gradient in INS-1E cells. These experiments show that both proteins colocalize with insulin-containing secretory granules but are absent from synaptic-like microvesicles. Further immunofluorescence studies performed in primary pancreatic endocrine cells revealed that Syt V is present in glucagon-secreting α-cells, whereas Syt IX is associated with insulin granules in β-cells. Transient overexpression of Syt V and Syt IX did not alter exocytosis in INS-1E cells. Finally, reduction of the expression of both Syt isoforms by RNA interference did not change basal secretion. Remarkably, hormone release in response to glucose was selectively and strongly reduced, indicating that Syt V and Syt IX are directly involved in the Ca2+-dependent stimulation of exocytosis.
Comparison of Natural Product Use Between Primary Care and Nephrology Patients
Authors: Grabe Darren W , Garrison Gina Daubney
Published: June 2004

BACKGROUND:

The use of natural products is increasing, but healthcare professionals may underestimate the use of these agents by patients. It is unknown whether natural product use differs between primary care and specialty clinic patients, such as those in a nephrology clinic.

OBJECTIVE:

To compare patterns of natural product use between primary care and nephrology clinic patients.

METHODS:

One thousand adult patients from each clinic were randomly mailed an anonymous questionnaire to determine current and past use of natural products.

RESULTS:

A total of 491 surveys were returned, for an overall response rate of 26% (25% primary care; 28% nephrology clinic). Current use of natural products was similar between the primary care and nephrology groups (34% vs 29%, respectively; p = NS). Primary care patients were more likely to have taken a natural product in the past (57% vs 45%; p < 0.05); Echinacea was the most common product taken by those patients (26%). Green tea was the most common natural product taken by nephrology clinic patients (18%). More primary care patients took Echinacea compared with nephrology clinic patients (26% vs 12%; p < 0.01). Adverse reactions led to discontinuation of the natural product in 7% of respondents.

CONCLUSIONS:

Active use of natural products was similar between the survey respondents. Documentation and monitoring of natural product use by healthcare professionals working with primary care and nephrology clinic patients are recommended.
Intensive Insulin Therapy for Critically III Patients
Authors: Lewis Kelly S , Kane-Gill Sandra L , Bobek Mary Beth , Dasta Joseph F
Published: June 2004

OBJECTIVE:

To evaluate the clinical outcomes of glycemic control of intensive insulin therapy and recommend its place in the management of critically ill patients.

DATA SOURCES:

Searches of MEDLINE (1966—March 2004) and Cochrane Library, as well as an extensive manual review of abstracts were performed using the key search terms hyperglycemia, insulin, intensive care unit, critically ill, outcomes, and guidelines and algorithms.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes.

DATA SYNTHESIS:

Mortality among patients with prolonged critical illness exceeds 20%, and most deaths are attributable to sepsis and multisystem organ failure. Hyperglycemia is common in critically ill patients, even in those with no history of diabetes mellitus. Maintaining normoglycemia with insulin in critically ill patients has been shown to improve neurologic, cardiovascular, and infectious outcomes. Most importantly, morbidity and mortality are reduced with aggressive insulin therapy. This information can be implemented into protocols to maintain strict control of glucose.

CONCLUSIONS:

Use of insulin protocols in critically ill patients improves blood glucose control and reduces morbidity and mortality in critically ill populations. Glucose levels in critically ill patients should be controlled through implementation of insulin protocols with the goal to achieve normoglycemia, regardless of a history of diabetes. Frequent monitoring is imperative to avoid hypoglycemia.
Approximate Equivalent Rosuvastatin Doses for Temporary Statin Interchange Programs
Authors: Kendrach Michael G , Kelly-Freeman Maisha
Published: June 2004

OBJECTIVE:

To estimate approximate doses of rosuvastatin equivalent to the other hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for a temporary substitution program.

DATA SOURCES:

A literature search was conducted to locate clinical trials directly comparing rosuvastatin with other statins that evaluated the magnitude of cholesterol lowering.

DATA SYNTHESIS:

The mean low-density lipoprotein and total cholesterol values from the clinical trials were assessed. Study results indicate that rosuvastatin is not equivalent to other statins on a milligram-to-milligram basis.

CONCLUSIONS:

Rosuvastatin appears to be at least 2 and 4 times as potent as atorvastatin and simvastatin, respectively, and at least 8 times as potent as pravastatin and lovastatin.
The Paperless Labeling Initiative: A Proof-of-Concept Study
Authors: Ruchalski Charles
Published: June 2004

BACKGROUND:

Traditional paper professional package inserts (PPIs) are used on a daily basis by a variety of healthcare providers to locate and disseminate drug information. Unfortunately, paper PPIs are sometimes not accessible to the healthcare provider, appear unreadable due to varied font sizes, and are often considered not to be user-friendly. In December 2000, the Food and Drug Administration proposed regulations that would revise the format of PPIs.

OBJECTIVE:

To determine whether electronic delivery of PPI information is achievable in community pharmacy practice settings.

METHODS:

Electronic PPIs are an alternative means of delivering this information. This 12-week proof-of-concept study evaluated the Health Information Designs/Thomson Healthcare and Etreby Computer Company for electronic delivery of PPIs in 6 chain and 4 independent community pharmacies, with 5 pharmacies evaluating each system. Participating pharmacists were asked 9 questions designed to determine the feasibility of implementing electronic PPI delivery, as well as pharmacist satisfaction with each system.

RESULTS:

Pharmacists deemed both systems to be accessible and user-friendly. Pharmacists from both groups felt that the electronic PPIs were challenging to read and that printing took too long.

CONCLUSIONS:

Future studies in a more diverse selection of dispensing sites, including pharmacies (community and hospital based), clinics, and physician practices, need to be performed to maximize the use of electronic PPIs.
Bevacizumab: An Angiogenesis Inhibitor with Efficacy in Colorectal and Other Malignancies
Authors: Zondor Stacey D , Medina Patrick J
Published: June 2004

OBJECTIVE:

To review the pharmacology, pharmacokinetics, and pivotal clinical trials for bevacizumab, emphasizing its use in colorectal cancer.

DATA SOURCES:

A PubMed/MEDLINE search was conducted (1966—April 2004) using the following terms: bevacizumab, Avastin, anti-VEGF, anti-angiogenesis, and colorectal cancer. Additional data sources included meeting abstracts, bibliographies from identified articles, and information from the manufacturer.

STUDY SELECTION AND DATA EXTRACTION:

Preclinical and clinical trials that used bevacizumab for the treatment of colorectal cancer and other malignancies were selected from the data sources. All published, randomized clinical trials evaluating bevacizumab in colorectal cancer were included in this review.

DATA SYNTHESIS:

Despite advances in chemotherapy, current therapeutic options for metastatic disease provide only temporary benefit for most patients. Bevacizumab is the first anti-cancer agent shown to provide benefit for patients with cancer by inhibiting angiogenesis. Bevacizumab has shown significant activity in the treatment of many cancers, including metastatic colorectal cancer. When used in combination with fluorouracil-based chemotherapy, bevacizumab improves overall response rates, time to progression, and survival in patients with metastatic colorectal cancer. Common toxicities associated with bevacizumab include hypertension, bleeding episodes, and thrombotic events.

CONCLUSIONS:

Although clinical knowledge on the effectiveness of bevacizumab is limited, early data indicate that it is a promising agent, with a novel mechanism of action, for patients with metastatic cancer, including colorectal cancer.
Rhabdomyolysis Caused by Commiphora mukul, a Natural Lipid-Lowering Agent
Authors: Bianchi Antonio , Cantù Paola , Firenzuoli Fabio , Mazzanti Gabriela , Menniti-Ippolito Francesca , Raschetti Roberto
Published: June 2004

OBJECTIVE:

To report a case of rhabdomyolysis caused by Commiphora mukul, a natural lipid-lowering agent.

CASE SUMMARY:

A 55-year-old man was taking an extract of C. mukul 300 mg 3 times daily to lower his cholesterol level. He developed rhabdomyolysis with hemoglobinuria after 2 weeks of treatment. Laboratory tests showed creatine kinase 144 600 IU/L (reference range 24–195), myoglobin >3000 ng/mL (28–72), lactate dehydrogenase 7157 IU/L (230–460), aspartate aminotransferase 1115 IU/L (10–35), and alanine aminotransferase 205 IU/L (10–35). Analysis of a urine sample was 2+ positive for hemoglobin. All parameters returned to normal after the herbal preparation was discontinued.

DISCUSSION:

The Naranjo probability scale indicates C. mukul as the possible cause of rhabdomyolysis in our patient. Drug-induced rhabdomyolysis is an established but rare adverse effect of high doses of cholesterol-lowering agents (statins) or interactions between drugs (eg, statins and fibrates). As of May 28, 2004, to our knowledge, this is the first reported case of rhabdomyolysis following C. mukul ingestion.

CONCLUSIONS:

Our report describes a case of rhabdomyolysis possibly caused by C. mukul and underlines the need for active surveillance of natural products.
Selective Serotonin-Reuptake Inhibitors for the Treatment of Hot Flashes
Authors: Koch Yvonne De Sloover , Ernst Michael E
Published: June 2004

OBJECTIVE:

To review the literature evaluating the use of selective serotonin-reuptake inhibitors (SSRIs) for the treatment of hot flashes.

DATA SOURCES:

Biomedical literature was accessed through MEDLINE (1966—June 2003), MD Consult, and references of reviewed articles. Key search terms used were hot flashes, vasomotor symptoms, antidepressants, and SSRIs.

DATA SYNTHESIS:

Recent evidence from the Women's Health Initiative precludes the use of traditional hormonal therapy in some women. Nonhormonal therapies are possible options, but conflicting evidence of efficacy exists.

CONCLUSIONS:

Although further studies are warranted, preliminary data suggest that SSRIs are generally modestly successful in reducing the frequency and severity of hot flashes.
Gemifloxacin: A New Fluoroquinolone Approved for Treatment of Respiratory Infections
Authors: Yoo Bong K , Triller Darren M , Yong Chul-Soon , Lodise Thomas P
Published: June 2004

OBJECTIVE:

To evaluate the microbiology, pharmacokinetic parameters, drug interactions, and results of the available clinical trials of gemifloxacin for the treatment of community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis (AECB).

DATA SOURCES:

MEDLINE (1966–September 2003) was searched for primary and review articles. Data from the manufacturer were also included. Key words included adverse effects, clinical trials, drug interactions, gemifloxacin, and pharmacokinetic parameters.

STUDY SELECTION AND DATA EXTRACTION:

All articles and product labeling concerning gemifloxacin, a fluoroquinolone antibiotic recently approved by the Food and Drug Administration for treatment of CAP and AECB, were included for review.

DATA SYNTHESIS:

Compared with currently available fluoroquinolones, gemifloxacin demonstrated improved in vitro activity against Streptococcus pneumoniae (minimum inhibitory concentration for 90% eradication 0.03 μg/mL) and similar activity against gram-negative respiratory pathogens ( Haemophilus influenzae, Moraxella catarrhalis) and atypical pathogens such as Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. Gemifloxacin, consistent with other available fluoroquinolones, has insufficient activity against methicillin-resistant Staphylococcus aureus to allow clinical use for such infections. Gemifloxacin has adequate bioavailability and a favorable drug interaction profile. Gemifloxacin was comparable to commonly employed nonfluoroquinolone regimens for treatment of CAP and AECB, although the studies were designed to demonstrate equivalence. Gemifloxacin once daily for 5–7 days was well tolerated in controlled and uncontrolled clinical studies. Available clinical data, however, are insufficient to draw clinical or toxicologic distinctions between gemifloxacin and other fluoroquinolones.

CONCLUSIONS:

Gemifloxacin may be a suitable choice for empiric treatment of CAP or AECB. However, due to the significant history of fluoroquinolone-induced hepatic failure and dermatologic complications, the use of this drug should be closely monitored.
Nonsteroidal Antiinflammatory Drug Use among Patients with GI Bleeding
Authors: Dominick Kelli L , Bosworth Hayden B , Jeffreys Amy S , Grambow Steven C , Oddone Eugene Z , Horner Ronnie D
Published: June 2004

BACKGROUND:

Previous studies have suggested that recommended gastroprotective strategies such as gastroprotective agents (GPAs) and cyclooxygenase (COX) 2 inhibitors may be underutilized among individuals at risk for nonsteroidal antiinflammatory drug (NSAID)-related gastrointestinal (GI) bleeding.

OBJECTIVE:

To examine the use of traditional NSAIDs, COX-2 inhibitors, and GPAs among patients recently hospitalized for GI bleeding.

METHODS:

This was a retrospective cohort study of a national sample of 4338 veterans hospitalized for GI bleeding between January and June 1999. Prescription drug use was examined for 6 months following hospitalization. We examined relationships of subject characteristics (age, race, gender, geographic region, diagnosis of arthritis) to prescription of a high-risk NSAID, defined as a traditional NSAID but no GPA within 60 days before or after the NSAID.

RESULTS:

Approximately 20% of subjects were prescribed an NSAID or COX-2 inhibitor, but only 5% were prescribed a traditional NSAID with no GPA. In a multivariable analysis, subjects <65 years of age and those with arthritis were more likely to be prescribed a traditional NSAID without a GPA. No other subject characteristics were related to receipt of a high-risk prescription.

CONCLUSIONS:

In a national sample of veterans with a recent hospitalization for GI bleeding, high-risk NSAID prescriptions were uncommon. Underuse of gastroprotective strategies may be more common in patients with less recent GI bleeding—related hospitalization. Strategies to remind physicians and pharmacists to screen for GI risk factors may help to sustain appropriate prescribing and reduce NSAID-related adverse events.
Estimate of Uncertainty of Measurement from a Single-Laboratory Validation Study: Application to the Determination of Lead in Blood
Authors: Patriarca Marina , Castelli Marco , Corsetti Federica , Menditto Antonio
Published: June 2004

Background: Lead is an environmental pollutant, and human exposure is assessed by monitoring lead concentrations in blood. Because the main source of environmental exposure has been the use of leaded gasoline, its phase-out has led to decreased lead concentrations in the general population. Therefore, validated analytical methods for the determination of lower lead concentrations in blood (<150 μg/L) are needed. In addition, new ISO standards require that laboratories determine and specify the uncertainty of their results.

Methods: We validated a method to determine lead in blood at concentrations up to 150 μg/L by electrothermal atomic absorption spectrometry with Zeeman background correction according to EURACHEM guidelines. Blood samples were diluted (1:1 by volume) with 2 mL/L Triton X-100. NH4H2PO4 (5 g/L) and Mg(NO3)2 (0.5 g/L) were used as modifiers. Matrix-matched standards were used for calibration.

Results: We determined the limits of detection (3.1 μg/L) and quantification (9.4 μg/L). Repeatability and intermediate imprecision within the range 35–150 μg/L were <5.5% and <6.0%, respectively. We assessed trueness by use of certified reference materials, by recovery tests, and by comparison with target values of other reference materials (candidate external quality assessment samples). The expanded uncertainty ranged from 20% to 16% (with a confidence level of 95%) depending on concentration.

Conclusions: This study provides a working example of the estimate of uncertainty from method performance data according to the EURACHEM/CITAC guidelines. The estimated uncertainty is compatible with quality specifications for the analysis of lead in blood adopted in the US and the European Union.
Denaturing HPLC Profiling of the ABCA4 Gene for Reliable Detection of Allelic Variations
Authors: Stenirri Stefania , Fermo Isabella , Battistella Stefania , Galbiati Silvia , Soriani Nadia , Paroni Rita , Manitto Maria Pia , Martina Elisabetta , Brancato Rosario , Allikmets Rando , Ferrari Maurizio , Cremonesi Laura
Published: June 2004

Background: Mutations in the retina-specific ABC transporter (ABCA4) gene have been associated with several forms of macular degenerations. Because the high complexity of the molecular genotype makes scanning of the ABCA4 gene cumbersome, we describe here the first use of denaturing HPLC (DHPLC) to screen for ABCA4 mutations.

Methods: Temperature conditions were designed for all 50 exons based on effective separation of 83 samples carrying 86 sequence variations and 19 mutagenized controls. For validation, samples from 23 previously characterized Stargardt patients were subjected to DHPLC profiling. Subsequently, samples from a cohort of 30 patients affected by various forms of macular degeneration were subjected to DHPLC scanning under the same conditions.

Results: DHPLC profiling not only identified all 132 sequence alterations previously detected by double-gradient denaturing gradient gel electrophoresis but also identified 5 sequence alterations that this approach had missed. Moreover, DHPLC scanning of an additional panel of 30 previously untested patients led to the identification of 26 different mutations and 29 polymorphisms, accounting for 203 sequence variations on 29 of the 30 patients screened. In total, the DHPLC approach allowed us to identify 16 mutations that had never been reported before.

Conclusions: These results provide strong support for the use of DHPLC for molecular characterization of the ABCA4 gene.
Residual Categories and Disciplinary Knowledge: Personal Identity in Sociological and Forensic Investigations
Authors: Williams Robin
Published: June 2004

A central feature of the development of sociological knowledge is the formulation and use of “descriptive frames of reference” within which theoretical and empirical work may be critically assessed. This article considers the way in which one such frame of reference—that developed by Erving Goffman to represent the variety of human science understandings of the nature of identity in social interaction—distinguished between “personal,” “social,” and “self” identity. The relative neglect of the first of these three categorizations is noted. Following Garfinkel's suggestions for the “respecification” of social analysis, this article suggests the usefulness of an approach to the neglected issue of personal identity that suspends theoretical stipulation about an abstract noun in favor of an ethnographic study of a particular occupational group—forensic investigators—for whom an orientation to personal identities is a recurrent accountable practical concern.
The Potential Contributions of Quantitative Research to Symbolic Interactionism
Authors: Ulmer Jeffery T. , Wilson Mindy S.
Published: June 2004

Symbolic interactionism is often mischaracterized as a perspective that rejects quantitative research. We argue that the rich conceptual tradition of symbolic interactionism allows for the use of quantitative data and statistical analysis within a pragmatist epistemology and that this is desirable, especially in conjunction with qualitative data. We discuss types of quantitative data and their appropriate uses and then describe types of contemporary multivariate statistical methods and what they offer. To illustrate these data and analytic techniques, we draw from examples in our area of specialization, criminology, and from our own quantitative work. Researchers can use quantitative data and methods in the service of six core symbolic interactionist concerns—meaning, variation, comparisons, situations, contexts, and probability—and we contend that quantification and statistics pose no threat to the interactionist perspective. In fact, the principled, critical use of quantitative research can enhance it.
Situational Analyses: Grounded Theory Mapping After the Postmodern Turn
Authors: Clarke Adele E.
Published: June 2004

To better address differences and complexities of social life articulated through the postmodern turn, grounded theory is being regenerated and updated. Based on Strauss's ecological frameworks in his social worlds and arenas theory, I offer situational maps and analyses as innovative supplements to the basic social process analyses characteristic of traditional grounded theory. There are three kinds of analytic maps: maps of situations including all the key human and nonhuman elements, maps of social worlds and arenas, and maps of positionality along salient analytic axes. This article introduces all three kinds of maps and explicates one—situational maps—as a means of coherently elucidating and analyzing some of the complexities and instabilities of social life.
Grounded Neural Networking: Modeling Complex Quantitative Data
Authors: Castellani Brian , Castellani John , Spray S. Lee
Published: June 2004

The latest advances in artificial intelligence software (neural networking) have finally made it possible for qualitative researchers to apply the grounded theory method to the study of complex quantitative databases in a manner consistent with the postpositivistic, neopragmatic assumptions of most symbolic interactionists. The strength of neural networking for the study of quantitative data is twofold: it blurs the boundaries between qualitative and quantitative analysis, and it allows grounded theorists to embrace the complexity of quantitative data. The specific technique most useful to grounded theory is the Self‐Organizing Map (SOM). To demonstrate the utility of the SOM we (1) provide a brief review of grounded theory, focusing on how it was originally intended as a comparative method applicable to both quantitative and qualitative data; (2) examine how the SOM is compatible with the traditional techniques of grounded theory; and (3) demonstrate how the SOM assists grounded theory by applying it to an example based on our research.
Beyond Indigenous Authenticity: Reflections on the Insider/Outsider Debate in Immigration Research
Authors: Kusow Abdi M.
Published: June 2004

The insider/outsider debate in field research has recently been identified as one of the more important areas of needed research in immigration scholarship. My fieldwork as a native ethnographer among Somali immigrants to Canada is used to further that argument by showing the insatiability of categories such as native ethnographers and that the insider/outsider roles are products of the particular situation in which a given fieldwork takes place and not from the status characteristics per se of the researcher.
Muted Masculinity as an Outsider Strategy: Gender Sharing in Ethnographic Work with Wives of Professional Athletes
Authors: Ortiz Steven M.
Published: June 2004

Using findings from a study of the world of the wives of professional athletes, this article explores the complex motivations for and displays of trust, rapport, and group acceptance during ethnographic research. Episodic exchanges between a male ethnographer and female collaborators revealed subtle issues of gender and perceived relative worth. This article proposes the outsider strategy of “muted masculinity” as a means of exploring ethnographic issues in which the boundaries between insiders and outsiders are uncertain.
Mutual Interests, Different Lenses: Current Neuroscience and Symbolic Interaction
Authors: Franks David D.
Published: June 2004

As reflective thinkers, symbolic interactionists may well be curious about the organ with which we think. Leading neuroscientists are quite aware that a working brain depends on other brains. This article considers selected neuroscience approaches to topics traditionally addressed by symbolic interactionists including some confirmations, refinements, and challenges from current neuroscience. Confirmations support features of Mead's “objective reality of perspectives” and a relational epistemology, the inevitability of ad hoc “accounts,” self‐consciousness as behavioral control, and “self unity” as constantly re‐created illusion. Divergence between neuroscience and symbolic interaction mainly involves new evidence for the importance of unconscious cognition, emotion, and memory in shaping human behavior. The rooting of cognitive and perceptual processes in motor activity challenges the extremes of the “linguistic turn.” Refinement involves reasons for attending to the embodied salience of thoughts produced by “somatic markers” rather than mere content.
Biological Determinism and Symbolic Interaction: Hereditary Streams and Cultural Roads
Authors: Dingwall Robert , Nerlich Brigitte , Hillyard Samantha
Published: June 2004

This article discusses current claims to have demonstrated a biological basis for elements of human behavior. It argues that many of these are seriously flawed by their misunderstandings of the nature of culture and social interaction, which leads to the adoption of an inappropriate realist epistemology. These issues were extensively debated during the late nineteenth and early twentieth century when the intellectual and institutional boundaries between the social and biological sciences were more fluid. The arguments of that period about the role of “instinct” in human behavior are important resources for responding to the recent revival of biological determinism. As defined by Blumer and Strauss, however, symbolic interactionism has moved away from its engagement with biology. This article argues for reengagement and for a reappraisal of the historical resources available to sociologists in sifting the “imperialist” claims of biology while acknowledging the importance of embodiment as a constraint on social constructionism.
The Politics of Presentation: Goffman and Total Institutions
Authors: Becker Howard S.
Published: June 2004

Erving Goffman's essay on total institutions exemplifies his solution to a major problem in the presentation of social science thinking and results: how can we describe concrete social phenomena without using the descriptive terms already in use in the organization studied? Existing terminology embodies the perspectives of participants in the organization and so accepts all of those people's conventional judgments. This makes it impossible to isolate a class of similar social objects about which generalizations can be made. Goffman avoided this trap by creating a neutral but specific technical language and by a rigorously comparative analysis.
Myocardial Infarction in Women: A Critical Appraisal of Gender Differences in Outcomes
Authors: Bell Dawn M. , Nappi Jean
Published: June 2004

In every year since 1984, cardiovascular disease has claimed the lives of more women than men. Data from randomized trials indicate that gender contributes to increased mortality after myocardial infarction independent of other risk factors, but additional confounding variables cannot be discounted. Data from registry databases indicate that women are less likely to receive medically proven therapies for myocardial infarction. Women experience more vague symptoms, which may account for underuse of effective therapies. In addition, they may benefit less from thrombolytic therapy than men. Increased use of thrombolytic therapy has resulted in a continued decrease in cardiovascular deaths for men, but not for women. It is unclear if this disparity is a result of inequitable access to therapy or decreased efficacy of these agents in women.
The Psychometric and Cardiac Effects of Pseudoephedrine in the Hyperbaric Environment
Authors: Taylor David McD. , O'Toole Kevin S. , Auble Thomas E. , Ryan Christopher M. , Sherman David R.
Published: June 2004

Study Objectives. To examine the psychometric and cardiac effects of pseudoephedrine at 1 and 3 atmospheres (atm) of pressure (0 and 66 feet of sea water, respectively), and to make recommendations about the agent's safety in the diving environment.

Design. Double‐blind, placebo‐controlled, crossover study.

Setting. Monoplace hyperbaric chamber of a university hospital.

Subjects. Thirty active divers (mean age 38 yrs).

Intervention. A bank of seven tests was used to assess cognitive function during four different simulated dive combinations: placebo‐1 atm, placebo‐3 atm, pseudoephedrine‐1 atm, and pseudoephedrine‐3 atm.

Measurements and Main Results. Heart rate and cardiac rhythm were recorded during all dives. Repeated‐measures analysis of variance was used to analyze the effects of pseudoephedrine, depth, and drug‐depth interaction. No significant, independent effects of pseudoephedrine were seen on any of the seven psychometric test scores (p<0.05), although the drug tended to increase anxiety scores (p=0.092). Depth resulted in a significant increase in anxiety scores (p=0.021) and a significant decrease in verbal fluency test scores (p=0.041); it had no significant effects on the other five psychometric tests (p>0.05). Pseudoephedrine caused a significant increase (p=0.036) in mean heart rate, and depth caused a significant decrease (p=0.013). Neither pseudoephedrine nor depth affected cardiac rhythm.

Conclusion. Pseudoephedrine does not cause significant alterations in psychometric performance at 3 atm of pressure that might increase the risk of diving. Depth causes significant adverse effects on anxiety levels and semantic memory at 3 atm. Pseudoephedrine and depth have significant but opposite effects on heart rate; although, these effects are unlikely to be clinically significant during diving. It is unlikely that pseudoephedrine adds significant risk to the diver.
The Psychometric and Cardiac Effects of Dimenhydrinate in the Hyperbaric Environment
Authors: Taylor David McD. , O'Toole Kevin S. , Auble Thomas E. , Ryan Christopher M. , Sherman David R.
Published: June 2004

Study Objectives. To examine the psychometric and cardiac effects of dimenhydrinate at 1 and 3 atmospheres (atm) of pressure (0 and 66 feet of sea water, respectively), and to make recommendations about the drug's safety in the diving environment.

Design. Double‐blind, placebo‐controlled, crossover study.

Setting. Monoplace hyperbaric chamber of a university hospital.

Subjects. Thirty active divers (mean age 38 yrs).

Interventions. A bank of seven tests was used to assess cognitive function during four different dive combinations: placebo‐1 atm, placebo‐3 atm, dimenhydrinate‐1 atm, and dimenhydrinate‐3 atm.

Measurements and Main Results. Heart rate and cardiac rhythm were recorded during all dives. Repeated‐measures multivariate analysis of variance was used to analyze the effects of dimenhydrinate, depth, and drug‐depth interaction. Dimenhydrinate resulted in a significant decrease in scores of mental flexibility (trail‐making, part B, p<0.05) but had no effect on scores in the six other psychometric tests (p>0.05). It had no effect on mean heart rate (p>0.05), although frequent unifocal ventricular ectopic beats occurred in two subjects after ingestion of the drug. Depth resulted in a significant decrease in verbal memory test scores (p=0.001) and mean heart rate (p<0.001).

Conclusion. Dimenhydrinate adversely affects mental flexibility. This effect, when added to the adverse effect of depth on memory, may contribute to the dangers of diving.