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Background: Secondary stroke prevention guidelines recommend antithrombotic agents such as over-the-counter aspirin, prescription antiplatelet agents, or anticoagulant agents. Purpose: The study was designed to measure whether use of outpatient antithrombotic agents is increasing among stroke survivors. Methods: The sample consisted of 4168 people who self-reported cerebrovascular disease and who participated in the Medical Expenditure Panel Survey, an annual representative sample of the U.S., during the years 2000–2006. Use of antithrombotic agents was calculated from face-to-face interviews about the use of aspirin and from pharmacies about the use of prescription medications. Cochran–Armitage tests were used to detect temporal trends and multivariate models to identify predictors of use of antithrombotic agents. Results: Pooling results across the 7 years, it was found that 57% were taking aspirin, 66% were using any antiplatelet agent, and 75% were using any antithrombotic agent. After excluding people who said aspirin was unsafe, 81% were using any antithrombotic agent. During the study period, use of prescription antiplatelet agents increased (p<0.001) but there was no temporal change in use of antithrombotic agents overall. In multivariate models, being aged >65 years, male gender, non-Hispanic ethnicity, having a usual source of care, and poor or fair health status were associated with use of an antithrombotic agent (p<0.05). Conclusions: Although a high percentage of stroke survivors appear to use an antithrombotic agent, further research should investigate whether and how to improve care among the remaining 20% of stroke survivors, particularly among younger, female, and Hispanic patients. [Copyright &y& Elsevier]

The article presents the origin of growth factors such as nerve growth factor (NGF) and epidermal growth factor (EGF). The author explains that the original neuroembryological experiments started in the laboratories of Drs. Viktor Hamburger and Rita Levi-Montalcini. Then, the author got involved in the experiment and decided to examine some of the metabolic effects of EGF on epidermal cultures. Pedro Cuatrecasas discovered that EGF can stimulate the growth of human fibroblasts when cultured.

During the course of the studies on the nerve growth factor of the submaxillary gland of the male mouse (1), it was observed that extracts of these glands, when injected into new-born mice, caused precocious opening of the eyelid and eruption of the incisors. A polypeptide responsible for this effect has been isolated (2). The biological activity was subsequently found to he due to a direct stimulation of the proliferation and keratinization of epidermal tissue. The following summary of the chemical and biological properties of the epidermal growth factor (EGF) is a condensation of a review (3). [ABSTRACT FROM AUTHOR]

Abstract: The etiology and mechanisms of stroke could differ in cancer compared to non-cancer patients due to altered blood coagulability and/or non-bacterial thrombotic endocarditis (NBTE). These conditions could be either missed by using inappropriate diagnostic methods or misinterpreted. For instance, certain techniques (transthoracic echocardiography, TTE) may provide false-negative results and delay appropriate therapy. On the other hand, these patients, by having atypical findings, may challenge the differential between bacterial and sterile valvular heart disease. Cerebrovascular disease in cancer patients is often aggressive with tendency to recurrent events and rapid neurological devastation. Timely diagnosis is crucial. Current treatment approach to NBTE includes anticoagulation. We report a case of multiple embolic strokes in a patient diagnosed with lung cancer. Primary and secondary stroke prevention is discussed with relevant review of the literature. [Copyright &y& Elsevier]

Purpose SBI-087 is a Small Modular Immunopharmaceutical Protein™(SMIP™) drug that binds to CD20 and has been reported to deplete B cells in murine/primate studies. The safety, tolerability and pharmacokinetic/pharmacodynamic properties of SBI-087 were evaluated in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Methods Single-dose SBI-087 was evaluated in 2 Phase I, open-label, escalating-dose studies in patients with RA or SLE. The studies included 6 IV/4 SC escalating doses (RA) and 1 IV/4 SC escalating doses (SLE). Escalation was determined by tolerability/rate of B-cell depletion. Serum was collected for analyses of pharmacokinetic and pharmacodynamic (CD19 + B cells) properties and immunogenicity. Patients were followed until B-cell counts were normalized or stabilized. Safety, tolerability was evaluated from adverse events, physical examinations, vital sign measurements, ECG, and clinical laboratory results. Findings Sixty patients with RA (IV, 28; SC, 32) and 30 patients with SLE (6 per cohort) were enrolled. Mild to moderate infusion reactions occurred in several patients at the top doses in the RA study despite a pretreatment regimen of IV doses. Unanticipated reactions after SC administration of SBI-087 included fever, chills, and malaise, seen on the day of dosing in the lowest-dose cohorts in both studies. These events were abrogated in subsequent cohorts by a pre/postdose treatment regimen consisting of oral corticosteroids, acetaminophen, and an antihistamine. SBI-087 clearance (IV) ranged from 22 to 229 mL/h; volume of distribution at steady state ranged from 5 to 12 L. Apparent clearance (SC) ranged from 44.7 to 105 mL/h; volume of distribution ranged from 14.3 to 32.1 L. Overall, PK properties were similar at equivalent doses between IV/SC administrations in patients with RA/SLE. Mean t ½ (IV) ranged from 2.1 to 10.7 days (less at lower doses). SBI-087 concentration and B-cell depletion were generally dose proportional across IV and SC cohorts. However, the extent of B-cell depletion was less, and rate of repletion was faster, in patients with SLE versus RA. In both studies, B-cell repletion to baseline did not occur in the majority of patients by the end of the observation period. Overall, the prevalence and type of adverse events were similar to those seen with other anti-CD20–depleting agents. Implications In patients with mild RA/SLE, SBI-087 was well tolerated when administered intravenously or subcutaneously with pre- and posttreatment regimens. B-cell depletion is long lasting, and the duration and extent of depletion may be greater in RA compared with SLE. SBI-087 exhibited slow elimination and low distribution in both populations. Clinicaltrials.gov identifiers: NCT00641225 (RA) and NCT00714116 (SLE). [ABSTRACT FROM AUTHOR]

Background: Secondary stroke prevention guidelines recommend antithrombotic agents such as over-the-counter aspirin, prescription antiplatelet agents, or anticoagulant agents.Purpose: The study was designed to measure whether use of outpatient antithrombotic agents is increasing among stroke survivors.Methods: The sample consisted of 4168 people who self-reported cerebrovascular disease and who participated in the Medical Expenditure Panel Survey, an annual representative sample of the U.S., during the years 2000-2006. Use of antithrombotic agents was calculated from face-to-face interviews about the use of aspirin and from pharmacies about the use of prescription medications. Cochran-Armitage tests were used to detect temporal trends and multivariate models to identify predictors of use of antithrombotic agents.Results: Pooling results across the 7 years, it was found that 57% were taking aspirin, 66% were using any antiplatelet agent, and 75% were using any antithrombotic agent. After excluding people who said aspirin was unsafe, 81% were using any antithrombotic agent. During the study period, use of prescription antiplatelet agents increased (p<0.001) but there was no temporal change in use of antithrombotic agents overall. In multivariate models, being aged >65 years, male gender, non-Hispanic ethnicity, having a usual source of care, and poor or fair health status were associated with use of an antithrombotic agent (p<0.05).Conclusions: Although a high percentage of stroke survivors appear to use an antithrombotic agent, further research should investigate whether and how to improve care among the remaining 20% of stroke survivors, particularly among younger, female, and Hispanic patients. [ABSTRACT FROM AUTHOR]

Ribonuclease E (RNase E) is a multifunctional endoribonuclease that has been evolutionarily conserved in both Gram-positive and Gram-negative bacteria. X-ray crystallography and biochemical studies have concluded that the Escherichia coli RNase E protein functions as a homotetramer formed by Zn linkage of dimers within a region extending from amino acid residues 416 through 529 of the 116-kDa protein. Using fragments of RNase E proteins from E. coli and Haemophilus influenzae, we show here that RNase E derivatives that are as short as 395 amino acid residues and that lack the Zn-link region shown previously to be essential for tetramer formation (i.e. amino acid residues 400 - 415) are catalytically active enzymes that retain the 5′ to 3′ scanning ability and cleavage site specificity characteristic of full-length RNase E and that also confer colony forming ability on me null mutant bacteria. Further truncation leads to loss of these properties. Our results, which identify a minimal catalytically active RNase E sequence, indicate that contrary to current models, a tetrameric quaternary structure is not required for RNase E to carry out its core enzymatic functions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the frequency of upper gastrointestinal (GI) tract adverse events associated with risedronate during two (2-year) randomized, double-blind, parallel-group, placebo-controlled studies. PATIENTS AND METHODS: Male and female patients aged 40 to 80 years with mild to moderate medial-compartment knee osteoarthritis were enrolled. Data were pooled and analyzed for risedronate at 5 mg and at 15 mg once daily and compared with placebo. The results of the once-weekly dosages (35 or 50 mg) were assessed separately. RESULTS: A total of 2483 patients were randomized: 622 to placebo, 628 to risedronate at 5 mg/d, 609 to risedronate at 15 mg/d, 310 to risedronate at 35 mg once weekly, and 314 to risedronate at 50 mg once weekly. During the study, 77% of patients were regular nonsteroidal anti-inflammatory drug (NSAID) and/or analgesic users (defined as those who took medication ≥3 days per week), and 68% were regular NSAID users. The number of upper GI tract adverse events was similar between treatment groups, with no dose-related response: 161 for placebo, 176 for risedronate at 5 mg/d. and 150 for risedronate at 15 mg/d. The time to the first upper GI tract adverse event was similar between treatment groups. There was no difference in the frequency of upper GI tract adverse events in risedronate-treated patients compared with patients who were regular users of NSAIDs or NSAIDs and/or analgesics. Findings were similar for those in the once-weekly risedronate groups. CONCLUSION: The results of this study show that risedronate regimens at 5 mg/d or 15 mg/d as well as once weekly at 35 mg or 50 mg are not associated with an increased frequency of upper GI tract adverse events, even in patients who have an increased risk for such events. [ABSTRACT FROM AUTHOR]

Abstract: Based on the chromosomal locations of genes inferred from sequence analysis to be essential for the viability of Streptomyces coelicolor, Bentley et al. [Bentley, S.D., et al. 2002. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2), Nature 417, 141–147.] have suggested that a 4.9 Mb central region of the linear S. coelicolor chromosome encodes ‘core’ functions expressed during vegetative growth of this species, while 1.5 Mb and 2.3 Mb chromosomal DNA segments lateral to this core encode auxiliary functions proposed to be required under other growth conditions. To examine this hypothesis and experimentally identify genes expressed during vegetative growth of S. coelicolor cultures, we used DNA microarrays to measure globally the abundance of S. coelicolor transcripts in cells growing in liquid medium. We found that, overall, genes corresponding to the 4.9 Mb core region of the S. coelicolor M145 chromosome were more highly expressed under non-limiting growth conditions than genes in the 1.5 Mb left and 2.3 Mb right chromosome arms, supporting the notion of the core versus auxiliary organization of genes on the chromosome. To examine how this chromosomal distribution of transcripts changes under other growth conditions, we also measured gene expression changes during stationary phase and several stress conditions. During stationary phase, the composition of S. coelicolor transcripts appears to shift from large quantities of growth-related transcripts encoded in the core region to those of less characterized genes, which may be essential for differentiation and other physiological responses, encoded throughout the chromosome. After temperature and osmotic upshifts, we found that S. coelicolor transiently induces a set of several hundred genes located throughout the chromosome, which may function in response mechanisms common to the two stress conditions. [Copyright &y& Elsevier]