The Department has hosted several meetings of the FKL Research Centre for Quality in Medicine Use throughout the period of the report. MEMBERSHIP OF EXTERNAL BOARDS AND COMMITTEES EXTERNAL PROFESSIONAL POSITIONS.
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INTERACTION OF ANTIVIRAL AND ANTICANCER DRUGS WITH THE HUMAN Na + NUCLEOSIDE COTRANSPORTER-1 hCNT1 ; . I.M. Larryoz1, F.J. Casado2, M. Pastor-Anglada2 and M.P. Lostao1. 1Departamento de Fisiologa y Nutricin, Universidad de Navarra, Pamplona; 2Departament de Bioqumica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. J. Physiol. Biochem., 60 2 ; , 127, 2004. Background and Aims: The human concentrative Na + nucleoside transporter 1 hCNT1 ; is a high affinity transporter responsible for the uptake of natural pyrimidine nucleosides that may be also involved in the transport of anticancer and antiviral nucleoside-derived drugs. In the present work, we have investigated the interaction of selected drugs with hCNT1 and compared their kinetic properties with those of the natural nucleosides to obtain information about the structural requirements for the nucleoside derivatives to be transported by hCNT1. Methods: Functional studies were performed using the two-electrode voltage clamp technique applied to Xenopus laevis oocytes expressing hCNT1. Results and conclusions: Apparent affinity constant K0.5 ; was similar for uridine, cytidine and thymidine ~30 M ; . The anticancer drugs gemcitabine 2', 2'-difluoro-deoxycytidine ; and 5-DFUR 5'-deoxy-5-fluorouridine ; showed a K0.5 of 185 and 24539 M respectively. Uridine and thymidine maximal current Imax ; was similar, but cytidine and gemcitabine Imax was half of that for uridine. On the contrary, Imax for 5'-DFUR was 1.5-fold higher than uridine Imax. Cytidine and gemcitabine present a NH2 group in the 4 position where the other three nucleosides have an O, which could explain the decrease in their Imax. Furthermore, gemcitabine contains two F in the 2 position that may contribute to the increase in affinity. The lack of an OH group in the 5' position and the presence of a F the 5 position in 5DFUR, may explain the increase on K0.5 and Imax. Several inhibitors of HIV-1 reverse transcriptase were also tested. AZT 3'-azido-3'-deoxythymidine ; and d4T 2', 3'didehidro3'deoxythymidine ; were transported with low affinity K0.5 of 0.960.14 and 15.64.7 mM respectively ; , however, Imax was 2 and 5-fold respectively higher than uridine Imax. ddC 2', 3'-dideoxycytidine ; did not induce any inward current but inhibited the uridine-induced Na + inward current and the Na + -leak current with a Ki of 5.51.5 mM. The antiviral drugs lack the 3' hydroxyl group of the sugar which indicates that this position may be a key structural determinant for nucleoside recognition and transport. Nevertheless, the azido group in that position AZT ; and the double bound between C 3' and 4' d4T ; could increase the turnover rate of the transport process, for example, usp.
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Clinical Neuroscience 242: 329-336. 2 ; Armitage, R., Madhukar, T., Hoffmann, R. and Rush, J. 1997 ; . Relationship between objective and subjective sleep measures in depressed patients and healthy controls. Depression and Anxiety 5: 97-102. 600.L Insomnia is Associated with Altered Circadian Interleukin-6 and TNF Secretion Vgontzas AN, 1 Papanicolaou DA, 2 Zoumakis M, 2 Bixler EO, 1 Prolo P, 3 Lin HM, 4 Vela-Bueno A, 5 Kales A, 1 Chrousos GP1 1 ; Sleep Research and Treatment Center, Department of Psychiatry, The Pennsylvania State University College of Medicine, Hershey, PA, 2 ; Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 3 ; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, 4 ; Health Evaluation Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, 5 ; Department of Psychiatry, Autonomous University, Madrid, Spain Introduction: Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by long sleep latencies or increased wake time during the night and increased fatigue during the day, although in objective daytime sleep testing, insomniacs are unable to fall asleep. We recently reported that chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitaryadrenal HPA ; axis consistent with the view that insomnia is a disorder of behavorial and physiological hyperarousal. Interleukin-6 IL-6 ; and tumor necrosis factor TNF ; are fatigue-inducing cytokines. The circadian secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. Both IL-6 and TNF stimulate the activity of the HPA axis, and their secretion is suppressed by glucocorticoids. Based on the above described associations, we explored whether the circadian secretion of IL-6 and TNF is altered in insomniacs. Methods: Eleven young insomniacs 6 men and 5 women ; and 11 8 men and 3 women ; age-and-body-mass-index BMI ; matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for four consecutive nights and serial twenty-four hour plasma measures of IL-6 and TNF were obtained during the fourth day. Results: Insomniacs compared to controls slept poorly sleep latency and wake were increased whereas percentage sleep time was decreased during baseline nights, all P 0.05 ; . The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, mean IL-6 levels were borderline significantly elevated in insomniacs compared to controls in the mid-afternoon and evening pre-sleep period 1500-2300, P 0.07 ; . Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from early morning 0500 ; to evening 2000 ; in insomniacs compared to controls. Also, TNFa secretion in controls showed a statistically significant circadian rhythm with a peak close to the offset of sleep; such a rhythm was not present in insomniacs. Conclusions: Chronic insomnia is associated with a shift of IL-6 secretion from early morning to evening, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 secretion, combined with a 24h hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty falling asleep during the daytime and or the nighttime. The interaction between IL-6 and cortisol levels may determine the timing, quantity and quality of sleep, sleepiness and fatigue in physiologic and pathologic situations. SLEEP, Vol. 24, Abstract Supplement 2001 A342.
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PREVALENCE OF ZOONOTIC PATHOGENS IN DOGS VISITING HUMAN HOSPITAL PATIENTS IN ONTARIO. S. Lefebvre1, J. S. Weese2, D. Waltner-Toews1, A. Peregrine3, R. ReidSmith1. Depts. of Population Medicine1, Clinical Studies2 and Pathobiology3 , University of Guelph, Canada. Visitation of hospitalized humans by dogs and other companion animals is becoming commonplace. While the therapeutic value of such practices has been investigated, the potential health hazards, both to the patients and the dogs, has not. This information is especially important in light of increasing concerns about nosocomial infections in healthcare facilities. This cross-sectional study measured the prevalence of potential zoonotic pathogens in a group of 102 healthy dogs actively involved in visitation programs in Ontario. A standardized questionnaire was administered to each of the dogs' owners to obtain dog and program information. Fecal samples, aural, nasal, oral, pharyngeal and rectal swabs, as well as hair-coat brushings, were collected from all dogs. Salmonella spp was isolated from six fecal samples, vancomycinresistant enterococci from five, extended-spectrum beta lactamase E. coli from six, and Clostridium difficile from 58. Pasteurella multocida and P. canis were isolated from 29 oral swabs. Fecal flotation found two dogs to be shedding Toxocara canis and one other to be shedding Ancylostoma caninum. Enzyme immunoassays detected Giardia spp antigen in seven fecal samples, but failed to detect any Cryptosporidium spp. With C. difficile excluded, no one dog was found to carry more than one enteric pathogen. Methicillinresistant Staphylococcus aureus was not isolated from any nasal or pharyngeal swabs or from feces. Similarly, Pseudomonas aeruginosa, group A streptococci and Microsporum canis were not isolated from any aural, pharyngeal or hair samples, respectively. Only spaying neutering was identified as a statistically significant protective factor against shedding Salmonella OR 0.10, 95% C.I. 0.29 0.69, p .001 ; . None of the other factors, such as antimicrobial history, animal's diet or degree of interaction with patients, were significant for any organism; however, a few patterns are worth noting. None of the 11 dogs that tested positive for multidrug-resistant bacteria had been hospitalized for anything other than sterilization, and only six of these had prior antimicrobial exposure. In addition, all dogs interacted with other dogs on a regular basis, whether during exercise or as part of a multi-dog household. Follow-up with the ESBL E. coli-positive dogs showed at least half of the other dogs six out of a total of 10 ; in the multi-pet households were also infected - further evidence of the potential for dog-to-dog spread. The significance of these findings, particularly the high prevalence of C. difficile, warrants cautious consideration. At this point, all that can be said with certainty is that dogs can carry many organisms of potentially pathogenic consequence without displaying clinical signs. In light of this, veterinarians are in a unique position to protect the health of their patients, the owners, and the people they visit through health certification and education programs. Further, veterinarians and physicians should work together to better evaluate the risks of these potential pathogens and develop objective criteria for screening of hospital visitation dogs and aciphex, for example, side effects of zyloprim.
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Welcome to this edition of Dialysis Dialogue, a newsletter published by the North Dakota Department of Health, Division of Health Facilities. Dialysis Dialogue is designed to help dialysis departments stay up-to-date on various issues. Please share with your dialysis staff.
RECOMMENDED to consult other resources CPS, pharmacists, attending physicians ; before applying information in this manual for patient care. The Drugs & Drugs Editorial Committee cannot be held responsible for any harm, direct or indirect, caused as a result of application of information contained within this manual and adalat.
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This study compared the treatment received by patients with anxiety disorders from primary care physicians and psychiatrists. Primary care patients at 15 sites were screened for anxiety symptoms. Those screening positive for anxiety symptoms were interviewed to assess for anxiety disorders. Information on psychiatric treatment received and provider of pharmacological treatment was collected. Of 539 primary care participants with at least one anxiety disorder, 47.3% were untreated. Nearly 21% were receiving medication only for psychiatric problems, 7.2% were receiving psychotherapy alone and 24.5% were receiving both medication and psychotherapy. Patients receiving psychopharmacological treatment received similar medications, often at similar dosages, regardless of whether their prescriber was a primary care physician or a psychiatrist, because zyloprim drug.
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