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Sir, Bacterial infections are a recurrent problem in patients with chronic obstructive pulmonary disease. The bacterial pathogens most likely to be involved in communityacquired respiratory infections in these patients are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Among these species resistance to empirically administered antimicrobial therapy occurs, and this can be the cause of treatment failure. An 83-year-old male patient with a history of severe emphysema who had been subjected to bilobectomy in 1981 for carcinoma of the lung, was admitted to hospital because of an exacerbation of his obstructive pulmonary disease in October 1995. He had been treated for several days with cefaclor without clinical improvement. Microbiological examination of the purulent sputum showed, per microscopic field, 2050 leucocytes, 010 Grampositive cocci and 50100 Gram-negative bacilli. The bacilli were remarkably long and slim and therefore morphologically suspect for a Pseudomonas species. Antimicrobial therapy was started with ciprofloxacin orally 500 mg twice daily. The next day Klebsiella oxytoca and H. influenzae were grown in culture. The isolate of H. influenzae strain no. 24482 ; was confirmed as biovar IV, serotype e by Dr Reubsaet RIVM, Bilthoven ; . Susceptibility tests were done according to NCCLS guidelines1 by the agar-dilution method with haemophilus test agar Oxoid ; , an inoculum of 104 cfu spot and 20 h incubation at 35 C and in 5% CO2. H. influenzae Rd, kindly donated by Dr L. van Alphen Academic Medical Centre, Amsterdam ; , was used as a reference Table ; . Strain 24482 was resistant to ciprofloxacin and to cotrimoxazole, but susceptible to the -lactam antibiotics and to tetracycline. Absence of clinical improvement combined with these laboratory findings resulted in a switch to co-amoxiclav 625 mg three times daily po. The.
Dantas RO, Villanova MG. Esophageal motility impairment in Plummer-Vinson syndrome. Correction by iron treatment. Dig Dis Sci 1993; 38: 968-971. Ekberg O, Nylander G. Webs and web-like formations in the pharynx and cervical esophagus. Diagn Imaging 1983; 52: 10-18. Larsson LG, Sandstrom A, Westling P. Relationship of PlummerVinson disease to cancer of the upper alimentary tract in Sweden. Cancer Res 1975; 35: 3308-3316. Chisholm M. The association between webs, iron and post cricoid carcinoma. Postgrad Med J 1974; 50: 215-219. Hutter CF. Plummer Vinson syndrome. Br J Radiol 1956; 29: 81-83. Jacobs A, Kilpatrick GS. The Paterson-Kelly syndrome. Br Med J 1964; 2: 79-82. Baird IM, Dodge OG, Palmer FJ, Wawman RJ. The tongue and esophagus in iron deficiency anemia and the effect of iron therapy. J Clin Pathol 1961; 14: 603-609. Khosla SN. Cricoid webs-incidence and follow-up study in Indian patients. Postgrad Med J 1984; 60: 346-348. Chen TS, Chen PS. Rise and fall of the Plummer-Vinson syndrome. J Gastroenterol Hepatol 1994; 9: 654-658. Uygur-Bayramicli O, Tuncer K, Dolapcioglu C. Plummer-Vinson syndrome presenting with an esophageal stricture. J Clin Gastroenterol 1999; 29: 291-292. Ykselen V, Karaoglu A, Yasa MH. Plummer-Vinson syndrome: a report of three cases. Int J Clin Pract 2003; 57: 646-648.
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Drugs Requiring Prior Authorization Influenza Medications Relenza Relenza: Minimum age requirement: 13 years old. Diagnosis of Influenza A or Influenza B. Covered only for patients at high risk from diagnosed and documented disease states of immunodeficiency. This includes HIV AIDS or other diseases of the immune system; long-term radiation treatment; long-term treatment with drugs such as steroids, oncology agents, or immunosuppressive agents; or fragility due to extreme age greater than 65 years ; . Prior Approval is limited to one box of 20 amps per year. Tamiflu: Minimum age requirement: 13 years old. Diagnosis of Influenza A or Influenza B. Covered only for patients at high risk from diagnosed and documented disease states of immunodeficiency. This includes HIV AIDS or other diseases of the immune system; long-term radiation treatment; long-term treatment with drugs such as steroids, oncology agents, or immunosuppressive agents; or fragility due to extreme age greater than 65 years ; . Prior approval is limited to 10 capsules per year. OR Prophylaxis for Influenza A or B for age 13 and older. Documentation that demonstrates that one other household member or residential member currently has documented influenza A or B. Covered only for patients at high risk from diagnosed and documented disease states of severe cardiopulmonary conditions, immuno-compromised patients, fragility due to extreme age greater than 65 years ; . Prior approval is limited to a 7-day course with 14 capsules. TREATMENT MUST BE STARTED WITHIN 72 HOURS OF DIAGNOSIS. Amitza: Minimum age requirement - 18 years old. Diagnosis of Chronic Idiopathic Constipation. Documented failure within the last 12 months using one fiber laxative and two stimulant laxative products. Drug induced constipation must be ruled out. Initial authorization is granted for 6 months - patient may have a second authorization after a trial off Amitza using other laxatives for at least 30 days. The lifetime maximum is a total of 1 year of therapy with Amitza. Zelnorm: Chronic Idiopathic Constipation age requirement is age 18-65. Documented Diagnosis of Chronic Idiopathic Constipation. Documented failure within the last 12 months using one fiber laxative and two stimulant laxative products. Drug induced constipation must be ruled out. OR Irritable Bowel Syndrome minimum age requirement - 18 years old. Documented diagnosis of Irritable Bowel Syndrome. Primary bowel symptom is constipation. Drug induced Constipation is ruled out. Initial authorization is granted for 6 months - patient may have a second authorization after a trial off Zelnorm using other laxatives for at least 30 days. The lifetime maximum is a total of 1 year of therapy with Zelnorm. Documented diagnosis of chronic liver failure, hepatic encephalopathy, chronic portal hypertension, or Spina Bifida. Prior authorization is only required for 6000ml's per month. This drug will not be approved for use as general laxative for over 6000ml's monthly. Initial authorization is granted for 6 months - renewals require a telephone call from the physician's office or pharmacy. Page 17 of 27.
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Overview of Common Causes of Chronic Cough9 1. In patients with chronic cough and a normal chest roentgenogram finding who are nonsmokers and are not receiving therapy with an and remodulin.
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APPENDIX 1: BABY FRIENDLY INITIATIVE The Baby Friendly Hospital initiative9 BFHI ; was developed and launched, in 1991, jointly by WHO and UNICEF. It is a global initiative to protect breastfeeding and aims to give every baby the best start in life by creating a health care environment where breastfeeding is the norm thus helping to reduce the levels of infant morbidity and mortality in each country. The objectives are to: Enable mothers to make an informed choice about how to feed their newborns. Support early initiation of breastfeeding. Promote exclusive breastfeeding for the first 6 months. Ensure the cessation of free and low cost infant formula supply to hospitals; and Include, possibly at a later stage and where needed, other mother and infant health care issues and renagel.
The Pancreatic Cancer Action Network announces the launch of the Pilot Grant Awards Program. The goal of the Pilot Grant Program is to support innovative research in pancreatic cancer. This research may be basic, translational, or clinical in nature. Particular consideration will be given to projects that are innovative, non-duplicative of other efforts and have the potential for national application. Applications were due April 2, 2007. Look at the website, pancan , and or the next issue of the newsletter for more information about the program and, very soon, for information about the grantees who will be recipients of this new award.
| Relenza flu virusFor the first time in the world, the sprayable peel-off film was introduced on the production line of an automotive manufacturer. The technology was established through the optimization of the Bayhydrol component and the application technology. The antifouling effects identified in extensive field trials were not sufficient to satisfy the technical milestones. The project was abandoned at the end of 2002 given the lack of short- or medium-term realizability. Successful launch of thin packaging films C20P ; , substituting films of 33 percent greater thickness and also possessing technical advantages. Market presentation of new high-purity hydroxypropylmethylcelluloses HPMC ; as formulation aids for foodstuff, cosmetic and pharmaceutical products Walocel HM and renova.
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PULMONARY VASCULAR CAPACITANCE IS A STRONG PREDICTOR OF MORTALITY IN PATIENTS WITH IDIOPATHIC AND SCLERODERMA-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION Hadi N. Skouri MD * Zuheir Abrahams MD Wilfried Mullens MD David O. Taylor MD Omar A. Minai MD Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Pulmonary vascular capacitance PC ; defined as the ratio of stroke volume to pulmonary pulse pressure SV PP ; has been recently shown as a strong predictor of mortality in idiopathic pulmonary arterial hypertension IPAH ; . Since it reflects properties of the large and medium sized pulmonary vessels, we hypothesized that low PC would also a predictor of mortality in patients with scleroderma-associated PAH SSC-PAH ; . METHODS: We analyzed hemodynamic data from the initial right heart catheterization RHC ; of patients with IPAH and SSC-PAH. PAH was defined as mPAP 25 mmHg and PVR 3 Woods units. Survival was determined by SSDI database. Statistical analysis used chi-square test and Wilcoxon rank sum tests to compare differences between both groups. RESULTS: Data of 90 patients 58 IPAH and 32 SSC-PAH ; were analyzed. Patients in the SSC-PAH group were significantly older 59 10 yrs vs. 45 15 yrs; p 0.001 ; . RV systolic pressure, mean PAP, and PVR were significantly higher in the IPAH group. Mean PC was 1.01 0.65 in IPAH group and 1.40 0.81 in SSC-PAH group with a p-value 0.012. There was no significant difference in the two groups with regard to TPG, SV, CO, PCWP, and mean RAP. In the IPAH group 31% of patients died over a follow up period of 4.2 2.3 years while 40.6%of patients in the SSC-PAH group died over a period of 2.5 1.7 years P-value 0.001 ; . CONCLUSION: Even though patients in the SSC-PAH group had lower mean PAP, PVR, RV systolic pressure and a higher pulmonary capacitance, they had a significantly shorter period of survival. PC was a strong predictor of mortality in patients with IPAH and SSC-PAH. Further studies comparing these groups are warranted. CLINICAL IMPLICATIONS: Pulmonary capacitance can be used as a prognostic marker in SSC-PAH as it is in IPAH.Potential to be used as a marker in response to therapy. DISCLOSURE: Hadi Skouri, No Financial Disclosure Information; No Product Research Disclosure Information and reserpine.
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3 INTRODUCTION Severe burns are associated with a hypermetabolic response in which muscle protein is used to fuel the increase in energy expenditure. Typical features of the response include increased body temperature, recruitment of neutrophils, changes in lipid metabolism, increased gluconeogenesis, and stimulation of protective pathways such as coagulation and complement activation, hormonal changes, and increased muscle catabolism 32 ; . These changes lead to increased energy expenditure and futile substrate cycling, with depletion of nutritional and functional fat and protein stores 5, 30 ; . Protein catabolism is increased after a severe burn leading to a breakdown of functional structural proteins which results in the loss of lean muscle mass 10, 21 ; . One of the primary mediators of the hypermetabolic response is thought to be endogenous catecholamines 19, 41 ; . The increase in catecholamine plasma levels found early after burn trauma leads to a hyperdynamic circulation 2, 40 ; , increased basal metabolic rate 34 ; , and increased catabolism of structural protein in skeletal muscle 20, 21 ; . -adrenergic blockade has been shown to be effective in posttraumatic hypermetabolism by decreasing thermogenesis 22 ; , decreasing increased heart rate 29 ; and cardiac work 3 ; , lowering resting energy expenditure 8 ; , and attenuating muscle catabolism 23 ; . We have used several anabolic agents to effectively diminish muscle catabolism in burn patients. Insulin has been shown beneficial in protein metabolism primarily by stimulating protein synthesis 14, 35 ; . Recombinant human growth hormone and IGF-1BP3 have also shown efficacy in improving muscle protein kinetics and wound healing in severely burned children 12, 18, 24 ; . Testosterone can increase protein synthesis.
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Spread of influenza. Prevention of influenza among household contacts is important in minimizing community outbreaks. A recent study evaluated the efficacy of postexposure prophylaxis with oseltamivir among household contacts of a person infected with an index case of influenza.126 Efficacy in prevention of clinical influenza among household contacts older than 11 years was 89%, compared with placebo recipients, when prophylaxis was initiated within 48 hours of exposure. This occurred even in the absence of treatment of the person with the index case of influenza. Oseltamivir is approved by the FDA for prophylaxis in individuals 13 years and older. A similar level of protection among persons 5 years and older using zanamivir has been demonstrated in a family study; however, this drug is not currently licensed for this indication.127 NA inhibitors are licensed by the FDA for treatment of uncomplicated disease caused by influenza A or B when symptoms have been present for fewer than 48 hours.123 Zanamivir Relenza [GlaxoSmith Kline, Research Triangle Park, NC] ; is an inhaled topical powder that is licensed for treatment of influenza in children as young as 7 years. The drug is administered using a breath-activated inhalation device that delivers approximately 7% to 21% of the inhaled dose to the lungs. A dose of 10 mg is administered twice daily for 5 days. Patients should receive specific instructions on the use of the delivery system. Oseltamivir Tamiflu [Roche Laboratories, Nutley, NJ] ; is an oral formulation tablet or suspension ; that is cleaved by esterases in the gastrointestinal tract or blood, resulting in approximately 80% bioavailability. Oseltamivir has been licensed for treatment of children older than 1 year. For children, the dose is 2 mg kg, administered twice daily maximum adult dose is 75 mg twice a day ; for 5 days. In clinical trials, viral shedding in nasal secretions was significantly decreased compared with placebo recipients, suggesting decreased risk of viral transmission in patients who receive treatment. Zanamivir treatment was studied in a randomized, controlled trial in 346 children between 5 and 12 years of age who were infected with influenza A or B.124 Treatment with zanamivir decreased symptoms by a median of 1.25 days compared with placebo, representing a 24% decrease in duration of symptoms and a 15% more rapid return to normal activity. No significant difference was found between zanamivir and placebo groups in terms of antimicrobial use 12% vs 15% ; . There was no difference in occurrence of adverse events between zanamivir recipients and placebo recipients. Oseltamivir treatment of influenza has been evaluated in children between 1 and 12 years of age in a randomized, double-blind, placebo-controlled study.125 Among 457 children with documented influenza infection who were treated within 48 hours of onset of symptoms, the median duration of illness was decreased by 36 hours in the oseltamivir group. Incidence of otitis media was decreased by 44% in oseltamivir recipients compared with the placebo group 12% vs 21% ; . There was a significant decrease in the number of antimicrobial prescriptions for chil13 of 18 and restasis.
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Tamoxifen, a nonsteroidal triphenylethylene, is currently the endocrine therapeutic agent of choice for all stages of breast cancer. It was also recently approved for use as a chemopreventive agent in women with high risk of contracting this disease in the future. Despite its well documented beneficial effects, tamoxifen use is associated with several major problems including serious drug-drug interactions. Several clinical trials indicate that tamoxifen has the propensity to alter the drug elimination pathway s ; , resulting in markedly reduced plasma and relenza.
There are numerous ma huang-containing herbal dietary supplements available on the market that are advertised for various uses, including bodybuilding, weight loss, enhanced energy, or improved memory eg, Ripped Fuel, Hydroxycut; Metabolife, Metabolife International, Inc., San Diego, CA; Herbalife, Herbalife, Inc., Century City, CA; Energel, PVL Nutrients, Ltd., Port Coquitlam, BC, Canada; herbal ecstasy, herbal phen-fen ; . Ma huang, which is derived from plants of the genus Ephedra, contains the alkaloids norephedrine, norpseudoephedrine, pseudoephedrine, and ephedrine, with the first two being minor components and ephedrine accounting for 30 to 90% of the total alkaloid content. Pseudoephedrine, which is the second major constituent in most ma huangcontaining products, is less potent and less likely to cause central nervous system stimulation.2 The actual amount of ephedrine and other ephedra alkaloids found in a product depends on which Ephedra species is used more than one species may be used in a given product ; , where the plant is and restoril.
3. Results and discussion 3.1. Effect of solids concentration The influence of solids concentration on slurry rheology is significant since various ranges of solids concentrations can lead to different types of flow curves, as shown in Fig. 2. The result shows the rheological properties of seven different solids concentrations of a limestone slurry b100 Am, i.e., raw 1: d 50 24.68 Am; d 90 97.3 Am, ; without any dispersant at a temperature of 25 F 0.2 8C. Clearly, the slurry rheological behaviour is transformed from a weakly dilatant characteristic shearthickening ; to an evidently pseudoplastic shear-thinning ; one with a yield stress when the solids concentration is increased from 60 wt.% 35.71 vol.% ; to 78.5 wt.% 57.49 vol.% ; . At a solids concentration V 65 wt.% 40.75 vol.% ; , the slurry presents a weakly dilatant shear-thickening ; flow. This is because in a dilute slurry i.e., V 65 wt.% or 40.75 vol.% ; , the inter-particle distance is so large that the limestone particles in the slurry are not subjected to the attractive van der Waals forces between the particles but free to move as individuals. At lower shear rates, the particles have enough opportunities to slip over each other. At higher shear rates, the shearing process is more and more rapid so that the particles cannot move around freely any longer. The local accumulation of solid particles causes the slurry to behave like a solid system. In a dilatant system, however, this state is not stable. As long as the external force is removed, the particles without any tendency to adhere are distributed more uniformly in the suspension. At the solids concentration up to 67 wt.% or 42.92 vol.%, the flowability of the slurry exhibits a pseudoplastic shear-thinning ; characteristic without a definite yield stress at shear rates less than 663 s 1 and a weakly dilatant shear-thickening ; one at shear rates larger than 663 s 1. This indicates that in a lower range of shear rates, the attractive interparticle force is predominant over the hydrodynamic force exerted by a flow field at 67 wt.% of solids concentration, as opposed to shear rates larger than 663 s 1. With further increasing the solids concentration to 70 wt.% i.e., 46.36 vol.% ; or more, the slurry rheology is changed into a pseudoplastic flow with an evident shear yield stress at shear rates below 362 s 1, followed by a transition to a Bingham plastic flow with a higher extrapolated Bingham yield stress ; at shear rates above 362 s 1. Furthermore, the degree of pseudoplasticity and the shear yield stress increase with increasing solids concentration when the solids concentration is larger.
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The centers for disease control and prevention recommends using oseltamivir tamiflu ; or zanamivir relenza ; , which are active against both influenza a and b for patients who need to be treated and revlimid.
For more information about the EECP program call 857-5545. Physician Referral Hotline: 857-DR4U 857-3748 ; trinityhealth and remicade.
Offset in the cell cycle, these nuclei must respond to different cell cycle cues. Although macronuclear chromosomes segregate randomly, chromosome copy number is maintained in a manner somewhat analogous to bacterial plasmids for review, see Dobbs et al., 1994 ; . The imprecision of amitotic macronuclear division raises the possibility that an ATR-like intra-S-phase checkpoint is dispensable for macronuclear chromosome homeostasis. Furthermore, unconventional mechanisms have evolved to compensate for the associated genic imbalances. Partial endoreplication cycles and the elimination of "excess DNA" in the form of macronuclear extrusion bodies maintain macronuclear DNA content and gene copy number within a narrow range Cleffmann, 1968; Doerder and Debault, 1975; Bodenbender et al., 1992 ; . Because these compensating pathways do not operate in the diploid, mitotic micronucleus, one would predict that the micronucleus uses conventional DNA damage checkpoint pathways to maintain genome stability. One argument against this idea is that fact that micronuclear aneuploidy does not arrest vegetative cell cycle progression. "Functionally amicronucleate, " hypo-diploid "star" strains divide normally and have an unlimited life span Allen, 1967 ; , and some related tetrahymenid species lack a micronucleus. The integrity of the micronucleus only comes into play during conjugation, because it contains the sole source of transmitted nuclear genes. We obtained preliminary evidence for a macronuclear S-phase checkpoint during our analysis of tif1-1: : neo mutants, which among other things are partially defective in macronuclear S-phase progression Morrison et al., 2005 ; . TIF1-deficient cells exhibit a prolonged macronuclear S phase, that once complete, is followed by a further delay in macronuclear division and cytokinesis Morrison et al., 2005 ; . Whereas macronuclear divisions are frequently aberrant in TIF1 mutants, the observed defect in S phase progression and subsequent delay in macronuclear division and cytokinesis argue that macronuclear and cytoplasmic cell cycles are coordinately regulated. Tif1p binds essential cisacting replication determinants in the rDNA origin, in vitro and in vivo Saha and Kapler, 2000; Saha et al., 2001 ; and was recently shown to regulate rDNA origin activation, functioning in a repressive capacity to prevent precocious initiation during macronuclear S phase Morrison et al., 2005 ; . Because macronuclear S phase is prolonged in Tif1p-deficient strains, Tif1p might regulate initiation and or the elongation of replication forks in other non-rDNA ; macronuclear chromosomes. Here, we show that Tif1p is required to maintain genome integrity in the mitotic germline micronucleus. We demonstrate that wild-type T. thermophila elicits an intra-S-phase DNA damage checkpoint response that has the hallmarks of the highly conserved ATR-dependent pathway. Furthermore, we show that the intra-S-phase checkpoint pathway promotes chromosome homeostasis in both the diploid mitotic micronucleus and the polyploid amitotic macronucleus. Most significantly, we demonstrate that Tif1p is required to activate the intra-S-phase checkpoint response in both nuclear compartments. These observations, in conjunction with the previously described role for Tif1p at the rDNA origin Morrison et al., 2005 ; , suggest that this protein contributes to chromosome homeostasis through its action at origins and at elongating replication forks. MATERIALS AND METHODS Manipulation of T. thermophila Strains and reyataz.
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Targeted therapy now generally refers to inhibiting specific signal-transduction molecules important in cell growth. Multiple signal transduction pathways that are important in the growth and death of cells have been identified and a review of all of the therapeutic targets is almost impossible.82-84 In addition, although in the traditional sense these are targets on the prostate cancer cells, several agents now target the endothelial cell as well as other cells in the tumor microenvironment such as the osteoblast Figure 6 ; . Cytokines and growth factors that stimulate prostate cancer cells or supporting stromal cells can be inhibited using several different strategies Figure 6 ; . The prototypical cytokine to describe these strategies is the inhibition of vascular endothelial growth factor VEGF ; . VEGF is the primary cytokine released by tumor cells to stimulate new blood growth and several different strategies are under development to block its function.85-87 VEGF binding to its receptor can be blocked with an antibody that binds to VEGF itself such as bevacizumab.86 Alternatively, an antibody can bind to the VEGF receptor itself and block function.87 The activation of VEGF receptors can also be blocked with a small molecule inhibitor. Growth factor receptors function through the activation of tyrosine kinase. Tyrosine kinases can be blocked at the level of the receptor or by interrupting its downstream signaling Figure 6 ; . PTK787 is an oral aminophthalazine, which acts as a tyrosine kinase inhibitor that binds to and inhibits the function of all known VEGF receptors.88 The novel biaryl urea BAY 43-9006 is an oral potent inhibitor that inhibits several receptor tyrosine kinases involved in neovascularization and tumor progression both by binding to the receptor and by inhibiting the downstream Ras Raf signaling.89, 90 The growth of new blood vessels can also be blocked by inhibiting integrin function. Tumor-related blood vessels sprout into the extracellular matrix ECM ; in a process that is dependent on the ability of the proliferating.
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