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Depending on the reaction conditions, the reaction of elemental Pd with H2SeO4 in sealed glass tubes at 350C leads to red single crystals of Pd SeO3 ; or to yellow-orange single crystals of Pd SeO4 ; . When SeO3 is added to the reaction mixture, yellow-orange single crystals of Pd Se2O5 ; are obtained. The IR spectra show the typical bands for oxoselenate anions.
Rehabilitative Services Members are covered for rehabilitative services in a Substance Abuse Treatment Facility for non-Hospital Inpatient therapy for thirty 30 ; days per Benefit Period. Additional days are available in exchange for sessions of Outpatient or partial hospitalization on a two-to-one basis to secure up to fifteen additional non-hospital, residential alcohol treatment days. Benefits are limited to ninety 90 ; days per lifetime. Treatment is provided in a facility which meets minimum standards for client-to-staff ratios and staff qualifications which are established by the Bureau of Drug and Alcohol Programs and is appropriately licensed by the Department of Health as an alcoholism or drug addiction treatment program. Before the Member may qualify to receive benefits under this section, a licensed Physician or licensed Behavioral Health professional must certify the Member as a person suffering from alcohol or other Substance Abuse or Substance Dependence and refer the Member for the appropriate treatment. Inpatient and Rehabilitative Services Inpatient and rehabilitative services in a facility include, but are not limited to.
Measuring the change incurred in applications' source code caused by the migration process is important for various reasons. First, they are correlated with the amount of effort needed to convert applications to Datom abstractions. Second, they are a clear indication of the consequences of adopting a more abstract API as an underlying storage infrastructure. Finally, by analysing the final form of the source code and by comparing it with its original version, it is possible to evaluate whether the storage system API may represent a better software tool for programmers in the given context. However, it is necessary to keep in mind that applications created from the start using the Datom API may exhibit a neater integration with its facilities. The source code metrics collected in this study aim to reveal if the adoption of the Datom API improves the way in which programmers deal with persistencerelated tasks. Additionally, they are also useful to indicate to what extent the new API abstractions modify the interaction of programmers with persistent data. The relationship between internal software attributes collected by source code metrics and external attributes such as understandability, usability, or maintainability have been suggested by a number of studies. In general, it is recognised that reducing the number of lines of code has a positive impact on the understandability and maintainability of the software [GSAW98]. Maintaining large applications requires a lot of effort, and big code bases are vulnerable to error. The Datom API would likely augment the quality of the application if it is able to reduce the size of applications, as long as the same functionality is provided. However, reducing the lines of code is not fully indicative of an improved software product. It is also necessary to analyse how the code is transformed and what is the impact on the morphology of the application caused by the introduction of a different technology. This involves analysing how pervasive the Datom API is and what the compromises in its employment are. The use of the Datom API is expected to reduce the size of the source code and to hide low-level interactions with the file system. It should augment the degree of abstraction that developers are able to manipulate through the storage system API in order to improve code understandability and maintainability. Additionally, it should greatly simplify data retrieving tasks by making code clear and simple. With the Datom API, manual parsing and serialisation of application abstractions should be fully eliminated. 143.
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The coercion n of the functor X 1 is defined as the identity n0 : 1 - and the morphism n2 1 Note that the endofunctors X X X and X 1 are strong and symmetric, but we do not care about this additional property here. The following result is folklore: Corollary 16 Let C 1 ; be a symmetric monoidal category. The tensor unit is a terminal object and the tensor product is a cartesian product if and only if there exists a pair of monoidal natural transformations d and e with components dA : A - defining a comonoid A, dA , eA ; for every object A. Proof. The direction ; is easy, and left as exercise to the reader. The other direction ; established by applying Proposition 15. To that purpose, we show that Diagram 43 ; commutes for all objects A and B, and that the component e1 coincides with the identity. This is deduced by an elementary diagram chasing in which the assumption that d and e are monoidal is here to ensure that e1 id eA.
Reflection of success in both microbial killing and suppression of the emergence of resistance. Our studies with the in vitro PD model of tuberculosis demonstrated that despite rifampin's short t1 2, its long PAE prevented regrowth during the entire 1-week dosing interval, so that cycles of killing and regrowth were not encountered. Standard PAE assays confirmed the long duration of rifampin's PAE and that the PAE was the most closely associated with Cmax MIC. On the other hand, when two exposures of 7 mg liter with different durations of exposure were examined, they had virtually identical PAE durations, demonstrating that the duration of exposure had a minimal relationship to the PAE. In the past, other researchers have demonstrated that rifampin indeed has a long PAE. Chan et al. exposed M. tuberculosis to a rifampin Cmax MIC of 32 and demonstrated a PAE of 2.8 days 5 ; . This harmonizes well with our own result, in which a Cmax MIC of 64.1 approximately double the value of 32 ; had a PAE double the one demonstrated by Chan et al. 5 ; . Indeed, a reexamination of a recent clinical trial in which several doses of rifapentine were administered to patients reveals that a 1.84 times increase in fCmax MIC resulted in a 1.75 times increase in the "lag period" to regrowth 2 versus 3.5 days ; after the decline of the serum rifapentine concentrations to below the MIC 41 ; . Thus, for rifampin and other rifamycins, the PAE seems to be closely related to the Cmax MIC. What this means is that whether one looks at microbial killing, resistance suppression, or PAE, the effect of rifampin is concentration dependent. The concentration-dependent effects of rifampin may, in part, be explained by what appeared to be enhanced rifampin entry at higher concentrations in the bacillary milieu. The reasons are unclear, but the findings suggest a role for saturable efflux transporter proteins. Piddock et al. have demonstrated that rifampin accumulation in wild-type M. tuberculosis increases in the presence of reserpine, consistent with a lowlevel efflux pump 36 ; . Higher concentrations in the microenvironment may be more able to overcome the effects of the pump. Once inside the cell, rifampin's macrocyclic ring acts by inhibition of an intracellular target, rpoB. Rifampin forms a very stable drug-enzyme complex with rpoB, a process that is complete within 10 min of incubation and that is not enhanced by a longer incubation 23, 46 ; . We theorize that higher peak concentrations may enable the achievement of higher rifampin intracellular concentrations, making it more likely to inhibit poor-affinity rpoB rifampin binding sites in relatively resistant subpopulations. Since all measures of microbial effect microbial killing, resistance suppression, and PAE ; are concentration dependent, it is the size of the rifampin dose rather than the time above the threshold which will have a major impact on rifampin's effect. When one examines the population PKs of patients treated with 600 mg of rifampin 35 ; and takes into account the fact that the rifampin MIC90 for clinical isolates is 0.125 mg liter 29 ; , then many patients are expected to achieve rifampin AUC MIC and Cmax MIC ratios associated with suboptimal microbial killing and resistance suppression. Therefore, higher doses of rifampin will likely improve both microbial killing and resistance suppression, as long as patients can tolerate them. This lends experimental PK-PD support to the calls for the use of higher doses by Peloquin 34 ; and Weiner and colleagues.
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Wisdom consists of the choice of the best, among the facts accessible to Understanding. It r oe upssh , n ident pr e n gaybthog em nt n Iit th e r poe t sad t os'oe t i er tsh ef s i spontaneous intelligent and comprehensive submission, to a gift which it perceives as the dominant one. As such it is discrimination between Good and Evil, the Knowledge of the two opposites. If Understanding is total Knowledge, Wisdom is the use of which it is made. It is in some way the superior aspect, being the result of the action of Faith and Charity, of the Mercury Principle and the Salt Principle. Wisdom makes us judge all things by judging them according to the highest of Causes, from which all others depend and which itself depends on no other. It is by this virtue that the Adept can reach the highest degree of knowledge accessible to humankind here below, since this knowledge does not live in the event of general perception, nor in Intelligence as knowledge of Good and Evil, but in the event of specific perception, which is, all in all, the Knowledge of Good alone, of its complete knowledge. And here finally is Charity, which is the basis of the birth of Wisdom within us. In fact, absolute Charity, as we have seen, flows from an act of complete love, by which Man wishes for God the Infinite Good that Faith allows him to know Him, and he desires, for himself and for all other Beings, this same Good, inseparable from God. Seeing that he only seeks Good; having understood it, defined it, he no longer knows how to confuse it with its opposite. In all that the trawl-net of his understanding of things will bring, o h v i `os itsin God, it is the act of total love which will serve him as a f ie' s sn le touchstone. Wisdom is the purifying filter of the action of Understanding within him and rifaximin.
11 Narang P K, Lewis R C, Bianchine J R. Rifabutin absorption in humans: relative bioavailability and food effect. Clin Pharmacol Ther 1992; 52: 335341. Cocchiara G, Strolin Benedetti M, Vicario G P, et al. Urinary metabolites of rifabutin, a new antimycobacterial agent, in human volunteers. Xenobiotica 1989; 19: 769780. Iatsimirskaia E, Tulebaev S, Storozhuk E, et al. Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin Pharmacol Ther 1997; 61: 554562. Bennett P N, John V A, Whitmarsh V B. Effect of rifampicin on metoprolol and antipyrine kinetics. Br J Clin Pharmacol 1982; 13: 387391. Bocherding S M, Bastian T L, Self T H, Abou-Shala N, Leduc B W, Lalonde R L. Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism. Antimicrob Agents Chemother 1992; 36: 15531558. Ohnhaus E E, Brockmeyer N, Dylewicz P, Habicht H. The effect of antipyrine and rifampin on the metabolism of diltiazem. Clin Pharmacol Ther 1987; 42: 148156. Ohnhaus E E, Park B K. Measurement of urinary 6 -hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol 1979; 15: 139145. Perucca E, Grimaldi R, Frigo G M, Sardi A, Monig H, Ohnhaus E E. Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects. Eur J Clin Pharmacol 1988; 34: 595599. Vital Durand D, Hampden C, Boobis A R, Park B K, Davies D S. Induction of mixed function oxidase activity in man by rifapentine MDL 473 ; , a long-acting rifamycin derivative. Br J Clin Pharmacol 1986; 21: 17. Ged C, Rouillon J M, Pichard L, et al. The increase in urinary excretion of 6 -hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br J Clin Pharmacol 1989; 28: 373387. Ohnhaus E E, Breckenridge A M, Park B K. Urinary excretion of 6 -hydroxycortisol and the time course measurement of enzyme induction in man. Eur J Clin Pharmacol 1989; 36: 3946. Dickinson J M, Mitchison D A. In vitro properties of rifapentine MDL473 ; relevant to its use in intermittent chemotherapy of tuberculosis. Tubercle 1987; 68: 113119. Scavizzi A, Baldelli F, Capparelli G, et al. In vitro susceptibility of mycobacterial isolates from AIDS patients. J Chemother 1995; 7 Suppl 4 ; : 8789. 24 Keung A, Eller M G, McKenzie K A, Weir S J. Single and multiple dose pharmacokinetics of rifapentine and its active metabolite 25-desacetyl-rifapentine in man: Part II. Int J Tuberc Lung Dis 1999; 3: 437444. Gillum J G, Israel D S, Polk R E. Pharmacokinetic drug interactions with antimicrobial agents. Clin Pharmacokinet 1993; 25: 450482. Park B K, Breckenridge A M. Clinical implications of enzyme induction and enzyme inhibition. Clin Pharmacokinet 1981; 6: 124. Park B K, Kitteringham N R, Pirmohamed M, Tucker G T. Relevance of induction of human drug-metabolizing enzymes: pharmacological and toxicological implications. Br J Clin Pharmacol 1996; 41: 477491. Leinweber F-J. Possible physiological roles of carboxylic ester hydrolases. Drug Metab Rev 1987; 18: 379439. Vernon A. USPHS Study 22, the rifapentine clinical trial. TB Notes 1996; 1: 1820. Yan B Y, Zhu L Z, Chang F Y. A controlled clinical trial of DL473-containing regimens of chemotherapy for bacillary pulmonary tuberculosis: results at 3 years [abstr]. Rev Respir Dis 1990; 141: A435.
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Rifapentine and Isoniazid in the continuation phuse of a 6-month regimen. Interim report: no activity of Isoniazid in the continuation phase Tarn CM, Chan SL, Kam KM, Sim E, Staples D, Sole KM. Al-Ghusein H, Mitchison DA. International Journal of `Tuberculosis and Lung Disease 2000, 4 3 ; , 262 and riluzole.
Aren't resources from Drug Endangered Child Protection Act used to assist local LE with kids removed from homes of meth users and producers? Arian Campo-Flores: Such pressures are increasingly applied by Congress from districts ravaged by the drug.They were highly critical of an admin proposal to cut funds from 2 federal grant programs aimed to help local LE [so] much of the funding was restored. Atlanta GA: My daughter, 23, is a meth addict.Her addiction has nearly killed us both. What is the single best thing each of us can do to combat this? Not just on a personal level, this isn't going to go away because the government is fighting it, it's not going to go away until enough of us are doing what we should--but what is that? Arian Campo-Flores: Tough question.public awareness--people may be less prone to try it if they know how destructive it is. Learn to cope with stress without resorting to something like meth.Thanks to all of you for great questions. 2005 Newsweek, Inc.
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RIFAPENTINE is an antibiotic whose antimicrobial spectrum is similar in scope to other rifamycin analogues, including rifampin and rifabutin.13 Although the rifamycin antibiotics share a common chemical structure and mechanism of antibacterial activity, modifications of the basic rifamycin SV structure produce differences in the lipid solubility of each derivative.4 As a result, distinguishing differences in the pharmacokinetic profiles among members of this class of antibiotics have been identified, including differences in metabolic pathways, tissue penetration, and elimination half-life t1 2 ; .47 The absorption and disposition of rifapentine have been characterized in previous studies.6, 810 In contrast to rifampin, 5, 7 absorption of rifapentine following oral administration was enhanced by ingestion of food, 8, 9 whereas a high-fat meal had little effect on the extent of absorption of rifabutin.11 Similar to rifampin, 5, 7 the primary metabolic pathways of rifapentine are desacetylation at the 25-carbon by esterases.
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Alanine aminotransferase 10 times upper limit of normal ; hepatotoxicity occurred in 2 206 1% ; participants assigned to rifapentine and INH vs. 20 193 10% ; participants assigned to rifampin and pyrazinamide p 0.001 ; . The mean and median AST and ALT in participants assigned to rifapentine remained within normal limits and did not change over the first eight weeks of therapy, whereas mean, but not median, AST and ALT levels rose in participants assigned to rifampin and pyrazinamide Table 4 ; . Thus, most participants tolerated the rifampin pyrazinamide regimen with no evidence of liver injury, but a significant minority had substantial elevations in liver enzymes. No patient had symptomatic hepatotoxicity, and none was hospitalized. Hepatotoxicity did not occur before four weeks, and the majority of cases 13 20 ; were detected only at week 8, after treatment was completed. Participants treated with rifampin and pyrazinamide who developed hepatotoxicity had similar baseline characteristics as those who did not, with no differences in sex, age, initial AST or bilirubin levels or body weight Table 5 ; . Dosages of pyrazinamide and rifampin did not differ between those with and without liver toxicity. One patient who developed hepatotoxicity while taking rifampin and pyrazinamide also reported heavy alcohol intake, which was felt to contribute to this adverse event. All participants had resolution of hepatotoxicity within 4 to 12 weeks. Subsequent testing of 16 of the subjects with hepatotoxicity showed evidence of prior hepatitis A in all hepatitis A IgG antibody positive ; , but no evidence of acute viral hepatitis hepatitis A IgM antibody negative, hepatitis B core antigen negative ; . Other participants were not tested for hepatitis A antibodies, which are positive in the majority of Brazilian adults.21, 22.
Metchock, C. Pachucki, L. Stanton, A. Vernon, M. E. Villarino, Y. C. Wang, M. Weiner, and S. Weis. 2002. Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial. Lancet 360: 528534. Blumberg, H. M., W. J. Burman, R. E. Chaisson, C. L. Daley, S. C. Etkind, L. N. Friedman, P. Fujiwara, M. Grzemska, P. C. Hopewell, M. D. Iseman, R. M. Jasmer, V. Koppaka, R. I. Menzies, R. J. O'Brien, R. R. Reves, L. B. Reichman, P. M. Simone, J. R. Starke, and A. A. Vernon. 2003. American Thoracic Society Centers for Disease Control and Prevention Infectious Diseases Society of America: treatment of tuberculosis. Am. J. Respir. Crit. Care Med. 167: 603662. Bock, N. N., T. R. Sterling, C. D. Hamilton, C. Pachucki, Y. C. Wang, D. S. Conwell, A. Mosher, M. Samuels, and A. Vernon. 2002. A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1, 200 mg plus isoniazid in the continuation phase of tuberculosis treatment. Am. J. Respir. Crit. Care Med. 165: 15261530. Brooks, J. V., and I. M. Orme. 1998. Evaluation of once-weekly therapy for tuberculosis using isoniazid plus rifamycins in the mouse aerosol infection model. Antimicrob. Agents Chemother. 42: 30473048. Bryskier, A. 1999. Ansamycines, p. 947971. In A. Bryskier ed. ; , Antibiotiques, agents antibacteriens et antifongiques. Ellipses, Paris, France. Daniel, N., N. Lounis, B. Ji, R. J. O'Brien, A. Vernon, L. J. Geiter, M. Szpytma, C. Truffot-Pernot, G. Hejblum, and J. Grosset. 2000. Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens. Am. J. Respir. Crit. Care Med. 161: 15721577. Dickinson, J. M., and D. A. Mitchison. 1987. In vitro properties of rifapentine MDL473 ; relevant to its use in intermittent chemotherapy of tuberculosis. Tubercle 68: 113118. Gosling, R. D., L. O. Uiso, N. E. Sam, E. Bongard, E. G. Kanduma, M. Nyindo, R. W. Morris, and S. H. Gillespie. 2003. The bactericidal activity of moxifloxacin in patients with pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 168: 13421345. Grosset, J. 2003. Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary. Antimicrob. Agents Chemother. 47: 833836. Grosset, J., and B. Ji. 1998. Experimental chemotherapy of mycobacterial diseases, p. 5197. In P. R. Gandharam and P. Jenkins ed. ; , Mycobacteria, vol. II. Marcel Dekker, New York, N.Y. Hu, Y., A. R. Coates, and D. A. Mitchison. 2003. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47: 653657. Ji, B., N. Lounis, C. Maslo, C. Truffot-Pernot, P. Bonnafous, and J. Grosset. 1998. In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42: 20662069. Ji, B., C. Truffot-Pernot, C. Lacroix, M. C. Raviglione, R. J. O'Brien, P. Olliaro, G. Roscigno, and J. Grosset. 1993. Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. Am. Rev. Respir. Dis. 148: 15411546. Langdon, G., J. J. Wilkins, P. J. Smith, and H. McIlleron. 2004. Consecutivedose pharmacokinetics of rifapentine in patients diagnosed with pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 8: 862867. Lenaerts, A. M., S. E. Chase, A. J. Chmielewski, and M. H. Cynamon. 1999. Evaluation of rifapentine in long-term treatment regimens for tuberculosis in mice. Antimicrob. Agents Chemother. 43: 23562360. Lounis, N., A. Bentoucha, C. Truffot-Pernot, B. Ji, R. J. O'Brien, A. Vernon, G. Roscigno, and J. Grosset. 2001. Effectiveness of once-weekly rifapentine and moxifloxacin regimens against Mycobacterium tuberculosis in mice. Antimicrob. Agents Chemother. 45: 34823486. Lubasch, A., I. Keller, K. Borner, P. Koeppe, and H. Lode. 2000. Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers. Antimicrob. Agents Chemother. 44: 26002603. Maher, D., P. Chaulet, S. Spinaci, and A. Harries. 1997. Treatment of tuberculosis: guidelines for national programmes, 2nd ed. World Health Organization, Geneva, Switzerland. McCune, R. M., Jr., W. McDermott, and R. Tompsett. 1956. The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug. J. Exp. Med. 104: 763802. Miyazaki, E., M. Miyazaki, J. M. Chen, R. E. Chaisson, and W. R. Bishai. 1999. Moxifloxacin BAY12-8039 ; , a new 8-methoxyquinolone, is active in a mouse model of tuberculosis. Antimicrob. Agents Chemother. 43: 8589. Nuermberger, E. L., T. Yoshimatsu, S. Tyagi, K. Williams, I. Rosenthal, R. J. O'Brien, A. A. Vernon, R. E. Chaisson, W. R. Bishai, and J. H. Grosset. 2004. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am. J. Respir. Crit. Care Med. 170: 11311134. Piessens, W., and E. Nardell. 2000. Pathogenesis of tuberculosis, p. 241260. In L. B. Reichman and E. Hershfield ed. ; , Tuberculosis: a comprehensive international approach, vol. 144. Marcel Dekker, New York, N.Y and rituxan.
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Twelve men and four women, mean age, 3 6 + - 9 years, received a single 600-mg oral dose of rifapentine in an open-label, randomized two-way, complete crossover study.
ROBERT A. AUGUSTYNIAK, 1 HEIDI L. COLLINS, 1 ERIC J. ANSORGE, 1 NOREEN F. ROSSI, 2 AND DONAL S. O'LEARY1 1 Department of Physiology, Wayne State University School of Medicine; and 2Department of Medicine, John D. Dingell Veterans Administration Medical Center, Detroit, Michigan 48201 and rms.
Rifapentine and its 25-desacetyl metabolite have demonstrated in vitro activity against rifamycin-susceptible strains of Mycobacterium tuberculosis including cidal activity against phagocytized M. tuberculosis organisms grown in activated human macrophages. In vitro results indicate that rifapentine MIC values for M. tuberculosis organisms are influenced by study conditions. Rifapentine MIC values were substantially increased employing egg-based medium compared to liquid or agar-based solid media. The addition of Tween 80 in these assays has been shown to lower MIC values for rifamycin compounds. In mouse infection studies a therapeutic effect, in terms of enhanced survival time or reduction of organ bioburden, has been observed in M. tuberculosis-infected animals treated with various intermittent rifapentine-containing regimens. Animal studies have shown that the activity of rifapentine is influenced by dose and frequency of administration. Susceptibility testing for Mycobacterium tuberculosis Breakpoints to determine whether clinical isolates of M. tuberculosis are susceptible or resistant to rifapentine have not been established. The clinical relevance of rifapentine in vitro susceptibility test results for other mycobacterial species has not been determined. CLINICAL TRIALS A total of 722 patients were enrolled in Clinical Study 008, an open label, prospective, randomized, parallel group, active controlled trial, for the treatment of pulmonary tuberculosis. This population was mostly comprised of Black 60% ; or Multiracial 31% ; patients and the mean standard deviation age was 37 11 years. Treatment groups were comparable with respect to age and race. The percentage of male patients was higher in the rifapentine combination group 80% ; than in the rifampin combination group 73% ; . The study was divided into two phases on the basis of dosing frequency. For the first phase, designated as the Intensive Phase, 361 patients were randomized to receive rifapentine, isoniazid, pyrazinamide, and ethambutol for 60 days and 361 patients were randomized to receive rifampin, isoniazid, pyrazinamide, and ethambutol for 60 days. Ethambutol was to be discontinued once baseline susceptibility test results were available. ; Rifapentine and isoniazid were each administered at a fixed dose regardless of body weight. Rifampin, pyrazinamide, and ethambutol were administered based on body weight according to Table 2-1. Note: All drugs were administered daily in the Intensive Phase except for rifapentine which was administered twice weekly. During the second phase, designated as the Continuation Phase, 321 patients who had received rifapentine in the Intensive Phase continued to receive rifapentine and isoniazid once weekly for up to 120 days. Three hundred seven patients who had received rifampin in the Intensive Phase continued to receive rifampin and isoniazid during the Continuation Phase twice weekly for up to 120 days. Rifampin and isoniazid were administered based on body weight according to Table 21. Patients in either treatment group were scheduled to receive study drug over a 180-day period with a subsequent 24-month follow-up. Additionally, both treatment groups received pyridoxine Vitamin B6 ; over the 180-day treatment period and rifapentine.
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AGE-DEPENDENT CEREBROVASCULAR DILATIONS 17. Leffler, C. W., A. L. Fedinec, and M. Shibata. Prostacyclin receptor activation and pial arteriolar dilation after endothelial injury in piglets. Stroke 26: 21032111, 1995. Leffler, C. W., R. Mirro, L. J. Pharris, and M. Shibata. Permissive role of prostacyclin in cerebral vasodilation to hypercapnia in newborn pigs. Am. J. Physiol. 267 Heart Circ. Physiol. 36 ; : H285H291, 1994. 19. Liu, S. F., A. A. Hislop, S. G. Haworth, and P. J. Barnes. Developmental changes in endothelium-dependent pulmonary vasodilatation in pigs. Br. J. Pharmacol. 106: 324330, 1992. Mirro, R. D. W. Busija, W. M. Armstead, and C. W. Leffler. Histamine dilates pial arterioles of newborn pigs through prostanoid production. Am. J. Physiol. 254 Heart Circ. Physiol. 23 ; : H1023H1026, 1988. 21. Nitter, W. H., L. F. Johnsen, and M. Eriksen. Acute effects of indomethacin on cerebral blood flow in man. Pharmacology 51: 4855, 1995. Nowicki, P. T., and C. A. Nankervis. The role of the circulation in the pathogenesis of necrotizing enterocolitis. Clin. Perinatol. 21: 219234, 1994. Okamoto, H. A. G. Hudetz, R. J. Roman, Z. J. Bosnjak, and J. P. Kampine. Neuronal NOS-derived NO plays permissive role in cerebral blood flow response to hypercapnia. Am. J. Physiol. 272 Heart Circ. Physiol. 41 ; : H559H566, 1997. 24. Ottosson, A. I. Jansen, and L. Edvinsson. Characterization of histamine receptors in isolated human cerebral arteries. Br. J. Pharmacol. 94: 901907, 1988. Parfenova, H. M. Shibata, S. Zuckerman, R. Mirro, and C. W. Leffler. Cyclic nucleotides and cerebrovascular tone in newborn pigs. Am. J. Physiol. 265 Heart Circ. Physiol. 34 ; : H1972H1982, 1993. 26. Pearce, W. J., A. D. Hull, D. M. Long, and L. K. Longo. Developmental changes in ovine cerebral artery composition and reactivity. Am. J. Physiol. 261 Regulatory Integrative Comp. Physiol. 30 ; : R458R465, 1991. 27. Pearce, W. J., A. D. Hull, D. M. Long, and C. R. White. Effects of maturation on cyclic GMP-dependent vasodilation in ovine basilar and carotid arteries. Pediatr. Res. 36: 2533, 1994. Sandor, P. K. Komajati, M. Reivich, and I. Nyary. Major role of nitric oxide in the mediation of regional CO2 responsiveness. J. Cereb. Blood Flow Metab. 14: 4958, 1994. Satoh, H., and J. Inui. Endothelial cell-dependent relaxation and contraction induced by histamine in the isolated guinea-pig pulmonary artery. Eur. J. Pharmacol. 97: 321324, 1984. Schumann, P., O. Touzani, A. R. Young, L. Verard, R. Morello, and E. T. MacKenzie. Effects of indomethacin on cerebral blood flow and oxygen metabolism: a positron emission tomographic investigation in the anaesthetized baboon. Neurosci. Lett. 220: 137141, 1996 and robaxin.
Several mechanical techniques may enhance pharmacological fibrinolysis. Passage of a micro-wire through an occlusion during IA fibrinolytic procedures is a form of augmented fibrinolysis, not only directly disrupting the clot but also increasing penetration of fibrinolytic agent throughout the target thrombus.36 Endovascular US techniques to enhance enzymatic, intra-arterially delivered fibrinolytic agents are being developed in a manner complementary to external US techniques to enhance intravenously administered fibrinolytics. The EKOS MicroLysUS infusion catheter EKOS Corp ; system for augmented thrombolysis was tested in a small, multicenter safety and feasibility trial within 6 hours after onset of anterior and 13 hours of posterior circulation ischemia. Partial or complete recanalization was achieved within 1 hour of therapy start in 8 of 57% ; , and symptomatic hemorrhagic transformation occurred in 2 of ; .37 The Interventional Management of Stroke Trialists are currently investigating a strategy of upfront intravenous tPA followed by IA tPA administered via the EKOS catheter for lytic augmentation.
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