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999. Available: : fhi en RH Pubs booksReports fpfinancing servcost ; 93. JOHN SNOW, INC. and WORLD HEALTH ORGANIZATION WHO ; . Do no harm: Injection safety in the context of infection prevention and control, training tools and job aids. Forthcoming ; 94. JOHN SNOW, INC. DELIVER. The logistics handbook: A practical guide for supply chain managers in family planning and health programs. Arlington, Virginia, John Snow, Inc. DELIVER, 000. 99. LANDE, R.E. New era for injectables. Population Reports, Series K, No. 5. Baltimore, Johns Hopkins School of Public Health, Population Information Program, Aug. 995. 3 p. 00. LEI, Z.W., WU, S.C., GARCEAU, R.J., JIANG, S., YANG, Q.Z., WANG, W.L., and VANDER MEULEN, T.C. Effect of pretreatment counseling on discontinuation rates in Chinese women given depomedroxyprogesterone acetate for contraception. Contraception 53 6 ; : 35736. Jun. 996. 07. MATHENY, G. Family planning programs: Getting the most for the money. International Family Planning Perspectives 30 3 ; : 3438. Sep. 004. 08. MAULDIN, W.P. and MILLER, V.C. Contraceptive use and commodity costs in developing countries, 994005. New York, United Nations Population Fund UNFPA ; , 994. 64 p. 09. MCCARRAHER, D. Factors to consider in adding injectables to CBD programs. Presented at the Community-Based Provision of Injectables: Current Developments and Collaboration for Action Meeting, Baltimore, JHPIEGO, Jan. 9, 006. 3. MERCER, A., ASHRAF, A., HUQ, N.L., HASEEN, F., UDDIN, A.H., and REZA, M. Use of family planning services in the transition to a static clinic system in Bangladesh: 99800. International Family Planning Perspectives 3 ; : 53. Sep. 005 MORRONI, C., MYER, L., MOSS, M., and HOFFMAN, M. Preferences between injectable contraceptive methods among South African women. Contraception 73 6 ; : 59860. Jun. 006. 5. NECOCHEA, E. and BOSSEMEYER, D. Standards-based management and recognitionA field guide: A practical approach for improving the performance and quality of health services. Baltimore, JHPIEGO, 005. 84 p. Available: : pdf aid.gov pdf docs PNADF43 ; 8. NERSESIAN, P., CESARZ, V., COCHRAN, A., MBOYANE, J., and SCHMIDT, K. Safe injection and waste management: A reference for logistics advisors. Arlington, Virginia, John Snow, Inc. DELIVER , 004. 39. PHILLIPS, J.F., HOSSAIN, M.B., HUQUE, A.A., and AKBAR, J. A case study of contraceptive introduction: Domiciliary depo-medroxyprogesterone acetate services in rural Bangladesh. Segal, S.J., Tsui, A.O., and Rogers, S.M., eds. In: Demographic and Programmatic Consequences of Contraceptive Innovations. New York, Plenum Press, 989. 748 p. 40. PIOTROW, P.T., KINCAID, D.L., RIMON, J.G.D., RINEHART, W., and SAMSON, K. Health communication: Lessons from family planning and reproductive health. Westport, Connecticut, Praeger, 997. 307 p. 4. POPULATION ACTION INTERNATIONAL. Defining reproductive health supplies: A survey of international programs. Washington, D.C. , Population Action International, Apr. 00. 8 p. 5. PROGRAM FOR APPROPRIATE TECHNOLOGY IN HEALTH PATH ; . Introducing auto-disable syringes and sharps disposal containers with DMPA. PATH, Jul. 9, 006. 0 p. Available: : path files SI CNVP5904 English ; 54. RAHMAN, M.B., JANOWITZ, B., CHOWDHURY, J.H., and JAMIL, K. Productivity and costs for family planning service delivery in Bangladesh: The government program. Associates for Community and Population Research, Jun. 996. 46 p. 56. RAO, R. and PANDIT, T. Nepal: Contraceptive security. Issues, findings, and recommendations. Arlington, Virginia, John Snow, Inc. DELIVER, Jan. 004. 30 p. Available: : portalprd.jsi pls portal docs PAGE DEL CONTENT PGG DEL PUBLICATION PG DEL COUNTRY RPT PG NEPAL CONTRACEPTIVE SECURITY R ; 6. ROGERS, E.M. Diffusion of innovations. 4th ed. Free Press, 995. 59 p. 63. ROSS, J., STOVER, J., and ADELAJA, D. Profiles for family planning and reproductive health programs: 6 countries. Futures Group, 005. 8 p. Available: : constellafutures Documents Profiles6FPed ; 64. ROUTH, S., ASHRAF, A., STOECKEL, J., and BARKAT-E-KHUDA. Consequence of the shift from domiciliary distribution to site-based family planning services in Bangladesh. Studies in Family Planning 7 ; : 889. Jun. 00. Available: : guttmacher pubs journals 7080 ; 65. RUMINJO, J.K., SEKADDEKIGONDU, C.B., KARANJA, J.G., RIVERA, R., and NASUTION, M. Comparative acceptability of combined and progestin-only injectable contraceptives in Kenya. Contraception 7: 3845. 005. SETTY, V. Organizing work better. Population Reports, Series Q, No Baltimore, Johns Hopkins Bloomberg School of Public Health, The INFO Project, Winter 004. Available: : infoforhealth pr q0 index.shtml ; 73. SHELTON, J.D. Contraception for women on first-line antiretrovirals ARVs ; . Baltimore, Johns Hopkins Bloomberg School of Public Health, The INFO Project, Mar. 5, Global Health Technical Briefs ; Available: : maqweb techbriefs tb5arv.shtml ; 75. SIMMONS, R., FAJANS, P., and LUBIS, F. Contraceptive.

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Table 3. Amino acid substitutions in GrlA, GyrA, GrlB, GyrB of the second and third step mutants resistant to ciprofloxacin C ; , moxifloxacin M ; , levofloxacin L ; , sparfloxacin S ; and trovafloxacin T ; Amino acid changes GrlAa, Ser-80 Pheb Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe Phe GrlA, Glu-84 Val Val Val Val Val GyrA, Ser-84 Leu Leu Leu Leu Leu Leu Leu GyrA, Glu-88 Lys Lys Lys Lys Lys GyrA, Ser-112 Pro Pro Pro Pro GrlB, Glu-422 Asp Asp Asp Asp Asp Asp Asp GrlB, Asp-432 Gly Gly Gly Gly Gly Gly Gly GrlB, Pro-451 Ser Ser Ser Ser Ser Ser Ser Ser GyrB, Pro-456 Ser Ser Ser.
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June 9, 2000--Provider Update: Generic substitution for Dilantin : Notified Providers as stated in the Provider Bulletin of May 12, 2000, PACE notified the physicians of all PACE cardholders currently receiving Dilantin of the impending mandatory substitution and provided a Medical Exception Form if the prescriber did not wish the cardholder to receive the generic. July 14, 2000--PACENET Deductible Reminder: Notified Providers that any providers refusing to submit PACENET deductible claims through the on-line claims adjudication system at the time of presentation or prior to dispensing the prescription are in violation of their PACE PACENET Provider Agreement. Failure to abide by the terms and conditions of the Provider Agreement could result in provider termination and or suspension of payments by the Department of Aging until such non-compliance is corrected. August 4, 2000--Dispensing Date & Nursing Home Providers: Notified Providers our Bulletin of April 7, 2000, instructed that all claims for cardholders residing in nursing homes are to be submitted to PACE on the date that they are dispensed. Subsequently, the Department has reviewed issues raised by nursing home providers and providers who service nursing homes regarding this requirement. Although the Department recognizes that it cannot dictate a nursing home's medication dispensing policy, the Program does encourage the submission of claims for those chronic maintenance drugs to be on monthly basis. The authorizations apply ONLY to those cardholders residing in nursing homes who are subject to the nursing home's controlled environment and internal drug utilization review policy. August 18, 2000--Vaniqa : Notified Providers that PACE will NOT reimburse for Bristol-Myers Squibb and Gillette's Vaniqa eflornithine HCL ; cream recently approved by the FDA for the treatment of unwanted facial hair in women. September 15, 2000--Other Prescription Coverage: Notified Providers that effective October 16, 2000, PACE will edit claims for PACE cardholders with dual coverage. Providers enrolled in other third party point-of-sale prescription plans must have the ability to ``dual bill.'' PACE is to be billed after the claim is adjudicated by the primary insurer but prior to dispensing. November 10, 2000--Reminder of Other Prescription Coverage: Notified Providers that PACE denies claims for cardholders identified as having other insurance if the provider submits the claim with an incorrect ``other coverage'' value. December 1, 2000--Manufacturers' Rebate: Notified Providers that Act 128-1992 amending the Lottery Fund Preservation Act, in part, requires all pharmaceutical manufacturers to have in effect a rebate agreement with the PACE Program if they wish to have their products covered. Sidmak Laboratories, Labeler Code 50111 is being added to PACE's non-participating list. Sidmak's products are no longer reimbursable effective December 18, 2000. December 15, 2000--Sidmak Laboratories Reinstatement: Notified Providers that the Department of Aging advises that Sidmak Laboratories, Labeler Code 50111 will continue to participate in the Manufacturers' Rebate Program. Providers should disregard the previous December 18, 2000 termination announcement. PACE PROVIDER BULLETINS: 1999 2 19 Kytril and Zofran : Reminder to providers that PACE will reimburse only on the 20% not reimbursed by DMER 2 19 99: Optometrists's Prescribing Privileges: Provides PACE Providers with a list of medications permitted by Department of Health regulation to be prescribed by optometrists. Warns providers to not dispense and bill the Program for pharmaceuticals that are prohibited by regulation from being prescribed by optometrists. 2 19 99: Optometrist's License Numbers: Notifies providers that Optometrists certified to prescribe and administer pharmaceutical agents for therapeutic purposes under section 4.1 of the Optometric Practice and Licensure Act are being issued a license with a suffix of ``T.'' 3 5 99: PACENET Deductible: Reminder to PACE Providers that the 0 PACENET deductible is accumulated based on each individual cardholder's enrollment year; not the calendar year. 4 9 99: Notified PACE Providers that effective May 14, 1999, PACE will mandate substitution on the following medications: Lasix , Depakene , Mysoline , Quinaglute Dura-tabs , Mexitil , Tegretol and all sustained-release Theophylline preparations. 4 9 99: Betoptic Solution: Notified PACE Providers that Alcon Laboratories had informed PACE that it had discontinued production of Betoptic solution in the 2.5 and 5 ml sizes. 4 30 99: Propulsid Drug to Drug Interactions: Notifies providers that effective May 10, 1999, PACE will review history across all providers and reject all prescriptions in the drug classes which are contraindicated for patients using Propulsid. 5 7 99: Drug Utilization Review Program: Notified Providers that effective May 15, 1999, several new and revised maximum daily dose criteria, duration criteria and duplicate criteria will be added to the PACE ProDUR Program. 7 2 99: Trovan Trovafloxacin Alatrofloxacin Mesylate ; : Notified Providers that effective July 6, 1999, PACE will deny all claims for Trovan . In accordance with FDA recommendations, PACE will reimburse for Trovan only through the Medical Exception Process. 7 2 99: Medicare Reimbursable Chemotherapeutics: Notified Providers that effective July 12, 1999, the following pharmaceuticals will be included with those products being reimbursed by the PACE PACENET Program at 20%: Oaklide and Neumega July 16, 1999--HISMANAL . Notified Providers that effective July 26, 1999, PACE will no longer reimburse for HISMANAL . This action is in response to Janssen Pharmaceutica informing the U.S. Food and Drug Administration that it has voluntarily decided to discontinue the manufacturing and distribution of HISMANAL 10 mg tablets.

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In-vitro fluoroquinolone activities Table I. Continued Organism no. of strains ; S. marcescens 20 ; Antimicrobial agent clinafloxacin trovafloxacin ciprofloxacin imipenem ampicillin aztreonam ceftazidime amikacin clinafloxacin trovafloxacin ciprofloxacin imipenem cefsulodin ceftazidime piperacillin amikacin clinafloxacin trovafloxacin ciprofloxacin imipenem piperacillin ceftazidime cefsulodin amikacin clinafloxacin trovafloxacin ciprofloxacin imipenem piperacillin ceftazidime cefsulodin amikacin clinafloxacin trovafloxacin ciprofloxacin imipenem penicillin G cefoxitin clindamycin metronidazole clinafloxacin trovafloxacin ciprofloxacin MIC mg L ; MIC50 MIC90 0.03 0.25 0.06 and ubiquinone. For any item to be covered by Medicare, it must: 1 ; be eligible for a defined Medicare benefit category, 2 ; be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member, and 3 ; meet all other applicable Medicare statutory and regulatory requirements. For the items addressed in this medical policy, the criteria for "reasonable and necessary" are defined by the following indications and limitations of coverage and or medical necessity. For an item addressed in this policy to be covered by Medicare, a written signed and dated order must be received by the supplier prior to delivery of the item. If the supplier delivers the item prior to receipt of a written order, it will be denied as noncovered. If the written order is not obtained prior to delivery, payment will not be made for that item even if a written order is subsequently obtained. If a similar item is subsequently provided by an unrelated supplier who has obtained a written order prior to delivery, it will be eligible for coverage. A group 1 mattress overlay or mattress E0180 E0189, E0196 E0199, A4640 ; is covered if the patient meets: A. Criterion 1, or B. Criteria 2 or 3 and at least one of criteria 4 7. 1 ; Completely immobile i.e., patient cannot make changes in body position without assistance. 2 ; Limited mobility i.e., patient cannot independently make changes in body position significant enough to alleviate pressure. 3 ; Any stage pressure ulcer on the trunk or pelvis. 4 ; Impaired nutritional status. 5 ; Fecal or urinary incontinence. 6 ; Altered sensory perception. 7 ; Compromised circulatory status.

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VOL. 45, 2001 TABLE 1. Gemifloxacin and trovafloxacin concentrations determined in urine by HPLC and by bioassay and AUC!

Collected for up to 96 postdosing, and the total radioactivity excreted in these matrices was determined by liquid scintillation counting. In addition, four dogs and four monkeys were orally administered trovafloxacin at a dose of 10 mg kg. Serial urine samples were collected from 0 to 48 postdosing. Aliquots 0.5 ml ; of each urine sample from dogs and monkeys were treated prior to assay by using each of the following three treatments: i ; buffering samples with a pH 3 phosphate buffer 0.025 M ; , ii ; incubation with 500 l of 0.1 N sodium hydroxide at 37 C for 1 h and then neutralization and buffering with the pH 3 buffer, and iii ; incubation with 10 l of Glusulase and 500 l of pH 4.5 buffer 0.13 M phosphate ; at 37 C for 1 h and then a treatment with the pH 3 buffer. The treated samples were analyzed for trovafloxacin. Determination of trovafloxacin in serum. The concentrations of trovafloxacin in serum and urine were determined by a reverse-phase high-performance liquid chromatography HPLC ; method with UV detection, as reported previously 13 ; . Following solid-phase extraction, chromatographic separation was accomplished by using a C18 column and a phosphate mobile phase 0.04 M H3PO4 acetonitriletetrabutyl ammonium hydroxide0.005 M D-4 reagent [83: 16.85: 0.05: 0.1; vol vol vol vol; pH 3] ; . Trovafloxacin and the internal standard a methyl derivative of trovafloxacin ; were detected by UV at A275. The calibration curves were linear over a concentration range of 0.1 to 20.0 g ml R2 0.999 ; . The average recoveries were greater than 70% for both compounds. The intraday and interday coefficients of variation in both urine and serum were less than 10%. Determination of trovafloxacin in tissue and body fluids. Tissue or body fluid trovafloxacin concentrations were determined by HPLC. Tissue samples 0.5 g or 0.5 ml ; were homogenized with 5 ml of extraction mixture 0.15 M H3ClO4 and 0.15 M H3PO4 in a 50% CH3OH aqueous solution ; and the internal standard, and the mixture was centrifuged at 1, 000 g. The supernatant was decanted and evaporated to dryness. The residue was redissolved in 2 ml phosphate solution 0.025 M KH2PO4 [pH 3.0] ; , which was extracted twice with 5 ml of ethyl acetate. Following evaporation of the ethyl acetate to dryness, the residue was redissolved in 0.5 ml of mobile phase, which was then washed with 1 ml of hexane. After the removal of hexane layer, the sample was introduced onto the HPLC column. The calibration curves were linear over a concentration range of 0.2 to 30.0 g g R2 0.998 ; . The average recovery was 60 to 70% for both trovafloxacin and the internal standard. Intraday and interday coefficients of variation were less than 5%. Serum protein binding and blood plasma ratios. Serum protein binding of trovafloxacin in rats, dogs, and monkeys was examined by an equilibrium dialysis method at nominal starting concentrations in serum of 1 and 5 g ml. Dialysis was performed in 1.36-ml dialysis cell blocks Equilibrium Dialyzer; Spectra Por, Houston, Tex. ; separated with Spectra Por membranes molecular weight cutoff, 12, 000 to 14, 000 ; . The membranes were prepared by sequentially soaking them in HPLC-grade water, 30% ethanol, and 0.1 M phosphate buffer pH 7.4 ; for 30, 60, and 30 min, respectively. The dialysis cells were immersed in a water bath at 37 C and were rotated on a dialysis wheel at 20 rpm. The time to reach equilibrium was previously determined to be 6 the end of dialysis, aliquots from both the serum and the buffer sides were collected for determination of trovafloxacin content by the HPLC-UV method. Each serum sample was dialyzed in duplicate, with postdialysis buffer and serum samples assayed in triplicate. The percentage of free trovafloxacin in serum was estimated, with adjustment for osmotically induced volume shifts across the membrane 1 ; . For determination of blood plasma ratios, fresh blood was collected from rats, dogs, and monkeys n 3 each ; in clear glass test tubes containing 20 IU of heparin per ml of blood. The pooled blood was cooled on ice until it was used, which was within 30 min of collection. To 20-ml scintillation vials containing 2 ml of blood, 0.01 Ci of [14C]trovafloxacin, and different amounts of nonlabeled trovafloxacin were added to make final trovafloxacin concentrations of 0.5, and 20 g ml. The trovafloxacin-spiked blood aliquots were incubated at 37 C for 20 min, after which time the plasma was separated by centrifugation. Aliquots of the plasma were then assayed for radioactivity by liquid scintillation counting. Blood plasma ratios were calculated as the ratio of the radioactivity in the whole blood to that in plasma. Pharmacokinetic analysis. Pharmacokinetic parameters were calculated by noncompartmental analyses 7 ; . The terminal phase rate constant z ; was estimated by least-squares regression analysis of the concentration-time data obtained over the terminal log-linear phase. The corresponding half-life t1 2 ; was ln 2 z. The area under the concentrationcalculated from the equation t1 2 time curves from time zero to infinity AUC0 ; was calculated by the linear trapezoidal rule with extrapolation to infinity. The maximum concentration of drug in serum Cmax ; was obtained directly from the concentration in serum data, with Tmax defined as the time of the first occurrence of Cmax. The systemic clearance CL ; was obtained as the ratio of intravenous dose AUC0 , and the volume of distribution Varea ; was estimated as CL z. The oral bioavailability F ; was calculated as the ratio of the dose-corrected AUC0 following oral and intravenous administration. Results are expressed as the mean and the standard deviation. The significance of the data was evaluated by Student's t test. Values of P of 0.05 were considered significant and valcyte.

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Fig. 3. Cellular response of the Crk-based reporter. Wild-type MEFs stimulated with H2O2 displayed a FRET increase in the cytosol over 20 min but no change in the nucleus a ; . Null cells did not display such an increase. An antiphospho-Y221Crk Western blot of crude cell lysates from NIH 3T3 cells transfected with the Crk-based indicator shows an increase in phosphorylation of the indicator on PDGF stimulation b ; . Phosphorylation is suppressed by pretreating cells with the Abl inhibitor STI-571. The emission ratio time course c ; for different regions of the PDGF-stimulated cell depicted in d shows a cytoplasmic increase in FRET followed by a dramatic FRET increase within the PDGF-induced membrane ruffles. Corresponding images of the YFP fluorescence show that the Abl reporter concentrates in the membrane ruffles e and valerian.

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