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Source: IMS Health drug monitor 1999; EMEA and FDA data; Trouiller, et al. 1999 ; DALY: disability-adjusted-life years WHO World Health report, 2000, data are available at: : who.int whr ; 3 Anti-infectives class includes the following sub-classes: antibiotics, antituberculosis, antivirals, vaccines and immunoglobulins. 4 AIDS antiviral drugs 20 approved antiretrovirals and antiproteases ; and drugs for opportunistic infections 6 approved drugs ; are included. Atovaquone is quoted in two sub-classes malaria and opportunistic infections indication ; 5 Approved anti-tuberculosis drugs are: pyrazinamide, rifabutin, rifapentine. 6 - Antiparasitics drugs approved for a tropical disease indication: benznidazole, nifurtimox Chagas' disease albendazole helminthic infection liposomal amphotericin B, pentamidine reformulation of already approved drugs ; and eflornithine human African trypanosomiasis artemether, atovaquone, halofantrine, mefloquine malaria ivermectin onchocerciasis oxamniquine, praziquantel schistosomiasis ; . - Miltefosine is approved as a cytostatic and still under investigation for visceral leishmaniasis. * From: Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases : a deficient market and a public health failure. Lancet 2002, in press.
1. Krance RA, Hurwitz CA, Head DR, et al. Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases. J Clin Oncol. 2001; 19: 2804-2811. Gordon MS, Young ML, Tallman MS, et al. Phase II trial of 2-chlorodeoxyadenosine in patients with relapsed refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group ECOG ; , E5995. Leuk Res. 2000; 24: 871875.
Journal of Antimicrobial Chemotherapy DOI: 10.1093 jac dkg487 Advance Access publication 12 November 2003
Pear to outweigh the risks of treatment in areas endemic for hookworm, roundworm, schistosomiasis, and whipworm, 93-95 but further study focusing on the safety of drug treatments for neglected tropical diseases is needed, particularly for children and women. One challenge raised by the mass administration of neglected tropical disease drug treatments is that the dosing of several drugs eg, diethylcarbamazine, ivermectin, levamisole, praziquantel, pyrantel-oxantel ; requires individualization by weight or height
In order to evaluate the drug interaction, two in vitro studies were performed: a single drug exposure study and a drug combination exposure study. Single drug exposure study. Stock solutions of albendazole sulphoxide and praziquantel were prepared in DMSO and ethanol, respectively. To determine the concentration that produced 50% effect EC50 ; , working solutions of praziquantel and albendazole sulphoxide were prepared in culture medium to obtain concentrations from 0.005 to 0.04 mg mL and from 0.021 to 0.16 mg mL, respectively. Cysts incubated in the culture medium containing 0.0125% DMSO or 0.01% ethanol served as controls. Cell culture flasks were carefully filled with 5 mL of the culture medium containing each drug, DMSO or ethanol; 25 cysts were deposited into each flask and were incubated at 37 C with a 5% CO2 atmosphere and 98% relative humidity. The culture medium was changed every day. Each experiment was run in triplicate. During incubation, the cysts were observed every day for 11 days with an inverted light microscope Reichert, 569 ; and the mortality of the cysts was registered. The criteria to assess parasite mortality were loss of vesicular fluid, paralysis of membrane and collapse of parasites. The EC50 values and 95% confidence limits of praziquantel and albendazole sulphoxide were calculated by the log.
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Dongbao Yu et al. that most villagers in the region were infected through means other than daily water utilization. Villagers' awareness of schistosomiasis Around 82% 512 respondents ; of household heads thought that the main health threat to their communities was schistosomiasis, followed by hepatitis 9.6% ; , common cold 3.8% ; , diarrhoea 0.2% ; and other 4.5% ; . This suggests widespread recognition of the threat to health of schistosomiasis infection in endemic areas. Among those surveyed, 94.4% 593 persons ; could correctly explain how the infection was acquired, while only 5.6% of the respondents gave the wrong answer or did not know. Most household heads 89.8% ; were familiar with one or more symptoms of schistosomiasis. However, while 401 respondents gave the correct answers on how to prevent schistosomiasis, as many as 136 individuals 21.7% ; said there was no way to prevent infection and the remaining 14.2% said that they did not know. Only 17.8% of the respondents reported full confidence in the efficacy of praziquantel treatment; 65.6% were uncertain, 4.3% reported no confidence, and 12.3% do not know. Asked about their opinions on praziquantel treatment, 27.8% of the respondents said it was harmful to health, 40.0% disagreed and 32.2% did not know see Appendix for questions ; Table 2 ; . Willingness to pay for treatment and undertake voluntary control work Survey responses indicated low willingness to pay for the cost of curative services for schistosomiasis 181; 30.9% ; , but the majority of household heads 72.3% ; were willing to undertake voluntary work for schistosomiasis control assigned to them by the local government Table 3 ; . Willingness differed on the basis of endemicity. Villagers in Type II areas were most willing to pay for curative service, while villagers in Type I and Type III areas were less prepared to do so. On the other hand, villagers in Type I areas were most willing to undertake volunteer work involving manual labour, such as mollusciciding and environmental modification for snail control. The reasons given by respondents for their reluctance to pay for curative services were as follows. Most 50.3% ; believed that since treatment for schistosomiasis had been free in the past, it should continue to be free now; 28.7% felt that there were too many infections in the area and reduction was a government responsibility; the remaining respondents 18.8% ; stated that they could not afford to pay for the service or said that the service was too expensive. Hence most residents opposed to paying for curative services were influenced by the previous policy of free treatment for schistosomiasis, the only disease so treated in these areas. Those respondents 172 ; who gave reasons for their unwillingness to carry out schistosomiasis control work on a voluntary basis mentioned that they were already assigned too much voluntary work, such as work for water conservancy projects 43% ; , they had no time 40.1% ; , or it was not their business 11% ; . The remainder 5.8% ; were unable to give a reason and prevnar.
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The current first choice of drug is praziquantel, a isoquinoline-pyrazine derivative 2-cyclohexylcarbonyl1, 2, 3, ; Droncit, and other trade names ; . This has a single dose ED90 90% of the worms eliminated ; of 2.3 1.5-3.7 ; mg kg bw for E. granulosus 138 ; and of 4.6 2.1-10.1 ; mg kg bw for E. multilocularis. The recommended dose of praziquantel for dogs and cats is 5.0 mg kg bw for oral treatment and 5.7 mg kg bw for intramuscular administration. In these dosages, the drug is highly effective against immature and mature intestinal stages of E. granulosus, E. multilocularis, Taenia species and some other Cestode genera 10, 93, 138 ; . However, the drug is not ovicidal 124 ; . In most of the studies, a single oral administration of praziquantel 5.0 mg kg bw ; was 100% effective against E. granulosus and E. multilocularis in all of the treated dogs, and only in some trials low residual worm burdens were reported 10, 93 ; . For example, in one study a single treatment 5.0 mg kg bw per os ; of five dogs had an average efficacy of 99.9% against E. multilocularis 115 ; . Although the efficacy of praziquantel is highly reliable in almost all cases, the possibility of low residual worm burdens in some of the treated animals cannot be excluded, notably if mistakes of drug administration occur. According to a recent observation, 60 viable E. granulosus specimens were found in one of four dogs which had been experimentally infected with protoscoleces of the parasite and treated with correct doses of a combination of praziquantel, pyrantel embonate and febantel after 30 days. In addition to the living E. granulosus specimens, a single 75-cm long Spirometra erinacei tapeworm was recovered from this dog 68 ; . The reason for this apparent lack of full efficacy is unknown, but the case indicates that treatment failure may occasionally occur in practice. Praziquantel is available as tablets to be administered orally, and an injectable solution for intramuscular administration subcutaneous injection is less effective against Echinococcus ; 138 ; . A spot-on formulation for use in cats was 100% effective against Taenia taeniaeformis, Dipylidium caninum and E. multilocularis 44, 72 ; Medicated baits were used in the People's Republic of China for the treatment of dogs 65 mg praziquantel per bait ; 17 ; , and for treating of wild foxes in Germany 50 mg praziquantel per bait ; 119 ; . Praziquantel is safe safety index in dogs 36 ; to use in pregnant animals, and dogs tolerate high doses for extended periods without organ damage or disturbance to the reproductive processes 6, 126 ; . Epsiprantel, a more recently developed drug, is an isoquinoline-pyrazine derivative structurally similar to praziquantel: 2- cyclohexylcaronyl ; -4-oxo-, 1, 2, 3, ; . Epsiprantel Cestex ; is available as coated tablet for oral administration to dogs at 5.5 mg kg bw and to cats at 2.75 mg kg bw. The drug is highly efficacious against Taenia species and Dipylidium caninum in dogs and cats 18, 84, 93 ; , and also against Echinococcus species. In two studies 8, 134 ; , a single oral dose of 5.0 mg kg bw eliminated an average of 99.9% of the 28-day-old or 41-day-old stages of E. granulosus from dogs. However, in these trials only 2 out of 10 dogs were free of E. granulosus after treatment. A higher dose of 7.5 mg kg bw did not.
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Decd. do lay off the following articles to wit . Given under our hands and seals March the 8th 1852 .W. Blackwelder [#5271], D. G. Holbrook, Caleb Phifer [p. 377 misnumbered, should be p. 577 ; ] We the undersigned having been duly sworn proceeded to lay off one years provision for Esther Blackwelder [#527 1] widow of D. Blackwelder [#527] decd. and family and have laid off as follows to wit . submitted under our hands and seals this 17th day of February 1852 . Winecoff, Ibzan Cannon, D. Leitaker [p. 378 misnumbered, should be p. 578 ; ] Dower In pursuance of an order of Court made at January Sessions 1852, we whose names are hereunto annexed being summoned as jurors to lay off the one third of the lands and tenements of which the aforesaid David Blackwelder [#527] died seized and possessed of in the state aforesaid and we being duly summoned and sworn proceeded to view and divide and put her the said Esther Blackwelder [#527 1] widow of the aforesaid David Blackwelder decd. in possession of the same viz. including the mansion house, spring and other out houses in which the aforesaid David Blackwelder decd. dwelt next and before his death . stake in the Salisbury Road . containing forty-nine acres . Given under our hands and seals this 16th day of Febuary 1852 . Jul 1852, Third Monday: [p. 412 misnumbered, should be p. 612 ; ] Land Sale . obedience to an order of court at April Term last, I, W. Blackwelder [#5271] as administrator of David Blackwelder [#527] decd., after giving due notice proceeded on the 20th day of May 1852, at the late residence of the decd. to expose to public sale two tracts or parcels of land belonging to the estate of said David Blackwelder decd. on a credit of six months when and where R. W. Foard became the purchaser of one tract of sixty-seven acres at the price of eight hundred and five dollars, whereupon he the said R. W. Foard executed to me bond and security for the purchase money and E. R. Blackwelder [#5273] became the purchaser of the other tract of twenty-five acres at the price of one hundred and eighty dollars for which he also executed to me his note with security according to the terms of sale . Blackwelder Adm of David Blackwelder dec. Oct 1852, Third Monday: Jan 1853, Third Monday: [p. 436 misnumbered, should be p. 636 ; ] Deeds Deed from W. Blackwelder [#5271] administrator of David Blackwelder [#527] deceased to Robert W. Foard dated January 18th 1853 Deed from Monroe Blackwelder [#5243], Elizabeth Blackwelder [#524 1], Malvina Blackwelder [#5242], Rowan Blackwelder [#5245], Daniel M. Blackwelder [#5246], Elizabeth Blackwelder [#5244], Delilah Ingle [#5241] and Henry Ingle [#5241 1] to Charles Barnhardt dated June 7th 1852 and primaquine.
Crvopreservation techniques The leukapheresis and bone marrow products were cryopreserved in 10% dimethyl sulfoxide DMSO ; and 20% autologous plasma using a controlled-rate liquid nitrogen freezer Cryo-Med, Mt Clemens, Ml ; and stored in the vapor phase of a liquid nitrogen freezer. At the time of autologous bone marrow day 0 ; and or PBPC.
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Fig 4. A ; Comparison of M1mycer cells in the presence or abafter treatment with 11-6. Shown are photosence of -estradiol micrographs of May-GrUnwald-Giemsa-stained cytospin smears. Cells were treated with IL-6 for 4 days original magnification, X 300 ; . B ; Inductionof DNA fragmentation by IL-6 in M 1 lanes 1 and 2 ; . M 1mycer-6 lanes 3 and 4 ; . and M lmycer-6 plus fl-estradd lanes 5 and 6 ; . Cells were seeded at 0.1 X 106 mL, after 4 days were reseeded at the same concentration, and hm"ted after 7 days for DNA extraction. DNA extraction and electrophoresis were as described in Materials and Methods. Lanes 1. 3, and 5 were without IL-6; lanes 2, 4, and 6 were with IL-6 and primidone.
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The associations between potentially inappropriate medication use and selected population characteristics were evaluated by analysis of variance and logistic regressions. To assess use of potentially inappropriate medications during the 10-year period from 1987 to 1996, we compared findings from the 1996 MEPS with previously pub.
We thank all the doctors, midwives, and epilepsy specialist nurses who recruited patients and to the women with epilepsy who gave their consent to take part in the study and provided outcome data. We are grateful to the Epilepsy Research Foundation and Epilepsy Action for their support of this project. The study was made possible by a research grant from the Epilepsy Research Foundation and a number of educational grants from pharmaceutical companies Glaxo-Smith-Kline, Sanofi-Aventis, UCB-Phama, Janssen-Cilag, Pfizer. ; An internet based web site detailing the aims of the UK Epilepsy and Pregnancy register was made possible by a grant from Glaxo-Smith-Kline and probenecid.
Minor loss of joint space; and meniscal calcinosis. Thus, younger, more active patients with mild to moderate disease are ideal candidates for viscosupplementation. Patients with more severe disease can, and do, respond well to the therapy but this response tends to last for a shorter time than in those patients with mild to moderate disease.
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Prevention would be better than care Editor--Edwards et al point out that the main cause of HIV in prisoners is injecting drug use.1 Work done in Scottish prisons indicates that 4% of the male prison populaBMJ VOLUME 323 28 JULY 2001 bmj and praziquantel.
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Follow up 3 years' follow-up ; in patients undergoing autologous stem cell transplantation. Such experience has to be collected within a clinical study and analyzed by experts in the field and by regulatory authorities before healthy donors are routinely treated with growth factors. In general, a good history of clinical safety low incidences of adverse events and immunogenicity ; may be a more appropriate consideration for choosing a G-CSF product in these patients than any cost savings achieved with the use of a biosimilar and procaine.
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Fluke Corporation PO Box 9090, Everett, WA USA 98206 Fluke Europe B.V. PO Box 1186, 5602 BD Eindhoven, The Netherlands For more information call: U.S.A. 800 ; 443-5853 or Fax 425 ; 446-5116 Europe 31 40 ; 2 675 200 or Fax 31 40 ; 2 675 222 Canada 905 ; 890-7600 or Fax 905 ; 890-6866 Other countries 425 ; 446-5500 or Fax 425 ; 446-5116 Web access: : fluke.
1. Praziquantel is an anthelmintic used in both human and veterinary medicine. It is included in Annex II of Council Regulation EEC ; No 2377 90 for use is non-lactating sheep. The ADI was established at 0-0.17 mg kg bw. Pharmacologically active substance s ; Praziquantel Animal species Ovine Other provisions For use in non-lactating sheep only and procarbazine
AND J. C. CoRIIANI. 1988. Evaluation of praziquantel against infections induced Nanophyetus salmincola in coyotes and dogs. American Journal of Veterinary Research 49: 563-565. , J. S. CREENI, C. W. LL.vrluns, ANI ; B. R. LI, sI EI1. juvenile coyotes: 1987. Salmon Clinical poisoning evaluation disease and infecin and prevnar
The pathologist was also found to have been incompetent in several respects in performing the postmortem examination on Harry and to have failed in his duty as an expert witness. Delivering the GMC's verdict, the chairman, Peter Richards, said, "Whatever your own views, even if reasonable, you had a responsibility as an experienced forensic pathologist to consider whether test results might need to be openly discussed, before being discounted, in order to prevent any risk of a miscarriage of justice and procrit.
Praziquantel works for all types of blood flukes. Metrifonate and oxamniquine work for some kinds of blood flu'kes. For dosages see p. 377. Medicines should be given under direction of an experienced health worker.
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