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Immunocompromised mouse model, we infected mice i.p. with 1 104 blastospores of CP. Test compound s ; either alone or in combination were administered orally by gavage 6 h postinfection and once daily thereafter for 5 days. A control group received 0.1 ml of saline by the same route as the placebo regimens. Organs of dead and killed mice at the 19th day after infection were collected for H&E periodic acid Schiff staining, homogenized in sterile saline, diluted, and spread onto sabouraud dextrose agar plates. Colony counts were determined after 48 h at 35C for calculation of geometric means. Comparative efficacy assessed by changes in the fungal density in kidney, lung, and brain tissue of the infected mice after treatment, percent survival, and MST were undertaken for each test compound s ; either alone or in combination. Data obtained from four consecutive experiments showed that preparations of either BEA or KTC did not have any significant therapeutic effect on the survival rate of infected mice compared with the placebo group Fig. 4 ; . The course of infection indicates that the MST was 8.9 1.4, 9.3 and 8.4 0.6 days for the placebo control, 0.5 mg kg BEA, and 0.5 mg kg KTC-treated groups, respectively Table 2 ; , and all of the mice in these groups died at day 10 after infection. Increasing doses of KTC prolonged significantly P 0.01 ; the MST to 14.2 1.8 and 19.4 2.0 days for the 10 mg kg and 50 mg kg KTC-treated groups, respectively. The remaining fungi [log10 cfu cell g ; ] in kidney was reduced from 8.9 to 7.6 and 5.5, respectively, as was the case in brain and lungs. However, the dosage of 50 mg kg administered in mice caused high liver toxicity and, for example, sildenafil without prescription.
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1. Repta, A.J. 1981 ; Alteration of Apparent Solubility through Complexation, Techniques of Solubilization of Drugs, ed. M Decker pp. 135-157 2. Higuchi, T., Connors, K. 1965 ; Advances in Analytical Chemistry and Instrumentation, ed. C Reilley Vol 4 pp. 117-212 3. Okimoto, K. et al, 1996 ; "The Interaction of Charged and Uncharged Drugs with Neutral HP-B-CD ; and Anionically Charged SBE7-B-CD ; B-Cyclodextrins, " Pharmaceutical Research, 13 2 ; , 256-264 4. Okimoto, K. 1994 ; University of Kansas unpublished research and starlix.
Ministry of Social Justice and Empowerment 13. CHILDLINE 14. Cochrane reviews in acute respiratory infections, cystic fibrosis and Airways groups in collaboration with Cochrane collaboration and South Asia Cochrane network. PGIMER 14. Promoting Kangaroo Mother Care in Indiawith juvenile rheumatoid arthritis. 16. Detection of anti-diphtheria and anti-tetanus antibodies in children with HIV infection. 17. Growth of Head and Face in Patients with Juvenile Rheumatoid Arthritis: A Mixed Longitudinal Study. 18. Growth of sub-cutaneous fat and muscle in transfusion dependent beta-thalassemia children: a mixed longitudinal anthropometric study. 19. Behavioral and developmental profile of young children with attention deficit hyperactivity disorder. 20. Neuropsychological profile of children with attention deficit hyperactivity disorder. 21. Glivec Imatinib mesylate ; in chronic myeloid leukemia in children. Participation in the ` Glivec International Patient Assistance Program GIPAP ; , in India, 'approved by the Max Foundation and Novartis Pharma A.G. 22. Treatment of chronic hepatitis C virus infection with interferon alfa and ribavarin in patients with transfusion dependent thalassemia 23. Randomized controlled trial to study the efficacy of fenugreek in the treatment of inadequate breast milk output 24. Television viewing habits of children and adolescents and their parental attitudes. 25. Role of spirulina in children with asthma. 26. Sildenaf9l in Persistent Pulmonary hypertension in Newborn. 27. Clinical and investigative profile of children with suspected interstitial lung disease with special reference to ventilation scintigraphy. 28. Effect of dietary supplementation with spirulina in children with bronchial asthma. Departmental 29. Growth of cranio-facial region of children with Down Syndrome: a mixed longitudinal study. 30. A longitudinal study of physical growth of Punjabi children from birth to 18 years of life. 31. A community based longitudinal auxological assessment of rural Haryanavi children. 32. Mixed longitudinal study of physical growth and pubertal changes in transfusion dependent beta-thalassemia children during adolescence. 240 PGIMER initiative 15. Comparison of IgM rheumatoid factor with IgG and IgA rheumatoid factors in children.
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Patients were excluded from the sildenafil trial in the general population if they had penile anatomical defects, a primary diagnosis of another sexual disorder eg premature ejaculation ; , spinal cord injury, any major psychiatric disorder not well controlled with treatment, poorly controlled diabetes mellitus, active peptic ulcer disease, history of alcohol or substance abuse, major hematologic, renal or hepatic abnormalities, or a recent stroke or myocardial infarction, or if they were receiving nitrate therapy and tagamet.
| Sildenafil chemical bondIn this controlled study, a new PDE5 inhibitor was associated with a prolonged duration of action, an attribute that may minimize the limitations of symptomatic treatment by enlarging the window of efficacy. The initial enthusiasm regarding oral PDE5 inhibitors was due to their simplicity and convenience relative to alternative therapies for ED, many of which required significant lifestyle accommodations in order to plan and execute a successful sexual encounter. Newer generation agents that further reduce the demands of therapy in regard to planning sexual activity are likely to be well received by patients who cannot always be confident when intimacy will occur. Large, controlled studies comparing PDE5 inhibitors are needed to further evaluate differences in onset and duration. The ability of tadalafil to provide more rapid erections than placebo over 24 hours is consistent with a half-life of approximately 17.5 hours. While the pharmacokinetic differences between PDE5 inhibitors is discussed in the next section, the activity observed in this RigiScanTM study has been amply reinforced by the phase III data in which 81% of tadalafil-treated patients reported improved erections in four 12-week on-demand protocols Brock et al. AUA 2002, Abstract 713 ; . In those four trials, which included 972 patients, efficacy was consistent in mild-to-severe ED of psychogenic, organic, or mixed etiology. Following regulatory approval of vardenafil, there were several anecdotal reports of patients who achieved a response on the newer agent after failing sildenafil, an observation that has provided preliminary support for the potential for differences among drugs in this class. The approval of a third agent is expected to further expand choice for oral ED therapy, particularly as the differences between tadalafil and sildenafil appear to be more marked than the differences between vardenafil and sildenafil. While there is no comparison of duration of effect between PDE5 inhibitors, a clinical study by Porst et al confirmed that tadalafil continued to exert improvement on erectile function over 36 hours, demonstrating that the long half-life of this agent translates into a long duration of activity. The ability of any PDE5 inhibitor to provide benefit when a prior PDE5 inhibitor was ineffective needs to be formally evaluated, but objective differences between drugs in this class provide a theoretical basis for differences in response overall as well as differences in response in the individual patient. Interpatient variability in relative benefits from a drug therapy is a common phenomenon, but patient preferences for ED therapy may have a particular influence on the likelihood of treatment success. Even modest differences in PDE5 inhibitor activity may be clinically important when the patient's experience is affected. Due to this potential for interpatient variability, the expansion of oral therapies for ED may yield an incremental increase in the proportion of patients who are successfully managed even if overall success rates prove to be similar.
Q62 What are the optimum methods of management for sexual dysfunction in adults with Type 1 diabetes? Author Title Reference Yr N Price, D. E., Gingell, J. C., Gepi-Attee, S., Wareham, K., Yates, Boolell, M. 1998 ; . Sildenafil: Study of a novel oral treatment for erectile dysfunction in diabetic men. Diabetic Medicine, 15, 821-825. N 21 participants UK Research Design Aim Population Sites 2 Randomised controlled trial To assess the efficacy and safety of 25mg or 50 mg of sildenafil taken as a single dose, followed by once daily dosing for 10 days in diabetic men with ED. Penile plethysmography was used to measure rigidity at the base of the penis and at the tip of the penis below the glans. After 15min of continuous recording, a single dose of sildenafil or placebo 25mg or 50mg ; was administered. Using video's and magazines, visual sexual stimulation commenced 30min after dosing and continued for 90min. The duration min ; of penile rigidity greater than60% was monitored. Daily diary records of erectile activity grading scale 1-4 ; and a global efficacy question did the quality of their erections improve during the 10 days you took the treatment? ; were used to evaluate once-daily dosing with 25mg or 50mg of Sildennafil or placebo for 10 days. Sildenaful 25mg or 50mg Placebo Penile plethysmography RigiScan, Dacomed Corporation, Minneapolis, Minnesota, USA ; . Daily diary records of erectile activity grading scale 1-4 ; Global efficacy question did the quality of their erections improve during the 10 days you took the treatment? ; Type 1: N 7; Type 2: N 14 ; , Mean age 51yrs Age range: 42yrs-65yrs, Mean duration of diabetes 11yrs 3-32yrs ; Penile rigidity After a single dose of sildenafil, the adjusted geometric mean 95% CI ; duration min ; of penile rigidity greater than60% at the base of the penis during visual stimulation was significantly increased with 50mg of sildenafil compared with placebo 25mg sildenafil: 5.0 1.9-12.4 50mg sildenafil: 10.1 4.2-23.1, p 0.0053 versus placebo ; and placebo: 2.8 0.7-8.4 ; . At the tip of the penis the adjusted geometric mean duration of rigidity was 1.2 0.2-3.8 ; for 25mg of sildenafil, 2.2 0.7-6.0 ; for 50mg of sildenafil p 0.0126 vs placebo ; and 0.4 -0.2-2.1 ; for placebo. Daily diary records of erectile activity Both 25mg and 50mg doses of sildenafil significantly increased the total number of erections hard enough for sexual and temovate.
Clinicians from 1 to 16 y, the average being 2 y. Clinicians' assessment of the etiology of the men's erectile dysfunction was 52% psychogenic, 22% organic, 22% mixed, and 3% unclear. All patients received sildenafil and continued in psychotherapy. Some men were seen weekly, others every 2 months. The dose of sildenafil was adjusted as necessary to optimize the possibility that the patients could successfully accomplish intercourse. Patients were evaluated twice at approximately 5 weeks and again at 10 weeks after receiving the first sildenafil prescription. Qualitative data characterizing patients' responses were gathered and classified into 1 of 7 categories: four variants of success and three variants of failure. The first success category, maximum success S1 ; , applied to patients who, after taking the drug one or more times, no longer needed it to accomplish intercourse. Performance anxiety was diminished enough that the man's biological capacities were again sufficient. There were no partner complaints. The next best success category, drug-dependent success S2 ; , typified the case where sildenafil was always necessary to consummate a satisfying intercourse experience. Without sildenafil, the sexual experience was labeled as unsuccessful by one or both partners. The third category, drug-dependent success with the development of a new sexual symptom S3 ; , is self-descriptive. Although intercourse occurred, either the man or woman developed a desire, arousal, orgasmic, or pain symptom. Minimum success, improvement but no intercourse S4 ; , described the man who had an erection firm enough to engage in sexual intercourse, but who also had psychological resistances that prevented intercourse from occurring. The first category of failure, transient unsustainable improvement F1 ; , identified patients for whom sildenafol reliably generated a firm erection and intercourse occurred on occasion; however, the erection was not used by the couple, the ability to achieve an erection was not valued enough by them to behave sexually, or one partner developed a crippling sexual symptom such as aversion. The second failure category, resistance failure F2 ; , was given to patients or couples who were unable to overcome their reluctance to taking a drug. Finally, pharmacologic failure F3 ; described the group who, after dose adjustments and assurances that the drug was being properly taken, did not have any improvement in erectile ability. At the first follow-up visit, sildenxfil combined with psychotherapy was found to improve erections for 67% of the men the four success categories, S1 S4, plus the first failure category, F1 ; . Fifty-five percent of the sample was able to have successful intercourse S1 S3 ; . Fifty-two percent had ideal.
| Within von Keitz et al. Results of preference analysis for each of the three dose comparisons was presented in graphic form, alongside the overall preference result in the paper, and also in the text of the results section relating to patient preference. Blinding was maintained throughout the study and so the issue of the actual dose of medicine taken by patients might be considered of secondary importance compared to comparisons of `efficacious doses' of a medicine. Some patients n 74 ; randomised to skldenafil 50mg considered that it was sufficiently efficacious and therefore did not request upward titration. Therefore, comparison between sildenafil 50mg and tadalafil 20mg in this case compared `efficacious doses' of each medicine. Such comparison was of scientific merit. Comparison of tadalafil 20mg and sildenafil patients who were `denied' upward titration was the only comparison with obvious bias. Again these patients remained blinded to the fact that upward titration was denied and received an identical placebo tablet. Upward titration of sildenafil was `denied' in 34 of the 181 patients who completed the study. The limitation concerning the 35% capping of sildenafil titration was highlighted in the discussion section of the paper and in the conclusion section. However, the authors reaffirmed the overall result of the study, which was supported with the evidence that similar ratios of patient preference for tadalafil were seen in all three subgroups of sildenafil users including those on maximum dose therapy. Again this limitation was discussed in detail in both editorial comments, which were attached to the paper. Tadalafil 10mg was not used in the study design. Von Keitz et al reported the results of a study conducted in the US, Spain and Germany, between January and September 2002. Tadalafil was launched in Europe in 2003. It was stated in the discussion section of the paper that `When the study was designed, tadalafil 20mg was proposed as the recommended starting dose for ED treatment'. The discussion section of the paper and the Montorsi editorial noted that 10mg was the recommended starting dose in some countries and as mentioned above the European prescribing information was attached to the paper. Lilly therefore refuted Pfizer's allegation that von Keitz et al was scientifically `meaningless' and misled health professionals because of an `inappropriate comparison of maximum dose tadalafil with the lower doses of sildenafil'. This conclusion was supported by the reasons discussed above. Most significantly, there was evidence within the paper of appropriate comparisons at the maximum dose of each medicine. In addition, while the trial design did not provide appropriate comparisons at the starting doses, the overall result was supported by the fact that similar results were seen on analysis of the individual sildenafil doses and blinding of dose escalation was maintained. Furthermore, any potential limitations secondary to the dosages used in the trial design were made clear numerous times throughout the paper and in the accompanying editorials. Lilly stated that a blinded comparison of two medicines with different pharmacokinetic properties and terbinafine.
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After primary roots were removed, cucumber explants were put into petri dishes containing water control ; , 10 m of the auxin IAA Fluka, Buchs, Switzerland ; , or 10 m the NO donor SNP Merck, Darmstadt, Germany ; and kept at 25C for different periods according to the experiment. As a control, 200 m 2- 4-carboxyphenyl ; -4, 4, 5, potassium salt c-PTIO, Molecular Probes, Eugene, OR ; was added together with SNP or IAA. Where indicated, explants were incubated with 50 m of the GC inhibitor 6-anilino-5, 8-quinolinedione LY83583, Sigma-Aldrich, St. Louis ; or with 1 m of the cell-permeable cGMP derivative 8-Br-cGMP Sigma-Aldrich ; or with different concentrations of the PDE inhibitor sildenafil citrate 1-[[3- 6, 7-dihydro-1-methyl7-oxo-3 propyl-1 H-pyrazolo [4, 3-d] pyrimidin-5-yl ; -4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate ; , Viagra, Pfizer, New York ; as indicated. For preparation of sildenafil citrate, tablets of Viagra were ground up and dissolved in distilled water. The mix was shaken for at least 5 min and gently centrifuged to remove all the insoluble material. The concentrations of the compounds used for experiments were supported by published results Durner et al., 1998; Pagnussat et al., 2002.
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Among all patients who participated in placebo-controlled trials of sildenafil, the incidence of myocardial infarction was slightly lower among those taking the study medication.
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An inflow of blood, which then leads to an erection. Cyclic guanosine monophosphate cGMP ; is then hydrolysed back to the inactive GMP by phosphodiesteras type 5 PDE5 ; Anonymous, 1998 ; . The level of cGMP is therefore controlled by the activation of cyclic nucleotide cyclase and the breakdown by PDE5. It is the latter that sildenafil acts upon. Men who suffer from erectile dysfunction often produce too little amounts of NO. This means that the small amount of cGMP they produce is broken down at the same rate and therefore does not have time to accumulate and cause a prolonged vasodilatation effect. Sildenatil works by inhibiting the enzyme PDE5 by occupying its active site. This means that cGMP is not hydrolysed as fast and this allows the smooth muscle to relax leading to increased blood flow into the organ and therefore penile erection ch, ic.as , Department.
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INTRODUCTION: The Adult Treatment Panel ATP ; III recommendations, which were issued on May 15, 2001, are the first update from the National Cholesterol Education Program NCEP ; in nearly a decade with several significant changes from its previous guidelines. Although physicians have been encouraged to adhere to the NCEP guidelines for the treatment of hyperlipidemia, they lack the tools that present the information in a comprehensive, easy to use format. The objectives of the program are to provide highlights on the key changes in the management of hyperlipidemia as well as comparative information on lipid-lowering therapies with respect to clinical efficacy, safety, and cost in a pocket guide that practitioners can easily utilize at the point of care. METHODS: A clinical pharmacy workgroup was formed to develop a pocket reference card that focused on the assessment and treatment of hyperlipidemia for primary and secondary prevention of cardiovascular events in accordance to the ATP III recommendations. Information on lipid-lowering therapies including drug products available on the Health Net of California Recommended Drug List was also featured.
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TAXONOMY UPDATE ADD OR EDIT DRUG TAXONOMIES TAXONOMY NAME 1 ; 2 ; 3 ; AUDIT DIABETES EDUC TOPICS APCL DM NUTRITION TOPICS DM AUDIT DIET EDUC TOPICS DM AUDIT EXERCISE EDUC TOPICS DM AUDIT OTHER EDUC TOPICS DM AUDIT SMOKING CESS EDUC BGP GPRA EX EDUC TOPICS Enter ?? for more actions Jun 27, 2005 10: DESCRIPTION DM AUDIT DIABETES EDUC TOPICS PHOENIX IMS #9 DM AUDIT DIET EDUC TOPICS DM AUDIT EXERCISE EDUC TOPICS DM AUDIT OTHER EDUC TOPICS DM AUDIT SMOKING CESS EDUC BGP GPRA EX EDUC TOPICS Page: 1 of 1.
The Program for Minority Research Training in Psychiatry PMRTP ; is funded by the National Institute of Mental Health. Through it, the American Psychiatric Association sponsors training of minority medical students, psychiatric residents, and fellows who are interested in research by providing advice, placement assistance, tuition, stipends, travel and other expenses. The director of the program is James Thompson, MD; the project manager is Ernesto Guerra. For more information, call the toll-free number for the PMRTP 1-800-852-1390, or 202-682-6225, email eguerra psych , or write to PMRTP at the American Psychiatric Association, 1400 K Street NW, Washington, DC 20005.
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