3,645 research outputs found
Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents
No full textDevelopment of a malaria vaccine candidate based on virosome technology
No full textMalaria is an infectious disease caused by protozoan pathogens of the genus
Plasmodium. The most important species affecting humans is P. falciparum
transmitted by the bite of female Anopheles mosquitoes during a blood meal. About
40% of the world’s population is exposed to the parasite and 350 to 500 million cases
of disease and more than one millions deaths are reported every year. Almost 80%
of these cases occur in sub-Saharan Africa, where mainly children younger than five
years and pregnant women are affected. Due to problems with arising resistance of
mosquitoes against insecticides and parasites against drugs, the development of a
malaria vaccine is an urgent need. It has been shown more than 30 years ago that
sterile protection against malaria infection is feasible by vaccination with irradiated
sporozoites. Since then many malaria vaccine candidates have been developed but
there is no vaccine on the market to date.
We have established a strategy to develop synthetic peptides of P. falciparum
antigens for inclusion in a multi-stage multivalent malaria subunit vaccine based on
the immunopotentiating reconstituted influenza virosome (IRIV) technology. IRIVs are
an already registered delivery/adjuvant system based on liposomes incorporating
influenza surface proteins hemagglutinin and neuraminidase. IRIVs enhance and
facilitate the delivery of antigens to antigen presenting cells. This technology allows a
stepwise lead peptide optimization based on parasite-binding properties of antibodies
elicited after immunization of experimental animals with virosomally-formulated
peptide-phospholipid conjugates. In this thesis the development steps of three
peptide antigens are described: UK-39 a peptide derived from the sporozoite antigen
circumsporozoite protein (CSP), AMA49-CPE derived from the blood-stage protein
apical membrane antigen 1 (AMA-1) and FB-23 derived from the blood-stage protein
serine repeat antigen 5 (SERA5). All optimized peptides induced parasite crossreactive
antibodies in experimental animals. Virosomal formulations of the antigens
UK-39 and AMA49-CPE were carried into a phase 1 clinical trial. Both vaccine
components were safe and immunogenic in malaria-naïve volunteers. Two
immunizations with appropriate doses of UK-39 or AMA49-CPE were enough to
induce high titers of parasite-binding antibodies. Combined delivery of the two
peptides did not interfere with the development of an antibody response to either of
the two antigens. The antibody responses were affinity maturated and long-lived,
indicating the formation of B cell memory. Purified total IgG from UK-39 immunized
volunteers inhibited sporozoite migration, invasion and development in a dose
dependent manner. Further clinical trials with this two-component vaccine candidate
are ongoing and new peptide candidates like FB-23 have been developed and are
now ready for preclinical and clinical profiling
Steady-State Pharmacokinetics of Nevirapine Extended-Release Tablets in HIV-1 Infected Children and Adolescents: An Open-Label, Multiple Dose, Cross-Over Study.
No full textPharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents.
No full textOBJECTIVES: To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents. DESIGN: Phase I, nonrandomized, open-label study in two stages. METHODS: Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200 mg twice daily) combination antiretroviral regimen. RESULTS: Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757 ng/ml (680), respectively; area under the plasma concentration-time curve over 12 h was 4050 (3602) and 6141 ng h/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses. CONCLUSION: Etravirine 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials
Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children
No full textObjective. To compare the immunogenicity and safety of a virosome-adjuvanted influenza vaccine (Inflexal V; Berna Biotech, Berne, Switzerland) and a split influenza vaccine (Fluarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) in children. Subjects and methods. The subjects, 453 children ages 6 to 71 months, were stratified into primed and unprimed and age groups (6 to 35 and 36 to 71 months) and then randomized 1:1 to receive virosome-adjuvanted (n = 224) or split influenza vaccine (n = 229), a half or full dose was given intramuscularly according to age. Unprimed children received a second dose after 4 weeks. Blood samples (n = 326) collected pre-and 28 days postvaccination were analyzed by hemagglutination inhibition test. Safety assessments were made at baseline and follow-up visits by the investigators and by parents for the 4 days after vaccinations. Results. Both vaccines induced an effective immune response. Seroconversion rates (≥4-fold titer rise) against the WHO recommended strains A/New Caledonia (H3N2), A/Moscow (H1N1) and B/Hongkong (B) were 80.1, 66.0 and 90.4% for the virosome-adjuvanted and 75.9, 62.9 and 89.4% for the split influenza vaccine, respectively. Unprimed children's seroconversion rates for H3N2 were significantly higher (P = 0.02) for the virosome-adjuvanted (88.8%) than for split influenza vaccine (77.5%). Seroprotection rates (titer of ≥ 40) for H3N2, H1N1 and B, respectively, were 87.8, 80.1 and 90.4% after vaccination with the virosome-adjuvanted vaccine and 82.9, 78.2 and 89.4% after the split influenza vaccine. Unprimed children's seroprotection rate was significantly higher (P = 0.03) for H3N2 after the virosome-adjuvanted (88.8%) than those for the split influenza vaccine (78.3%). Equivalent geometric mean titer fold increases were evident for both vaccines. No serious adverse events were seen. Pain/tenderness, redness and swelling/induration was found in 25.4, 11.2 and 8.9% for the virosome-adjuvanted vaccine and in 24.0, 9.2 and 6.1% for the split influenza vaccine, respectively. The rates of fever, malaise/irritability and shivering was 6.3, 11.6 and 2.7% for the virosome-adjuvanted vaccine and 8.3, 11.8 and 2.6% for the split influenza vaccine, respectively. Conclusions. The virosome-adjuvanted influenza vaccine showed greater immunogenicity over the split influenza vaccine in unprimed children and showed a trend toward better immunogenicity in the rest of the study population. Both vaccines were well-tolerated
Breaking through the Silence: Illegality of Performing Resuscitation Procedures on the Newly-Dead
No full textIsraeli author Daniel Sperling brings to a light a disturbing practice that is taking place in some teaching hospitals throughout the world - the practice of resuscitation procedures on newly dead patients without the consent of the next-of-kin. Mr. Sperling examines some of the policies and procedures in place to prevent such practice and also looks at the ethical principles that should guide such procedures. The paper also reviews the general issue of consent in the context of medical decision-making and discusses potential legal claims that might be available to persons who have not been consulted or informed before such procedures are performed. The evolving jurisprudence surrounding the treatment of the newly dead is analyzed and Mr. Sperling concludes by suggesting ways to improve upon the procedures currently in place at some teaching facilities
Konnatale Toxoplasmose
No full textZusammenfassungBei einer primären Toxoplasmose in der Schwangerschaft besteht für den Fetus das Risiko einer konnatalen Infektion durch diaplazentare Transmission von Toxoplasma gondii. Das Risiko einer fetalen Infektion nimmt dabei mit der Schwangerschaftsdauer zu, während die Schwere der Symptomatik mit zunehmendem Gestationsalter abnimmt. Bei den meisten infizierten Neugeborenen finden sich klinisch inapparente Infektionen, aber auch postnatal unauffällige Kinder sind einem Risiko von späteren Folgeschäden ausgesetzt. Neben neurologischen Entwicklungsstörungen ist vor allem das Risiko einer Retinochoroiditis von Bedeutung, die sich auch erst im späteren Leben manifestieren kann. Eine frühzeitige Erkennung einer Primärinfektion in der Schwangerschaft ist Voraussetzung, um durch eine frühzeitige anti-parasitäre Therapie, das Risiko einer fetalen Schädigung zu reduzieren. Durch eine post-natale Therapie kann vermutlich zusätzlich das Risiko der Langzeitkomplikationen gesenkt werden. Neugeborene mit Verdacht auf eine konnatale Toxoplasmose müssen sorgfältig hinsichtlich einer konnatalen Infektion untersucht werden und Säuglinge mit einer gesicherten Infektion benötigen langfristige Nachuntersuchungen hinsichtlich möglicher Spätschäden, insbesondere der Manifestation einer Retinochoroiditis.</jats:p
Ad Serenißimum Principem ac Dn. Dn. Augustum Iuniorem, Ducem Brunovicensium & Lunaeburgensium ... In Luctuoso Obitum ... Dorotheae Anhaltinae, &c. Coniugis Beatissimae memoriae Allocutio : Stylo Humili / Paulus Sperling. f.
No full textTractatus physico-medicus de morbis totius substantiae et cognatis quaestionibus
No full textpro D. Daniele Sennerto, facult. medicae in Witteberg. academia professore & seniore &c. contra D. Johannem Freitagium, medic. in Groningae & Omlandiae academia profess. Po. conscriptus a M. Johanne SperlingenBogensignaturen: A-N
Highlights der neuen Leitlinie zur Diagnostik und Therapie der Tuberkulose im Kindes- und Jugendalter
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