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Biomedical subjects

B Keller-Stanislawski

Publications and source records attributed to B Keller-Stanislawski.

13 recordsLinked to original sources
PubMed2004

[Thiomersal and immunisations].

Thiomersal was used in the 1930s for the first time for the preservation of vaccines to prevent bacterial and fungal contamination. Thiomersal is an organic compound containing 49% mercury (Hg) by weight. It is generally well known that mercury and its compounds, including thiomersal, ethylmercury, and methylmercury, act as nephro- and neurotoxicants, however, at much higher doses than used in vaccines. In the 1990s the question of toxicity of thiomersal in vaccines was reassessed since the numbers of vaccines recommended for routine administration to infants and children, and therefore the cumulative thiomersal dose in children, increased in some countries. Various international committees (European Agency for the Evaluation of Medicinal Products, EMEA, US Public Health Service/American Academy of Pediatrics, Institute of Medicine, IOM) concluded after an extensive risk/benefit analysis that scientific evidence is inadequate to reject or explicitly recommend thiomerosal-containing vaccines for children. However (in line with the global goal of reducing exposure to mercury), they recommended promoting the elimination of thiomerosal from paediatric vaccines. This has largely been achieved in Germany. Today a child in Germany can be immunised in accordance with the official recommendations (STIKO) almost without the administration of thiomerosal (residual amounts). Results of new pharmacokinetic and epidemiological studies are discussed. The evidence available to date does not support the hypothesis of a potential relationship between neurodevelopmental disorders and thiomersal-containing vaccines.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

[Adverse events following immunisation in Germany from 1.1.2001 to 31.12.2003].

The German Protection Act against Infection (Infektionsschutzgesetz) came into effect on 1 January 2001. Physicians must report complications after vaccination to local heath authorities according to Article 6 No. 3. . The local heath authorities send notifications to the Paul-Ehrlich-Institut (PEI). Between 1 January 2001 and 31 December 2003, a total of 941 reports from local public health authorities were registered in a central database and assessed. Compared to the number of reports of suspected adverse drug reactions sent to the PEI independently in the same time period by the pharmaceutical companies and the German Drug Commissions (Arzneimittelkommissionen) (n=2.338), underreporting has to be considered. Age distribution in the reports from local public health authorities revealed the following pattern: 33.8% of reports concerned adults (18-59 years old), 25.4% children aged 1-6 years, 16.9% infants, 11.3% adults (>60 years), 8.9% children aged 7-14 years and 1.9% adolescents aged 15-17 years. In 1.8% the age was not reported. The causal relationship was assessed by the PEI as proven in 0.2%, probable in 41.6%, likely in 27.5% and unlikely in 6.6%. In 11.9% assessment was not possible and in 11.8% of the reports follow-up information has been requested. Comparison to the reports from other sources revealed no major difference in respect to quality and content.

Adolescent↗
PubMed2001

Causality assessment of suspected virus transmission by human plasma products.

BACKGROUND: Causality assessment of reports on suspected virus transmission is crucial for early detection of infectious plasma products. Commonly used algorithms, such as the WHO criteria, do not meet the specific requirements for causality assessment of suspected virus transmission. STUDY DESIGN AND METHODS: A special algorithm, based on nucleic acid amplification and gene sequencing technology, effectiveness of validated virus-inactivation methods, empirical data concerning the safety record of the product, and information on batch-related infection clusters, was developed. The algorithm is focused on laboratory test results or otherwise standardized data, with few clinical data being required. To facilitate practical application, the algorithm has been converted into a graphical decision tree. RESULTS: The feasibility of the algorithm is shown by causality assessment of sample cases. Three cases are presented with the details of each case used in the 12-question checklist. The answers provided by the checklist led to the causality classification. CONCLUSION: The algorithm is a tool for evaluating reports of suspected virus transmission in a standardized manner. It thus has the potential to improve early signal detection in pharmacovigilance of plasma products by confirmation or exclusion of suspected infectivity in most cases.

Adult↗
PubMed1999

A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool.

Recently, several clusters of hepatitis A have been observed among hemophiliacs linked to factor VIII concentrates treated for virus inactivation solely with the solvent/detergent (S/D) method, a procedure that does not affect nonenveloped viruses such as the hepatitis A virus (HAV). A new outbreak of hepatitis A in six hemophiliacs treated with the same lot of a factor VIII preparation occurred recently in Germany. The objective of the study was to clarify whether these diseases were caused by the administration of the S/D-treated plasma product, rather than a community-acquired infection. Polymerase chain reactions designed to detect HAV nucleic acid have been carried out in the implicated factor VIII lots, in the corresponding plasma pools, and in serum samples of four out of six infected individuals. The nucleic acid sequences were determined in samples that resulted in positive amplification products. HAV sequences were found in one of the two plasma pools used for manufacture of the incriminated product, in the incriminated lot itself, and in all recipient sera tested so far, although the latter were collected up to 7 weeks after the onset of jaundice. The sequences obtained were completely identical, revealing a unique HAV strain of genotype IA. This study provides conclusive evidence that hepatitis A can be transmitted by factor VIII concentrates treated solely by the S/D procedure for virus inactivation. This inactivation method is not effective against nonenveloped viruses. Since a number of hepatitis A transmission episodes have been described with such preparations during the past 10 years, their continued use seems to be questionable unless additional virus removal or inactivation steps are introduced to prevent the transmission of nonenveloped viruses. Molecular approaches again proved to be reliable tools for elucidating the chain of virus transmission.

Adult↗
PubMed1994

Reactions of human keratinocytes in vitro after application of nicotine.

Nicotine is rapidly taken up by human keratinocytes (HaCaT cells) and after 3 h the uptake is approximately 50% of maximum. Cotinine, a metabolite of nicotine, was detected, thus demonstrating the metabolism of nicotine in HaCaT cells. Low nicotine concentrations (0.1-200 micrograms/ml) did not influence the incorporation rate of thymidine into DNA or amino acids into proteins. Inhibition of DNA and protein synthesis was only observed at concentrations > 200 micrograms/ml. After application of 400 micrograms/ml nicotine, the cells were vacuolated. This process was reversed after nicotine withdrawal. At low nicotine concentrations, no changes in microtubules and actin filaments could be detected. However, in the presence of nicotine (1-10 micrograms/ml), keratin filaments showed a more orderly pattern that controls, and the expression of the suprabasal keratins 1 and 10/11 was induced and increased according to the concentration of nicotine. The number of cornified envelopes also increased markedly. Nicotine concentrations > 100 micrograms/ml led to a disarrangement of keratin filaments and to a decrease in keratin expression and cornified envelope formation. Our results suggest that nicotine at concentrations up to 100 micrograms/ml is not an irritant but may induce cornification of the skin.

Cell Differentiation↗
PubMed1993

Transdermal nicotine substitution: pharmacokinetics of nicotine and cotinine.

The use of tobacco has resulted in major health related problems worldwide. Nicotine replacement is one of the most promising strategies in smoking cessation. The in vivo delivery rate and the pharmacokinetic properties of a recently developed transdermal nicotine system (TNS) was investigated in three separate studies. Two sizes (16 cm2 and 24 cm2) of the patches were tested. Mean daily nicotine delivery, expressed by a first order kinetic, varied between 0.9 and 1.0 mg/cm2 patch. The different sizes of the patches led to linearly dose-related nicotine plasma Cmax- and AUC-values. The nicotine levels achieved were in the same range with those of other nicotine patches and the chewing gum. As a result of multiple dose kinetic, no significant accumulation of nicotine was observed. Mean elimination half-life of nicotine after removal of the patches (3.5 +/- 1.8 h for the larger patch and 4.5 +/- 1.9 h for the smaller patch) was longer than reported values after i.v. administration, which was reported to vary between 40 and 120 min.

Administration, Cutaneous↗
PubMed1993

Transdermal nicotine in smoking cessation and involvement of non-specific influences.

The efficacy of a nicotine transdermal therapeutic system (TTS) (available size 10, 20 and 30 cm2; nicotine delivery rate = 0.7 mg/cm2/24 h) as an aid for smoking cessation, was evaluated in a randomized, single-blind, placebo-controlled, monocenter study using 160 heavy-smokers (> 20 cigarettes/day), male and female, who were divided into two matched parallel groups. The nicotine replacement treatment lasted for 3 months and was carried out according to the manufacturers recommendations. Abstinence was defined as smoking no cigarette during the last week of each month and COHb-levels < or = 1.2%. Efficacy was assessed using abstinence rates, withdrawal symptoms and cigarette consumption. Although at the commencement of the study all subjects expressed a high motivation to stop smoking, about a third were lost to follow-up at 4 weeks. This was attributed mainly to the lack of counselling and group dynamics. The greatest effect on smoking cessation and cigarette consumption was attributable to a non-specific aspect of treatment, i.e. the motivation to stop smoking on application of the first patch. On an intention-to-treat basis (all subjects), abstinence rates were 24% and 18% after 1 month, 24% and 14% after 2 months and 14% and 6% after 3 months for the nicotine-TTS and placebo-TTS, respectively. Nicotine-TTS was at least twice as effective as placebo in maintaining nicotine abstinence. The superiority of the nicotine-TTS was supported by the trend to a higher craving-for-cigarettes score and significantly higher blood COHb and cigarette consumption in the non-abstainers treated with placebo.

Administration, Cutaneous↗
PubMed1992

Pharmacokinetic profile of a novel slow release preparation of molsidomine.

A novel slow release preparation containing 24 mg molsidomine has been investigated in 6 healthy subjects. Individual concentration/time-profiles after the tablet showed two separate concentration peaks at 2.2 h and 15.0 h. The relative bioavailability of the slow release preparation in comparison to an aqueous solution of molsidomine was 0.67. The in vivo dissolution profile revealed either a progressive decrease in dissolution velocity caused by altered physico-chemical conditions in the ileum and the colon or a progressive reduction in the absorption constant. In all subjects deconvolution revealed a punctual increase in absorption about 15 h post-dose, coinciding with the second peak of the concentration/time-profile. Therapeutic plasma levels of molsidomine (greater than 5 ng.ml-1) were not maintained over 24 h by this slow release formulation.

Adult↗
PubMed1992

Pharmacokinetics of nicotine and cotinine after application of two different nicotine patches under steady state conditions.

Tobacco use has resulted in major health related problems world-wide. Transdermal nicotine replacement therapy is one of the most promising strategies in smoking cessation. In the present trial the pharmacokinetic properties of two matrix patches (A and B) were characterized and compared after daily application on day 4. Predose nicotine concentrations on day 4 with patch B were higher than with patch A (12.7 +/- 9.5 ng/ml vs. 8.3 +/- 5.3 ng/ml). With patch A there was a steeper increase up to the peak level, followed by a decline gradually up to 24 h. 24 h after application predose levels were reached again, demonstrating absence of significant accumulation of nicotine. The calculated elimination half-lives of nicotine (3.4 +/- 1.8 h after patch A and 3.3 +/- 2.0 h after patch B) were longer than after i.v. application (published values range from 40 to 120 min). Under steady state cotinine concentrations remained constant.

Administration, Cutaneous↗
PubMed1992

[Pharmacokinetics of low-dose isosorbide dinitrate and metabolites after buccal or oral administration].

The kinetics of isosorbide dinitrate (ISDN; CAS 87-33-2) and its metabolites isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) were examined after buccal and oral administration of 5 mg ISDN. Twelve healthy volunteers were included in a randomized cross-over study. The mean dose-corrected AUCs for total nitrate in serum after the two different preparations were in the same range. The relative bioavailability of ISDN applied buccally, however, was more than twice that after oral application. The metabolism of ISDN differed depending on the route of administration, where the AUC-ratios ISDN: IS-2-MN: IS-5-MN were 1:2.7:19.4 after buccal and 1:5.7:53.4 after oral application respectively. The absorption rate constants Ka for ISDN and the MRT after buccal and oral application did not differ significantly. The same holds for the mean residence time.

Administration, Buccal↗
PubMed1991

Pharmacokinetics of nicotine after application of a 30 cm2 nicotine patch under steady-state conditions.

Transdermal nicotine systems (Nicotinell 30) were applied daily to the skin of healthy nicotine-dependent smokers for 4 days. Blood samples were taken for the measurement of nicotine and cotinine in plasma using capillary gas chromatography with nitrogen detection. The plasma concentration-time profiles of nicotine and cotinine and the pharmacokinetic parameters cmax, tmax, AUC and the elimination half-life were determined under steady-state conditions. Nicotine levels after application of the 30 cm2 patch were in accord with published values for 10, 20 and 2 x 20 cm2 patches. The elimination half-life of nicotine after removal of the patch was longer than reported values obtained after i.v. application.

Administration, Cutaneous↗
PubMed1990

[Bioavailability of two slow-release formulations of verapamil].

The bioavailability of 2 slow release formulations (test (P) and reference (R)) of verapamil was investigated in a study with a randomised cross over design, 20 healthy male subjects were included. The mean peak plasma concentration (36.1 +/- 13.1 ng/ml) of the test preparation was reached after 3.75 +/- 0.8 h. The control preparation (R) produced peak values of 34.4 +/- 8.1 ng/ml after 5.6 +/- 3.1 h. MRT (P) was 17.6 +/- 8.2 h and for (R) was 21.1 +/- 7.5 h after (R). The 95-%-confidence interval of the two preparations differed by more than 20%. The release rate of (P) is slower than that of (R).

Adult↗