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Biomedical subjects

G Voss

Publications and source records attributed to G Voss.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.

BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.

Adult↗
PubMed2001

Characterization of HIV-specific proliferative T cell responses in HIV-infected persons.

Virus-specific helper T cell responses are thought to be an important host defense in HIV infection. The proliferative responses to HIV p24, p55, and gp120 were tested in a cohort of 27 HIV-infected subjects. Vigorous proliferative responses directed at the Gag protein with stimulation indices in excess of 6 were detected in 10 of the individuals tested but an Env-specific response was present in only 1 subject. Viral load and proliferative activity to Gag were inversely correlated in untreated individuals. Proliferation was also observed in some individuals treated in the chronic phase of infection, and responses were maintained over time in the absence of detectable viremia. Positive proliferative responses could also occasionally be detected in treated persons with CD4(+) cell counts below 200/microl. Thus, vigorous Gag-specific proliferative responses are present in a minority of HIV-infected individuals and can be detected in individuals receiving highly active antiretroviral therapy at advanced disease stages. Proliferative responses are maintained for an extended time period in the presence of antiviral therapy.

Adult↗
PubMed2001

Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria.

After initial successful evaluation of the circumsporozoite-based vaccine RTS,S/SBAS2, developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research, protective efficacy of several regimens against Plasmodium falciparum challenge was determined. A controlled phase 1/2a study evaluated 1 or 2 standard doses of RTS,S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received standard, one-half, or one-fifth doses. RTS,S/SBAS2 was safe and immunogenic in all groups. Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge, malaria developed in 7 of 10 who received 1 dose, in 7 of 14 who received 2 doses, in 3 of 6 who received 3 standard doses, in 3 of 7 who received 3 one-half doses, in 3 of 4 who received 3 one-fifth doses, and in 22 of 23 control subjects. Overall protective efficacy of RTS,S/SBAS2 was 41% (95% confidence interval, 22%-56%; P=.0006). This and previous studies have shown that 2 or 3 doses of RTS,S/SBAS2 protect against challenge with P. falciparum sporozoites.

Adolescent↗
PubMed2001

Absorption and disposition of levocetirizine, the eutomer of cetirizine, administered alone or as cetirizine to healthy volunteers.

The primary objective of the present study was to compare the absorption and disposition of levocetirizine, the eutomer of cetirizine, when administered alone (10 mg) or in presence of the distomer. An additional objective was also to investigate the configurational stability of levocetirizine in vivo in humans. The study was performed in a randomized, two-way cross-over, single-dose design with a wash-out phase of 7 days between the two periods. A total of 12 healthy male and 12 healthy female volunteers were included in the study. Bioequivalence can be concluded from the analysis of the pharmacokinetic parameters of levocetirizine when administered alone or as the racemate cetirizine. No chiral inversion occurs in humans when levocetirizine is administered, i.e. there is no formation of the distomer. When comparing the pharmacokinetic characteristics of levocetirizine and the distomer, the apparent volume of distribution of the eutomer is significantly smaller than that of the distomer (0.41 and 0.60 L/kg, respectively). For an H1-antagonist a small distribution volume can be considered as a positive aspect, both in terms of efficacy and safety. Moreover the non-renal clearance of levocetirizine is also significantly lower than that of the distomer (9.70 and 28.70 mL/min, respectively), which constitutes an additional positive aspect particularly as far as metabolism-based drug interactions are concerned. The information collected in the present study on the pharmacokinetics of levocetirizine and the distomer provide additional reasons for eliminating the distomer and developing levocetirizine as an improvement on cetirizine.

Absorption↗
PubMed2001

LAHYSTOTRAIN development and evaluation of a complex training system for hysteroscopy.

Hysteroscopy has already become an irreplaceable method in gynaecoloic diagnosis and therapy. In the diagnostic case the hysteroscope with a 30 degrees optic is insert transvaginally, in the therapeutic case the resectoscope with a 12 degrees optic is used. The endoscopic intervention requires special surgical skills for endoscope handling and remote instrument control. To acquire these skills currently hands-on training in clinical praxis has become standard, which is linked with higher danger for the women. To overcome current drawbacks of traditional training methods the European project LAHYSTOTRAIN was set up, that tries to combine Virtual Reality (VR), Multimedia (MM) technology, and Intelligent Tutoring Systems (ITS) to develop an alternative training system for hysteroscopic interventions. The first prototype of the LAHYSTOTRAIN demonstrator has been shown on several European conferences. An evaluation of the system was performed, with the idea, to collect feedback and impressions, that should be considered in further developments. This paper presents the LAHYSTOTRAIN prototype and the results of these evaluations.

Artificial Intelligence↗
PubMed2001

ICAPS an integrative computer-assisted planning system for pedicle screw insertion.

Robot Assisted Surgery (RAS) Systems win more and more recognition in the field of orthopaedics. Especially in Hip Surgery RAS has proved to be suited for application in medical routine. Often Robot Assisted Surgery Systems consist of a planning- and an interoperative component. According to specifications done with the planning software the tools are driven. Benefits of the robot assisted surgery should be higher precision and a better surgical outcome. In the co-operation project of several Fraunhofer Institutes "RoMed" (Robots and Manipulators for Medical Application) an exemplary application of robot aided spine surgery is developed [1]. The planning software used in this context is proposed in this article.

Bone Screws↗
PubMed2000

Simian immunodeficiency virus evades a dominant epitope-specific cytotoxic T lymphocyte response through a mutation resulting in the accelerated dissociation of viral peptide and MHC class I.

The ability of an AIDS virus to escape from immune containment by selective mutation away from recognition by CTL was explored in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. CTL recognition of a previously defined common viral mutation in an immunodominant SIVmac Gag epitope was evaluated. CTL were assessed for their ability to recognize a SIVmac Gag protein with a single residue 2 (T --> A) replacement in the minimal epitope peptide bound by the MHC class I molecule Mamu-A*01. SIVmac Gag-specific CTL lysed Mamu-A*01+ target cells infected with recombinant vaccinia virus expressing the wild-type but not the mutant Gag protein. In addition, CTL recognized the mutant epitope peptide less efficiently than the wild-type virus peptide. In studies to determine the mechanism by which the mutant virus evaded CTL recognition, this peptide was shown to bind Mamu-A*01 in a manner that was indistinguishable from the wild-type peptide. However, experiments in which an increasing duration of delay was introduced between peptide sensitization of target cells and the assessment of these cells as targets in killing assays suggest that the mutant peptide with a T --> A replacement had a higher off-rate from Mamu-A*01 than the wild-type peptide did. Therefore, these findings suggest that AIDS viruses can evade virus-specific CTL responses through the accelerated dissociation of mutant peptide from MHC class I.

Animals↗
PubMed2000

Crystal structures and thermotropic properties of alkyl alpha-D-glucopyranosides and their hydrates.

Thermotropic properties and crystal structures of alkyl alpha-D-glucopyranosides and their hydrates were estimated by X-ray, DSC and thermogravimetric measurements (TGA). Monohydrates rapidly lose their crystal water several degrees below the melting point of the anhydrous glucopyranosides. The melting points of the monohydrates measured in DSC pressure cells (chain length longer than seven) are lower, and the clearing points higher than those of the anhydrous glucosides. Layer distances of smectic and crystalline phases of anhydrous compounds were established. Melting points, densities and layer distances of the crystalline anhydrous glucopyranosides display strong even-odd effects. The strong decrease of these effects in the case of the monohydrates can be elucidated by the results of X-ray crystal structure analysis.

Calorimetry, Differential Scanning↗
PubMed2000

Rhinosurgical therapy planning via endonasal airflow simulation.

Nowadays, Computational Fluid Dynamics (CFD) methods play an important part in the production process of the automotive industry. Progress in recent years has made possible highly sophisticated airflow-simulation models that are used in engineering for optimization and verification of aerodynamics. The key purpose of the Simulation Tool for Airflow in the human Nose (STAN), developed at the Darmstadt University of Technology in cooperation with the University Hospital in Greifswald, is to use these techniques to support the rhinosurgeon in diagnosis and planning of therapy (Frühauf T, Mlynski G. Simulation and visualization of the air flow in the human nose. Proceedings of the First World Congress on Computational Medicine, Austin, Texas, 1994). A system has been developed that realizes a three-dimensional (3D) reconstruction of the endonasal cavities based on computer tomography (CT) scans. This semiautomatic reconstruction method requires minimal manual intervention. The surface model is used to create an unstructured 3D volume mesh suitable for finite volume simulations. In this way, an individual simulation based on patient-specific data can be realized. At the University Hospital in Greifswald, experimental investigations and measurements are made in nasal models to verify the simulation result. The goal of this project is to investigate individual nasal complaints and to detect respiratory disorders. The surgeon should be able to simulate the disordered respiration before performing a surgical procedure, and thereby increase the effectiveness of surgical planning.

Computer Simulation↗
PubMed2000

[VRATS--Virtual Reality Arthroscopy Training Simulator].

The subject of this paper is a highly interactive medical training system for arthroscopic surgery; this is based on computer graphics and virtual reality (VR) techniques and offers an alternative to conventional training methods. To provide the virtual environment, a realistic 3D representation of the knee joint is derived from 2D medical image data. The use of tracking techniques guarantees an intuitive handling of the surgical instruments. The system allows navigation via a virtual camera and interaction with the virtual anatomical structures. First approaches for the simulation of tissue deformation caused by collisions with the instruments are implemented. One important advantage over conventional training systems is the possibility of verifying the training progress. Work is in progress on the realization of tactile feedback with the aim of providing a higher degree of interactive realism.

Arthroscopy↗
PubMed2000

Planning system for computer assisted total knee replacement.

Total knee replacement (TKR) is a common orthopaedic surgical intervention and includes the removal of bone sections from the end of the femur and the top of the tibia for replacement by prosthetic components. Pain relief and functional improvement are predictable clinical results. But the accuracy of the alignment affects the surgical outcome and the longevity of the prosthesis. Hence, current total knee implantation systems attempt to align the knee joint in the mechanical axis for placement of the total knee components. These approaches use templates and plain radiographs for preoperative planning and alignment devices for bone cuts. To overcome the inherent inaccuracy of the presently used systems a computer-assisted planning system has been developed delivering the necessary control data for the intraoperative surgical robot system.

Arthroplasty, Replacement, Knee↗
PubMed2000

LAHYSTOTRAIN intelligent training system for laparoscopy and hysteroscopy.

Rapid developments in the medical field, as an expanding knowledge base and emerging new technologies require continuing medical education to achieve life long learning and to keep the surgeons up to date. Consequently, specific training is necessary to guarantee qualification of the surgeons. The goal of LAHYSTOTRAIN is to overcome the current drawbacks of traditional training methods for laparoscopic/hysteroscopic procedures. A computer-assisted simulator for training and quality control in laparoscopy and hysteroscopy is developed using Virtual Reality (VR), Multimedia (MM) technology, and Intelligent Tutoring Systems (ITS).

Artificial Intelligence↗
PubMed1999

Real-time simulation of tissue deformation for the nasal endoscopy simulator (NES).

Endonasal sinus surgery requires a great amount of training before it can be adequately performed. The complicated anatomy involved, the proximity of relevant structures, and the variability of the anatomy due to inborn or iatrogenic variations make several complications possible. Today, cadaver dissections are the "gold standard" for surgical training. To overcome the drawbacks of traditional training methods, the Fraunhofer Institute for Computer Graphics is currently developing a highly interactive medical simulation system for nasal endoscopy and endonasal sinus surgery, in cooperation with the Mainz University Hospital. For the simulation of a rhinoscopic procedure, not only are the realization of the 3D interaction and the geometric representation of the anatomical structures necessary, but also a real-time simulation of the deformation behavior constrained by the instrument collisions. The challenge is to close the gap between a maximal degree of realism and the required real-time conditions.

Cadaver↗
PubMed1999

Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine.

The RTS,S/SBAS2 vaccine confers sterile protection against Plasmodium falciparum sporozoite challenge. The mechanisms underlying this are of great interest, yet little is known about the immune effector mechanisms induced by this vaccine. The immune responses induced by RTS,S/SBAS2 were characterized in 10 malaria-naive volunteers. Several epitopes in the circumsporozoite protein (CSP) were identified as targets of cultured interferon (IFN)-gamma-secreting CD4+ T cells. RTS,S-specific IFN-gamma-secreting effector T cells were induced in 8 subjects; this ex vivo response mapped to a single peptide in Th2R. CSP-specific CD8+ cytotoxic T lymphocytes were not detected. RTS, S-specific IFN-gamma production was universal, whereas interleukin-4 and -5 production was rare. RTS,S-specific lymphoproliferative responses and antibodies to CSP were strongly induced in all volunteers. Responses waned with time but were boostable. Thus, RTS, S/SBAS2 is a potent inducer of Th1-type cellular and humoral immunity. These results highlight possible immune mechanisms of protection and have important implications for vaccine design in general.

Adult↗
PubMed1999

Use of major histocompatibility complex class I/peptide/beta2M tetramers to quantitate CD8(+) cytotoxic T lymphocytes specific for dominant and nondominant viral epitopes in simian-human immunodeficiency virus-infected rhesus monkeys.

To evaluate the impact of the diversity of antigen recognition by T lymphocytes on disease pathogenesis, we must be able to identify and analyze simultaneously cytotoxic T-lymphocyte (CTL) responses specific for multiple viral epitopes. Many of the studies of the role of CD8(+) CTLs in AIDS pathogenesis have been done with simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys. These studies have frequently made use of the well-defined SIV Gag CTL epitope p11C,C-M presented to CTL by the HLA-A homologue molecule Mamu-A*01. In the present study we identified and fine mapped two novel Mamu-A*01-restricted CTL epitopes: the SIVmac Pol-derived epitope p68A (STPPLVRLV) and the human immunodeficiency virus type 1 (HIV-1) Env-derived p41A epitope (YAPPISGQI). The frequency of CD8(+) CTLs specific for the p11C,C-M, p68A, and p41A epitopes was quantitated in the same animals with a panel of tetrameric Mamu-A*01/peptide/beta2m complexes. All SHIV-infected Mamu-A*01(+) rhesus monkeys tested had a high frequency of SIVmac Gag-specific CTLs to the p11C,C-M epitope. In contrast, only a fraction of the monkeys tested had detectable CTLs specific for the SIVmac Pol p68A and HIV-1 Env p41A epitopes, and these responses were detected at very low frequencies. Thus, the p11C,C-M-specific CD8(+) CTL response is dominant and the p41A- and p68A-specific CD8(+) CTL responses are nondominant. These results indicate that CD8(+) CTL responses to dominant CTL epitopes can be readily quantitated with the tetramer technology; however, CD8(+) CTL responses to nondominant epitopes, due to the low frequency of these epitope-specific cells, may be difficult to detect and quantitate by this approach.

Amino Acid Sequence↗
PubMed1999

A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia.

RTS,S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein (CSP) of Plasmodium falciparum linked to hepatitis B surface antigen (HBs) and combined with a novel adjuvant system (SBAS2). We have conducted a Phase I trial with three doses of this vaccine given at 0, 1, and 6 months to 20 semi-immune, adult, male volunteers in The Gambia to assess its safety and immunogenicity. Eighteen of the 20 volunteers completed the study. There were no clinically significant local or systemic adverse events following each vaccination. Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity. Antibody titers to both CSP and HBs showed a significant increase after vaccination; these were the largest after the third dose. We conclude that the RTS,S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP.

Adolescent↗
PubMed1999

Virtual cutting of anatomical structures.

In the context of medicine cutting is one of the most important operations. Many surgical tasks start with an incision, allowing the surgeon to access the region of interest, using either conventional or minimal invasive surgery techniques. The work presented herein should be seen in the context of surgical training and preoperative planning using computer assisted medical simulation systems. The main result of this work is the proposed cutting algorithm based on predefined templates. To integrate this approach in the existing surgical training simulator and to handle additional tasks like soft tissue deformation, needed by the medical environment, a generic simulation framework was developed. This framework is able to utilize given multiprocessor- and network-environments to achieve the desired realtime interactivity.

Algorithms↗