The cost-of-illness for invasive meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) in Germany

Introduction

Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.

Polymerizable amphiphiles, 2. Micellization of 1-O-3-(4-vinylphenyl)propyl-β-D-glucopyranose

1-O-3-(4-Vinylphenyl)propyl-β-D -glucopyranose ( 1 ) undergoes in water a closed association under formation of N-mers. The unimer/N-mer association is directly visible in the Schlieren pattern of ultracentrifugal synthetic boundary experiments. Association numbers and mass-concentration-based equilibrium constants of association were calculated from the variation of N-mer concentrations with unimer concentrations and from the concentration dependence of inverse apparent average molar masses as measured by both vapor phase osmometry and sedimentation equilibrium. Association numbers were also calculated from the combination of sedimentation coefficients with diffusion coefficients, sedimentation coefficients with intrinsic viscosities, and diffusion coefficients with interinsic viscosities as well as from the dependence of apparent mass-average molar masses on inverse apparent number-average molar masses. All methods gave in general different association numbers and equilibrium constants. The effect, which was not found for other non-ionic amphiphiles, is probably due to the existence of consecutive equilibria between the unimer and a low molar mass P-mer which associates to a higher molar mass R-mer. Viscosity data are in agreement with the picture of a spherical micelle for the dominant P-mers with about 10 water molecules per glucose residue. The micellization of 1 is both enthalpy- and entropy-driven, in contrast to the micellization of 1-O-octyl-β-D -glucopyranose which is a strictly entropy-driven process.     

Gene transfer experiments imply instructive role of major histocompatibility complex class I molecules in cellular peptide processing.

DBA/2-derived mouse tumor cells were transfected with the H-2 Kb gene. Naturally processed minor histocompatibility (H) peptides were extracted from both transfected and non-transfected cells by acid elution, and were separated by high-performance liquid chromatography. Kb-restricted minor H epitopes corresponding to H-4b and mapki, both encoded by non-major histocompatibility complex genes of DBA/2, were readily detected by the respective cytotoxic T lymphocyte in peptides extracted from Kb-transfected, but not from non-transfected or Db-transfected cells. Titration experiments indicated at least 3000-fold less copies of correctly processed Kb-restricted epitopes in cells without Kb as compared to cells with Kb. Since we estimate the copy number of Kb-restricted H-4b epitopes in Kb-expressing transfectants to be less than 1000 per cell, the pool size of H-4b epitopes correctly processed in the absence of Kb should be less than 1/3 copy per cell.     

Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent extended cold storage in University of Wisconsin solution in an extracorporeal rat liver perfusion and rat liver transplantation model.

Adequate flushing for liver donation requires large fluid volumes delivered at a high flow. This can be achieved more effectively with crystalloid solutions than with colloid-based solutions. This study examined the combination of initial histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent storage in University of Wisconsin solution (UW) to that of the single use of each solution. Livers from inbred Wistar rats were procured using aortic perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes using either solution. In a third group, after perfusion with HTK, organs were reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed after 24 hours of cold storage in the subsequent solution, as well as allotransplantation after 18 and 24 hours of cold storage. In extracorporeal perfusion, the HTK flush followed by UW storage was superior compared to the single use of either UW or HTK solution, as measured by portal venous pressure, bile flow, liver enzymes released into the effluent perfusate, glycerol leakage, and histological examinations. These data were consistent with the transplantation study. Histological damage and enzyme release after 5-day survival were lowest in the HTK flush and subsequent UW storage groups following 18 hours of cold storage; likewise, the 5-day survival was superior following 24 hours of cold storage. In conclusion, the combined use of HTK solution for initial graft rinse and subsequent storage in UW solution resulted in a cumulative protection. Choosing low-viscosity HTK solution for the initial organ flush may represent a feasible improvement in liver preservation, which also further reduces the required amount of UW solution.     

Tender points, depressive and functional symptoms: Comparison between fibromyalgia and major depression

Summary The degree of symptomatic overlap between fibromyalgia and major depression should be estimated by assessing the amount of local tenderness and the frequency and severity of depressive and functional symptoms. Tender points were assessed by palpation and symptoms by psychometric scales in 30 patients with fibromyalgia and 26 patients with major depression. The patients with fibromyalgia had markedly more tender points (16.5) than the depressive patients (1.3). In contrast, depressive and functional symptoms were present in both groups of patients, and some depressive patients (26%) also suffered from clinical pain. An increased sensitivity to pressure pain clearly distinguishes fibromyalgia from depression even if there is an overlap of other symptoms.     

Pathways of destruction in metacarpal and metatarsal joints of patients with rheumatoid arthritis.

219 metatarsal (MTP) and 69 metacarpal (MCP) capitulae obtained during surgery from patients with definite rheumatoid arthritis (RA) were histologically evaluated. This evaluation, focussing on primary pathways of joint destruction by tumor-like proliferated synovial cell masses revealed 3 pathways of aggression: Pathway A: In 15% aggression onto the articular cartilage only. Pathway B: In 49% direct invasion exclusively into the cortical bone. Pathway C: In 36% a "forceps-like" aggression, a combination of A and B in which the joint is attacked from both sides. In contrast to the hitherto conventional concepts, the findings of this study reveal a clear preference of the synovial aggression for the cortical bone rather than for the articular cartilage. The different concepts of joint destruction in RA are being discussed in the light of our findings. Thus, future pathogenetic considerations with regard to joint destruction in RA should take this fact into consideration.     

Identification of a naturally processed cyclin D1 T-helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry

T-helper (Th) cells play an important role in orchestrating the effector function of CTL in anti-tumor immunity. However, only a limited number of Th cell epitopes has been characterized. Here we describe a novel approach for identifying naturally processed and presented peptides derived from chosen antigens. This method combines a transfection step of antigen-presenting cells with a vector encoding a fusion protein between the Ii chain and the antigen of interest, elution of the HLA-bound peptides and identification of the antigen-derived peptides by mass spectrometric comparison to the non-transfected cells. In vitro-stimulated Th cells against the identified peptide of interest specifically recognize transfectants overexpressing the cognate antigen. Using this approach, we were able to identify the HLA-DR4-restricted Th cell epitope NPPSMVAAGSVVAAV derived from cyclin D1, which is frequently overexpressed in tumors. This method will help in identifying peptide candidates for vaccination studies for tumor immunotherapy.     

Depressed mediator release by inflammatory exudate cells in immunized rats following antigen challenge

The aim of the present study was to characterize leukocytes present in a local inflammatory reaction with respect to production of prostaglandin E (PGE) and the release of factors affecting lymphocyte function, which are produced by macrophages (interleukin-1) or stimulated lymphocytes (interleukin-2). Lewis rats immunized against bovine serum albumin (BSA) were challenged by intraperitoneal injection of antigen. The PGE release by peritoneal cells (PEC) was testedin vitro and found to be enhanced in immunized rats before BSA challenge. However, PEC harvested after the injection of antigen showed a marked reduction in prostaglandin production during the first 24 h. When these cells were tested for the secretion of lymphokines (IL-1, IL-2) the same depression was found.     

Peptide motifs of closely related HLA class I molecules encompass substantial differences.

The peptides presented by major histocompatibility complex class I molecules adhere to strict rules concerning peptide length and occupancy by certain amino acid residues at anchor positions. Peptides presented by HLA-A*0201 molecules, for example, are generally nonapeptides requiring Leu or Met at position 2 and an aliphatic residue, predominantly Val, at position 9. A closely related molecule, HLA-A*0205, differing from the former at four amino acid residues, has a related but substantially different peptide motif. A*0205-presented peptides are still nonapeptides, and position 9 is still aliphatic, although it is preferentially occupied by Leu instead of Val. Position 2 not only allows aliphatic residues but also polar ones. Occupancy at position 6, considered as an auxiliary anchor in A*0201, as well as non-anchor residues at positions 3, 4, and 8 are relatively well conserved between the two peptide motifs. Thus, although a number of the T cell epitopes presented by the two HLA-A2 forms is expected to be identical, a considerable number of epitopes should be different.