[Clinical autopsies in Switzerland : A status report]. / Klinische Obduktionen in der Schweiz : Ein Statusbericht.

BACKGROUND: The number of autopsies has been steadily declining worldwide over the past decades. The reasons for this are diverse. Legislation regarding opposition and consent rules does not appear to have had a significant impact on the autopsy rates. Above all, structural causes and the attitude of the medical profession are the reasons for this decline. The main argument for a high autopsy rate is the identification of diagnostic errors; however, diagnostic discrepancies are relatively independent of the rate of autopsies performed. At the University Hospital (UniversitätsSpital) Zurich it could be shown in a study that from 1972-2002 the frequency of relevant diagnostic discrepancies (classes I and II) decreased from 30% to 7%. OBJECTIVE: The aim of this article is to present the necessity of a stable autopsy rate and to examine the situation of the autopsy in Switzerland. MATERIAL AND METHODS: For this purpose, the importance of autopsies in the fields of quality assurance of medical diagnostics, cancer statistics, medical research as well as further education of doctors in Switzerland is shown. Efforts are being made by the pathologists to counteract the declining autopsy rates. RESULTS AND DISCUSSION: Declining autopsy numbers have a significant influence on cancer statistics. The rate of newly discovered tumors in autopsies in Switzerland decreased from 42% in 1980 to 17% in 2010. Pediatric autopsies are an important tool for quality assurance of medical diagnostics in neonatology and pediatrics in Switzerland, but the rate of autopsies carried out is also declining. Postmortem magnetic resonance imaging (MRI) examinations (virtopsy) could increase the acceptance of the parents for an autopsy in the future. Autopsies make an important contribution in research and in documentation of therapy-associated side effects and they are an important component of further education of the upcoming medical generations.

Therapeutic potential of human antisera to group B streptococcal glycoconjugate vaccines in neonatal mice.

Experimental immunoglobulin preparations for treatment of group B streptococcal (GBS) infections contain low levels of functional antibody and exhibit lot-to-lot variability. GBS capsular polysaccharide-protein conjugate vaccines have recently been shown to produce high serum levels of type-specific antibody in healthy volunteers. Treatment of neonatal mice 4 h after inoculation with an ordinarily lethal dose of GBS type Ia, Ib, or III with pooled human serum from adults who had received GBS type Ia capsular polysaccharide-tetanus toxoid vaccine (Ia CPS-TT), Ib CPS-TT, or III CPS-TT resulted in 63%, 70%, and 75% survival, respectively. In contrast, < or = 17% of the infected mice treated with normal human serum or saline survived. These results demonstrate the therapeutic activity of GBS polysaccharide conjugate vaccine-induced antiserum and provide a rationale for the use of these vaccines in producing a functional, high-titered intravenous immunoglobulin preparation for clinical use.

Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine.

Most cases of neonatal sepsis and meningitis caused by group B streptococci (GBS) are attributable to one of four major capsular serotypes: Ia, Ib, II, or III. Because resistance to infection with GBS has been correlated with the presence of serum antibodies to the type-specific capsular polysaccharides in both experimental animals and human neonates, efforts have been made to elicit protective immunity with GBS capsular polysaccharide vaccines. However, the GBS capsular polysaccharides alone are not highly immunogenic in either animals or human volunteers. Therefore, we and other investigators have attempted to enhance immunogenicity by coupling individual capsular polysaccharides to a carrier protein. Here we report the synthesis and immunogenicity in rabbits of a GBS type Ib polysaccharide-tetanus toxoid vaccine prepared by the direct, covalent attachment of tetanus toxoid to a selected number of sialic acid residues on the type-specific polysaccharide. In addition, the Ib polysaccharide-tetanus toxoid conjugate vaccine was combined with similar tetanus toxoid conjugates of GBS type Ia, II, and III polysaccharides to form a tetravalent GBS conjugate vaccine. Protective efficacy of the GBS tetravalent conjugate vaccine was demonstrated in a mouse maternal immunization-neonatal challenge model of GBS infection. The results support testing in human subjects of a multivalent GBS conjugate vaccine of this design, with the eventual goal of protecting newborns against GBS infection.

Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine.

Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbits inoculated. In competitive enzyme-linked immunosorbent assay, these antibodies reacted with high affinity to type Ia polysaccharide and with lower affinity to the structurally related GBS type Ib polysaccharide. Despite the lower binding affinity of the Ia-TT-induced antibodies for the type Ib polysaccharide, Ia-TT antiserum opsonized not only type Ia GBS but also type Ib GBS for killing by human blood leukocytes. Ia-TT antiserum was also evaluated in a mouse model designed to test the efficacy of maternal antibodies in protecting neonates against GBS infection. Pups born to dams that had received Ia-TT antiserum were protected against lethal challenge with either type Ia or Ib GBS. These studies using a polysaccharide-protein conjugate as an immunogen support the view that the carbohydrate immunodeterminant recognized on Ib strains by Ia antisera is a common epitope contained within the structurally related Ia and Ib capsular polysaccharides. Although antibodies elicited by Ia-TT had protective activity against both Ia and Ib strains, these antibodies reacted with lower affinity to Ib than to Ia polysaccharide.

Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein.

Group B streptococci (GBS) cause the majority of cases of neonatal sepsis and meningitis in the United States. Immunization of women of childbearing age is one strategy under consideration for the prevention of neonatal disease. The beta C protein, a 130-kDa antigen present in many clinical isolates of GBS, was purified from GBS by extraction into sodium dodecyl sulfate (SDS)-containing buffer, preparative SDS-polyacrylamide gel electrophoresis, and electroelution. Purified beta C protein antigen (25 micrograms) with Freund's adjuvant was used to immunize rabbits. Rabbits developed enzyme-linked immunosorbent assay titers of > 1:1.6 x 10(6), and sera from immunized rabbits were administered to pregnant mice. Their neonatal pups were then challenged with a strain of GBS expressing beta C protein; 68% of these pups were protected by immune antiserum, whereas no controls were protected (P < 0.001). The immune serum (diluted 1:100) facilitated opsonophagocytic killing of GBS strains expressing the beta C protein but not those that do not express the antigen (mean log kill +/- standard deviation = 0.71 +/- 0.8 log10 CFU for beta+ strains and 0.09 +/- 0.2 for beta- strains; P = 0.02). In subsequent experiments, adult female mice were actively immunized with two doses of 2, 5, or 10 micrograms of beta C protein 2 months prior to mating. One- to two-day-old offspring of these dams were challenged with GBS and were protected in a dose-dependent manner, with 96% survival in the high-dose (10-micrograms) group and 20% survival in a sham-immunized control group (P < 0.001). Thus, active immunization of mice with the GBS beta C protein confers protection against lethal infection with beta+ GBS to their offspring.

Neonatal mouse model of group B streptococcal infection.

Neonatal mice were infected with type III group B streptococcal (GBS) strain M781 by the intraperitoneal route. Age-related susceptibility to challenge was seen within the first 5 days of life. Quantitative blood cultures demonstrated a rapid increase in bacterial numbers during the first 30 h after challenge. Infected pups showed clinical signs of septicemia, and most succumbed within 48 h of challenge. Histopathologic evaluation of the neonates showed bacterial infection within 1 day after challenge. Pregnant adult mice were given a single inoculation of serum raised in rabbits against a tetanus toxoid-conjugated type III GBS polysaccharide vaccine. This serum passively protected 100% of the offspring. This neonatal mouse model of GBS infection and protection may be suitable for study of various forms of intervention.