Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation.

BACKGROUND: Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans. OBJECTIVE: To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system. RESULTS: In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles. CONCLUSION: Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.

Superior mesenteric artery syndrome in a 15-year-old boy during Ramadan.

UNLABELLED: A previously healthy 15-year-old boy who participated in Ramadan and recently suffered from a gastro-enteritis presented at the emergency room with abdominal pain, vomiting, and marked weight loss. Abdominal X-ray and computed tomography showed upper gastrointestinal obstruction and narrowing of the distance between superior mesenteric artery and aorta abdominalis. Through these findings, superior mesenteric artery syndrome was diagnosed. Treatment consisted of placement of a nasojejunal tube for enteral feeding until weight gain was substantial. Superior mesenteric artery syndrome is rare, with a prevalence varying between 0.013 and 0.3 %. It is characterized by compression of the third part of duodenum between aorta and superior mesenteric artery, thus causing signs and symptoms of upper gastrointestinal obstruction. CONCLUSION: In general, when signs and symptoms of upper gastrointestinal obstruction are accompanied with rapid weight loss, superior mesenteric artery syndrome should be considered.

Comparison of ELISA and toxin neutralization for the determination of tetanus antibodies.

In a sandwich ELISA for tetanus antibodies, the influence of the tetanus toxoid concentration used for coating microtiter plates has been studied. The antibody levels by toxin neutralization bioassay and by ELISA were studied for a population with known immunization history. By decreasing the tetanus toxoid concentration in ELISA from 5 to 0.2 Lf/ml, a better correlation was found between the ELISA results and the bioassay titers, but sera from recently immunized people still showed high ELISA titers. This phenomenon cannot be ascribed to nonspecific reactions since sera from nonimmunized people are negative in both assays. All sera negative in ELISA had, however, a bioassay titer beneath 0.01 IU/ml.

Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice.

Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use.

The enzyme-linked immunosorbent assay of meningococcal and some related Escherichia coli polysaccharides.

A non-competitive enzyme-linked immunosorbent assay (ELISA) system has been developed for the quantitative, sensitive and specific determination of meningococcal polysaccharides. A prerequisite, however, is the correspondence of the O-acetyl content and the molecular size of the polysaccharides in the samples and the reference preparation. If these characteristics differ, special precautions in the use of antibodies to both the O-acetylated and the non-O-acetylated variants have to be taken, including the testing of the sample in at no less than three dilutions.

Vaccine potential of meningococcal group C polysaccharide-tetanus toxoid conjugate.

The antibody response in mice to Neisseria meningitidis (meningococcal) group C polysaccharide could be modified by its conjugation to proteins, i.e. tetanus toxoid. Whereas the pure polysaccharide behaved as a T-independent antigen, the polysaccharide-protein conjugate was clearly a T-dependent antigen, as shown by the pronounced IgG response after the first dose and by the booster effect after the second dose. In comparison, group C polysaccharide-outer membrane protein complexes isolated from the cell-free culture liquid of a meningococcal culture induced only a low level of IgG antibodies. Conjugation did not result in a reversion of tetanus toxoid to toxin. Tetanus toxoid present in the conjugate was as immunogenic as tetanus vaccine.

Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines.

Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugates have been prepared by using high-molecular-weight polysaccharide and purified tetanus toxoid and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as a coupling reagent. The influence of three conditions of preparation was studied. Biochemical assays, the enzyme-linked immunosorbent assay, and isopycnic CsCl gradient ultracentrifugation have been used to characterize the conjugates. The polysaccharide-to-protein ratios of the various conjugate preparations showed differences. The ability of the group C polysaccharide component to react with specific antibodies was reduced, whereas most of the tetanus toxoid seemed to be hidden by the polysaccharide. The composition of the conjugate was not homogeneous, and at least 10% of free polysaccharide was present. Thermostability in lyophilized condition in the presence of lactose was excellent.

A modified ELISA technique for the titration of antibodies to polio virus as an alternative to a virus neutralization test.

An ELISA based on inhibition of antibody binding for the determination of antibodies to polio virus type I is described. F(ab1)2-fragments of bovine antibodies to polio virus type I are used as the capture antibody thus lowering the background staining. A good correlation was found between the poliovirus neutralizing antibody level and the antibody titers as determined by ELISA.

Preparation and physicochemical and immunological characterization of polysaccharide-outer membrane protein complexes of Neisseria meningitidis.

A crude complex containing group C polysaccharide, outer membrane proteins, and lipopolysaccharide (LPS) was isolated from the cell-free culture liquid of Neisseria meningitidis serogroup C, serotype 2a. Group C polysaccharide and LPS were removed from this complex, resulting in an outer membrane complex and a purified complex, respectively. Analysis by electron microscopy showed the outer membrane origin of the crude complex and the outer membrane complex, whereas such a structure was absent in the purified complex. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns of the three complexes were identical. Pyrolysis-mass spectrometry data correlated well with those obtained by the biochemical assays and suggested a low LPS content in the purified complex and a low polysaccharide content in the outer membrane complex. The purified complex was shown to be nonpyrogenic and could be prepared with the same yield as that of purified polysaccharide. The immunogenic activities of the complexes were studied in mice. The antibodies were measured by the enzyme-linked immunosorbent assay; and the bactericidal antibody assay. All complexes induced immunoglobulin G antibodies to group C polysaccharide as well as to the serotype antigen, although the removal of polysaccharide and LPS resulted in a reduction of the immunogenic activities of outer membrane complex and purified complex, respectively. A second dose of all complexes produced a clear booster effect of both antibody responses. The antibodies were bactericidal.

Immunoglobulin M and G antibody responses and persistence of these antibodies in adults after vaccination with a combined meningococcal group A and group C polysaccharide vaccine.

Adult volunteers were injected with a combined meningococcal group A and group C polysaccharide vaccine. Immunoglobulin M (IgM) and IgG antibody levels against both polysaccharides were measured in serum samples taken 14 days as well as 3 years after vaccination. For both group A and group C polysaccharides, the IgM and IgG antibody levels at 14 days postvaccination were positively related. The IgM-to-IgG antibody ratio at 14 days postvaccination was an indicator for the persistence of both IgM and IgG antibodies during the next 3 years; a high ratio meant a short persistence, whereas a low ratio was associated with a long persistence.