A mathematical approach to medical diagnosis: application to congenital heart disease.1961.

An equation of conditional probability is derived to express the logical process used by a clinician in making a diagnosis based on clinical data. Solutions of this equation take the form of a differential diagnosis. The probability that each disease represents the correct diagnosis in any particular patient can be calculated. Sufficient statistical data regarding the incidence of clinical signs, symptoms, and electrocardiographic findings in patients with congenital heart disease have been assembled to allow application of this approach to differential diagnosis in this field. This approach provides a means by which electronic computing equipment can be used to advantage in clinical medicine.

Epitopes of group A streptococcal M protein shared with antigens of articular cartilage and synovium.

Rabbit antisera evoked by purified pepsin-extracted group A streptococcal M proteins were screened for the presence of joint cross-reactive antibodies by indirect immunofluorescence using thin sections of mouse knee joints. Pep M1, M5, and M18 antisera contained antibodies that cross-reacted with chondrocytes, cartilage, and synovium. Immunofluorescence inhibition assays showed that some of the joint cross-reactive epitopes were shared among the three heterologous serotypes of M protein. The pep M5 joint cross-reactive epitopes were localized to three different synthetic peptides of the C-terminal region of pep M5. Immunoblot analyses showed that the M5 joint cross-reactive antibodies recognized two proteins of human synovium and cartilage of molecular mass 56 and 58 kDa. The cross-reactive antibodies binding to the 56-kDa protein were inhibited by purified vimentin in immunoblot inhibition experiments. M protein-specific antibodies from patients with acute rheumatic fever were also shown to cross-react with joint tissue in a pattern similar to the rabbit antisera. Rabbit and human M protein-specific antibodies that were bound to articular cartilage activated significant levels of complement when compared to control serum, suggesting that M protein joint cross-reactive antibodies could potentially be involved in the pathogenesis of ARF and arthritis.