Cardiac heterotransplantation. Morphological and immunohistological studies.

A vascularized heterograft model using outbred strains of animals was developed by transplanting mouse hearts heterotopically into rats. With this species desparity rapid but not immediate graft rejection was observed, with a predictably narrow range of graft survival times. Morphological and immunohistological studies showed early deposition of fibrinogen and vascular and myocardial inflammation without prominent or consistent localization of either IgG or C3. Later more extensive changes were observed, and deposition of IgG and C3 were more prominent in the grafts. Pretreatment of the recipient with cyclophosphamide alone or cyclophosphamide plus antigen prolonged graft survival; however, no statistically significant difference was noted between these groups. Morphological and immunohistological alterations preceded clinical rejection, and tissue injury appeared to be mediated by humoral and cellular immune mechanisms and by the coagulation system. This model is potentially useful for the study of heterotransplantation.

Terbutaline in the treatment of acute asthma in childhood.

Forty-eight children with known asthma (ranging in age from 2 to 16 years) were studied during an acute attack. Each received either terbutaline or epinephrine subcutaneously in a random double-blind fashion. Measurement of heart rate, respiratory rate, and systemic arterial systolic and diastolic blood pressures and careful clinical assessment of obstruction of the airway were made before and at 15, 30, and 60 minutes after the administration of the drugs. Appreciable and significant clinical improvement was noted in 19 of the 24 patients in both groups and was of comparable magnitude. A small, but significant, increase in heart rate was noted in those patients requiring only one injection of terbutaline, suggesting that the drug's selectivity for the lung is relative not absolute. The present study demonstrates that terbutaline is an effective bronchodilator drug in acute childhood asthma.

The human choroid plexus and autoimmune nephritis.

The choroid plexus resembles the glomerular basement membrane (GBM) and may be a site of injury or source of antigen in Goodpasture syndrome. Immunohistologic studies were performed on the choroid plexus of a patient with auto-immune nephritis and pulmonary hemorrhage. The studies showed linear deposition of host IgG, IGM, and beta1c. Antibody eluted from the diseased kidney fixed in a linear pattern to normal choroid plexus and could be absorbed by either choroid plexus or GBM. Antibody to choroid plexus fixed to GBM and the linear staining was no longer observed after absorption with GBM or choroid plexus. Antibody to GBM fixed to normal choroid plexus and was obsorbed by both choroid plexus and glomerular basement membrane. The studies suggest an immunologic relationship between choroid plexus and GBM and a role for the choroid plexus in autoimmune nephritis.

Cryoglobulins. III. Further studies on the nature, incidence, clinical, diagnostic, prognostic, and immunopathologic significance of cryoproteins in renal disease.

Serial serum samples from a large number of patients with immunologic renal disease, normal healthy controls, acute infections as well as non-immunological renal disease were studied for the presence, nature and properties of cryoproteins, and these correlated with serial renal functional, morphologic, immunohistologic and clinical fingings as well as serologic observations. A high incidence of cryoproteins were found in renal disease thought to be mediated by immune complexes. Cryoprecipitates were not detected in the other patients. The presence of fibrinogen in a serum cryoprecipitate was always associated with rapidly progressive disease and poor prognosis. An association between the detection of cryoproteins and the clinical and morphological activity of disease was observed. Persistence of cryoproteinemia was associated with progression and apparent disappearance with resolution or progression to end stage renal disease. In patients with hematuria or proteinuria of questionable significance cryoprotein detection was always associated with immune complex nephritis. Renal transplantation in the presence of cryoproteinemia was associated with recurrent nephritis in the graft. Cryoproteins were found to have biologic properties attributable to antigen-antibody complexes, to contain immune complexes of antigen and antibody and to have serologic factors concentrated. The detection of serum cryoglobulins was found to be a better index of clinical and morphologic activity of immune complex renal disease than was serum complement. As in our previous studies, these proteins appear to be of diagnostic and prognostic value in renal disease and provide a method of antigen identification in these disorders.