Autoimmunity in congenital rubella syndrome

Two hundred one deaf adolescents with congenital rubella syndrome and 83 age-matched deaf control subjects were evaluated for the presence of organ-specific antibodies directed against thyroid microsomes, thyroglobulin, pancreatic islets, adrenal cortex, and gastric parietal cells. Positive thyroid microsomal or thyroglobulin antibodies were found in 23.3% (47/201) of the rubella group and in 12.0% (10/83) of control subjects. Nine of 46 (19.6%) in the rubella group and two of nine (22.2%) control subjects with thyroid autoimmunity had thyroid gland dysfunction as indicated by elevated serum TSH concentrations. Neither islet cell nor adrenal cortical antibodies were detected in any subject tested; parietal cell antibodies were detected in 5.5% (8/146) of those in the rubella group and 8.8% (6/68) of control subjects tested, but occurred most frequently in subjects with thyroid autoimmunity (6/36, 16.7% vs 8/178, 4.5%; P less than 0.05). It is recommended that all patients with congenital rubella syndrome be screened for thyroid autoimmunity and that those with positive antibody titers be evaluated for the presence of thyroid dysfunction.     

Proteolytic enzymes as adjuncts to antimicrobial prophylaxis of contaminated wounds.

When a tissue is injured, its vessels exhibit a marked increase in vascular permeability. Blood proteins, including fibrinogen, traverse the vessel walls and lead to the development of a surface coagulum. This inflammatory response continues until primary closure of the wound edges is accomplished. The thickness of the surface coagulum is roughly proportional to the time interval between wounding and closure. This coagulum encompasses the surface contaminants, preventing contact with either topical or systemic antibiotics. The presence of this surface coagulum limits the time in which antibiotic prophylaxis is effective. At three hours after injury, antimicrobial prophylaxis of contaminated wounds has no therapeutic value. Hydrolysis of the protein coagulum by proteolytic enzymes enhances the activity of the antibiotic in experimental wounds. The success of proteolytic enzymes as adjuncts to delayed antibiotic treatment can be correlated with the clot lysis activity of the enzymes in vitro. Travase, the most potent fibrinolytic enzyme, is the most effective adjunct to delayed antibiotic therapy of contaminated wounds. In contrast, the active enzymes found in Elase, which exhibit no significant clot lysis activity in vitro, do not potentiate the activity of antibiotics in wounds subjected to a delay in treatment. Travase prolongs the period of effective topical antibiotic action for at least eight hours in experimental contaminated wounds. The therapeutic merit of Travase is also apparent when the antibiotic is administered systemically. Travase shows promise as an adjunct to a variety of antibiotics that are effective against both gram-positive and gram-negative organisms. The results of these experimental studies support our belief that clinical studies support our belief that clinical studies should now be initiated to test the therapeutic value of Travase as an adjunct to antibiotics in heavily contaminated wounds subjected to an unavoidable delay in treatment.     

Debridement: An essential component of traumatic wound care

The harmful influences of devitalized tissue on wound defenses are documented and the importance of wound debridement in the care of the traumatic wound is stressed. All devitalized soft tissues damaged the host's defenses and encouraged the development of infection. The capacity of devitalized muscle, fat, and skin to enhance infection was comparable. The infection-potentiating effect of skin was enhanced by exposing it to a dry thermal injury. The mechanisms by which devitalized soft tissue enhanced infection are several. The devitalized soft tissue acts as a culture medium promoting bacterial growth. In addition, the devitalized tissue inhibits leukocyte phagocytosis of bacteria and subsequent kill. Finally, the anaerobic environment within the devitalized tissue may also limit leukocyte function.     

Field potential and single unit analyses of the avian dorsal motor nucleus of the vagus and criteria for identifying vagal cardiac cells of origin

The compound action potential components and their associated fiber contingents were investigated in the pigeon vagus nerve with a view toward identifying the vagal cardioinhibitory fibers. In the cervical vagus, the compound action potential evoked by electrical stimulation included four major components that conducted at 17.0-30.0 (A-wave), 8.0-14.5 (B2-wave) and 0.8-2.0 (C-wave) m/sec. Cardiac slowing was not elicited until activation of the Bl-wave, and the bradycardic response was maximal when this component was maximized. Electron microscopic analysis of the cervical vagus revealed myelinated fibers 1.1-6.8 micron in diameter and unmyelinated fibers 0.3-1.4 micron in diameter. A contingent of myelinated fibers approximately 2-4 micron in diameter apparently generated the Bl-wave, while the prominent unmyelinated fiber contingent (37%) accounted for the C-wave. Analysis of various vagal branches indicated that approximatley 20% of the cervical vagal fibers exit the main trunk between cervical and mid-thoracic levels, but few of these are the larger myelinated fibers greater than 2 micron in diameter. The upper abdominal vagus consists largely of unmyelinated and small myelinated fibers, and consequently the vast majority of larger myelinated fibers found in the cervical vagus exit between mid-thoracic and upper abdominal levels, presumably in the cardiac branches. Direct examination of the cardiac branches confirmed this. Thus, it is concluded that the Bl-wave of the compound action potential is uniquely associated with cardiac slowing, that this component is generated by myelinated fibers ranging from 2 to 4 micron in diameter, and that almost all such fibers are destined for the cardiac branches of the vagus.     

The molecular basis of HCV-mediated immune dysregulation

Chronic hepatitis C virus (HCV) infection, which occurs in over 85% of patients and causes mild to severe liver disease, is a growing burden to health systems worldwide. The propensity of HCV to establish persistent infection suggests that the virus, which is non-cytopathic, has evolved one or more mechanisms aimed at evading host immunity. In addition to the appearance of quasispecies, which may arise under selective pressure during B and T cell responses, HCV gene products interact with host proteins in order to subvert immune surveillance. Gaining insight into these interactions may provide the basis for novel therapies aimed at preventing chronic HCV infection.