Cellular immunity in vitro. I. Immunologically mediated enhancement of macrophage bactericidal capacity.

An in vitro model of cellular immunity in the guinea pig was established. Animals were immunized with tubercle bacilli, bovine gamma globulin, or picrylated human serum albumin in complete Freund's adjuvant. Oil-induced peritoneal exudates from immune and control animals were cultured overnight with and without specific antigen. The cultures were washed and the macrophage monolayers were infected with Listeria monocytogenes. At intervals the monolayers were lysed and the numbers of viable intracellular bacteria were quantitated by pour plate cultures. Random monolayers were also evaluated in sequence by visually counting the intracellular bacteria on Gram-stained plates. Both methods demonstrated that the macrophages from immune animals had markedly enhanced listericidal activity when the peritoneal exudates were cultured with antigen before infection. Macrophage migration inhibition was also demonstrated under these conditions. The experiments reported here describe an in vitro model of cellular immunity which will allow separation and recombination of cell types and direct assay of cell products in efforts to elucidate further the mechanisms of the immunologically mediated enhancement of macrophage bactericidal capacity.

Patient-directed, nonprescription approaches to cardiovascular disease.

The control of coronary artery disease requires both physician-directed interventions and patient-directed lifestyle changes that may include nonprescription supplements. All patients should be encouraged to exercise regularly. They should be advised to avoid exposure to tobacco smoke and to strive to attain ideal body weight. Patients should also be encouraged to establish diets that are low in cholesterol and fat and high in dietary fiber. Supplements of water-soluble fiber may be useful for selected patients. Diets rich in antioxidant vitamins should also be stressed. Antioxidant supplements may be warranted in individuals with coronary artery disease or risk factors. Pending further study, patients should be encouraged to consume more fish but not fish oil supplements. Therapeutic doses of niacin should not be used without medical supervision. Chromium and other nutritional supplements, however, may merit consideration in selected cases. Physicians should stress the use of nonpharmacologic means to reduce blood pressure and discuss interventions that could reduce excessive stress. With appropriate screening and precautions, selected individuals should benefit from low-dose aspirin prophylaxis and possibly from low-dose alcohol consumption. Because these patient-directed interventions receive less attention in the scientific literature, they were selected for review herein.

Hormonal hyperthermia: endocrinologic causes of fever.

Although hyperthermia is a component of many endocrine diseases, it is uncommon for fever to be the presenting manifestation of hormonal disorders. During a four year period we encountered six patients, hospitalized principally because of fever, who were found to have endocrine causes for the fever. In all, the admitting diagnosis was infection; three were suspected of having tuberculosis, two of gram-negative bacteremia and one of endocarditis. Except for asymptomatic bacteriuria in one patient (who remained febrile despite appropriate antibiotic therapy) infection was ruled out in all cases, and fever was attributed to "masked" thyrotoxicosis, triiodothyronine (T3) toxicosis, subacute thyroiditis, primary adrenal insufficiency, secondary adrenal insufficiency and pheochromocytoma. In a seventh patient, extreme pyrexia developed in the setting of the thyroid storm. The importance of hormonal mechanisms in thermoregulation is discussed.

Creatine kinase levels after jogging in patients with cardiac disease.

Acute muscle injury is a well-documented complication of strenuous exercise, but milder forms of exertion have not been studied in detail. This report describes a patient undergoing cardiac rehabilitation in whom atypical chest pain developed and who was treated for a myocardial infarction only because of an elevated creatine kinase level. Serum creatine kinase levels were determined before and after exercise in 27 patients undergoing cardiac rehabilitation. In 21 patients who jogged less than three miles, creatine kinase levels were not appreciably changed. In six patients who jogged more than three miles, the mean creatine kinase level rose from 41 to 54 mU/ml, an increase of 31 percent. In four of these six patients, creatine kinase levels rose to abnormal levels, but MB creatine kinase levels remained normal, with no clinical evidence of myocardial ischemia. Serum creatine kinase levels should be interpreted with caution in the setting of even modest exercise.

Hemophilus influenzae in hospitalized adults: current perspectives.

In an eight year period 16 cases of serious extrapulmonary Hemophilus influenzae infection in adults were identified, including cases of meningitis, pericarditis, epiglottitis, empyema, cellulitis, osteomyelitis, endometritis, urinary tract infection, orbital cellulitis, primary peritonitis, mesenteric lymphadenitis and aortic graft infection. An 18 month prospective study of H. influenzae infection in hospitalized adults identified 10 cases of bronchitis, 25 of pneumonia and 65 of respiratory tract colonization, but there were no extrapulmonary infections. In 29 percent of the respiratory tract infections, H. influenzae appeared to be a nosocomial pathogen; in 71 percent, the infection was mixed. Finally, 110 clinical isolates of H. influenzae were studied for antimicrobial susceptibility. Eight percent were ampicillin resistant, two strains were resistant to tetracycline and one to chloramphenicol, but all were susceptible to trimethoprim-sulfamethoxazole and cefamandole.

Chronic lymphadenopathic toxoplasmosis. A case with marked hyperglobulinemia and impaired delayed hypersensitivity responses during active infection.

A patient with lymphadenopathic toxoplasmosis characterized by prolonged symptoms and repeated relapses with isolation of toxoplasma from lymph nodes is described. As the disease persisted and progressed, striking immunologic changes occurred that ultimately resulted in a state of extreme hyperglobulinemia associated with impaired delayed hypersensitivity responses. The case in question illustrates that progressive infection may occur in the face of high antibody levels of all immunoglobulin types whereas the only demonstrable immunologic impairment was of delayed hypersensitivity.

Computed tomography and histologic results in the early stages of endotoxin-injured pig lungs as a model for adult respiratory distress syndrome.

RATIONALE AND OBJECTIVES: To determine early radiographic changes in diffuse alveolar injury, the authors correlated computed tomography (CT) and histopathology in pigs with recurrent endotoxinemia. METHODS: Five pigs received recurrent endotoxin over a 17-hour period. Three pigs received physiologic saline and served as controls. Hemodynamic and blood-gas data were analyzed. CT was performed immediately before killing the animals. The lungs were cut into 5-mm-thick slices in the same axis as the CT scans and were investigated by light and electron microscopy. RESULTS: Hemodynamic data, blood-gas analysis, and morphologic changes closely simulated the clinical situation of septic shock in the five pigs that had received endotoxin. Results of histologic examination depicted changes similar to those associated with adult respiratory distress syndrome (ARDS). CT clearly demonstrated both interstitial, and to a minor degree, intra-alveolar lesions in the endotoxin-injected group, which correlated well with dilated lymph vessels, thickened interstitium, and areas of dystelectasis on histologic examination. Although there was a rather uniform clinical picture, CT and histologic findings showed different degrees of involvement. CONCLUSIONS: CT clearly depicts changes in endotoxin-injured pig lungs in an early clinical state, which are similar to changes associated with ARDS on histologic examination.