Interaction in vitro between myocardial cells and autologous lymphocytes and sera from patients with rheumatic carditis.

The cytotoxicity of antimyocardial antibodies and peripheral blood lymphocytes from patients with rheumatic carditis on autologous myocardial cells was investigated. Although sera obtained after open-heart surgery from seven out of eight patients with rheumatic carditis were bound to cultures of autologous myocardial cells, they were not cytotoxic. Peripheral blood leukocytes obtained both before and after surgery from one of these eight patients aggregated around and underwent blast transformation when exposed to autologous myocardial cells in vitro, but not after exposure to autologous skin fibroblasts. Only the postoperative leukocytes from another of these eight patients aggregated around autologous myocardial cells in vitro; however, these lymphocytes were also not cytotoxic to autologous myocardium. To investigate the effect of antimyocardial antibodies on myocardial function, antimyocardial antibodies were added to the culture medium of pulsating cultures of mouse myocardial explants. Although antimyocardial antibody from 27 patients with chronic rheumatic carditis and seven postcardiotomy patients had no effect on the pulsation of the mouse myocardial cultures, serum gamma-globulin from a patient suffering from acute rheumatic fever with myocardial involvement first accelerated and then gradually stopped the pulsation of mouse myocardial explants.     

Goodpasture's syndrome associated with skin involvement

To our knowledge, skin lesions associated with Goodpasture's syndrome have not been reported to date. A patient developed discrete, macular, erythematous lesions on the instep of his foot, noted at the time of his admission to the hospital for treatment of Goodpasture's syndrome. Investigation showed perivasculitis and significant deposits of IgM and C3 at the dermoepidermal junction in the lesion site but not in the nearby skin. IgM deposits in the skin are unusual and the same immunoglobulin is found in the kidney in this syndrome. IgM deposit was absent from control samples of skin from four other patients with this syndrome. It is possible that these findings are significant.     

Mechanism of tyramine-induced migraine: similarity with dopamine and interactions with disulfiram and propranolol in migraine patients

In a double-blind crossover study, 8 patients with classical migraine received disulfiram (400 mg/day) for 6 days, alternating with matched placebo tablets at 2 weekly intervals. Intravenous dopamine and tyramine pressor tests were performed on the 3rd and 6th days of each phase, respectively. 50-75% of patients experienced migraine attacks within 24 h of a test. There was no difference in the incidence of attacks between dopamine and tyramine injections. The number of migraine-free days was more during the placebo week than during disulfiram treatment (p less than 0.05). The post-tyramine migraine index correlated directly with the amount of tyramine administered during the dose-response test (r = 0.66), but no such relationship was found with dopamine. In a further study, post-tyramine migraine was observed in only 1 of 5 patients treated with propranolol (80 mg/day) for 4 weeks. Neither disulfiram nor propranolol influenced the tyramine pressor sensitivity. It is concluded that increased adrenergic activity is responsible for more frequent attacks during disulfiram medication. A similar mechanism probably is responsible for post-dopamine/tyramine migraine in susceptible subjects. It is unlikely that tyramine plays any specific role, except via its effect on the adrenergic system, in the pathogenesis of migraine attacks. However, the tyramine challenge test can be useful in the evaluation of a putative antimigranous activity of a new drug.     

Systolic time intervals in the differential diagnosis of constrictive pericarditis and cardiomyopathy.

Systolic time intervals (STI) were measured from simultaneously recorded phonocardiograms, carotid pulse tracings, and electrocardiograms in 11 patients with constrictive pericarditis and in 10 patients with cardiomyopathy to assess the value of STI in the differential diagnosis of the two conditions. The predicted ejection fraction was calculated from the STI. The results were compared and found significantly different in the two groups of patients. The ratio PEP/LVET and the ejection fraction were found to have greater discriminatory values and separated the two groups clearly. Measurement of STI, a simple, noninvasive bedside technique, appears to be useful in distinguishing between constrictive pericarditis and cardiomyopathy.     

Plasma arginine vasopressin in hyponatraemic patients receiving diuretics

Random estimations of plasma arginine vasopressin concentration were undertaken in 6 non-oedematous patients receiving diuretic therapy for hypertension, who were admitted to hospital with severe hyponatraemia. Hyponatraemia resolved within 2 weeks of discontinuing the diuretic. Measurable amounts of plasma arginine vasopressin were detected in all 6 patients. Sequential biochemical measurements in one patient, performed when plasma sodium concentration and osmolality were returning to the normal range, disclosed that urine osmolality remained higher than plasma osmolality during the first 5 days, when urine volume and sodium excretion were low. Thus the rise in plasma sodium was not initially related to water diuresis. The ability to excrete a water load was severely limited on the fifth day, but improved progressively by the tenth and seventeenth days. Diuretic-induced hyponatraemia is associated with incomplete suppression of anti-diuretic hormone secretion arising from non-osmotic stimulation, in conjunction with transient impairment of renal diluting ability which could be due to net sodium deficit.     

Crystalline inclusions associated with lung adenomas in C57BLxC3H F1 mice

In a study on lung adenomas induced by the administration of a single intragastric dose of sodium thiocyanate, diethylnitrosamine, or its precursors to 15-day-old C57BLxC3H F1 mice the occurrence of crystalline inclusions in pulmonary parenchyma was noted. A correlation between crystalline deposits and number and type of adenomas seen between 46 and 110 weeks was observed. In 45/61 adenomas, eosinophilic cells containing inclusions were seen scattered in the pulmonary tissue, adjacent to tumor areas, in desquamated cells in the bronchioles, in the lumens of the submucosal bronchial glands, and within the alveoli. By contrast 7/85 mice without adenomas showed inclusions (4/7 mice had pneumonitis). The inclusions stained with bromophenol blue, were PAS positive diastase resistant and showed varying amounts of alpha-1-antitrypsin, IgG, and IgA by immunoperoxidase technique. Ultrastructure revealed membrane bound rods with a lattice pattern.     

Inhibition of human renal cancer by methotrexate linked to a monoclonal antibody

The monoclonal antibody DAL K29 against a human renal cell carcinoma associated cell surface antigen was covalently linked to the antifolate methotrexate with full retention of antibody reactivity and partial retention of drug activity. In a colony inhibition assay, antibody-conjugated methotrexate was 400% more potent in inhibiting the growth of the human kidney cancer line Caki-1 than equimolar amounts of the free drug. Comparable amounts of the antifolate linked to normal mouse IgG did not inhibit the growth of Caki-1 cells. Furthermore, the methotrexate-DAL K29 conjugate had no effect on the two nontarget human cell lines tested, melanoma M21 and B cell leukemia D10-1 cells, even when the conjugate contained amounts of methotrexate equivalent to the 50% inhibitory concentration of the free drug for the nontarget cell lines or an amount equivalent to the 50% inhibitory concentration of the conjugated drug for Caki-1 cells.