Acute Febrile Phase Research Articles

Ultrastructural localization of immunoglobulin M in activated B-cells in patients with epidemic hemorrhagic fever using gold probe

Our previous electron microscopic studies have shown for the first time that the atypical lymphoid cells in the peripheral blood of patients with epidemic hemorrhagic fever (EHF) during the acute febrile phase of the illness appeared to be activated B-cells and plasma cells of various developmental stages. But it is still not a tall clear whether those initially activated cells were actually B-cells. In this study, an indirect immuno gold staining method for the detection of B-cell surface antigen was used.Peripheral blood mononuclear cells were isolated from anticoagulated venous blood of 3 EHF patients (2—7 days of illness) and control donors by centrifugation at 2,500 Xg for 15 min. The cells obtained from the buffy coat were washed in TBS and resuspended in TBS-5% BSA. Unfixed cells were in cubated insuspension in step I with monoclonal antibody (MS27) directed against human IgM (μ Chain) for 30 min at 37±C. After washing in TBS—BSA, the gold probe was applied to the cells in step II incubation with GAM-G15 reagent for 45 min at RT. The gold probe was prepared in our laboratory according to Slot and Geuze. After the third washing in TBS-BSA, the cell pellets were fixed, dehydrated and embedded in Epon 812.

Spontaneous tumor necrosis factor production in Kawasaki disease

Tumor necrosis factor production by peripheral blood mononuclear cells was measured in 18 patients with Kawasaki disease. In patients studied during the acute febrile phase of their disease, there was increased spontaneous TNF production (mean 26.9 +/- 40.3 U/ml) compared with that of control subjects (1.0 +/- .86 U/ml) (p less than or equal to 0.025). Spontaneous TNF production by patients tested in the subacute or convalescent phase of the illness was significantly lower than that in patients tested during the acute illness (p less than or equal to 0.025). In all patients studied with serial acute and subacute-convalescent samples, TNF production was normal in the follow-up samples. Because TNF is a potent mediator of inflammation and causes damage to vascular endothelial cells, we suggest that TNF may be important in the pathogenesis of both the immune activation and endothelial cell damage characteristic of this illness.

Determinants of low serum concentrations of salicylates in patients with Kawasaki disease

The mechanisms leading to the previously reported difficulties in achieving therapeutic serum concentrations of salicylates in Kawasaki disease were studied in eight children, once during the acute (febrile) phase and again during the nonfebrile (subacute) phase of the disease. Salicylate bioavailability was impaired during the acute phase of the disease (47.7% +/- 6.6%), and increased significantly thereafter to 75.1% +/- 9.3%. During the febrile phase there was a significant correlation between salicylate bioavailability and steady-state serum concentrations. Salicylate renal clearance was significantly higher during the febrile phase (14.45 +/- 2.5 mL/kg.h), compared with the nonfebrile phase (7 +/- 1.6 mL/kg.h, P less than 0.05). The change in salicylate clearance could be explained by decreased protein binding in the acute phase (82.5% +/- 1.9%) with substantially more free salicylates caused by significantly lower serum albumin concentrations. Changes in urine metabolites during the acute and subacute phases were consistent with the changes in dose administered (100 mg/kg in the acute phase vs 10 mg/kg in the subacute phase). The pattern of metabolites excreted in the urine of children with Kawasaki disease receiving 100 mg/kg was similar to that in children with juvenile rheumatoid arthritis receiving the same dose.

Kawasaki syndrome: a new infectious disease?

Kawasaki syndrome is a newly described, acute symptom complex of children that has a predictable clinical course. The acute febrile phase of the syndrome is characterized by multisystem acute inflammatory changes. The subacute phase follows with the rheumatic manifestations of arthritis, myocarditis, and thrombocytosis. The syndrome is self-limited in most children but is associated with coronary artery aneurysms in 15%--20% and sudden death due to coronary thrombosis in 2%. Vasculitis of coronary and other medium-sized muscular arteries characterizes fatal cases. The peak age affected is 12 months (range, six weeks to eight years). Japanese children are overrepresented among cases, whereas Caucasian children are underrepresented. Cases have been reported worldwide with the highest prevalence in Japan and among Japanese in Hawaii. Epidemic outbreaks have occurred in scattered areas of the United States and Japan. The etiology is unknown, although clinical, epidemiologic, and immunologic features suggest an acute infectious trigger to an immunologically mediated, generalized vasculitis.

Serum inhibition of lymphocyte transformation in a case of pulmonary tuberculosis

Immunological function was investigated in a patient with pulmonary tuberculosis which was refractory to conventional chemotherapy. The patient failed to express delayed cutaneous hypersensitivity (DH) in vivo to antigens which stimulated her lymphocytes to proliferate in vitro. Her serum inhibited the in vitro proliferative responses of autologous lymphocytes, and of homologous lymphocytes from normal healthy individuals. This inhibitory activity was maximal during an acute febrile phase of her illness and diminished with eventual resolution of her tuberculosis. The relationship of this serum inhibitory activity to the immune response and possible implications for therapy are discussed.

Treatment of the acute febrile phase of Carrión's disease with chloramphenicol.

Summary Each of 19 patients undergoing the acute febrile phase of Carrion's disease received, in divided doses, approximately 17.0 gm. oral chloramphenicol in five days. After initial dosage with chloramphenicol, temperature usually returned to normal within 24 hours. A reticulocyte response averaging nine per cent (varying between 6.8% and 36%) was evident shortly after the beginning of chloramphenicol therapy. Although some coccoid forms of the bartonellae remained in the red cells, the bacillary form disappeared in 24 hours. Red cell count and red cell size were reestablished. Relapse was infrequent; when it occurred, further administration of chloramphenicol resulted in recovery. Three of the patients were also infected with Salmonella; one of these died, the other two made a gradual recovery. Since Carrion's disease and a Salmonella infection are likely to co-exist, chloramphenicol is suggested as the drug of choice to combat both the bartonellosis and the complicating salmonellosis. Large doses of chloramphenicol had no depressing influence on blood formation.

Medical management of hemorrhagic fever.

Hemorrhagic fever is a perplexing problem, which thus far has been only partially solved. The causative organism, vector, and mode of transmission have not been defined. Many of the clinical and pathological findings are bizarre and unusual. Pathological physiology is puzzling. The spotty geographic incidence, the semiyearly outbreaks, and the limited endemic areas are all remarkable facets. The therapeutic management of the condition has proved equally perplexing. All measures that normally would be expected to be effective have been disappointing. No single agent has been shown to have dramatic effect. In fact, antibiotics, corticotropin (ACTH), cortisone, convalescent serum, convalescent whole blood, and the galaxy of agents used in the hemorrhagic diatheses have failed to have significant effect. Clinical management has resolved itself essentially into symptomatic care plus some measures that at first glance seem unphysiological, yet have reduced the death rate to 4%. The acute febrile phase of this condition