Kupffer cell modulation of the systemic immune response

The effects of global hepatic injury and of Kupffer cell activation on systemic immunity were studied in an in vivo rat model, using the diameters of the delayed-type hypersensitivity (DTH) response to keyhole limpet hemocyanin and of a subcutaneous Staphylococcus aureus abscess as measures of systemic immunoresponsiveness. Hepatic injury with carbon tetrachloride resulted in significant suppression of the DTH score (5.5 +/- 0.7 vs 8.8 +/- 0.8 mm). Kupffer cell activation with intraportal Escherichia coli was likewise suppressive (DTH score, 4.4 +/- 0.5 vs 6.1 +/- 0.4 mm for animals receiving systemic E coli); the magnitude of this suppression correlated with the numbers of organisms extracted by the liver. Conversely, Kupffer cell ablation with carrageenan lessened the immunosuppressive effects of anesthesia and surgery (DTH score, 8.5 +/- 0.9 vs 6.8 +/- 0.6 mm for controls; S aureus abscess, 4.1 +/- 0.4 vs 5.7 +/- 0.4 mm for controls). These results indicate that Kupffer cells can modulate the systemic immune response and suggest that gram-negative portal bacteremia with resultant Kupffer cell activation may contribute to the immunologic derangements characteristic of trauma and critical surgical illness.     

Muscle membrane polarisation after provocative tests, and after cooling: the normal CMAP changes to be expected.

OBJECTIVE: To know the range of changes of compound muscle action potentials (CMAPs) in the muscles innervated by the ulnar nerve after diverse provocative tests, 14 healthy patients were studied with the same protocol. METHODS: CMAPs were measured at rest, just after a short exercise test (SET), during short 5 and 10c/s repetitive nerve stimulation (RNS) trains, at approximately 32 and approximately 20 degrees C. RESULTS: At 32 degrees C, the SET induced a significant but transient enlargement of the CMAPs (amplitude increased by 8.3%, duration decreased by 9%) that was only partially reproduced by RNS trains, except for a significant shortening of the CMAPs at 10c/s. At 20 degrees C without exercise, CMAPs increased significantly by approximately 30% in amplitude, duration and area, and after the SET the inverse of what has been seen at 32 degrees C was observed (amplitude decreased by 1.7% and duration increased by 9%). RNS at 20 degrees C produced a marked interpatient heterogeneity except for a significant shortening of the CMAPs at 10c/s. In one pure autonomic failure patient, the infusion of norepinephrine induced potentiation of the responses at rest and a decrease in the expected changes after provocative tests. CONCLUSIONS: CMAP amplitude and duration are significantly modified just after the SET at 32 degrees C, at rest at 20 degrees C and after RNS at 10c/s but not at 5c/s. Although providing indirect evidence, these findings indicate that provocative tests make the muscle membrane hyperexcitable by the way of a direct influence on the electrical events and by an indirect local catecholamine spillover.     

Failure to demonstrate complement activation during bronchial challenge test

In order to demonstrate a possible complement activation during early bronchospastic reaction in asthma, we have measured plasmatic C3d (a split product of C3) and the C3d/C3 index, both of which are sensitive indices of complement activation. Twenty-nine allergenic bronchial challenge tests were accomplished, with an absence of response in six cases, an early reaction in sixteen cases and a dual reaction in seven cases. Changes in plasmatic C3d or C3d/C3 five min after an early reaction, or five min after the last dose of allergen (in the six cases without bronchial response) were insignificant. However, complement activation in the lungs during asthmatic reaction cannot be completely excluded without studies using the bronchoalveolar technique.     

Relationship of resting energy expenditure with liver function and nutritional status in patients with alcoholic cirrhosis.

Resting energy expenditures (REEs) were measured in 40 alcoholic cirrhotic (AC) patients by indirect calorimetry and corrected for 24-h urinary creatinine and excretion. These REEs were compared according to the stage of severity of the cirrhosis, the nutritional status, and the presence or absence of alcoholic hepatitis (AH). Mean REE was not significantly different between the Child class A, B, and C patients, even when corrected for 24-h urinary creatinine. Mean REE was significantly less in malnourished AC than in well-nourished patients (1308 +/- 285 vs. 1531 +/- 255 kcal, p less than 0.02). However, when measured energy expenditure was corrected for 24-h urinary creatinine, the difference between the two groups of patients disappeared (1800 +/- 540 kcal/g creatinine in malnourished patients vs. 1890 +/- 780 kcal/g creatinine in well-nourished patients). Finally, there was no significant difference between the REE, corrected or not, for the 24-h urinary creatinine in AC with or without AH. Thus, when REE is normalized to lean body mass, represented by 24-h urinary creatinine, the metabolic activity in AC is not dependent on the severity of the cirrhosis, nutritional status, or existence of AH.     

In vitro development and stability of tolerance to cloxacillin and vancomycin inStaphylococcus aureus

The stability of tolerance ofStaphylococcus aureus during subculturing at 37°C and development of this property after repeated exposure to cloxacillin or vancomycin were investigated in vitro. Four of five tolerant strains lost this property during repeated subculturing at 37°C for 50 days. Conversely, tolerance emerged in two of four nontolerant strains after repeated cycles of exposure to 25 µg of cloxacillin/ml or 10 µg of vancomycin/ml alternating with growth in antibiotic-free medium. Previous in vivo exposure to cloxacillin did not enhance the development of tolerance in vitro. MICs of both cloxacillin and vancomycin did not change significantly during this procedure. Whether the conversion of nontolerant strains to the tolerant state can also occur during antibiotic exposure in treatment of patients remains to be determined.