In-vivo studies on Haemaccel-fibronectin interaction in man

An enzyme-linked immunoassay has been recently set up for direct measurement of the binding capacity of plasma fibronectin to gelatin. This binding capacity could be completely inhibited in vitro by an eight-fold excess of gelatin, of Haemaccel, but not of Geloplasma. On the contrary, the levels of immunoreactive fibronectin measured by laser nephelometry did not change, in presence of 10 to 1000 micrograms ml-1 of gelatin, of Haemaccel or of Geloplasma. When infused into normal volunteers, Haemaccel provoked a strong and immediate inhibition of the plasma fibronectin binding capacity to gelatin. This inhibition was dose-dependent and maximal after infusion of 500 ml of Haemaccel. Twenty-four hours after this infusion, there was a progressive recovery of the gelatin-binding capacity, which was almost completely achieved 96 h later. The formation of complexes between Haemaccel and fibronectin was demonstrated by gel filtration chromatography and by affinity chromatography. Immunoreactive plasma fibronectin levels remained unchanged up to 24 h after infusion of 500 ml of Haemaccel. A transient decline to 50% of its initial value then occurred the second day after the infusion. Therefore, a delay existed between the formation of fibronectin-Haemaccel complexes and their elimination from the bloodstream. This delay decreased when smaller volumes of Haemaccel were infused, which strongly suggests that plasma fibronectin is cleared by means of Haemaccel and does not seem to play a role of opsonin in these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous balloon dilatation of calcific aortic valve stenosis: anatomical and haemodynamic evaluation.

Two groups of elderly patients with calcified aortic stenosis were treated by balloon dilatation. In group 1, the valve was dilated just before surgical replacement of the valve. The valvar and annular changes occurring during dilatation were examined visually. In 20 of the 26 patients in this group there was no change. In the six remaining patients mobilisation of friable calcific deposits (1 case), slight tearing of the commissure (4 cases), or tearing of the aortic ring (1 case) were seen. Dilatation did not appear to alter valvar rigidity. In 14 patients (group 2) the haemodynamic gradient across the aortic valve was measured before and immediately after dilatation and one week after the procedure. Dilatation produced an immediate significant decrease of the aortic mean gradient and a significant increase of the aortic valve area. Eight days later the mean gradient had increased and the aortic valve area had decreased. Nevertheless there was a significant difference between the initial gradient and the gradient eight days after dilatation. The initial aortic valve area was also significantly larger than the area eight days after dilatation. The aortic valve gradient rose significantly in the eight days after dilatation and at follow up the gradients were those of severe aortic stenosis.     

Intravenous Lidocaine Infusion Facilitates Acute Rehabilitation after Laparoscopic Colectomy

Background: Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy.

Methods: Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg [middle dot] kg-1 [middle dot] h-1 intraoperatively and 1.33 mg [middle dot] kg-1 [middle dot] h-1 for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25-75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests. P < 0.05 was considered statistically significant.

Results: Patient demographics were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33] h; P < 0.001), defecation (28 [24-37] vs. 51 [41-70] h; P = 0.001), and hospital discharge (2 [2-3] vs. 3 [3-4] days; P = 0.001) were significantly shorter in patients who received lidocaine. Lidocaine significantly reduced opioid consumption (8 [5-18] vs. 22 [14-36] mg; P = 0.005) and postoperative pain and fatigue scores. In contrast, endocrine and metabolic responses were similar in the two groups.     

Study of the protective effects of hyperimmune immunoglobulins G and M against endotoxin in mice and rats

We prepared solutions of human IgM and IgG to various lipopolysaccharide (LPS) species. These were then tested, along with solutions of non-LPS specific human IgG or IgM, for their ability to confer passive immunity against experimental endotoxemia in two animal models. The immunoglobulins were first tested for an effect on the lethality induced by seven different LPSs in actinomycin-D sensitized mice, or by three different bacteria in normal mice. When the immunoglobulins were administered 1 h before challenge, a small protective effect was observed. This protection was dependent upon both the anti-LPS agent, the chemical composition of the LPS, or the strain of Gram-negative bacteria used for injection. The anti-LPS IgM and IgG preparations reduced the mortality induced by Escherichia coli but not by Serratia marcescens or Klebsiella pneumoniae, indicating protection by strain-specific antibodies. When the antibodies were preincubated with LPS or bacteria for 30 min before administration, almost complete protection was seen. The influence of these immunoglobulin preparations or of human albumin (as a control) on the hypotensive and vascular-permeabilizing effects of LPS in rats was then studied. A dose-dependent inhibitory effect was observed with IgG preparations and albumin. At 200 mg/kg, anti-LPS IgG reduced the effects of LPS, while at 400 mg/kg, both anti-LPS and normal IgG preparations showed protection, as did human albumin used at the same dose. The IgM-enriched preparation worsened the initial hypotensive phase after LPS, whereas the anti-LPS IgM significantly reduced the second phase of the hypotension, but only at the largest dose of 400 mg/kg. In this second model using the rat, a clear difference between the activity of IgG and IgM was thus observed. We conclude that pretreatment with human immunoglobulins from large plasma pools modestly, but significantly, attenuated the effects of murine and rat Gram-negative sepsis, but that protection was incomplete. Our results suggest that single regimen intervention strategies may not be sufficient to influence the course of the disease. Received: 12 December 1998     

Epstein-Barr virus infection in 59 orthotopic liver transplant patients

Fifty-nine orthotopic liver transplant (OLT) patients were studied after transplantation to detect Epstein-Barr virus (EBV) primoinfection and reactivation. Nineteen, all children under 10 years, were EBV seronegative. Seroconversion occurred in 12 (63.3%) of the seronegative patients. Most of these patients (10/12) seroconverted 2 or 3 months after transplantation; 11 out of the 12 demonstrated clinical signs at the time of seroconversion. From 9 primoinfected patients tested for EBV excretion, 8 were found to be positive. Serological evidence of reactivation was found in 9 out 40 (22.5%) seropositive patients and EBV was isolated from 5 (56%). Eleven pediatrie OLT patients with primoinfection showed high and persistent titers of anti-EA antibodies (from 132 to > 1256), when tested at least 3 months after serovonversion; however, anti-EBNA antibodies failed to develop in 5 patients and remained persistently low in 4. These patients with high EA and with negative or low EBNA titers constitute an at risk group for EBV-related lymphoproliferative syndrome (LpS). At presently, after a period of follow-up ranging from 3 months to 3 years, none of our 12 primoinfected patients have developed any lymphoproliferative evolution. However, in 1, during the acute phase, lymphoblasts and lymphoproliferation were observed in a tonsil biopsy.     

New evaluation therapies for sepsis

This article presents an analysis of the literature of the last 2 years on the treatment of sepsis and septic shock. It appears that most of the antimediator therapies applied in phase II or III clinical trials yielded disappointing results. But, many other therapeutic approaches are proposed or are ongoing, and many papers report critical analysis of the reasons for the lack of success of past clinical trials.