Biomedical subjects
Publications and source records attributed to M Lamy.
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The goal of this project was to find and collect high concentrations of endotoxin-specific antibodies for therapeutic IgG- or IgM-enriched preparations. Various enzyme-linked immunosorbent assays (ELISAs) were developed to perform longitudinal studies of the serological response to a large panel of smooth and rough purified lipopolysaccharide (LPS) extracts in a population of healthy blood donors. To accomplish this, 1612 human serum samples from volunteer blood donors collected by seven different blood banks in Belgium were screened and specific IgM and IgG activities were measured. Approximately 17% of the donors had anti-LPS concentrations higher than 40 mg L-1. Of these, 10.9% had anti-smooth LPS antibodies, 3.7% had anti-rough LPS antibodies and 2.8% were found to be positive towards both types of LPS. The mean anti-LPS antibody concentration was 8 mg L-1 for rough LPS and 14 mg L-1 for smooth LPS. Age- and sex-related distributions of the activities indicated that the greatest prevalence of high anti-LPS concentration was in women aged 40-49 years and in men older than 60 years. Differential absorption experiments showed that the pooled serum of selected blood donors contained a mixture of specific and cross-reacting antibodies. We detected predominantly anti-LPS activities due to the IgG1 and IgG2 subclasses. The range of specificities to different LPS was increased by the pooling of selected sera. It was concluded that pools of naturally occurring specific anti-LPS immunoglobulin antibodies may be obtained in Belgium by screening blood donors using ELISAs that we have developed.
To address the question of whether delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of the arachidonic acid derived product prostaglandin E2 (PGE2). 10 healthy male subjects were submitted to eccentric and concentric isokinetic exercises on a Kin Trex device at 60 degrees/s angular velocity. Exercise consisted of 8 stages of 5 maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases. There was an interval of at least 30 days between eccentric and concentric testing, and the order of the two exercise sessions was randomly assigned. The subjective presence and intensity of DOMS was evaluated using a visual analogue scale, immediately, following 24 h and 48 h after each test. Five blood samples were drawn from an antecubital vein: at rest before exercise, immediately after, after 30 min recovery, 24 h and 48 h after the tests. The magnitude of the acute inflammatory response to exercise was assessed by measuring plasma levels of polymorphonuclear elastase ([EL]), myeloperoxidase ([MPO]) and PGE2 ([PGE2]). Using two way analysis of variance, it appeared that only eccentric exercise significantly increased [EL] and DOMS, especially of the hamstring muscles. Furthermore, a significant decrease in eccentric peak torque of this muscle group only was observed on day 2 after eccentric work (- 21%; P < 0.002). Serum activity of creatine kinase and serum concentration of myoglobin increased significantly 24 and 48 h after both exercise tests. However, these variables reached significantly higher values following eccentric contractions 48 h after exercise. Mean [PGE2] in the two exercise modes remained unchanged over time and were practically equal at each time point. On the basis of these findings, we conclude that the magnitude of polymorphonuclear (PMN) activation, muscle damage, and DOMS are greater after eccentric than after concentric muscle contractions. However, the hypothesized interplay between muscle damage, increased PGE2 production, DOMS sensations, and reduced isokinetic muscle performance was not substantiated by the present results.
Propofol has been reported to have antioxidant properties and to inhibit lipid peroxidation. In this study, we examined the ability of propofol to inhibit lipid peroxidation induced by three free radical systems (hydroxyl, ferryl, and oxo-ferryl radicals), and we compared the effect of propofol with that of vitamin E, an endogenous antioxidant. Lipid peroxidation was induced by exposing a linoleic acid emulsion to either water gamma radiation, a ferrous iron-ascorbate solution, or human hemoglobin, generating the hydroxyl, ferryl, and oxo-ferryl radicals, respectively. Each experiment was performed in triplicate with and without propofol or vitamin E at concentrations between 10(-5) and 10(-4) M. Lipid peroxidation was quantified by gas chromatography measurement of the pentane released (nmoles) from lipid decomposition. In each condition, a significant dose-response relationship was found between the release of pentane and the concentration of either propofol or vitamin E. The antioxidant activities of both agents were similar but significantly higher against the hydroxyl than the ferryl and oxo-ferryl radicals. The study suggests that propofol could be beneficial as an anesthetic or sedative drug in patients presenting pathologies associated with free radical reactions.
We studied the time-course of action of atracurium 0.5 mg kg-1 and rocuronium 0.6 mg kg-1 in 24 healthy adult patients. Anesthesia was induced with thiopentone and sufentanil, and maintained with 50% nitrous oxide and 1% enflurane in oxygen. Neuromuscular transmission was monitored by stimulating the ulnar nerve at the wrist and measuring the acceleration of the thumb using the TOF-Guard accelerograph monitor. Supramaximal stimuli of 0.2 ms duration were applied in a single twitch stimulation mode at 1 Hz frequency until completion of block, and in train-of four (TOF) sequence at 2 Hz every 15 sec thereafter. Onset time was longer with atracurium (mean +/- SD:90 +/- 18 sec) than with rocuronium (49 +/- 6 sec). Clinical duration of action (Tl25) was longer with atracurium (52.3 +/- 7.2 min) than with rocuronium (40.0 +/- 6.4 min). Recovery index (Tl25-Tl75) and time for TOF ratio to recover to 0.75 were 17.8 +/- 4.2 and 73.9 +/- 8.8 min with atracurium, and 13.8 +/- 4.1 and 70.4 +/- 14.1 min with rocuronium. The differences between both groups were statistically significant except the difference in the time for TOF to return to 0.75.
Inhaled nitric oxide (NO) has been reported to promote selective pulmonary vasodilation and better arterial oxygenation in cases of adult respiratory distress syndrome (ARDS) with pulmonary hypertension (PHT). However, the clinical relevance of these changes and their effects on outcome remain to be proven, since long-term inhalation carries a potential risk of toxicity. We used NO to treat a patient who developed postpneumonectomy ARDS with severe PHT and right ventricular failure. NO resulted in better oxygenation and markedly improved hemodynamic status. As the underlying disease progressively worsened the patient became fully dependent on NO for hemodynamic support, and he died after 24 days of effective supportive therapy with inhaled NO.
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In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were not affected by these experimental conditions. Free radical production in this model was also measured directly using electron spin resonance (ESR) spectroscopy associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the venous blood arising from the ischemic kidney. The signal consisted of a triplet of doublets. In contrast, no signal could be detected in control blood samples taken prior to inducing ischemia. The burst of free radical production occurred in the early phase after restoration of flow in the kidneys rendered ischemic, as evidenced by a signal of weak intensity which generally appeared within the third minute after reperfusion and progressively increased to form a well-defined asymmetric signal following 10 min of reperfusion. The precise nature of free radicals trapped by the PBN agent remains, however, to be elucidated, but analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and asymmetry of the central doublets suggests that the ESR signal may arise from a nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or carbon-centered radicals of lipid origin. As evidenced by both direct and indirect measurements, exchange of rabbit blood immediately after inducing renal ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not exacerbate free radical production mediated by an ischemia reperfusion phenomenon, a typical situation found in a resuscitation setting.
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Although pain after laparoscopic cholecystectomy is less intense than after open cholecystectomy, some patients still experience considerable discomfort. Furthermore, the characteristics of postlaparoscopy pain differ considerably from those seen after laparotomy. Therefore, we investigated the time course of different pain components after laparoscopic cholecystectomy and the effects of intraperitoneal bupivacaine on these different components. Forty ASA physical status grade I-II patients were randomly assigned to receive either 80 mL of bupivacaine 0.125% with epinephrine 1/200,000 (n = 20) or the same volume of saline (n = 20) instilled under the right hemidiaphragm at the end of surgery. Intensity of total pain, visceral pain, parietal pain, and shoulder pain was assessed 1, 2, 4, 6, 8, 24, and 48 h after surgery. Analgesic consumption was also recorded. Patient data were similar in the two groups. In the saline group, visceral pain was significantly more intense than parietal pain at each time point; visceral and parietal pain were greater than shoulder pain during the first 8 h postoperatively. Intraperitoneal bupivacaine did not significantly affect any of the different components of postoperative pain. Analgesic consumption was similar in the two groups. This study demonstrates that visceral pain accounts for most of the pain experienced after laparoscopic cholecystectomy. Intraperitoneal bupivacaine is not effective for treating any type of pain after laparoscopic cholecystectomy.
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The acute respiratory distress syndrome (ARDS), a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies carries a high morbidity, mortality (10-90%) and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those whose wish to know the true incidence and outcome on this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.
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