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Biomedical subjects

J Marty

Publications and source records attributed to J Marty.

At least 91 records · Page 5Linked to original sources

Relationships between formation of micronuclei and DNA adducts and EROD activity in newts following exposure to benzo(a)pyrene.

The aim of this study was to determine whether the micronucleus test, using the larvae of a lower invertebrate, the newt Pleurodeles waltl, is suitable for evaluating the overall genotoxicity of polluted water (AFNOR Standard, 1992). The study used the pollutant model benzo(a)pyrene (BaP). After having shown that BaP is metabolized by the larvae, the test was carried out under standard AFNOR conditions. We investigated the relationship between the BaP concentration, spectrofluorometric measurement of liver EROD activity, and two genotoxicity biomarkers: DNA adduct production (32P-postlabeling detection) and micronucleus formation in red blood cells (RBCs) (number of micronucleated RBCs per 1,000). A dose effect was found for all three biomarkers, which were seen to be linearly correlated showing that the biochemical mechanisms occurring in the newt larvae exposed to BaP are similar to those described in higher vertebrates. This result confirms the utility of the test for the evaluation of the overall hazard of a given aquatic environment.

Animals↗

[Evaluation of acute pain in prehospital medicine].

OBJECTIVE: To evaluate acute pain in prehospital setting. STUDY DESIGN: Prospective survey. PATIENTS: All eligible patients during a 3-month-period, excepted children less than 10-year-old. METHOD: Pain intensity was evaluated by verbal rating scale with 5 points (VRS), visual analog scale (VAS), demand for antalgics by the patient and the relief obtained. These data were collected at the beginning (T0) and the end (Tend) of medical management. Analgesic treatments were let at the physician's choice. RESULTS: A series of 255 patients were included (mean age 58 +/- 1.5 SEM, sex-ratio 57M/43F). Among them, 42% experienced pain at VRS. VAS could be used in 60% of patients. VRS evaluated by the patient was correlated to the VAS (P < 0.001). Among those with significant pain (defined by a VAS > or = 30 mm), only 31% asked for analgesia and 64% received analgesics. Pain scales (VRS and VAS) were significantly improved (P < 0.001) at the end of the medical management, except for patients who did not receive any treatment. However, mean VAS was still above 30 mm, even in patients receiving analgesics. Only 49% of patients expressed a good relief at the end of the medical management. CONCLUSION: Acute pain is frequently observed in prehospital emergency medicine. Pain scales such as VRS and VAS are used easily and convenient for the assessment of pain intensity in this context. However, even if pain is correctly evaluated, it is still inadequately treated. The reasons of these inadequacies must be assessed and corrected with pain treatment protocols including opioids.

Acute Disease↗

Thrombopoietin measurement in thrombocytosis: dysregulation and lack of feedback inhibition in essential thrombocythaemia.

Essential thrombocythaemia (ET), a myeloproliferative disorder (MPD) manifested by excessive platelet production, lacks a specific diagnostic test to facilitate differentiation from other thrombocytoses. We studied thrombopoietin (TPO) levels in 41 patients with thrombocytosis: 25 ET patients, eight with other MPD, and eight with reactive thrombocytosis. Mean age and platelet counts for these groups were comparable. TPO levels for 96 healthy individuals provided a reference range for normal. The majority of ET patients (19/25 or 76%) had normal TPO levels. No patient with ET had a TPO level below 75 pg/ml, compared with 57% of healthy donors and 8/16 (50%) patients with other thrombocytoses (P<0.05). TPO levels in ET are not appropriately down-regulated, as occurs with cytokines relevant to other MPD. In thrombocytosis, a TPO level <75 pg/ml indicates that ET is unlikely.

Adolescent↗

Role of endothelium in the modulation of isoflurane-induced vasodilatation in rat thoracic aorta.

The mechanisms by which endothelium attenuates vasodilation caused by isoflurane are not well understood. We examined the role of endothelium-derived substances, nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), prostanoids and endothelins in the response to isoflurane in rat thoracic aorta. Increasing cumulative concentrations of isoflurane were administered to aortic rings suspended in Hepes solution and preconstricted with either phenylephrine 10(-6) mol litre-1 or KCl 40 mmol litre-1 (which inhibit EDHF). Rings were intact, denuded or incubated with an inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNNA 5 x 10(-5) mol litre-1), an inhibitor of prostanoid synthesis (indomethacin 10(-5) mol litre-1) or a blocker of the vascular receptors to endothelins (cyclo (-D-trp-D-Asp-Pro-D-Val-Leu (BQ 123 10(-5) mol litre-1)- Endothelium attenuated isoflurane-induced vasodilation in KCl-constricted rings at concentrations of 4% (mean 95 (SEM 4)% vs 72 (4)%; P = 0.0005) and 5% (100 (4)% vs 80 (4)%; P = 0.0008) and in phenylephrine constricted rings at concentrations of 4% (54 (8)% vs 35 (3)%; P = 0.04) and 5% (78 (10)% vs 49 (5)%; P = 0.03). Relaxation was significantly greater in rings treated with LNNA than in intact rings at concentrations of 4% (85 (4)% vs 72 (4)%; P = 0.0005) and 5% (90 (4)% vs 80 (4)%; P = 0.0008). Indomethacin and BQ 123 did not alter isoflurane-induced vasodilation. We conclude that endothelium attenuated the vasodilator effect of isoflurane by a mechanism which was abolished by inhibition of nitric oxide. We hypothesize that isoflurane inhibits the release of nitric oxide, leading to a relative vasoconstriction counter-balancing its vasodilator effect. In contrast, EDHF, prostanoids and endothelins were not involved in the attenuation of isoflurane-induced vasodilatation.

Anesthetics, Inhalation↗

Influence of acute renal failure on FPIA rapid serum assay of midazolam and its main metabolite.

We recently developed a simple and fast assay technique, providing the possibility of monitoring of midazolam (M) during sedation. We compared HPLC vs FPIA for the measurement of the sum M plus alpha 1-hydroxymidazolam (OM), its main and pharmacologically active metabolite, in the serum of sedated ICU patients; this activity referred to as M-like. We identified certain patients in whom M-like activity appeared abnormally high in comparison with HPLC assays. Their common denominators were: long-term sedation with M, and seriously impaired renal function. Further, the conjugates of OM (OMG) accumulated in patients with acute renal failure could contribute to the sedation. We compared the metabolic and analytic behavior of M, OM, and OMG in 2 groups of sedated patients either presenting with normal renal functions (group 1) or with a picture of acute renal failure (group 2). Blood samples were assayed by HPLC and by FPIA and analysis was performed before and after hydrolysis of OMG. Before hydrolysis there was a dramatic accumulation of OMG in the patients of group 2, HPLC vs FPIA results were not different within group 1, while in group 2 the FPIA response exceeded that of HPLC. After hydrolysis, measurement by HPLC was greatly increased in group 2, in each group (vs HPLC) and from one group to another, the FPIA signal (the M-like activity) showed a significant increase. It would be important to take OMG into account as a coprotagonist in sedation whenever circumstances predispose to its accumulation.

Acute Kidney Injury↗

[Lung volume reduction surgery in emphysema].

Lung volume reduction surgery in emphysema has, as an objective, the reduction of dyspnoea and an increase in the exercise tolerance in patients with respiratory insufficiency suffering from diffuse emphysema. In principle the resection of the most diseased areas of emphysema leads to improvement in the mechanical properties of the emphysematous lung and correct pulmonary hyperinflation. The respiratory function benefits both objective and subjective, produced by surgery are real but transitory and inconstant depending in particular on the evolutionary profile of the emphysematous disease. The indications should be further refined and an objective comparison of different surgical techniques has not been achieved. The impact on the quality of life for these patients is unknown.

Bronchoscopy↗

Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer.

BACKGROUND: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocyte colony formation and platelet production. It is likely to be useful in the management of severe thrombocytopenia. To determine its clinical activity and safety, we gave it to patients with advanced cancer before chemotherapy. METHODS: Patients were randomly assigned to receive either PEG-rHuMGDF or placebo in a three to one ratio. PEG-rHuMGDF was given at a dose of 0.03, 0.1, 0.3, or 1.0 microgram/kg body weight. The study drug or placebo were administered daily by subcutaneous injection for up to 10 days or until a target platelet count was reached. FINDINGS: 17 patients, median age 59 years, received either PEG-rHuMGDF (13 patients) or placebo (four patients). PEG-rHuMGDF produced a dose-dependent increase in platelet counts. Patients given placebo. 0.03, and 0.1 microgram/kg of PEG-rHuMGDF had median increases in platelet counts of 16%, 12%, and 39%. Those receiving 0.3 and 1.0 microgram/kg of PEG-rHuMGDF had an increase in blood platelets of between 51% and 584%. Platelets rose from day 6 of PEG-rHuMGDF administration and continued to rise after stopping the drug. The platelet count peaked between days 12 and 18 and remained above 450 x 10(9)/L for up to 21 days. There were no alterations in white-blood-cell count or haematocrit, and low toxicity. Platelets taken from patients during PEG-rHuMGDF administration and at the time of peak platelet count were morphologically and functionally normal. INTERPRETATION: The potency with which PEG-rHuMGDF stimulates platelet production and its low toxicity indicate that this is likely to be a useful agent for the management of thrombocytopenia.

Dose-Response Relationship, Drug↗

[A study of practice patterns of albumin administration in surgical patients by anesthetists].

The establishment of guidelines has to take into account the current practice patterns. For the preparation of the consensus conference organized by the French Society of Anesthesia and intensive care (SFAR) on the prescription of albumin, an interview with a questionnaire was undertaken in order to assess the practice patterns of anaesthetists during the perioperative period. A group of 498 anaesthetists were interviewed during a congress. Two out of three prescribe albumin. In case of haemorrhage, the decision to administer albumin depends on the limits for using other colloids (for 65% of the responders), the amount of blood loss (46%) and albuminaemia (for only 26%). In other cases, albumin is mainly administered in the burn patient and for recurring ascite; albuminaemia is a decision criterion for one anesthetist out of two. About 25% of them use a 20% concentration, another 25% of them a 4% concentration and the remaining 50% use both concentrations. Adverse effects have been seen in less than 5% of the responders. These data have been presented at the consensus conference and can also be used for the assessment of the impact of the guidelines after their publication.

Adult↗

[Evaluation of direct theoretical cost of passage in anesthesia recovery room].

OBJECTIVE: To assess the direct cost of a stay in a postanaesthesia care unit (PACU). STUDY DESIGN: Standard cost study based on information gathered from staff and suppliers in accordance with government regulations and recommendations. Results reviewed by a group of anaesthesists. TYPE OF PACU: PACU working in ideal conditions with optimal safety conditions for and accommodation surgical patients). METHOD: Estimation of three cost components: 1) depreciation and maintenance costs of equipment, 2) physician and other staff wages, and 3) variable costs such as drugs and disposable devices. We computed an annual budget for three PACU which was defined according to size (4, 8 or 12 beds) and working hours. RESULTS: Fixed annual costs (staff and equipment) were 1,134,938 FF for a 4 bed room: 3,820,339 FF for an 8 bed room: and 6,481,792 FF for a 12 bed room. Variable costs per stay were 75,43 FF. The cost of a stay in an 8 bed PACU based on a rate of 3,500 stays per year therefore was 1,167 FF (87.0% for staff, 6.6% for equipment, 6.4% for variable costs).

Cost of Illness↗

Comparison of high-performance liquid chromatography and polyclonal fluorescence polarization immunoassay for the monitoring of midazolam in the plasma of intensive care unit patients.

Midazolam (M) is used as an induction agent for anesthesia. The main metabolite is alpha-hydroxymidazolam (OM), which is pharmacologically active. Use of M for sedation is a recent application, rapidly gaining favor. Monitoring of the level of sedation is fundamental in that an excessive and prolonged effect is associated with the risk of complications. Thus, it was felt both necessary and useful to measure circulating M levels. We compared a high-performance liquid chromatography (HPLC) assay with fluorescence polarization immunoassay (FPIA) for the measurement of M in the serum of 138 sedated patients in the intensive care unit (i.e., 179 samples). Response of the OM was also assessed. The degree of crossover of the metabolite was between 76.8 and 32.7%. The equation of the regression line for sigma HPLC (i.e., the sum M + OM) versus FPIA was TDx = 1.1585 sigma HPLC + 143.42 (R = 0.966). The 95% confidence interval for the slope was 1.1551, 1.1619. The regression slope differed significantly from 1 (p < 0.001) and shows that FPIA measurements overestimated concentrations obtained by HPLC on the order of 19%. The discrepancy between the two techniques was all the more notable when concentrations were > 1,000 ng/ml. The relative selectivity of Abbott industrial reagent in terms of benzodiazepines leads to the identification of what might be called a midazolam-like (M-like) activity covering both M and OM. The development of a global FPIA method for measurement of this M-like activity in sedated patients provides a satisfactory solution to the question raised.

Adult↗

[Is early extubation after surgery for esophageal cancer possible?].

In a series of 50 patients undergoing elective oesogastrectomy through a laparotomy and a right thoracotomy, the avoidance of overnight ventilatory support was made possible by the agreement of anaesthetists and surgeons on suitable policies. The attempt to extubate the patients immediately postoperatively differentiated two groups. For the first group (32 patients; 64%), early extubation could be performed and only one patient was reintubated and required prolonged ventilation. A second group comprised 18 patients who could not be extubated early (36%). For most of the patients in this second group extubation was only delayed until the next day, and recovery was otherwise uneventful. In three cases, however, pulmonary atelectasis with infection was a major problem, and these patients required broncho-endoscopies, and prolonged ventilatory support. Nevertheless, morbidity and mortality after oesophagectomy were significantly reduced in this series, compared with a previous study in the same hospital. Careful postoperative assessment of the patient is essential. The main factors leading to the decision for early extubation appeared to be: absence of serious cardiovascular history, absence of peroperative surgical complications, adequate rewarming, normal chest X-ray, and the presence of clinical criteria for extubation along with adequate arterial blood gases. If the above criteria can be achieved, then early extubation should be routine and can be safely performed in the majority of cases.

Adult↗

In vivo metabolism of benzo(a)pyrene in a lower vertebrate, the newt Pleurodeles walt.

The capacity of the newt to metabolize benzo(a)pyrene in vivo was investigated qualitatively and quantitatively: metabolism was found to be rapid. Treatment of bile with beta-glucuronidase and aryl-sulfatase released high proportions of diols and quinones. 3-Methylcholanthrene treatment shortened the elimination half-life of benzo(a)pyrene which was about three times shorter than the half-life found for non-3-methylcholanthrene-pretreated animals. Thus, a greater proportion of benzo(a)pyrene was converted into water-soluble products.

Animals↗

Effects of halothane, enflurane and isoflurane on contraction of rat aorta induced by endothelin-1.

Volatile anaesthetics induce hypotension by both indirect and direct effects; they have been reported to inhibit vasoconstriction produced by a variety of agonists. These studies were performed to see if halothane, enflurane and isoflurane attenuate endothelin-1-evoked contraction and if they interact with endothelium-dependent or -independent vasoactive substances. Rat aortic rings were suspended in aerated Krebs' solution (37 degrees C) and contracted by incremental doses of endothelin-1 5 x 10(-10) to 5 x 10(-8) mol litre-1. Volatile anaesthetics at 1 and 2 MAC were tested on endothelium intact and denuded rings. They were tested also on L-NAME incubated endothelium intact and indomethacin-incubated endothelium intact and denuded rings. Responses to endothelin-1 were compared in the presence and absence of volatile anaesthetics. Isoflurane at 1 and 2 MAC concentration, and enflurane at 2 MAC, induced a rightward shift of the dose-response curve obtained with endothelin-1 in both endothelium denuded and intact rings, associated with a decrease in maximal tension generated in the latter rings. In L-NAME-incubated endothelium intact rings and in indomethacin endothelium denuded rings, the anaesthetics induced a rightward shift of the dose-response curve without modification of maximal tension. In indomethacin-incubated endothelium intact rings there was significant attenuation of endothelin-1 contraction in control rings which was not enhanced by volatile anaesthetics in treated rings. The present study indicates that isoflurane at 1 and 2 MAC, and enflurane at 2 MAC, significantly decreased endothelin-1-induced contraction of isolated rat aorta. This inhibition was observed in both intact and denuded rings and probably involves mechanisms within the smooth muscle. Nevertheless, our results suggest that part of the anaesthetic-induced inhibition of endothelin-1-evoked vasocontraction involves an "indomethacin-like" effect on an endothelial-derived vasoconstricting cyclo-oxygenase product.

Anesthetics, Inhalation↗

Amphibian micronucleus test in vivo: evaluation of the genotoxicity of some major polycyclic aromatic hydrocarbons found in a crude oil.

The micronucleus test using erythrocytes of Pleurodeles waltl larvae (Amphibia, Salamandridae) was used to detect the possible genotoxicity of four polycyclic aromatic hydrocarbons (naphthalene, anthracene, phenanthrene and benzo[a]pyrene), which represent a major fraction of crude oil. Larvae were reared in water containing the test compound and the levels of micronucleated red blood cells were compared with those found in larvae reared in control water. The results are compared with published data from other tests used to evaluate the clastogenic or mutagenic properties of compounds. The results obtained confirm that benzo[a]pyrene has a strong genotoxic potential, whereas the genotoxicity of naphthalene is weak; in contrast, anthracene and phenanthrene gave a negative response.

Animals↗

Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam.

The effect of aging on the pharmacodynamics of midazolam was investigated in a double-blinded study involving 39 consenting patients ranging in age from 39 to 77 yr. Midazolam was infused intravenously (i.v.) using a pharmacokinetic model-driven drug infusion device to achieve a plasma midazolam concentration that was held constant for the 10-min duration of the study. Blood samples were obtained from the radial artery at 5 and 10 min for subsequent measurement of the plasma midazolam concentrations. With the 10-min sample, the patients were also assessed for the presence or absence of responsiveness to verbal command. To ensure that the pharmacodynamic end-point was assessed under the condition of a relative steady-state effect-site midazolam concentration, only those patients (n = 33) in whom the plasma midazolam concentration at 10 min was within 30% of the measured concentration at 5 min were included in the subsequent data analyses. Logistic regression was used to fit the verbal command response/no response data to a mathematical model that included patient age and the plasma midazolam concentration measured at 10 min. Cp50, the steady-state plasma midazolam concentration at which 50% of patients would be expected not to respond to a specific stimulus (e.g., verbal command), was calculated as a function of age from the parameterized logistic model. The midazolam Cp50 for response to verbal command decreased significantly (P = 0.034) with increasing patient age, demonstrating that aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam independent of pharmacokinetic factors.

Adult↗