PubMed Health⌕ Search

Biomedical subjects

F Nicolas

Publications and source records attributed to F Nicolas.

At least 19 recordsLinked to original sources
PubMed1999

A multi-laboratory evaluation of cryopreserved monkey hepatocyte functions for use in pharmaco-toxicology.

Ethical, economic and technical reasons hinder regular supply of freshly isolated hepatocytes from higher mammals such as monkey for preclinical evaluation of drugs. Hence, we aimed at developing optimal and reproducible protocols to cryopreserve and thaw parenchymal liver cells from this major toxicological species. Before the routine use of these protocols, we validated them through a multi-laboratory study. Dissociation of the whole animal liver resulted in obtaining 1-5 billion parenchymal cells with a viability of about 86%. An appropriate fraction (around 20%) of the freshly isolated cells was immediately set in primary culture and various hepato-specific tests were performed to examine their metabolic, biochemical and toxicological functions as well as their ultrastructural characteristics. The major part of the hepatocytes was frozen and their functionality checked using the same parameters after thawing. The characterization of fresh and thawed monkey hepatocytes demonstrated the maintenance of various hepato-specific functions. Indeed, cryopreserved hepatocytes were able to survive and to function in culture as well as their fresh counterparts. The ability for synthesis (proteins, ATP, GSH) and conjugation and secretion of biliary acids was preserved after deep freeze storage. A better stability of drug metabolizing activities than in rodent hepatocytes was observed in monkey. After thawing, Phase I and Phase II activities (cytochrome P450, ethoxycoumarin-O-deethylase, aldrin epoxidase, epoxide hydrolase, glutathione transferase, glutathione reductase and glutathione peroxidase) were well preserved. The metabolic patterns of several drugs were qualitatively and quantitatively similar before and after cryopreservation. Lastly, cytotoxicity tests suggested that the freezing/thawing steps did not change cell sensitivity to toxic compounds.

Adenosine Triphosphate↗
PubMed1998

Nosocomial Acinetobacter baumannii infections: microbiological and clinical epidemiology.

BACKGROUND: Acinetobacter baumannii is an important opportunistic pathogen that is rapidly evolving toward multidrug resistance and is involved in various nosocomial infections that are often severe. It is difficult to prevent A. baumannii infection because A. baumannii is ubiquitous and the epidemiology of the infections it causes is complex. OBJECTIVE: To study the epidemiology of A. baumannii infections and assess the relation between fluoroquinolone use and the persistence of multidrug-resistant clones. DESIGN: Three case-control studies and a retrospective cohort study. SETTING: A 20-bed medical and surgical intensive care unit. PATIENTS: Acinetobacter baumannii was isolated from 45 patients in urine (31%), the lower respiratory tract (26.7%), wounds (17.8%), blood (11.1%), skin (6.7%), cerebrospinal fluid (4.4%), and sinus specimens (2.2%). One death was due to A. baumannii infection. MEASUREMENTS: Antimicrobial resistance pattern and molecular typing were used to characterize isolates. The incidence of A. baumannii infection and the use of fluoroquinolones were calculated annually. RESULTS: Initially, 28 patients developed A. baumannii infection. Eleven isolates had the same antimicrobial susceptibility profile, genotypic profile, or both (epidemic cases), and 17 were heterogeneous (endemic cases). A surgical procedure done in an emergency operating room was the main risk factor for epidemic cases, whereas previous receipt of a fluoroquinolone was the only risk factor for endemic cases. The opening of a new operating room combined with the restriction of fluoroquinolone use contributed to a transitory reduction in the incidence of infection. When a third epidemiologic study was done, previous receipt of a fluoroquinolone was again an independent risk factor and a parallel was seen between the amount of intravenous fluoroquinolones prescribed and the incidence of endemic infection. CONCLUSION: Epidemic infections coexisted with endemic infections favored by the selection pressure of intravenous fluoroquinolones.

Acinetobacter↗
PubMed1998

Non-selective effects of adenosine A1 receptor ligands on energy metabolism and macromolecular biosynthesis in cultured central neurons.

To investigate the effects of adenosine A1 receptor activation on energy metabolism and RNA and protein biosynthesis in central neurons, cultured neurons from the rat forebrain were exposed for 1 hr to 72 hr to various concentrations (10 nM-100 microM) of the selective A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) or the A1 receptor antagonist 8-cyclopentyltheophylline (CPT). At all concentrations tested, the adenosinergic compounds did not affect cell viability within 72 hr of treatment, except for CPT, which reduced viability by 19.7% when used at the concentration of 100 microM. Energy metabolism was analysed by studying the specific uptake of 2-D-[3H]deoxyglucose ([3H]2DG). Rates of RNA and protein biosynthesis were assessed by the measurement of [3H]uridine and [3H]leucine incorporation, respectively. Neuronal [3H]2DG uptake was increased by 16% (P < 0.01) after 8 hr in the presence of 100 microM CCPA, whereas 100 microM CPT for 24 hr also increased [3H]2DG uptake (8%, P < 0.01). At these concentrations, both ligands inhibited [3H]uridine incorporation after a 3-hr treatment by 92% and 30%, respectively. CCPA never altered [3H]leucine incorporation when compared to controls, and CPT significantly inhibited protein synthesis only at 10-100 microM. Additional experiments to analyse the influence of A1 ligands on the transport of [3H]2DG, [3H]leucine and [3H]uridine suggested that CCPA and CPT, which interact functionally with adenosine receptors by regulating cyclic AMP production in this model, are able to alter energy metabolism and RNA synthesis in central neurons in a nonspecific manner by interacting with glucose and uridine transporters.

Adenosine↗
PubMed1998

[Ethical aspects concerning nosocomial infections].

Ethical issues about nosocomial infections have to be considered in two fields: the daily practice and the doctors participation in the institutional or suprainstitutional committees, involved in various administrative, strategic or financial measures aiming at the control and the prevention of nosocomial infections. In daily practice the ethical rules are founded on the principles of individual good: regarding nosocomial infection the principle of non maleficence is the most relevant. Physicians, nurses or other health professional may have a part of responsibility in a nosocomial infection. However there are many impediments to their acknowledgement of their own moral responsibility. The most important impediments may be: a) the more and more collective approach of care in many hospitals wards; b) the fact that the consequences of a nosocomial infection in one patient can extend to patients in other structures and, thus, can remain ignored by those who are responsible for this infection; c) paradoxically enough, the high attention paid to the theoretical issues concerning nosocomial infection. It must be kept in mind, too, that the ethical issues concerning nosocomial infections include the necessity for providing the patients with adequate and truthful information about the risks of nosocomial infection, in every hospital or ward, and--if it happens--about the nosocomial nature of an infectious complication. There is also some concern about the fact that the various modalities of legal responsibility and indemnification for a nosocomial infection, that the law has already specified or could define in a near future, may have a negative influence on the capacity of many care providers to keep a feeling of their moral responsibility. In the official committees devoted to decide administrative, strategic or financial measures able to help scientific research and to induce better practice in the surveillance and the prevention of nosocomial infections, the ethical principles at use are not only those of good but also those of justice. The balance between these ethical principles is delicate, however, for doctors, the main concern should be to avoid any distortion of the debate which could result from their confusing use of the principles of good.

Cross Infection↗
PubMed1998

[Laparoscopic surgical treatment of simple cysts of the kidney].

OBJECTIVE: To demonstrate the efficacy of laparoscopic treatment of symptomatic renal cysts or cysts suspicious of malignancy. MATERIAL AND METHODS: 10 patients (mean age: 58 years) were operated by laparoscopy either for compressive or symptomatic cysts (7 cases), or for cysts suspicious of malignancy (3 cases). The mean cyst diameter was 7.8 cm. All patients were evaluated by preoperative CT scan. There were 8 Bosniak type I and 3 Bosniak type II cysts. RESULTS: The procedure was performed via an intraperitoneal approach (8 cases) or via a retroperitoneal approach (2 cases). The mean operating time was 92 min and the mean hospital stay was 5.4 days. One patient was operated (conversion to lumbotomy) for uncontrolled haemorrhage of the base of the cyst. The 10 cysts were found to be benign histologically. All 10 patients are asymptomatic (mean follow-up: 8.3 months) with disappearance of the cyst on the follow-up CT scan. CONCLUSION: Laparoscopic treatment of renal cysts is feasible and effective. However, this treatment must be reserved for Bosniak type I and II cysts, associated with a low risk of malignancy.

Adult↗
PubMed1997

[Malaria in expatriates in Africa. 154 cases. Clinical problems and therapeutic difficulties].

OBJECTIVES: Malaria is a major health priority. The aim of this study was to describe clinical expression, laboratory findings and therapeutic aspects of Plasmodium falciparum malaria observed in a French military population stationed in Gabon. PATIENTS AND METHODS: One hundred fifty-four cases of P. falciparum malaria were observed between July 1, 1994 and February 29, 1996. In 145 cases malarial fever predominated and in 9 others further complications occurred. Mean age of the patients was 23.7 years and mean delay to consultation was 30 hours. Seventy-two percent of the patients stated they took prophylaxis (chloroquine-proguanil) regularly. RESULTS: Pain generally accompanied the episodes of fever. There were 21 atypical cases. Parasitemia was < 25000 HPM in 70% of the cases. Blood counts showed leukopenia, lymphopenia, and thombopenia. Plasma cholesterol was low and lactic acid dehydrogenase levels were elevated. Halofantrine was used for curative treatment (2 doses with a 7 day interval) in 145 cases. Intravenous quinine was used in 9 cases. DISCUSSION: This series demonstrates the importance of malarial morbidity in French military men stationed in Africa and confirmed the performance of the acridine orange test. It also emphasized the importance of indirect laboratory findings for early diagnosis of malaria in foreigners living in Africa. A new dosage of halofantrine is proposed for the second injection due to cardiac toxicity.

Adult↗
PubMed1997

Quality of life 6 months after intensive care: results of a prospective multicenter study using a generic health status scale and a satisfaction scale.

OBJECTIVE: To assess the quality of life of intensive care survivors 6 months after discharge. DESIGN: Multicenter prospective study. SETTING: Medical-surgical intensive care units (ICUs) of four French university hospitals. PATIENTS: Among the 589 patients admitted to the four ICUs between 1 January and 31 March 1989, 329 were investigated. MEASUREMENTS AND RESULTS: A generic scale assessing health-related quality of life, the Nottingham Health Profile (NHP), a satisfaction scale, the Perceived Quality of Life scale (PQOL) and a questionnaire on professional status were sent by mail 6 months after discharge. Data concerning age, severity of acute illness (assessed by the Simplified Acute Physiology Score) and main diagnosis were recorded. A total of 223 questionnaires (67.8 %) were analysable. The professional status remained unchanged in 79.7% of the patients, despite a significant (p < 0.01) increase (15.3 vs 22.1%) in sick leave. Quality of life, assessed with NHP, was fair (50th percentile = 0.73 on a 0 to 1 scale), whereas satisfaction measured by PQOL was lower (50th percentile = 0.61). Both scales correlated well (z = 9.853; p = 0.0001) but with a large dispersion. The NHP scale showed a severe reduction in energy, sleep and emotional reactions, whereas social isolation, pain and physical handicap were infrequent. Family support was rated with the PQOL score as very good, whereas dissatisfaction concerning recreational and professional activities was expressed. Subsequent sick leave was associated with a poor quality of life (p < 0.05). Quality of life was mainly a function of the diagnosis, not of age and severity of illness: patients admitted for suicide attempt or chronic obstructive pulmonary disease fared poorly. CONCLUSIONS: Quality of life measured with a health-related quality of life scale and a satisfaction scale 6 months after an ICU stay depended on the admission diagnosis. Different dimensions of quality of life were variably affected.

Adolescent↗
PubMed1997

Replacement fluids in plasmapheresis: cross-over comparative study.

OBJECTIVE: To compare the tolerance and the cost of three replacement fluids in plasmapheresis: albumin 4% alone, albumin 4% + dextran 40, or albumin 4% + hydroxyethylstarch 6%. DESIGN: A one center randomized, cross-over, comparative study designed to explore the tolerance and the colloid oncotic pressure in patients undergoing plasmapheresis. PATIENTS: 225 plasmapheresis procedures were performed in 27 patients. MEASUREMENTS AND RESULTS: Hemodynamic tolerance was good in the three treatment groups. Serum protein concentration after plasmapheresis was significantly lower in the albumin + hydroxyethylstarch group, followed by albumin + dextran 40, versus albumin alone. Colloid oncotic pressure before and after exchange was similar in the three groups. CONCLUSIONS: The clinical use of 25-30% of hydroxyethylstarch 6% or dextran 40 with albumin 4% was clinically well tolerated and associated with a 12% decrease of the cost of substitution solutions.

Adult↗
PubMed1997

[Use of Glasgow coma scale by anesthesia and intensive care internists in brain injured patients].

OBJECTIVE: To evaluate the quality and reliability of the Glasgow coma scale (GCS) score when determined, in head trauma patients, by trainees in anaesthesiology. STUDY DESIGN: Prospective survey. USERS: One hundred trainees in their first to fourth year of training in anaesthesiology. METHODOLOGY: A questionnaire completed by the trainees concerning: demographic data; place, time and qualification of the physician determining the first GCS score; time and qualification of the physician determining the subsequent GCS score; assessment of the GCS score in case of asymmetrical motor response, tracheal intubation, bilateral eyelid oedema, or circulatory or ventilatory failure. RESULTS: Sixty questionnaires were available for analysis. Lack of compliance with the rules for the GCS score evaluation resulted in many errors by most of the trainees. Only a few of them determined an accurate GCS score in cases of asymmetric motor response or impossibility to determine verbal or ocular response. Finally, GCS scores were determined later only very rarely. CONCLUSION: In order to provide optimal care and allow an accurate assessment of therapeutic efficiency, special attention should be given to the teaching of the GCS scoring method in head trauma patients.

Anesthesiology↗
PubMed1996

Increase of cytochrome P-450 1A and glutathione transferase transcripts in cultured hepatocytes from dogs, monkeys, and humans after cryopreservation.

The study was designed to investigate the effects of phenobarbital (PB), 3-methylcholanthrene (3-MC), and oltipraz (OPZ), a synthetic derivative of 1,2-dithiole-3-thione, on the levels of cytochrome P450 1A1/2 and gluthathione transferase (GST) mRNAs in both fresh and cryopreserved human, monkey, and dog hepatocytes in primary culture. GST alpha mRNAs were demonstrated in liver parenchymal cells from the three species: after 4 days of culture, their basal levels were decreased, but were strongly higher in PB- and OPZ-treated cells from the three species. In contrast 3-MC was mostly effective on human hepatocytes. The increased levels of GST alpha mRNAs in the presence of PB or OPZ were not observed in all cell populations. GST mu mRNAs, which were detected in both dog and monkey hepatocytes, were induced only in the presence of OPZ. GST pi mRNAs were expressed in dog hepatocytes but did not respond to any of the inducers. In all cases, similar effects were observed in fresh and thawed hepatocytes. Similarly, CYP1A1/2 transcripts were induced by 3-MC in both fresh and cryopreserved cells from the three species but also after OPZ treatment for monkey hepatocytes. These findings demonstrate that enzymes which play a major role in bioactivation/detoxication of xenobiotics remain expressed and inducible in hepatocytes from various species after cryopreservation and thawing.

Animals↗
PubMed1996

Short-term impact of the European Consensus Conference on the use of selective decontamination of the digestive tract with antibiotics in ICU patients.

Because it remained controversial, the use of selective digestive decontamination (SDD) in patients in the intensive care unit (ICU) was chosen as the topic of the first European Consensus Conference in Intensive Care Medicine (ECCICM) in December, 1991. The Consensus Bureau decided to assess the impact of this conference 2 years afterwards. For this purpose, a questionnaire was sent to the members of the European Society of Intensive Care Medicine, the Societé de Réanimation de Langue Française and the Societé Française d'Anesthesie et Réanimation before the conference. The recommendations following the conference discouraged the systematic use of SDD in ventilated patients and urged the monitoring of bacterial resistance and adapting antibiotics to epidemiology of the units. Two years after the conference, the same questionnaire was sent to those physicians who had responded to the first one. Eighteen percent used SDD for all ventilated patients and 17% remain users after 2 years. Among the occasional (32%) or continual (17%) users of SDD, the regimens used were mostly intravenous cefotaxime (60% of systemic antibiotics) and a topical combination of polymixin E, tobramycin, and amphotericin B (62% of overall topical combinations). The antibiotics used were unchanged after 2 years in almost all cases. In conclusion, the short-term impact of the Consensus Conference on SDD in ICU patients has been poor. This may be related to the continuing insufficiency of strong, definite data regarding the impact of this technique upon mortality and the theoretical risk of resistance to antibiotics, thus allowing physicians to stick to their policies until there is new evidence.

Anti-Bacterial Agents↗
PubMed1996

Adenosine physiology and pharmacology: how about A2 receptors?

Adenosine participates in the physiology of central and peripheral tissues through several subtypes of G-protein-coupled receptors. Positively linked to adenylate cyclase, A2 receptors have been subdivided into A2a and A2b sites on the basis of their molecular, biochemical and pharmacological properties. They exhibit selective distribution, and are implicated in the modulation of psychomotor activity, circulation, respiration, and metabolism. Recent data support the evidence that adenosine A2 receptor properties may prove useful in future drug development, and selective manipulation of receptor-associated biologic effects might be relevant in the treatment of various disorders, including psychiatric diseases, hypoxia/ischemia, inflammation or erythrocytosis.

Adenosine↗
PubMed1996

[Hemodynamic changes induced by apnea test in patients with brain death].

OBJECTIVE: In France, an apnoea test is compulsory to confirm brain death. This test results in a major hypercarbia and respiratory acidosis. This study aimed to assess haemodynamic changes elicited by the apnoea test. STUDY DESIGN: Prospective clinical study. PATIENTS: Fifteen patients with brain death METHODS: Before the apnoea test, the lungs were ventilated with pure oxygen for 20 minutes. Thereafter, the test was conducted with continuous oxygen flow through the endotracheal tube, and SpO2 monitoring. Blood gases and haemodynamic parameters, including systemic arterial pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index and right ventricular function parameters were assessed before, during and 20 minutes after the apnoea test. Mean values at the various times were compared. RESULTS: Hypercarbia and acidosis induced a major pulmonary hypertension and an increase in cardiac output, associated with a decrease in systemic vascular resistances. Despite pulmonary hypertension and acidosis, right ventricular function was maintained. All haemodynamic modifications were reversed by reventilation. CONCLUSION: Apnoea test induces a reversible pulmonary hypertension that is seemingly not deleterious for right ventricular function. Apnoea test probably does not alter viability of the donor's organs.

Acidosis, Respiratory↗
PubMed1996

Hemodiafiltration in pentobarbital poisoning.

We report the use of continuous venovenous hemodiafiltration (CVVHD) in a case of massive intentional ingestion of pentobarbital associated with severe coma and hypotension. Despite a poor hemodynamic state, toxic epuration (15% of drug ingested) was obtained. However, death occurred 7 hr after the end of treatment. This report suggests that CVVHD can be effective in the treatment of massive pentobarbital intoxication.

Acute Disease↗
PubMed1995

In vitro evaluation of donor liver preservation fluids on human hepatocyte function.

Successful liver transplantation depends on adequate preservation of cellular function. We therefore tested the effects of two currently used liver preservation fluids, Euro-Collins (EC) solution and University of Wisconsin (UW) solution, on the viability and some functional activities of hepatocytes isolated from human livers. Cells in primary culture were maintained under hypoxic (95% N2/5% CO2) and hypothermic (4 degrees C) conditions for 24 h, either in EC or UW solution. This treatment did not result in significant hepatocyte damage, as judged by phase contrast microscopy, intracellular LDH release, and the MTT mitochondrial test. However, neutral red uptake indicated that lysosomal functions were slightly affected (35% decrease) when compared to control conditions. At the end of the hypoxia/hypothermia period, hepatocyte monolayers were incubated at 37 degrees C under normoxic conditions for 24 h, in order to simulate the reperfusion of a transplanted liver. Three drugs--midazolam, diazepam, zidovudine--were used as diagnostic substrates to check the metabolic abilities of human hepatocytes replaced in normal conditions. Both phase I (hydroxylation, demethylation) and phase II (glucuronidation) metabolic reactions were affected by the hypoxia/hypothermia shock. Indeed, a 30%-50% decrease in these activities was observed as compared to values obtained in control hepatocytes. No difference could, however, be found at the cellular level regarding the solution used for cold storage. These results suggest that the superiority of UW over EC solution, already reported in clinical practice after transplantation of preserved human livers, was not due to a better preservation of the hepatocytes.

Antimetabolites↗