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Biomedical subjects

F Arnaud

Publications and source records attributed to F Arnaud.

At least 19 recordsLinked to original sources

A 300 year history of lead contamination in northern French Alps reconstructed from distant lake sediment records.

Lead concentrations and isotopic ratios were measured along two well-dated sediment cores from two distant lakes: Anterne (2100 m a.s.l.) and Le Bourget (270 m a.s.l.), submitted to low and high direct human impact and covering the last 250 and 600 years, respectively. The measurement of lead in old sediment samples (>3000 BP) permits, in using mixing-models, the determination of lead concentration, flux and isotopic composition of purely anthropogenic origin. We thus show that since ca. 1800 AD the regional increase in lead contamination was mostly driven by coal consumption ((206)Pb/(207)Pb approximately 1.17-1.19; (206)Pb/(204)Pb approximately 18.3-18.6), which peaks around 1915 AD. The increasing usage of leaded gasoline, introduced in the 1920s, was recorded in both lakes by increasing Pb concentrations and decreasing Pb isotope ratios. A peak around 1970 ((206)Pb/(207)Pb approximately 1.13-1.16; (206)Pb/(204)Pb approximately 17.6-18.0) corresponds to the worldwide recorded leaded gasoline maximum of consumption. The 1973 oil crisis is characterised by a drastic drop of lead fluxes in both lakes (from approximately 35 to <20 mg cm(-2) yr(-1)). In the late 1980s, environmental policies made the Lake Anterne flux drop to pre-1900 values (<10 mg cm(-2) yr(-1)) while Lake Le Bourget is always submitted to an important flux (approximately 25 mg cm(-2) yr(-1)). The good match of our distant records, together and with a previously established series in an ice core from Mont Blanc, provides confidence in the use of sediments as archives of lead contamination. The integration of the Mont Blanc ice core results from Rosman et al. with our data highlights, from 1990 onward, a decoupling in lead sources between the high elevation sites (Lake Anterne and Mont Blanc ice core), submitted to a mixture of long-distance and regional contamination and the low elevation site (Lake Le Bourget), where regional contamination is predominant.

Altitude↗

[Discharge of very preterm infants from neonatology: check list].

Key elements of the check list for neonatal discharge include: discharge discussion with parents, relation with maternal and child welfare assistants and family practitioner, scheduling of follow-up visits, request for insurance coverage, parental presence allowance, special education allowance, debriefing with nurses and nurses providers, clinical and biological appraisal, discharge prescription. For a former extremely premature baby, going home - often after a long hospitalization and a variety of pathologic problems - must be prepared and should not be decided in haste, not only for the baby and his/her parents, but also. for the neonatal staff!

France↗

Use of hollow fiber membrane filtration for the removal of DMSO from platelet concentrates.

It has been hypothesized that, in addition to freezing injury, some damage to platelets may result from the cell packing that occurs during removal of the cryoprotectant. This study examined DMSO removal by fluid exchange across hollow-fiber (HF) filters as an alternative to centrifugation. The DMSO solution with or without cell suspension was passed once through the filter. The optimum exchange during unloading of DMSO was determined by varying the flow rates in the external and internal compartments of the HF filter. Initially, buffered solutions of a 5% DMSO solution in the absence of platelets were pumped into the fibers and exchanged against PBS. The residual DMSO was determined by osmometry. The exchange of DMSO across the membrane was flow dependent and also influenced by the chemical nature of the HF fibers. No protocol using a reasonable rate flow through the fibers removed more than 95% of the DMSO in a single pass. The optimum protocol was achieved with polysynthane fibers with an internal flow rate of approximately 20 mi/min and an external flow rate of 100 ml/min. Subsequently, frozen/thawed platelet concentrates in DMSO were washed using centrifugation and compared to the HF filtration method. Platelet quality was assayed by flow cytometry, cell count, morphology and osmotic stress test. Both filtration and centrifugal washing techniques resulted in comparable morphological scores and numbers of discoid cells. When agents reducing platelet activation were added, platelet quality was improved after washing by either technique. The lower platelet osmotic response with HF filtration than with centrifugation while using activation inhibitors was attributed to the remaining amount of the inhibitors. All other parameters tested were similar. The expression of CD62P was equivalent with both techniques, and centrifugation did not activate platelets more than filtration contrary to what was originally anticipated. In conclusion, platelet quality was comparable after washing by either technique but hollow fiber filtration does remove cryoprotectant more rapidly than does centrifugation.

Blood Platelets↗

Expression of the Idefix retrotransposon in early follicle cells in the germarium of Drosophila melanogaster is determined by its LTR sequences and a specific genomic context.

Retrotransposons are transcriptionally activated in different tissues and cell types by a variety of genomic and environmental factors. Transcription of LTR retrotransposons is controlled by cis-acting regulatory sequences in the 5' LTR. Mobilization of two LTR retroelements, Idefix and ZAM, occurs in the unstable RevI line of Drosophila melanogaster, in which their copy numbers are high, while they are low in all other stocks tested. Here we show that both a full-length and a subgenomic Idefix transcript that are necessary for its mobilization are present in the Rev1 line, but not in the other lines. Studies on transgenic strains demonstrate that the 5' LTR of Idefix contains sequences that direct the tissue-specific expression of the retroelement in testes and ovaries of adult flies. In ovaries, expression occurs in the early follicle and in other somatic cells of the germarium, and is strictly associated with the unstable genetic context conferred by the RevI line. Control of tissue-specific Idefix expression by interactions between cis-acting sequences of its LTR and trans-acting genomic factors provides an opportunity to use this retroelement as a tool for the study of the early follicle cell lineage in the germarium.

Alternative Splicing↗

Human platelets activate porcine endothelial cells through a CD154-dependent pathway.

BACKGROUND: Delayed xenograft rejection is associated with endothelial cell activation, platelet sequestration, and subsequent thrombosis. We evaluated whether human platelets could directly activate porcine endothelium (PEC), and if so, whether this was mediated by an interaction between platelet-bound CD154 and PEC CD40. METHODS: Platelet activation was achieved by thrombin exposure and confirmed by evaluation of up-regulated CD62P and CD154. Co-incubation of platelets or D1.1 cells with PEC was performed, and PEC activation was evaluated by up-regulation of CD62E. RESULTS: Co-incubation of resting platelets that lacked significant expression of CD62P and were void of CD154 did not activate PEC. In contrast, thrombin-activated human platelets expressing considerable amounts of both CD62P and CD154 induced PEC activation. This activation could be completely inhibited by coincubation with a humanized monoclonal antibody directed at human CD154 (hu5c8). Similarly, human D1.1 cells expressing CD154 were shown to activate PEC in a CD154-dependent manner. CONCLUSION: Human CD154 expressed on activated human platelets or on T cells interacts with CD40 expressed on PEC leading to PEC activation. This interaction can be inhibited by a monoclonal antibody directed against CD154, suggesting that an interaction between human CD154 and PEC CD40 is at least in part responsible for PEC activation seen in delayed xenograft rejection. These data strengthen the rationale for the use of CD154-directed therapy in discordant xenotransplantation.

Animals↗

Endothelial and smooth muscle changes of the thoracic and abdominal aorta with various types of cryopreservation.

BACKGROUND: There is a need for cryopreserved arterial allografts in vascular surgery. Vitrification was examined as an alternative to slow cooling. Function of endothelial and adjacent cells was evaluated in the thoracic and abdominal regions of the porcine aorta. MATERIAL AND METHODS: Aortas from young pigs were harvested and cryopreserved with several treatments: slow cooling at 1 degrees C/min with 10% dimethyl sulfoxide (DMSO) and vitrification with a vitrification solution (VS), performed either in the presence (medium) or in the absence (air) of the cryoprotective medium surrounding the sample. Tetrazolium salt reduction and oxygen consumption were used to assess the mitochondrial activity of the endothelial cells and smooth muscle cells from the aorta. RESULTS: Fresh aorta showed an increased function from below the aortic arch to the iliac branch. Exposure to cryoprotective solutions reduced significantly the oxygen consumption of the abdominal sections. Samples from the thoracic region had a better response to cryopreservation than those from the abdominal region. There was a significant reduction in tetrazolium salt reduction and oxygen consumption when the samples were cryopreserved immersed in the medium. Significant flaking of the endothelium was observed after vitrification and contributes generally to lower the function. CONCLUSION: The thoracic region of the aortic wall was more tolerant to the preservation injury, and freezing with DMSO in air offered a better choice of preservation.

Animals↗

Frozen/thawed platelets: importance of osmotic tolerance and platelet subpopulations.

Me2SO cryopreserved platelets circulate in vivo, reduce bleeding time, and have hemostatic properties but their functional recovery is only half that of the fresh material. Poor osmotic response is often reported as the cause of the freezing injury. Osmotic excursions on 1- and 5-day-old platelets have been studied. Platelets stored for 5 days have a lesser capability to regulate their volume particularly after an initial swelling. This is attributed to the reduction of discoid cell number, 80% vs 62% for 1-day-old and 5-day-old platelets, respectively. After freezing, hypotonic stress response is reduced from 86 to 39% for 1-day-old and 73 to 31% for 5-day-old platelets. This reduction in function is supported by a similar reduction of discoid cells from 80 to 40% for 1-day-old and 62 to 32% for 5-day-old platelets. The integrity of the cytoskeleton is critical for the osmotic response. Freezing recovery is significantly lowered in the presence of propylene glycol, which alters actin. This contrasts with the recovery of platelets treated with anti-aggregating agents. Platelets show a greater viability after freezing and thawing when PGI2 is added. It is postulated that freshly collected platelets, which are heterogeneous, contain populations of cells that are more sensitive to freezing than others. More tolerant cells remain discoid after freezing and are also less susceptible to storage lesions. Therefore, the maintenance of the integrity of the membrane and the cytoskeleton should be considered for the development of preservation methodologies.

Blood Platelets↗

Freezing injury of granulocytes during slow cooling: role of the granules.

The granulocyte is an interesting model for studying the behavior of fragile cells at low temperature. A previous study suggested that during slow freezing the plasma membrane was not the primary site of injury and, as a corollary to this, we examined the damage occurring in the cytoplasmic compartment. The present study was designed to investigate the role of granules during cryoinjury of the granulocytes. Granulocytes were prepared from fresh blood and a population of granules was extracted by nitrogen cavitation. A graded freeze-thaw protocol was used to follow the release of beta-glucuronidase (beta-Glu), one of the hydrolytic enzymes present in granules. Granulocytes and granules were subjected to treatments simulating slow freezing conditions, and the release of beta-Glu was evaluated after exposure to increased hydrolytic enzymes and hypertonic salt concentration. It was found that, after thawing, granulocytes generally expressed more release than granules during graded freezing. The postthaw incubation period had no effect on enzyme release. Increase in salt concentration reduces beta-Glu activity. Direct exposure to hydrolytic enzymes produced similar injury on both granules and granulocytes, and salt combined with enzymes did not increase granule disruption. It is concluded that the effect of injured granules may be more apparent during rewarming when isotonicity is reestablished. Enzymes released extracellularly induce no extra injury to the granulocyte because of dilution effect; however, their release in the cytosol can cause a defect resulting in the loss of cell viability but no membrane disruption. Overall, the release of enzymes is seen as a secondary factor contributing to whole cell or membrane damage during slow freezing.

Cell Fractionation↗

Effect of a dopaminergic agonist, piribedil (Trivastal 50 mg LP), on visual and spatial integration in elderly subjects.

Dopamine acts as a neuromodulator in the retina. Dopaminergic deficiency of any origin, as observed in elderly subjects, is associated with altered visual performances, and more specifically with altered perception of contrasts. The goal of this study was to compare contrast vision in elderly subjects and young subjects (first phase, n = 20), then to compare this function in elderly subjects before and after 3 months of treatment with a dopaminergic agonist, piribedil (Trivastal 50 mg LP), administered once daily (second phase, n = 20). The perception of contrast was analysed using a test measuring sensitivity to colour contrast yielding threshold values for sensitivity to contrast in eight spatial frequencies and three colours (red, green, blue) and in two directions (horizontal and vertical). The results of the first phase of the study demonstrated that elderly subjects showed a decrease in contrast perception in comparison with young subjects, primarily in the high frequency range, and over the full range of stimulation for direction and colour. In the second phase, elderly subjects, in comparison with young subjects, showed altered visual contrast, again in the high frequency range, but also in the low frequency range for horizontal simulation with red and blue. After 3 months of treatment with piribedil the mean contrast sensitivity threshold, over the entire frequency range, had significantly increased (P less than 0.05) for all stimulations, apart for red in the vertical direction. These results underline the value of treatment with a dopaminergic agonist, piribedil in visual disturbances in patients with dopaminergic deficiency (Parkinson patients or elderly subjects).

Aged↗

Cryoinjury in human granulocytes and cytoplasts.

Although most isolated cells can be successfully cryopreserved, human granulocytes have little functional recovery after cryopreservation, even under optimized conditions. Cytoplasts, which are vesicles created from human granulocytes by depletion of organelles including granules and the nucleus, can carry out some of the complex functions of the parent granulocyte such as phagocytosis of bacteria, even after cryopreservation. Human granulocytes and cytoplasts were used in this comparative study of low-temperature responses to assess the relative importance of the plasma membrane and the granules in cryoinjury to human granulocytes. Boyle-van't Hoff plots of cell volume as a function of the reciprocal of osmolality showed that granulocytes and cytoplasts have similar osmometric behavior and equivalent osmotically inactive fractions. The hydraulic conductivities were also similar, indicating that the osmotic properties of the plasma membrane and cytoplasm were retained during preparation of the cytoplasts. Assessment of membrane integrity using fluorescein diacetate after graded freezing stresses showed that the low-temperature responses of cytoplasts were similar to those of human lymphocytes and hamster fibroblasts, with recoveries much higher than those of human granulocytes, particularly after post-thaw incubation at 37 degrees C. The results indicate that the plasma membrane is not the primary site of injury to granulocytes during freezing and thawing, and suggest that activation of cytoplasmic elements, such as granules, may constitute the early events in cryoinjury to human granulocytes. These studies have significance in approaches to the cryopreservation of granulocytes and other types of cells, such as platelets, with increased sensitivity to the conditions encountered during freezing and thawing.

Cell Membrane↗

Neuropathy in chronic obstructive pulmonary disease: a multicentre electrophysiological and clinical study.

The incidence and type of neuropathy in patients with chronic obstructive pulmonary disease (COPD) were assessed. In a selected group of 89 patients, abnormal nerve conduction studies were found in 44%. Electrophysiological signs of a generalized peripheral neuropathy were found in 5-18%, depending on diagnostic criteria. Lesions which were thought to be due to compression or other forms of trauma were present in a further 24%. In the patients with peripheral neuropathy, the changes were distally predominant, affected mainly sensory fibres, and were consistent with an axonal type of neuropathy. There was a significant correlation between age and the incidence of peripheral neuropathy. Electrophysiological evidence of neuropathy was three times as common as clinical evidence. Much of the variation in the reported incidence of neuropathy in COPD is probably due to imprecise diagnostic criteria.

Adult↗

Sequential treatment with low dose almitrine bismesylate in hypoxaemic chronic obstructive airways disease.

Daily dose schedules of 100-200 mg of almitrine bismesylate improve arterial blood gases in patients with hypoxaemic chronic obstructive airways disease (COPD) but dose related side effects are evident. In the present study, daily doses approximately half of those previously used were employed in a randomised double blind manner in 85 patients (age 35-79 years) with hypoxaemic COPD. After a one month period to check stability of arterial blood gases, patients were allocated to almitrine (A) or placebo (P) using an unequal code (60% A, 40% P). Tablets, 50-100 mg daily were stopped for one month after 3, 6 and 9 months to counteract drug accumulation. 50 patients in group A and 35 in group P were comparable on entry; mean age 65 (SD = 8) yrs., Pao2 7.8 (0.7) kPa (58.3 (5.0) mmHg), PaCO2 5.8 (0.8) kPa (43.2 (6.0) mmHg), forced expiratory volume in one second--FEV1 0.89 (0.25) l and 6 minute walking distance 296 (97) metres. The improvement in baseline PaO2 values was the same 0.8-1.3 kPa (6-9.8 mmHg) as with previous higher dose therapy. Approximately one third of patients did not respond, defined as PaO2 elevation > 0.67 kPa (5 mmHg). The sequential dosing scheme stabilised blood levels of almitrine within the therapeutic range of 280-300 ng.ml-1. After withdrawal of therapy arterial blood gases and spirometry reverted to pre-treatment levels, suggesting no permanent reversal of pathophysiology. Dose related side effects of breathlessness, indigestion and peripheral neuropathy were not observed. Nerve conduction studies revealed no difference in peripheral nerve dysfunction in hypoxaemic COPD between active and placebo therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Sequential administration of a reduced dose of almitrine to patients with chronic obstructive bronchopneumopathies. A controlled multicenter study].

Recent multi-centre studies have shown that high doses of Almitrine (100-200 mg per day), lead to a significant improvement in the hypoxaemia of patients presenting with chronic airflow obstruction, but that a high blood level (greater than 500 ng/ml) is often seen after 1 year, sometimes associated with signs of peripheral neuropathy. In order to maintain Almitrine blood levels in the range 200-300 ng/ml we have used an intermittent regime (with a "window" of 1 month every 3 months) and a dose limited to 100 mg per day. 102 hypoxic patients with chronic airflow obstruction, who were in a stable state were included. 65 patients were in the Almitrine group (A) and 37 patients in the placebo group (P). The treatment lasted for 1 year. In addition there was a 3 monthly follow up with arterial blood gases and spirometry, a clinical neurological examination and also electrophysiology, initially and after 6 and 12 months. 43% of patients in group A and 32% of patients in group P, left the study, most often due to poor cooperation, but sometimes as a result of side effects. After 12 months the PaO2 rose significantly in group A from 59.1 +/- 0.7 to 65.8 +/- 1.6 mmHg (p less than 0.001) whilst it was not changed in group P. The PaCO2 did not change in either group. On the other hand there was a significant fall in the subgroup of patients with hypercapnia in group A (p less than 0.001). The outcome of the neurological and electrophysiological assessments did not show any significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Is it possible to avoid a penal offence in carrying out ambulatory anesthesia?].

French jurisprudence about outpatient anaesthesia is resolutely unfavorable. It is principally based on the June 22nd 1972 decision of the cessation court, the highest court of justice in France. Preoperative non hospitalisation has been considered as a fault by negligence/carelessness of the practitioners. It resulted in their penal condemnation for involuntary injuries and compensation for the harm. This decision is linked with the evolution of the fault and the responsibility share between surgeon and anaesthetist. The post-operative phase seems to involve "theory of missing luck" (causality linkage or the detriment in itself), excluding a penal condemnation but not a partial compensation. Though some new legal considerations could be put forward, a written contract between physicians and patients is necessary in outpatient surgery, whereas the medical files and the organisation of the unit can prove the quality of medical care.

Ambulatory Surgical Procedures↗

Peripheral neuropathies in patients with chronic obstructive pulmonary disease: a multicenter prevalence study.

To investigate the prevalence and type of peripheral neuropathies (PNP) in patients with chronic obstructive pulmonary disease (COPD), we studied lung function and blood gases, clinical signs of PNP, and neurophysiological function in 151 patients with COPD without known risk factors for PNP. Mean (SD) age was 65 (10) years, mean arterial PO2 was 59 (9) mmHg, mean ratio of forced expiratory volume in the first second to vital capacity (FEV1.0/VC) was 42 (12%). Thirty patients (20%) had clinically detectable and 6 (4%) had subclinical PNP of mild degree. Fourteen (9%) of the patients with clinically detectable PNP had symptoms due to PNP. Prevalence of PNP increased with severity of hypoxemia (p less than 0.05) and was more pronounced in the lower than in the upper limbs. Age and the degree of hypoxemia were predictors to differentiate between COPD patients with and without PNP. Although the cause of PNP in COPD patients remains unknown, our observations suggest that chronic hypoxemia may contribute to PNP.

Adult↗