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Biomedical subjects

G Sicard

Publications and source records attributed to G Sicard.

At least 19 recordsLinked to original sources

Factors increasing the mortality rate for patients with ruptured abdominal aortic aneurysms.

The objective of this report was to analyze the current surgical results of operative treatment in patients suffering ruptured AAA (abdominal aortic aneurysms) and to define those independent predictive factors for mortality. During a period of 2 years, from January 1996 to December 1997, 144 patients operated on for ruptured AAA in 10 hospitals were included in a multicenter retrospective study. Among the collected variables concerning each patient, those with potential relation to surgical mortality were studied: gender, age, diabetes, hypertension, cardiopathy, pulmonary obstructive disease, preoperative renal dysfunction, symptomatic cerebrovascular disease, peripheral vascular disease, hematocrit on admission, preoperative hypotension < 80 mmHg, loss of consciousness, cardiac arrest, aortic aneurysm location (infrarenal versus non-infrarenal), iliac involvement, aneurysm size, type of rupture, left renal vein ligature, ligature of a patent inferior mesenteric artery, place of aortic cross-clamping, type of grafting, exclusion of both hypogastric arteries, venous technical complications, associated surgery, use of cell saver, intraoperative blood loss, and postoperative complications (renal failure, sepsis, coagulopathy, cardiac complications, pulmonary complications, colon ischemia, prosthetic graft complications, and need for reoperation). Those variables with statistical significance in the univariate analysis were introduced into a multivariate logistic regression model to determine the independent predictors of death. From our results we concluded that surgery for ruptured abdominal aortic aneurysms continues to have an excessively high mortality rate. Even though some preoperative variables could be identified as predictors of mortality, an absolute mortality risk has not yet been determined and the decision to negate surgery should be individualized rather than taken on that basis only. Early diagnosis and treatment of symptomatic aneurysms would improve mortality figures and selective screening should be contemplated.

Age Factors↗

A novel mechanism for skeletal resistance in uremia.

BACKGROUND: In treating secondary hyperparathyroidism, the target level of serum intact parathyroid hormone (I-PTH) should be three to five times normal to prevent adynamic bone disease. In circulation, there is a non-(1-84) PTH-truncated fragment, likely 7-84, which, in addition to PTH 1-84, is measured by most I-PTH immunoradiometric (IRMA) assays, giving erroneously high I-PTH values. We have developed a new IRMA assay in which the labeled antibody recognizes only the first six amino acids of the PTH molecule. Thus, this new IRMA assay (Whole PTH) measures only the biologically active 1-84 PTH molecule. METHODS: Using this new IRMA assay (Whole PTH) and the Nichols "intact" PTH assay, we compared the ability of each assay to recognize human PTH (hPTH) 1-84 and hPTH 7-84 and examined the percentage of non-1-84 PTH in circulation and in parathyroid glands. Possible antagonistic effects of the 7-84 PTH fragment on the biological activity of 1-84 PTH in rats were also tested. RESULTS: In 28 uremic patients, PTH values measured with the Nichols assay, representing a combined measurement of both hPTH 1-84 and hPTH 7-84, were 34% higher than with the Whole assay (hPTH 1-84 only); the median PTH was 523 versus 318 pg/mL (P < 0.001). Similar results were found in 14 renal transplant patients. In osteoblast-like cells, ROS 17.2, 1-84 PTH (10-8 mol/L) increased cAMP from 18.1 +/- 1.25 to 738 +/- 4.13 mmol/well. Conversely, the same concentration of 7-84 PTH had no effect. In parathyroidectomized rats fed a calcium-deficient diet, 7-84 PTH was not only biologically inactive, but had antagonistic effects on 1-84 PTH in bone. Plasma calcium was increased (0.65 mg/dL) two hours after 1-84 PTH treatment, while 7-84 PTH had no effect. When 1-84 PTH and 7-84 PTH were given simultaneously in a 1:1 molar ratio, the calcemic response to 1-84 PTH was decreased by 94%. In normal rats, the administration of 1-84 PTH increased renal fractional excretion of phosphate (11.9 to 27.7%, P < 0.001). However, when 1-84 PTH and 7-84 PTH were given simultaneously, the 7-84 PTH decreased the phosphaturic response by 50.2% (P < 0.005). Finally, in surgically excised parathyroid glands from six uremic patients, we found that 44.1% of the total intracellular PTH was the non-PTH (1-84), most likely PTH 7-84. CONCLUSION: In patients with chronic renal failure, the presence of high circulating levels of non-1-84 PTH fragments (most likely 7-84 PTH) detected by the "intact" assay and the antagonistic effects of 7-84 PTH on the biological activity of 1-84 PTH explain the need of higher levels of "intact" PTH to prevent adynamic bone disease.

Animals↗

Stress induces neurogenesis in non-neuronal cell cultures of adult olfactory epithelium.

Among the basal cells of the olfactory epithelium is a stem cell which divides and whose progeny differentiate into new sensory neurons throughout adult life. Olfactory neurogenesis is highly regulated, for example it is stimulated by epithelial damage. Previous reports implicate several growth factors in progenitor cell proliferation and neuronal differentiation in vitro but these studies differ in growth conditions and age of donors making it difficult to determine precisely the roles of neurogenic stimuli and their sites of action. The aims of the present study were to develop purified basal cell cultures from adult olfactory epithelium and to stimulate neurogenesis in defined growth conditions in order to elucidate the cellular mechanisms by which neurogenesis is stimulated after epithelial damage. We show here that differentiated olfactory sensory neurons arise after biochemical or mechanical stress of rat and mouse olfactory epithelial cell cultures in the absence of growth factors, complex media (e.g., serum, conditioned media, pituitary and hypothalamic extracts), or other cells (e.g., explants, feeder layers of glia, or other non-epithelial cells). Prior to the stress, these cultures contained basal cells and supporting cells but not neurons. After the stress, some cells differentiated into bipolar neurons expressing a number of neuronal proteins including olfactory marker protein. Bromodeoxyuridine experiments show that the differentiated neurons arose from recently divided cells which did not divide again before differentiating. We conclude that stress disrupts cell surface contacts to induce the immediate neuronal precursors to undergo final differentiation into olfactory sensory neurons. This may be a mechanism for enhanced neurogenesis after epithelial damage.

Age Factors↗

Functional anatomy of perceptual and semantic processing for odors.

The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.

Adult↗

Generation of neurons from a nonneuronal precursor in adult olfactory epithelium in vitro.

Within the olfactory epithelium is a stem cell which can divide and differentiate to produce new sensory neurons. The identity of the neuronal stem cell is unknown but one candidate is the horizontal basal cell which lies adjacent to the basement membrane and expresses keratin. Previous attempts to generate mature sensory neurons from purified horizontal basal cells in vitro were unsuccessful. We show here for the first time that olfactory neurogenesis can be reproduced in vitro from partially-purified cultures of adult rat precursor cells cultivated in a serum-free medium. Rat olfactory epithelium was dissected from the nasal septum and separated from the underlying lamina propria, and its cells were dissociated and grown in a medium containing epidermal growth factor for 5 days. Immunochemistry showed that only supporting cells (SUS1-positive) and horizontal basal cells (keratin-positive) survived for this period. At day 6, the cells were stressed either by passaging them or by a simple mechanical stress. In each case, a morphological and immunological differentiation was observed within 24-48 hr. Newly formed bipolar cells were found to be S100-, glial fibrillary acidic protein (GFAP-), neural cell adhesion molecule (N-CAM+), and/or microtubule-associated protein 5 (MAP-5+). After passaging 14% of the surviving cells were immature neurons (MAP-5+) and 4% were mature olfactory neurons (MAP-5+) and olfactory marker protein (OMP+)). In addition the same experiment was conducted on transgenic mice in which the lacZ gene was linked to the OMP promoter. Using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining we showed that OMP+ cells disappeared before day 5 in culture but reappeared after passaging. These results suggest that olfactory sensory neurons can arise from a non-neuronal precursor, probably the keratin-positive horizontal basal cell.

Animals↗

In vitro induction of apoptosis or differentiation by dopamine in an immortalized olfactory neuronal cell line.

A new neuronal cell line was generated by transfection of rat olfactory epithelium with immortalizing recombinant oncogene E1A of adenovirus-2. The resulting 13.S.1.24 line of transformed cells expressed an antigenic phenotype of olfactory neuronal progenitors. Addition of dopamine to 13.S.1.24 cultures induced reduction of cell number within 2 days. Two hallmarks of apoptosis were detected in dopamine-treated cultures: internucleosomal DNA fragmentation and nuclear condensation. Dopamine did not alter the cell proliferation rate, as assessed by [3H]thymidine incorporation. Dopamine also stimulated differentiation of surviving 13.S.1.24 cells into bipolar olfactory marker protein-immunoreactive neurons. Time-dependency assessments over 1 week of treatment indicated that apoptosis and differentiation induced by dopamine were concomitant. Both apoptosis and differentiation triggered by dopamine were dose-dependent, half-maximal effects being obtained with approximately 10 microM dopamine. Mediation of both effects by dopaminergic D2 receptors was supported by several observations: active dopamine doses in micromolar ranges, quinpirole agonism and eticlopride antagonism, D2-characteristic rank order of potency among the three agonists tested, and specific binding of a selective D2-like radioligand to 13.S.1.24 cells. The present data altogether indicated that dopamine commits immortalized olfactory neuronal cells in vitro either to apoptosis or to olfactory-like differentiation via D2 dopaminergic receptors.

Adenoviridae↗

Intraoperative salvage in patients undergoing elective abdominal aortic aneurysm repair: an analysis of cost and benefit.

PURPOSE: Although autologous blood procurement has become a standard of care in elective surgery, recent studies have questioned its cost-effectiveness. We therefore reviewed our 3-year experience with intraoperative cell salvage in patients who underwent elective abdominal aortic aneurysm repair. METHODS: A 3-year retrospective chart review of elective abdominal aortic aneurysm (infrarenal and suprarenal) repair was performed. Transthoracic repairs were excluded. RESULTS: Estimated blood lost was 1748 +/- 1236 ml, or 35% of baseline blood volume (5012 +/- 689 ml). Overall, 164 (89%) received red blood cell (RBC) transfusions (3.5 +/- 2.0 U/patient). The cost per patient for cell salvage was $315 +/- $97, representing 31% of all RBC costs and 24% of total blood component costs. Mean salvage volume infused was 578 +/- 600 ml; at a mean hematocrit level of 55.7% the RBC volume infused from salvage during surgery was 313 +/- 328 ml (representing 27% of total RBC volume lost during the hospital stay). This mean RBC volume salvaged represented the equivalent of 1.6 blood bank RBC units. The mean blood bank costs saved by using cell salvage was $248, or 79% of the $315 actually spent for salvage. We found no decrease in percentage of patients undergoing transfusion until salvage volumes that were infused exceeded 750 ml, or the equivalent of two blood bank units; all of these patients who benefitted had estimated blood lost > or = 1000 ml. CONCLUSIONS: We conclude that use of intraoperative cell salvage was most beneficial for patients who had estimated blood loss greater than or equal to 1000 ml and cell salvage volumes infused greater than or equal to 750 ml. Patients who are estimated to lose less than 1000 ml receive little benefit yet incur substantial costs from intraoperative cell salvage.

Aged↗

Is short-term odour recognition predictable from odour profile?

Smelling an odour induces a pattern of sensations, images and memories which participate in identification. It was proposed that perceptual memory performances for odours could be inferred from the description of these olfactory representations. The subject was asked to elaborate an odour descriptor profile, and a short-term odour recognition memory task was chosen to test the individual perceptual memory performance. Two pattern-recognition methods based on artificial neural networks and discriminant analysis were carried out and allowed odour profile and perceptual memory performance to be related. Insofar as the subjects gave dichotomic responses in the recognition memory task, each response could be evaluated in terms of correct or incorrect responses. Simulations indicated that the olfactory recognition memory performance can be predicted in man from odour-elicited semantic profiles by using artificial neural networks. It was also shown that all semantic descriptors do not participate in olfactory recognition to the same degree. Low-level information, such as intensity, familiarity and hedonic judgements, did not allow the artificial neural network to predict the olfactory performance. By contrast, high-level information, such as gustatory, olfactory and visual evocations, allowed artificial networks to make such predictions.

Adult↗

Isolation of mature olfactory neurones using retrograde labelling and flow cytometry.

Currently we can observe an increasing interest for epithelial olfactory neurones. Several laboratories are involved in elucidation of the odorant-molecule recognition process and transduction cascade which brings information to the olfactory bulb. Others use this model, unique in mammals, to accumulate new knowledge on the neurogenesis phenomenon. Here we describe a simple and efficient method to purify mature olfactory neurone populations extracted from the nasal cavity. The approach relies on retrograde axonal tracing followed by flow cytometry sorting. For this purpose we inject a fluorescent dye (Fast Blue or diI C18(3)) in the olfactory bulb of adult rats. Seven days later, we extract the nasal turbinates and separate the mucosa from the subjacent lamina propria. The tissue is enzymatically dissociated and the labelled cells are sorted with a flow cytometer. Purification of the mature olfactory neurones varies from 80 to 99%.

Amidines↗

Physiological and histological recovery of the olfactory mucosa of the frog after a dichlobenil injection.

Four days after a single systemic injection of 50 mg/kg of dichlobenil (2,6-dichlorobenzonitrile), the olfactory neuroepithelium of the frog is extensively damaged. At the same time, electrophysiological responses to odorant stimulations (2-heptanone, D-limonene, amyl acetate, camphor) are largely reduced. Pretreatment of the animals with metyrapone, an inhibitor of cytochrome P-450 enzymatic systems, inhibits the histological and physiological toxic effects of the dichlobenil injection. The olfactory tissue recovered 3 months after the dichlobenil injections and responses to odorant stimulations returned. The same dichlobenil injections did not induce lesions in the vomeronasal neuroepithelium.

Animals↗

Beneficial effects of donor-specific transfusions on long-term renal allograft function.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 163 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate, and 21 were two-haplotype disparate. Transient sensitization occurred in 2% and permanent sensitization in 7%. Over a 10-year period, the DST+Aza allograft survival rate is similar to the HLA-identical sibling transplants. The CMV sepsis rate was only 2%, and there were no lymphoproliferative neoplasms. The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (3%) argues for a modification of the immunologic response.

Azathioprine↗

The role of cholesterol accumulation in prosthetic vascular graft anastomotic intimal hyperplasia.

PURPOSE: To demonstrate that modulation of plasma cholesterol concentrations affects prosthetic vascular graft anastomotic intimal hyperplasia (AIH), aortic grafts were examined histologically and biochemically in 41 rabbits. METHODS: Twenty-seven rabbits were fed standard rabbit diet, whereas 14 were fed cholesterol-supplemented diet to induce hypercholesterolemia. RESULTS: A smooth muscle cell proliferative response, similar to AIH in humans, was seen equally at the proximal and distal anastomoses. However, surface area and thickness of AIH were significantly greater in rabbits with hypercholesterolemia. Anastomotic tissue cholesterol concentrations were fifteenfold higher in rabbits with hypercholesterolemia than in rabbits with normal cholesterol concentrations and anastomotic cholesterol concentrations were fivefold higher than in the aorta away from the graft in rabbits with hypercholesterolemia. Preferential deposition of radioiodinated dilactitol tyramine coupled to low-density lipoproteins, but not albumin, was demonstrated in anastomotic areas and grafts of rabbits with normal cholesterol concentrations as well. Surface area and thickness of AIH correlated closely with plasma and tissue cholesterol concentrations. CONCLUSIONS: Oxidized products of lipoproteins have been shown to stimulate production of growth factors that cause smooth muscle cell proliferation, migration, and synthetic function. It is likely they play an important part in prosthetic vascular graft AIH, similar to their role in atherogenesis.

Anastomosis, Surgical↗

Renal autotransplantation in the management of a ureteroarterial fistula: a case report and review of the literature.

A 57-year-old woman who had been treated with an indwelling ureteral stent for over a year was admitted with massive gross hematuria caused by a fistula between the left ureter and hypogastric artery. Despite intensive radiographic evaluation, the definitive diagnosis was made only at the time of surgical exploration. Because of radiation-induced retroperitoneal fibrosis, midureteral obstruction, and prior pelvic and abdominal surgery, primary ureteral repair was not possible, and renal autotransplantation was performed. This case illustrates the need to consider the diagnosis of ureteroarterial fistula in patients with massive hematuria who have chronic indwelling stents, and the feasibility of autotransplantation when primary ureteral repair is not feasible.

Arteries↗

A canine model of paired graft thrombosis.

A novel canine model for reliably producing graft thrombosis is described. Two unilateral aortoiliac bypasses are performed while preserving the integrity of the native vascular tree. These grafts are briefly mechanically occluded at the time of the initial operation, and they remain occluded postoperatively because flow is preferentially directed through the larger-caliber, thrombo-resistant native circulation. Percutaneous temporary intra-arterial balloon occlusion of the native vessels redirects flow into the occluded graft segments, which can be used in experimental protocols. This new model for studying graft thrombosis requires only a single, simple operative procedure, and easily allows secondary percutaneous graft manipulation.

Animals↗

Tolerance of gastric mucosal flap to postoperative irradiation.

When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered.

Aged↗

Olfactory discrimination over a wide concentration range. Comparison of receptor cell and bulb neuron abilities.

Until now, olfactory discrimination had never been investigated using stimuli delivered over a wide concentration range. However, the fact that intensity variations might influence qualitative discrimination has been suggested in numerous physiological and psychophysical studies. The aim of the present work was to investigate qualitative coding mechanisms when stimulus intensity varies. For this purpose, receptor cell and olfactory bulb neuron unit activities were recorded in response to 2-s pulse delivery of 4 odorants available at 20 discrete concentration values over a range from 1 x 10(-6) to 5.62 x 10(-2) of saturation. Two types of mathematical analyses, Pearson's r correlation coefficient calculation and principal component factor analysis, were applied to odor-evoked discharge frequencies. In both receptor cells and bulb neurons, qualitative discrimination abilities were found to increase with stimulus concentration. Furthermore, the results suggest that the olfactory bulb can send a discriminant and specific message at lower concentrations than the olfactory mucosa. The amplifying role of convergence of primary afferences onto olfactory glomeruli could account for this ability of the bulb neurons.

Action Potentials↗

Comparison of the sensitivity of C57BL/6J and AKR/J mice to airborne molecules of isovaleric acid and amyl acetate.

Wysocki et al. (1977) have previously compared the abilities of several inbred strains of mice to avoid odorized drinks after odor-aversion conditioning and have proposed C57BL/6 mice as an animal model to study the specific anosmia to isovaleric acid. We have compared the olfactory performances of C57BL/6J mice and AKR/J mice using one-bottle and two-bottle tests to study the latencies of contacts with odorized or control drinks after odor-aversion conditioning. In both inbred strains, sensitivities to airborne molecules of amyl acetate (control odor) or isovaleric acid are demonstrated. Differences in behavioral strategies are suggested but the results are consistent with the hypothesis of a selective hyposmia to isovaleric acid in C57BL/6J mice.

Animals↗