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Biomedical subjects

M Sperandio

Publications and source records attributed to M Sperandio.

At least 19 recordsLinked to original sources

DNA ploidy in proliferative verrucous leukoplakia.

Proliferative verrucous leukoplakia (PVL) is a clinicopathologically distinctive form of oral leukoplakia presenting with multifocal flat, nodular and verrucous lesions that progress inexorably to squamous carcinoma. The aims of this investigation were to describe the clinical and histopathological features of six cases of PVL and to determine whether lesional epithelium demonstrates DNA ploidy anomalies prior to malignant transformation. The clinical and pathological features of six patients were reviewed and all biopsy specimens were subjected to image-based DNA ploidy analysis. The female:male ratio was 5:1 and the average age on first biopsy was 66 years. Only one patient reported both tobacco smoking and alcohol intake. The most frequently affected sites were alveolar ridge and/or gingiva (6/6), buccal mucosa (3/6), palate (3/6), tongue (2/6), buccal sulcus (2/6), and lip (1/6). Three patients developed multiple primary carcinomas, either invasive or verrucous. A ploidy anomaly at any oral site would have predicted malignant transformation in four cases and probably in a fifth for whom DNA ploidy failed to meet diagnostic criteria but was suspicious of aneuploidy. The site of transformation was predicted by ploidy and histopathology for three carcinomas and a further carcinoma showed severe dysplasia and a suspicious ploidy result in adjacent tissue. Both conventional histopathology and DNA ploidy proved effective in predicting the site of transformation in this limited series.

Aged↗

Heterogeneity, histological features and DNA ploidy in oral carcinoma by image-based analysis.

Oral squamous carcinomas appear heterogeneous on DNA ploidy analysis. However, this may be partly a result of sample dilution or the detection limit of techniques. The aim of this study was to determine whether oral squamous carcinomas are heterogeneous for ploidy status using image-based ploidy analysis and to determine whether ploidy status correlates with histological parameters. Multiple samples from 42 oral squamous carcinomas were analysed for DNA ploidy using an image-based system and scored for histological parameters. 22 were uniformly aneuploid, 1 uniformly tetraploid and 3 uniformly diploid. 16 appeared heterogeneous but only 8 appeared to be genuinely heterogeneous when minor ploidy histogram peaks were taken into account. Ploidy was closely related to nuclear pleomorphism but not differentiation. Sample variation, detection limits and diagnostic criteria account for much of the ploidy heterogeneity observed. Confident diagnosis of diploid status in an oral squamous cell carcinoma requires a minimum of 5 samples.

Carcinoma, Squamous Cell↗

Evaluation of venous and arterial conduit patency by 16-slice spiral computed tomography.

BACKGROUND: Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. METHODS AND RESULTS: In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. CONCLUSIONS: MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.

Aged↗

Differential requirements for core2 glucosaminyltransferase for endothelial L-selectin ligand function in vivo.

L-selectin is a calcium-dependent lectin on leukocytes mediating leukocyte rolling in high endothelial venules and inflamed microvessels. Many selectin ligands require modification of glycoproteins by leukocyte core2 beta1,6-N-acetylglucosaminyltransferase (Core2GlcNAcT-I). To test the role of Core2GlcNAcT-I for L-selectin ligand biosynthesis, we investigated leukocyte rolling in venules of untreated and TNF-alpha-treated cremaster muscles and in Peyer's patch high endothelial venules (HEV) of Core2GlcNAcT-I null (core2(-/-)) mice. In the presence of blocking mAbs against P- and E-selectin, L-selectin-mediated leukocyte rolling was almost completely abolished in cremaster muscle venules of core2(-/-) mice, but not littermate control mice. By contrast, leukocyte rolling in Peyer's patch HEV was not significantly different between core2(-/-) and control mice. To probe L-selectin ligands more directly, we injected L-selectin-coated beads. These beads showed no rolling in cremaster muscle venules of core2(-/-) mice, but significant rolling in controls. In Peyer's patch HEV, beads coated with a low concentration of L-selectin showed reduced rolling in core2(-/-) mice. Beads coated with a 10-fold higher concentration of L-selectin rolled equivalently in core2(-/-) and control mice. Our data show that endothelial L-selectin ligands relevant for rolling in inflamed microvessels of the cremaster muscle are completely Core2GlcNAcT-I dependent. In contrast, L-selectin ligands in Peyer's patch HEV are only marginally affected by the absence of Core2GlcNAcT-I, but are sufficiently functional to support L-selectin-dependent leukocyte rolling in Core2GlcNAcT-I-deficient mice.

Animals↗

Severe impairment of leukocyte rolling in venules of core 2 glucosaminyltransferase-deficient mice.

Leukocyte capture and rolling are mediated by selectins expressed on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To investigate the role of core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I) for synthesis of functional selectin ligands in vivo, leukocyte rolling flux and velocity were studied in venules of untreated and tumor necrosis factor-alpha (TNFalpha)-pretreated autoperfused cremaster muscles of C2GlcNAcT-I-deficient (core 2(-/-)) and littermate control mice. In untreated core 2(-/-) mice, leukocyte rolling was dramatically reduced with markedly increased rolling velocities (81 +/- 4 microm/s vs 44 +/- 3 microm/s). The reduced rolling in core 2(-/-) mice was due mainly to severely impaired binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1). Some rolling remained after blocking PSGL-1 in controls but not in core 2(-/-) mice. In TNFalpha-pretreated mice, rolling was markedly reduced in core 2(-/-) mice owing to impaired P-selectin- and E-selectin-mediated rolling. Rolling velocities in core 2(-/-) mice treated with an E-selectin-blocking monoclonal antibody (59 +/- 4 microm/s) were significantly higher than in controls (14 +/- 1 microm/s), which provides further evidence for the severe impairment in P-selectin-mediated rolling. In conclusion, P-selectin ligands including PSGL-1 are largely C2GlcNAcT-I dependent. In addition, E-selectin-mediated rolling in vivo is partially dependent on the targeted C2GlcNAcT-I. (Blood. 2001;97:3812-3819)

Animals↗

Excess sludge production and costs due to phosphorus removal.

Based on data collected from 35 French wastewater treatment plants and on published data, excess sludge production and chemical consumption associated with phosphorus removal is estimated for the three following phosphorus removal processes: chemical precipitation, Enhanced Biological Phosphorus Removal and hybrid process. The influence of wastewater characteristics on excess sludge production are assessed. Chemical costs and costs associated with sludge disposal were calculated and results for the three phosphorus removal processes are compared. The global costs for phosphorus removal are then estimated.

Biodegradation, Environmental↗

The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium.

In a reconstituted flow chamber system, preincubation with chemokines can trigger the arrest of rolling monocytes, suggesting that this interaction could help recruit these cells to early atherosclerotic lesions. To date, however, the contribution of endothelium-derived chemokines found in these lesion to monocyte arrests has not been investigated. The endothelium of lesion-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE (mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic cell line or mouse blood monocytes perfused through carotid arteries of ApoE(-/-) mice was reduced by treating with either pertussis toxin, an antagonist of CXCR2, or an antibody to KC, but this process was insensitive to agents that blocked CCR-2 or JE. Conversely, monocyte accumulation more than doubled upon pre-perfusion of the carotid artery with KC but not with mouse MCP-1. Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD18 or intercellular adhesion molecule-1, almost completely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.

Animals↗

Effect of gamma radiation on dentin bond strength and morphology.

Sterilization by gamma radiation is a method often used for bone and extracted teeth banking. The bond strength of human dentin submitted to gamma rays has not been reported. Therefore, the aim of this study was to assess the effect of gamma radiation on dentin shear bond strength and morphology. The roots were removed from extracted human bicuspids and their crowns divided into two groups: an untreated control and crowns submitted to gamma radiation sterilization. The crowns were mounted in epoxy resin and the buccal enamel removed exposing the subjacent dentin. SBMPPlus adhesive system was applied to a 3-mm diameter area after 15 s of 35% phosphoric acid etching. The samples were mounted in composite resin cylinders and stored in distilled water at 37 degrees C for 24 h until the shear test. Dental fragments from both groups were prepared for SEM analysis. There was no statistically significant difference between the results of the shear test for the two groups according to the Tukey test (p > 0.05). Scanning electron micrographs also did not show alterations. These results indicate that gamma radiation neither affected the shear bond strength of SBMPPlus nor altered the dentin surface morphology.

Analysis of Variance↗

[Postoperative mortality a university Department of General Surgery: incidence of cardiac-related deaths].

OBJECTIVES: To evaluate the incidence of cardiac deaths following noncardiac nonvascular surgery. STUDY DESIGN: Retrospective survey. PATIENTS: All patients undergoing mainly endocrinous and digestive surgery in a University department of general surgery between 1991 and 1996. METHODS: Analysis of all deaths occurring intra- and postoperatively, until discharge of the patients. Demographic and medical data, including patent myocardial ischaemia and risk factors for coronary artery disease, were recorded and compared with a control group including all patients undergoing surgery from January to September 1996. RESULTS: In the 8,700 patients who underwent mainly endocrine neck surgery (66%), or intra-abdominal surgery (31%), the mortality rate (n = 96) was 1.1% (95% confidence interval [95% CI] = 0.9-1.3%). Patent myocardial ischaemia or high risk factors for coronary artery disease were existing in 24% of patients with neck surgery, 31% of those with intra-abdominal surgery, and in 60% of the deceased patients (P < 0.01 vs control group). Those who died were older, were in a higher ASA physical class, and had undergone an emergency procedure more often than patients of the control group (P < 0.002 for each parameter). Two cardiac deaths, in patients with a patent cardiopathy, were recorded (cardiac mortality: 0.02%; 95% CI = 0.003-0.08%). The main cause of death was infection (n = 46), followed by haemorrhage (n = 12). Seven deaths remained unexplained. CONCLUSION: This study suggests that cardiac morbidity is a rare cause of death after noncardiac nonvascular surgery.

Adult↗

Influence of the endothelial glycocalyx on cerebral blood flow in mice.

The endothelial surface layer (glycocalyx) of cerebral capillaries may increase resistance to blood flow. This hypothesis was investigated in mice by intravenous administration of heparinase (2500 IU/kg body weight in saline), which cleaves proteoglycan junctions of the glycocalyx. Morphology was investigated by transmission electron microscopy. Cerebral perfusion velocity was recorded before and during heparinase or saline treatment using laser-Doppler flowmetry. In addition, cerebral blood flow (CBF) was measured 10 minutes after heparinase or saline treatment using the iodo[14C]antipyrine method. Laser-Doppler flowmetry and CBF measurements were performed during normocapnia and severe hypercapnia (PCO2: 120 mm Hg). After heparinase, morphology showed a reduced thickness of the glycocalyx in cortical microvessels by 43% (P < 0.05) compared with saline-treated controls. Under normocapnic conditions, a 15% (P < 0.05) transient increase of cerebral flow velocity occurred 2.5 to 5 minutes after heparinase injection. Laser-Doppler flow and CBF returned to control values ten minutes after the injection. However, during severe hypercapnia, heparinase treatment resulted in a persisting increase in laser-Doppler flow (6%, P < 0.05) and CBF (30%, P < 0.05). These observations indicate the existence of a flow resistance in cerebral capillaries exerted by the glycocalyx. The transient nature of the CBF increase during normocapnia may be explained by a vascular compensation that is exhausted during severe hypercapnia.

Adaptation, Physiological↗

[Surgical treatment of benign thyroid nodules].

Benign thyroid nodules is a significant clinical problem since it involves more than 90% of all thyroid surgery. This has led the authors to perform a retrospective study of 190 patients suffering from this pathology out of 299 patients who underwent surgery from 1979 to 1995. 89 total thyroidectomies and 101 radical hemithyroidectomies were performed in patients suffering from benign thyroid nodules. Two cases of recurrent monolateral paralysis were found as well as 3 cases of permanent hypoparathyroidism in those patients who underwent total thyroidectomies. The results of numerous authors as well as the present case review indicate that more radical surgery does not significantly affect the degree of permanent complications. For this reason the authors are convinced that such radical surgery should be the treatment of choice, particularly in young patients whose life expectancy is long and where the likelihood of recurrence is greater.

Adult↗

Blood flow resistance during hemodilution: effect of plasma composition.

OBJECTIVES: To investigate the causes of wide variations in reported effects of hemodilution on flow resistance of vascular beds. METHODS: (a) In a meta-analysis of 28 prior studies, resistance values at hematocrits of zero (R0) and 0.45 (R0.45) were derived. Study design characteristics (presence of vasodilatory reserve or leukocytes, species, tissue, hemodiluent) were tested by ANOVA for their relation to the ratio R0/R0.45. (b) Experiments were performed to determine flow resistance during hemodilution in the rat mesentery with (n = 8) and without (n = 11) pretreatment with heparinase, which modifies the endothelial glycocalyx. (c) A mathematical flow simulation for mesenteric microvascular networks was used to predict resistance effects of hemodilution and of a hypothetical layer on the endothelial surface. RESULTS: (a) In prior studies using native plasma for hemodilution R0 averaged 50 +/- 8% of R0.45, while in studies using artificial solutions R0 averaged 32 +/- 12% of R0.45. The larger reduction of flow resistance upon dilution with artificial media is independent of viscosity and oncotic pressure. Other design characteristics did not show strong significant effects. (b) Present experiments showed large reductions of flow resistance with saline hemodilution which were nearly halved after heparinase pretreatment. (c) Resistance effects of hemodilution with plasma or after heparinase treatment agree with model predictions based on tube flow rheology of blood. The larger resistance effects of dilution with artificial media can be explained by the removal of an endothelial surface layer of approximately 1.5 microns thickness. CONCLUSIONS: The results imply that changes of plasma composition, due to use of artificial infusion media, influence peripheral resistance and tissue perfusion. They are consistent with the hypothesis that interactions between endothelial glycocalyx structures and plasma components lead to formation of a thick layer at the endothelial surface which increases flow resistance.

Animals↗

[PhysioFlex: a target-controlled self-regulating closed-circuit inhalation anesthesia regulator].

Physi Flex is the first commercially available apparatus capable for quantitative, or self-regulating target controlled inhalational anaesthesia, with a totally closed circuit, in adults and children. The fresh gas supply to the circuit is intermittent, automatically regulated by continuous monitoring of the volume and composition of the gas mixture in the breathing circuit. The circle system includes, instead of the two conventional one way valves, a blower creating a continuous unidirectional flow at 70 L.min-1. In addition to the CO2-absorber it contains an absorber with carbon, absorbing the anaesthetic vapour when switched into the circuit. The ventilator consists of four ventilating chambers, each one with a membrane separating the patient and the motor compartments. The displacement of the membranes generates and measures the tidal volume. Automatic ventilation is achieved by electric valves and motor gas, and manual ventilation using a bag. Spontaneous ventilation is also possible. The machine is operated via a computer with selects the number of ventilating chambers (one, two or four), and the tidal volume between 50 and 2,000 mL, depending on age, gender and weight of the patient. The computer maintains the gas volume and the gas and vapour concentrations at their preset values. The O2-flow and consumption, the N2O flow and uptake, FICO2 and FETCO2, FI and FET of the volatile anaesthetic, all other important data are displayed in a numerical and graphical form on a color screen and registered for a delayed analysis. The end tidal concentration of the volatile anaesthetic drives a stepmotor with a syringe containing the selected volatile anaesthetic agent with is directly injected into the breathing circuit where it is vaporized. Therefore the concentration of the anaesthetic vapour can be instantaneously increased with this injector at induction and lowered at end of anaesthesia with the carbon absorber, and the fresh gas consumption is significantly decreased.

Adult↗

Microvascular blood flow resistance: role of endothelial surface layer.

Observations of blood flow in microvascular networks have shown that the resistance to blood flow is about twice that expected from studies using narrow glass tubes. The goal of the present study was to test the hypothesis that a macromolecular layer (glycocalyx) lining the endothelial surface contributes to blood flow resistance. Changes in flow resistance in microvascular networks of the rat mesentery were observed with microinfusion of enzymes targeted at oligosaccharide side chains in the glycocalyx. Infusion of heparinase resulted in a sustained decrease in estimated flow resistance of 14-21%, hydrodynamically equivalent to a uniform increase of vessel diameter by approximately 1 micron. Infusion of neuraminidase led to accumulation of platelets on the endothelium and doubled flow resistance. Additional experiments in untreated vascular networks in which microvascular blood flow was reduced by partial microocclusion of the feeding arteriole showed a substantial increase of flow resistance at low flow rates (average capillary flow velocities < 100 diameters/s). These observations indicate that the glycocalyx has significant hemodynamic relevance that may increase at low flow rates, possibly because of a shear-dependent variation in glycocalyx thickness.

Animals↗

Interpleural infusion of 2% lidocaine with 1:200,000 epinephrine for postthoracotomy analgesia.

The value of intrapleural analgesia after thoracotomy is still controversial. We investigated the pharmacokinetics of interpleural analgesia in 14 patients with and without thoracic drainage (Groups TD+ and TD-, respectively) to determine the safety of the technique. The infusion led to a high steady-state concentration (Css) of 5.91 +/- 2.46 mg/mL in Group TD-. We then performed a placebo-controlled double-blind study on 16 patients to evaluate the analgesic effects of an interpleural infusion of 2% lidocaine using intravenous patient-controlled analgesia (PCA) with morphine and a visual analog scale score (VAS). In both studies an initial bolus of 3 mg/kg of 2% lidocaine was followed by an infusion of 1 mg.kg-1.h-1 for 48 h. The VAS score was slightly reduced after the bolus (6.6 +/- 1.0 vs 8.7 +/- 0.3; P < 0.05 vs the placebo group) but the cumulative doses of morphine were similar in both groups. There was a slight, but not sustained, improvement in pulmonary function test. In conclusion, interpleural analgesia by continuous infusion of lidocaine is poor after thoracotomy and may lead to blood levels in the toxic range.

Aged↗