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Biomedical subjects

P Fernandez

Publications and source records attributed to P Fernandez.

At least 37 records · Page 2Linked to original sources

Long-term (> or =20 yr) status of 14 cadaveric kidney-transplant recipients.

The aim of this study was to analyze the status of patients with a successful long-term (> or =20 yr) kidney graft. Nineteen (8.1%) of the 234 recipients who received a cadaveric kidney transplant between 1968 and 1978 in our center are still alive 21.7+/-1.6 yr (mean+/-standard error of the mean) later with a functioning allograft. Function, including measurement of the renal functional reserve (RFR), histological status, and morbidity were evaluated. Fourteen patients agreed to participate in this study. Their current immunosuppressive regimens combined prednisone (P)+azathioprine (AZA) (n=9), P+AZA+cyclosporine (CsA) (n=3) or P+CsA (n=2). Although they described their quality of life as good, 10 patients had mild hypertension, 5 developed 10 malignancies (9 cutaneous), 5 had replicative hepatitis, 8 had osteopenia, and 6 had cataracts, but none had diabetes mellitus. Proteinuria was detected in 6 patients, but was always less than 1 g/d. Mean serum creatinine was 1.28+/-0.28 mg/dL and glomerular filtration rate was 54.5+/-5.3 mL/min/1.73 m2. RFR was present for 4 patients with a mean value of +14.8+/-1.9 mL/min. Their functional status was not correlated with the histological lesions observed in concomitant transplant biopsies. Kidney grafts are able to function well even more than 20 yr post-transplantation, with some having a RFR whose significance remains unknown. Morbidity is of minor clinical severity, but could be further reduced with optimized management. Moreover, transplantation is much less costly than hemodialysis.

Adult↗

Research on factors allowing a risk assessment of spore-forming pathogenic bacteria in cooked chilled foods containing vegetables: a FAIR collaborative project.

Vegetables are frequent ingredients of cooked chilled foods and are frequently contaminated with spore-forming bacteria (SFB). Therefore, risk assessment studies have been carried out, including the following: hazard identification and characterisation--from an extensive literature review and expertise of the participants, B. cereus and C. botulinum were identified as the main hazards; exposure assessment--consisting of determination of the prevalence of hazardous SFB in cooked chilled foods containing vegetables and in unprocessed vegetables, and identification of SFB representative of the bacterial community in cooked chilled foods containing vegetables, determination of heat-resistance parameters and factors affecting heat resistance of SFB, determination of the growth kinetics of SFB in vegetable substrate and of the influence of controlling factors, validation of previous work in complex food systems and by challenge testing and information about process and storage conditions of cooked chilled foods containing vegetables. The paper illustrates some original results obtained in the course of the project. The results and information collected from scientific literature or from the expertise of the participants are integrated into the microbial risk assessment, using both a Bayesian belief network approach and a process risk model approach, previously applied to other foodborne hazards.

Bacillus cereus↗

Bis[2-(diphenylphosphinoyl)benzene] disulfide.

The title compound, [2-Ph(2)P(O)C(6)H(4)S](2) or C(36)H(28)O(2)P(2)S(2), obtained by electrochemical oxidation of 2-(diphenylphosphino)benzenethiol, has twofold crystallographic symmetry. Principal dimensions include S-S 2.0212 (15) A, S-C 1.786 (3) A and C-S-S-C 81.34 (14) degrees.

Journal Article↗

Parametric down conversion of X-ray photons.

Parametric down conversion of X-ray photons in diamond crystals was detected in two experiments, both using the phase-matching scheme first employed in the X-ray regime by Eisenberger & McCall [Phys. Rev. Lett. (1971), 26, 684-688]. The conversion events were detected by a combination of time-correlation spectroscopy and energy discrimination, using Si drift-chamber detectors. The time-correlation spectra give a direct comparison of the conversion rate over the accidental coincidence rate. Mechanisms for possible detection of false events and ways to cross check against them are discussed in detail.

Journal Article↗

Performance limits of direct cryogenically cooled silicon monochromators - experimental results at the APS.

The successful use of cryogenically cooled silicon monochromators at third-generation synchrotron facilities is well documented. At the Advanced Photon Source (APS) it has been shown that, at 100 mA operation with the standard APS undulator A, the cryogenically cooled silicon monochromator performs very well with minimal (<2 arcsec) or no observable thermal distortions. However, to date there has not been any systematic experimental study on the performance limits of this approach. This paper presents experimental results on the performance limits of these directly cooled crystals. The results show that if the beam is limited to the size of the radiation central cone then, at the APS, the crystal will still perform well at twice the present 100 mA single 2.4 m-long 3.3 cm-period undulator heat load. However, the performance would degrade rapidly if a much larger incident white-beam size is utilized.

Journal Article↗

Suppression of growth plate chondrocyte proliferation by corticosteroids.

Growth depression is a side effect of high-dose glucocorticoid therapy in childhood. It is partially mediated by alterations of the somatotropic hormone axis and partially by direct local effects on growth plate chondrocytes. The mechanisms of interaction of corticosteroids and somatotropic and calciotropic hormones at the cellular level were recently investigated in more detail, using experimental models of primary cultures of growth plate chondrocytes. In proliferative chondrocytes, growth hormone (GH) and the calciotropic hormones parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1alpha,25(OH)2D3] increase cell proliferation via stimulation of paracrine insulin-like growth factor-I (IGF-I) secretion. Corticosteroids decreased GH, and PTH or 1alpha,25(OH)2D3 stimulated cell growth in a dose-dependent manner. Corticosteroids in high doses reduced the expression of the GH receptor and type 1 IGF receptor. But the main antiproliferative molecular effect of corticosteroid was the reduction in basal and hormone-stimulated IGF-I secretion. The in vitro results are in accordance with the observation in animal experiments and in children treated with corticosteroids, demonstrating that the growth-depressing effect of corticosteroids can be compensated for by supraphysiological doses of GH or IGF-I.

Adrenal Cortex Hormones↗

[Sonographic evaluation of human male infertility].

The male partner is responsible for 50% of infertility in couples. Assessment of male infertility should include clinical examination, laboratory tests (semen analysis, dosage of gonadal and gonadotropic hormones) and sonographic examination of the urogenital tract. Male infertility is related to diverse abnormalities including testis lesions (infertility of secretory type) and obstructive disorders of the genital tract (infertility of excretory type). Sonographic examination with abdominal, scrotal and transrectal probes has become the major imaging modality to evaluate male infertility and especially to analyze infertility of excretory type related to inflammatory lesions, congenital agenesis of vas deferens and congenital cyst of the distal genital tract. The main purpose of this paper is to illustrate with sonography the normal anatomy of the male genital tract and to detail sonographic features of current pathologies responsible for human male infertility.

Diagnosis, Differential↗

Efficacy of a chlorine dioxide-containing mouthrinse in oral malodor.

Studies have suggested that when chlorine dioxide is contained in a mouthrinse, it neutralizes volatile sulfur compounds in mouth air. The efficacy of a chlorine dioxide-containing mouthrinse in the reduction of oral malodor was evaluated in a randomized, controlled, double-blind, parallel group study of 31 men and women. Subjects with a maximum odor pleasantness score of < or = -1 (slightly unpleasant/stale) on a 7-point ordinal scale at both screening and baseline were randomized to treatment with the chlorine dioxide-containing rinse (n = 16) or distilled water (negative control) (n = 15). Oral malodor was evaluated at baseline (prerinse) and at 2, 4, 8, 24, 48, 72, and 96 hours postrinse by both a trained, previously calibrated panel of organoleptic judges and a factory-calibrated portable sulfide monitor. The sulfide monitor measured concentrations of volatile sulfur compounds in the subjects' mouth air 3 minutes after completion of the organoleptic assessment at each time point. The correlation between the organoleptic assessments and log-transformed sulfide monitor values was evaluated. With the chlorine dioxide mouthrinse, a statistically significant improvement in odor pleasantness, reduction in odor intensity, and reduction in oral volatile sulfur compound concentrations compared to the water control were evident at 2 hours postrinse and persisted through 8 hours postrinse. The mean (+/- SD) odor pleasantness improved from -1.25 +/- 0.31 at baseline to -0.73 +/- 0.33 at 2 hours postrinse in the chlorine dioxide group compared to -1.40 +/- 0.38 at baseline to -1.31 +/- 0.67 at 2 hours in the control group (P < 0.01). Odor pleasantness reached its maximum change from baseline to 0.63 +/- 0.45 at 8 hours postrinse. The mean (+/- SD) log-transformed sulfide monitor measurement decreased from 5.40 +/- 0.29 at baseline to 5.17 +/- 0.13 at 2 hours postrinse in the chlorine dioxide group, but increased from 5.47 +/- 0.40 at baseline to 5.56 +/- 0.54 at 2 hours in the control group (P < 0.01). As measured by the sulfide monitor, the mean volatile sulfur compound concentration in the chlorine dioxide group reached its minimum level at 8 hours postrinse (change from baseline in the log-transformed Halimeter measurement of -0.35 +/- 0.31). Thus, this study demonstrates that a one-time use of a chlorine dioxide-containing mouthrinse significantly improves mouth odor pleasantness, reduces mouth odor intensity, and reduces volatile sulfur compound concentrations in mouth air for at least 8 hours after use.

Adult↗

Interference by the intracellular parasite Theileria parva with T-cell signal transduction pathways induces transformation and protection against apoptosis.

The intracellular parasite Theileria parva transforms bovine T-lymphocytes, inducing uncontrolled proliferation. Upon infection, cells cease to require antigenic stimulation and exogenous growth factors to proliferate. Earlier studies have shown that pathways triggered via stimulation of the T-cell receptor are silent in transformed cells. This is reflected by a lack of phosphorylation of key signalling molecules and the fact that proliferation is not inhibited by immunosuppressants such as cyclosporin and ascomycin that target calcineurin. This suggests that the parasite bypasses the normal T-cells activation pathways to induce proliferation. Among the MAP-kinase pathways, ERK and p38 are silent, and only Jun N-terminal kinase is activated. This appears to suffice to induce constitutive activation of the transcription factor AP-1. More recently, it could be shown that the presence of the parasite in the host cell cytoplasm also induces constitutive activation of NF-kappaB, a transcription factor involved in proliferation and protection against apoptosis. Activation is effectuated by parasite-induced degradation of IkappaBs, the cytoplasmic inhibitors which sequester NF-kappaB in the cytoplasm. NF-kappaB activation is resistant to the antioxidant N-acetyl cysteine and a range of other reagents, suggesting that activation might occur in an unorthodox manner. Studies using inhibitors and dominant negative mutants demonstrate that the parasite activates a NF-kappaB-dependent anti-apoptotic mechanism that protects the transformed cell form spontaneous apoptosis and is essential for maintaining the transformed state of the parasitised cell.

Animals↗

Effect of frequency and tidal volume on pleural pressure in rabbits during high frequency ventilation.

Regional effects of the chest wall on airway pressure transmission were studied during high frequency ventilation in anesthetized rabbits. We measured airway pressure (Paw), esophageal pressure (Pes), and costal pleural pressure (Ppl) by a rib capsule and flow and volume with a calibrated pneumotachograph. Using a closed circuit, pressures and flow were measured at varying frequencies (2-80 Hz) and tidal volumes (2-20 ml). Mean Pes and Ppl increased with flow amplitude above 100-250 ml/s, whereas mean Paw decreased, consistent with air trapping. Paw, Pes, and Ppl amplitudes increased monotonically with flow amplitude except above 400-500 ml/s, where the Ppl amplitude decreased suddenly. The latter occurring simultaneously with a sudden fall in mean Paw indicated airway flow limitation in costal regions. Flow instabilities during flow limitation were consistent with the large increase in the phase difference between Paw and Ppl and its variability, with frequency. By contrast, the phase difference between Paw and Pes and its variability were relatively small. These differences in Pes from Ppl responses might be caused by a difference in the impedance of the airway-mediastinum pathway or a direct transmission of tracheal pressure oscillations to the esophagus. The former suggests that constraints offered by the mediastinum and rib cage resulted in nonuniform ventilation during high frequency ventilation.

Animals↗

In vitro assessment of endothelial cell adhesion mechanism on vascular patches.

Endothelial cell (EC) seeding of small caliber vascular grafts prior to their implantation has proved to significantly improve long-term patency in humans. We have previously demonstrated that a monolayer of EC could be obtained on type I collagen-coated knitted ultrathin polyster grafts (InterVascular, La Ciotat, France). Thus, the aim of the present work was to understand the nature of cell adhesion mechanisms involved in the cell /biomaterial interface, using HemaCarotid (InterVascular) patches made of type I collagen-coated knitted ultrathin polyster (type I collagen is used to coat patches to attain low permeability). By means of quantitative attachment tests, adhesion blocking assays, RT-PCR for the expression of beta1 integrin mRNA, indirect immunofluorescence with antivinculin antibody, we were able to show that EC are able to adhere to such surfaces by the means (non-unique) of cell surface receptors of the beta1 integrin group. However, the latter are probably downregulated at the cell/biomaterial interface.

Journal Article↗

Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice.

A lifetime experiment using 4279 CBA/J mice was carried out to investigate whether the pre-conceptual exposure of sperm cells to X-ray radiation or urethane would result in an increased cancer risk in the untreated progeny, and/or increased susceptibility to cancer following exposure to a promoting agent. The study consisted of four main groups, namely a control group (saline), a urethane group (1 mg/g body wt) and two X-ray radiation groups (1 Gy, 2 Gy). At 1, 3 and 9 weeks after treatment, the males of these four parental groups were mated with untreated virgin females. The offspring of each parental group was divided into two subgroups: one received s.c. urethane (0.1 mg/g body wt once) as a promoter, the other saline, at the age of 6 weeks. All animals were evaluated for the occurrence of tumours. K-ras oncogene and p53 tumour suppressor gene mutations were investigated in frozen lung tumour samples. The female offspring of male parents exposed to X-rays 1 week before their mating showed a trend towards a higher tumour incidence of the haematopoietic system than the F1 controls. In addition, a higher percentage of bronchioloalveolar adenocarcinomas in male offspring born to irradiated paternals mated 1 week after X-ray treatment points to a plausible increased sensitivity of post-meiotic germ cell stages towards transgenerational carcinogenic effects. On the other hand, no increased tumour incidence and malignancy were observed in the offspring born to irradiated paternals mated 3 and 9 weeks after X-ray treatment. Paternal urethane treatment 1, 3 and 9 weeks prior to conception did not result in significantly altered incidence or malignancy of tumours of the lung, liver and haematopoietic tissue in the offspring. K-ras mutations increased during tumour progression from bronchioloalveolar hyperplasia to adenoma. Codon 61 K-ras mutations were more frequent in lung tumours of urethane-promoted progeny from irradiated parents than from control parents. P53 mutations were absent from these lung alterations.

Adenocarcinoma↗

Clinical performance of vascular grafts lined with endothelial cells.

The replacement of arteries with purely synthetic vascular prostheses often leads to the failure of such reconstructions when small-diameter or low-flow locations are concerned, due in part to the thrombogenicity of the internal graft surface. In order to improve long-term patency of these grafts, the concept of endothelial cell seeding has been suggested because this metabolically active endothelial surface plays major roles in preventing in vivo blood thrombosis and because vascular grafts placed in humans do not spontaneously form an endothelial monolayer whereas they do in animal models. The composite structure resulting from the combination of biologically active cells to prosthetic materials thus creates more biocompatible vascular substitutes. To achieve endothelialization of synthetic vascular grafts, previous efforts aimed at "one-stage" procedure (adding autologous endothelial cells to the graft at the time of implantation) in the 1980's seemed clinically feasible but results of reported clinical trials were controversial and mostly disappointing. An alternative method is an in vitro complete and preformed endothelial lining at the time of implantation: the "two-stage" procedure which implies harvest and culture of autologous endothelial cells. Up to date, the latter approach demonstrated its superiority in terms of significantly increased patency of the grafts that underwent endothelialization eight years earlier.

Blood Vessel Prosthesis↗

Value of captopril renal scintigraphy in hypertensive patients with renal failure.

UNLABELLED: The aims of this study were to show the value of captopril renal scintigraphy for detecting a renovascular cause in hypertensive patients with renal failure and to assess the ability to predict the beneficial effect of revascularization on renal function. METHODS: Thirty-eight patients with renal failure (mean glomerular filtration rate = 35 mL/min) underwent renal scintigraphy after injection of 99mTc-mercaptoacetyltriglycine. Baseline scintigraphy was performed, and the test was repeated 24 h later after oral administration of 50 mg captopril given 60 min before the test. RESULTS: In 5 of 6 patients with a renovascular cause for renal failure, and 2 of 3 patients with a probable arterial pathology, scintigraphy had a high probability. The result was indeterminate in the other 2 patients. In 5 of 11 patients with negative arteriography and 14 of 18 patients with probable absence of renovascular pathology, we found a low probability of functional renal artery stenosis. Six revascularization procedures were performed and were predictive of a beneficial effect in 5 patients. Time of peak activity was an effective predictor in each case. CONCLUSION: In hypertensive patients with renal failure, captopril renal scintigraphy can detect hemodynamic dysfunction downstream from a renal artery stenosis and can predict the beneficial effect of revascularization in some cases.

Adult↗

A novel potential application for 99mTc-HMPAO: endothelial cell labeling for in vitro investigation of cell-biomaterial interactions.

UNLABELLED: Good adherence of endothelial cells (ECs) seeded on vascular prostheses and cell retention under flow conditions are important factors to consider in the use of functionalized prostheses in vascular surgery. Because 111In-oxine radiolabeling presents disadvantages, we wondered whether, because of its well-known physical properties, 99mTc-hexamethyl propyleneamine oxime (HMPAO or exametazime) could be used. METHODS: The cytotoxicity of unlabeled HMPAO and 99mTc-HMPAO at increasing concentrations and activities was tested on monolayers of the EC line EA-hy-926. The influence of temperature and time on tracer incorporation into cells was also tested. The optimal labeling conditions were applied to evaluate the retention of ECs seeded on polyester grafts under flow conditions by gamma camera detection. RESULTS: The activity of 10 MBq/10(6) cells corresponding to 4.5 microg/10(6) cells of unlabeled HMPAO, applied for 3 h at 37 degrees C (cellular uptake = 18%), was the best compromise between the maintenance of cell viability and metabolic activity and efficient detection by the gamma camera. Spontaneous leakage was observed and analyzed by high-performance liquid chromatography. A cell loss of 13% after 180-min exposure to shear stress was obtained. CONCLUSION: Our data thus indicate the feasibility of using such a radiolabeling technique to investigate EC-biomaterial interactions.

Blood Vessel Prosthesis↗