Biomedical subjects
Publications and source records attributed to C Rey.
Most calcium phosphates used as biomaterials are well characterized high temperature compounds presenting both bulk and surface properties very different from those of bone mineral. The composition and structure of biomaterials and bone mineral are discussed in order to highlight the differences and determine their consequences on biological behaviour.
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In a cohort of 30 randomly selected hemophiliacs who were prospectively controlled for four years the predictive value of AIDS development was evaluated for serum markers of HIV infection and for lymphocytic subpopulations in peripheral blood. The patients were evaluated with a mean of 15.79 +/- 5.74 months, and overall antibodies, specific antibodies (anti-ENV and anti-p24), HIV antigen (Ag HIV) and lymphocyte subpopulations were determined. 50% of the hemophiliacs with positive serum Ag HIV (2/4) developed AIDS during the study, whereas this progression was not recorded in any anti-HIV positive, nonantigenic patient. The presence of Ag-HIV was detected at least two years before the diagnosis in these patients, and it was associated with the absence of anti-p24 in one or more determinations. The immune regulation parameters were not significantly different, at the beginning of the study, in the hemophiliacs who developed AIDS and in those who did not. However, the progression to AIDS was associated with a significantly smaller T4/T8 ratio at least one year before the diagnosis. Our results show that the development of AIDS in hemophiliacs is associated both with the presence of Ag-HIV in the serum and a reduction in the T4/T8 ratio, although the detection of the former appears to be earlier than that of the latter in this risk group.
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We studied the effects of a series of vasodilators on intrahepatic vascular resistance of isolated perfused cirrhotic rat livers in basal conditions and during norepinephrine-induced vasoconstriction. Cirrhosis was induced by repeated intraperitoneal injections of carbon tetrachloride. The vasodilators were a nonselective beta-adrenergic antagonist (propranolol), an alpha 1-adrenergic antagonist (prazosin), a nonselective beta-adrenergic agonist (isoproterenol), an alpha 2-agonist (clonidine), nitrovasodilators (nitroglycerin and nitroprusside), calcium channel blockers (verapamil, diltiazem, nifedipine), papaverine, diazoxide and pentoxifylline. In basal conditions, isoproterenol, nitroglycerin, papaverine, pentoxifylline and nitroprusside demonstrated significant vasodilatory activity. However, the response was weak and isoproterenol was the only drug active in the therapeutic range of concentrations. Propranolol, prazosin, verapamil, diltiazem, nifedipine and diazoxide were ineffective. Prazosin, papaverine and pentoxifylline reduced norepinephrine-induced vasoconstriction, whereas isoproterenol, clonidine and propranolol were ineffective. We conclude that several vasodilators can reduce resistance in the cirrhotic rat liver, but their potency is low and few are effective at therapeutic concentrations. Furthermore, their activity may be blunted when resistance is increased by norepinephrine.
The effects of two vasodilators, papaverine and pentoxifylline (a methylxanthine derivative), on liver function after 19 hr hypothermic preservation were investigated. Hypothermic preservation was performed according to the standard technique, and liver hemodynamics and function were studied during 70 min immediately after reperfusion in an isolated perfused rat liver system. No significant changes occurred after hypothermic storage for 5 hr. However, when the storage was prolonged to 19 hr, bile flow and taurocholate intrinsic clearance were significantly reduced; transaminase release was markedly increased and histological studies demonstrated centrilobular necrosis. Concomitantly, liver blood flow was significantly reduced and intrahepatic vascular resistance was increased. Papaverine and pentoxifylline administered during preservation and at the time of reperfusion significantly improved all parameters. The improvement was more pronounced after pentoxifylline, and this group showed no significant difference in any of the studied parameters from the control livers. The results show that two vasodilators significantly protect the liver during long hypothermic preservation. The data suggest that abnormalities of liver microcirculation are of major importance in the pathogenesis of liver injury after hypothermic storage.
Two babies with severe cardiac failure caused by a large arteriovenous malformation of the vein of Galen were evaluated with 2-dimensional ultrasound, pulsed and colour Doppler techniques. In both cases similar findings were recorded: dilated right cardiac chambers with high cardiac output in superior vena cava and ascending aorta; retrograde diastolic flow in descending aorta and continuous forward flow in arch arteries reflecting low resistance to flow in cerebral arteries; recirculation of microbubbles through the superior vena cava after passage unchanged through the cerebral malformation following contrast injection of saline into a peripheral vein or an arterial umbilical line. In addition, colour Doppler study of the brain clearly showed the malformation and the dilated straight sinus. Arteriovenous malformation of the vein of Galen can be noninvasively and easily detected by ultrasound studies of the heart and the brain.
In a prospective study of 37 individuals in Spain who did not have AIDS or AIDS-related complex but were positive for antibody to HIV, 164 sequentially taken serum samples were tested for the presence of the p24 antigen of HIV. Six of the subjects were antigenemic at entry to the study and five of the remaining 31 subjects seroconverted for HIV antigen during follow-up. Six (55%) of the 11 antigenemic patients but none of those without antigenemia developed AIDS. The interval from the time of first detection of HIV antigen to the diagnosis of AIDS varied greatly. The results confirm that individuals with HIV antigenemia run a significantly higher risk of developing AIDS.
The environment of carbonate ions in bones of different species (rat, rabbit, chicken, cow, human) was investigated by Fourier Transform Infrared Spectroscopy (FTIR) associated with a self-deconvolution technique. The carbonate bands in the v2 CO3(2-) domain show three components which were identified by using synthetic standards and different properties of the apatitic structure (ionic affinity for crystallographic locations, ionic exchange). The major component at 871 cm-1 is due to carbonate ions located in PO4(3-) sites (type B carbonate). A band at 878 cm-1 was exclusively assigned to carbonate ions substituting for OH-ions in the apatitic structure (type A carbonate). A band at 866 cm-1 not previously observed was shown to correspond to a labile carbonate environment. The intensity ratio of type A to type B carbonate appears remarkably constant in all bone samples. The 866 cm-1 carbonate band varies in its relative intensity in different species.
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When implanted subcutaneously in rats, devitalized bone particles (BP) elicit the differentiation of osteoclastic cells. Those cells can be distinguished from foreign body giant cells that form in response to particulate plastics. Osteoclast features include resorption of the bone substrate, ruffled borders, calcitonin receptors, tartrate-resistant acid phosphatase activity, and modulation by bone active agents. To determine whether expression of these features depends on specific components of the matrix, we characterized the multinucleated cells that developed in response to osteocalcin-deficient BPs, particulate microcrystalline hydroxyapatite (HA), and HA containing 0.1% osteocalcin, collagen, or bovine serum albumin. Only those particles that contained mineral and osteocalcin were associated with osteoclastic cells. These studies support the hypothesis that osteocalcin may function as a matrix signal in the differentiation of osteoclasts.
Resolution enhanced FT-IR spectroscopy shows that non-apatitic environments of phosphate and carbonate ions occur in bone mineral. The spectroscopic characteristics of these environments and their chemical and biological properties are reviewed. The potential effectiveness of FT-IR for the detailed study of bone mineral changes in bone disease is shown by analysis of several samples.
The records of 5 neonates with systemic arterial thrombosis (aortic in one case, peripheral in four cases) were reviewed. Fibrinolysis was performed with urokinase administered by infusion (1,000 to 4,000 U/kg/h). This treatment was combined with heparin therapy in 4 cases. Thrombosis was due to various causes: umbilical arterial catheter (1 case), disorders of supraventricular rhythm in utero (1 case), aneurysm of the ductus arteriosus with dysplastic aortic arch vessels (2 cases); one of these patients also had myocardiopathy. No cause could be found in a premature child weighing 1,300 g. The presenting symptoms of systemic arterial thrombosis are ischaemia of the extremities and suppression of peripheral pulses; heart failure with arterial hypertension is frequent. In our series the diagnosis was confirmed by doppler-ultrasonography in one case and by angiography in three cases (angiography in the left ventricule with foramen ovale, or umbilical aortography). Treatment with urokinase lasted 1.5 to 7 days. In 2 children the initial dosage had to be increased as there was no clinical improvement. Four children were completely cured; the fifth child, who had left renal thrombosis, shows slight functional impairment of the left kidney. There were no haemorrhagic complications. The fibrinolytic treatment with urokinase of systemic arterial thrombosis in the newborn is effective and has few drawbacks.
In order to establish the value of a small dose of trinitrine (0.4 mg less than 1 yr and 0.8 mg greater than 1 yr of age) to facilitate access to peripheral veins in the pediatric age group, 150 children were divided in 3 equal groups. In group 1, trinitrine was used whereas in group 2 vaseline was applied to the puncture site. In group 3, trinitrine was applied at a distance from the zone of puncture. The degree of difficulty of gaining access to the venous system was assessed through the use of scoring from 1 to 5. A score of 1 indicated easy access, 5 was indicative of failure. In order to determine the eventual hemodynamic effects of such a dose of trinitrine, 8 children were studied during a cardiac catheterization. Application of trinitrine on the zone of puncture made easier the peripheral venous approach in children under 1 year of age (p less than 0.02). No patient presented with headache or vertigo and no hemodynamic changes were observed during cardiac catheterization. The application of a small percutaneous dose of trinitrine on the zone of puncture seems to be a simple, efficacious and innocuous method to facilitate access to peripheral veins in infants.
We reviewed the clinical data on 23 patients operated on for constrictive pericarditis. Mean age was 35 years and 17 were males. The chief complaint was dyspnea (87%). Outstanding physical findings were venous hypertension (96%), hepatomegaly (78%), ascitis (57%), pulsus paradoxus (57%) and Kussmaul sign (43%). The ECG, although always abnormal was non contributory. Chest X ray findings included cardiomegaly (48%) and pericardial calcification (35%). Half of the cases showed pericardial thickening and abnormal septal motion on M mode echocardiography. An equalization of diastolic pressures and the dip and plateau sign was confirmed at cardiac catheterization in all cases. The etiology could be established in only 6 patients (tuberculosis 3, traumatic 2 and septic 1). Surgical mortality was 9% (2 patients). Follow up was available on 10 patients at a mean of 35 months, 9 in functional class I and 1 in FC II.
Dukes' classification is the most usually used method of staging in colorectal carcinoma. However the pitfalls of this classification may be attested by the multitude of modifications of Dukes' staging during the last sixty years. The aim of our study was to evaluate the influence of 25 variables on survival in colorectal carcinoma using the Cox model. This study was performed in 321 patients operated on for colorectal carcinoma. In the 252 patients who had had a curative resection univariate analysis showed that survival was related to 6 variables: age, juxtatumoral lymph node involvement, an abdominal mass, complicated carcinoma, duration of symptoms, and depth of tumor penetration. Stepwise analysis showed the independent influence of 7 variables on survival: age, lymph node involvement, depth of tumor penetration, duration of symptoms, direct spread, preexisting deficiencies, and sex. A byproduct of the regression coefficient of Cox' model was a numerical value for each of these predictive factors. A single composite score was obtained by adding the individual scores of factors from which a prediction of outcome can be made. Applying this model to each of the 252 patients resected for cure, we established three prognostic groups. They predict survival more accurately than the Dukes' system. Our scoring system based on multivariate analysis must successfully defined prognostic groups of patients in other series. Then, it should be recommended for staging in curative resection for colorectal carcinoma.
In order to investigate the mechanisms involved in some brain disorders at the membrane level, we studied the kinetics and biochemical properties of brain CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15), the rate-limiting enzyme of the two-step biosynthesis of phosphatidylcholine. This enzyme catalyzes the biosynthesis of CDPcholine from choline phosphate and CTP. We found that its subcellular localization (mainly in microsomal and cytosolic fractions) was different from that of phosphatidylethanolamine N-methyltransferase (EC 2.1.1.17), the enzyme of the alternative pathway for phosphatidylcholine synthesis. CTP:choline-phosphate cytidylyltransferase showed a Km of 10 mM for CTP and 0.3 mM for choline phosphate and exhibited a random mechanism. CDPcholine, the reaction product, was a competitive inhibitor of choline phosphate and CTP utilization and had a Ki of 0.090 mM. Both particulate and soluble enzymes required Mg2+ and exhibited an optimal pH at about 7. Cytosolic activity was enhanced by addition of unsaturated fatty acids or phospholipids extracted from brain membranes. Such an enhancement was increased with the centrifugation time used for preparing the soluble enzyme.